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    Clinical Trial Results:
    An Open-label, Multicenter, Phase 2 Study Evaluating the Efficacy and Safety of Daratumumab in Pediatric and Young Adult Subjects ≥1 and ≤30 Years of Age With Relapsed/Refractory Precursor B-cell or T-cell Acute Lymphoblastic Leukemia or Lymphoblastic Lymphoma

    Summary
    EudraCT number
    2017-003377-34
    Trial protocol
    GB   DE   BE   FR   ES   SE   NL   IT   Outside EU/EEA  
    Global end of trial date
    22 Sep 2022

    Results information
    Results version number
    v1(current)
    This version publication date
    07 Apr 2023
    First version publication date
    07 Apr 2023
    Other versions

    Trial information

    Close Top of page
    Trial identification
    Sponsor protocol code
    54767414ALL2005
    Additional study identifiers
    ISRCTN number
    -
    US NCT number
    NCT03384654
    WHO universal trial number (UTN)
    -
    Sponsors
    Sponsor organisation name
    Janssen Research & Development, LLC
    Sponsor organisation address
    920 Route 202, Raritan, United States, NJ 08869
    Public contact
    Clinical Registry Group, Janssen Research & Development, LLC, ClinicalTrialsEU@its.jnj.com
    Scientific contact
    Clinical Registry Group, Janssen Research & Development, LLC, ClinicalTrialsEU@its.jnj.com
    Paediatric regulatory details
    Is trial part of an agreed paediatric investigation plan (PIP)
    Yes
    EMA paediatric investigation plan number(s)
    EMEA-002152-PIP01-17
    Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?
    Yes
    Results analysis stage
    Analysis stage
    Final
    Date of interim/final analysis
    22 Sep 2022
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    22 Sep 2022
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    The main purpose of this trial was to evaluate the efficacy of daratumumab in addition to standard chemotherapy in pediatric subjects with relapse/refractory B-cell acute lymphoblastic leukemia (ALL) and T-cell ALL as measured by complete resposne (CR) rate.
    Protection of trial subjects
    This study was conducted in accordance with the ethical principles that have their origin in the Declaration of Helsinki and that are consistent with Good Clinical Practices and applicable regulatory requirements.
    Background therapy
    -
    Evidence for comparator
    -
    Actual start date of recruitment
    05 Jun 2018
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    No
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Belgium: 1
    Country: Number of subjects enrolled
    Germany: 2
    Country: Number of subjects enrolled
    Spain: 12
    Country: Number of subjects enrolled
    France: 5
    Country: Number of subjects enrolled
    United Kingdom: 5
    Country: Number of subjects enrolled
    Israel: 2
    Country: Number of subjects enrolled
    Italy: 6
    Country: Number of subjects enrolled
    Netherlands: 2
    Country: Number of subjects enrolled
    United States: 11
    Worldwide total number of subjects
    46
    EEA total number of subjects
    28
    Number of subjects enrolled per age group
    In utero
    0
    Preterm newborn - gestational age < 37 wk
    0
    Newborns (0-27 days)
    0
    Infants and toddlers (28 days-23 months)
    0
    Children (2-11 years)
    24
    Adolescents (12-17 years)
    15
    Adults (18-64 years)
    7
    From 65 to 84 years
    0
    85 years and over
    0

    Subject disposition

    Close Top of page
    Recruitment
    Recruitment details
    -

    Pre-assignment
    Screening details
    One subject of Cohort 1: B-cell ALL (1-17 Years) was not enrolled in the study and thus 46 subjects were enrolled in the study and treated with study drug. Out of 46 subjects, 45 subjects completed the study.

    Period 1
    Period 1 title
    Overall Study (overall period)
    Is this the baseline period?
    Yes
    Allocation method
    Not applicable
    Blinding used
    Not blinded

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    Cohort 1: B-cell acute lymphoblastic leukemia(ALL) (1-17Years)
    Arm description
    Subjects with relapsed/refractory B-cell ALL received intrathecal methotrexate (MTX) 8milligrams(mg):1-less than(<)2 years (y), 10mg:2- <3 Y, 12mg:3- <9 Y and 15 mg:greater than or equal to(>=) 9 Y on Cycle(C) 1 Day(D) 1(all) and C2 and later D1 each C (CNS negative); for CNS positive, with MTX, hydrocortisone(HC)/cytarabine(ARA-C) was used per local standard practice; daratumumab 16 milligrams per kilogram (mg/kg) as intravenous(IV) infusion weekly on D1,8,15 and 22 of C1 and 2 then every 2 weeks on D1,15 of C3 to 6 and every 4 weeks on D1 of C7 and onward;vincristine 1.5 milligrams per square meter(mg/m^2) IV once weekly on D1,8,15 and 22 of C1, then every 2 weeks on D1 and 15 of C2 and every 4 weeks on D1 of C3 and onward;prednisone 40mg/m^2 once daily on D1 to 28 of C1 and on D1 to 5 of C2 onward. Subjects received treatment until disease progression, unacceptable toxicity, or proceeding hematopoietic stem cell transplant after CR whichever came first(maximum duration:2.3 months).
    Arm type
    Experimental

    Investigational medicinal product name
    Daratumumab
    Investigational medicinal product code
    Other name
    JNJ-54767414
    Pharmaceutical forms
    Concentrate for solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Subjects received daratumumab 16 milligrams per kilogram (mg/kg) IV infusion weekly on Days 1, 8, 15 and 22 of Cycles 1 and 2 then every 2 weeks on Days 1 and 15 of Cycle 3 to 6 and every 4 weeks on Day 1 of Cycle 7 and onward.

    Investigational medicinal product name
    Vincristine
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Concentrate for solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Subjects received vincristine 1.5 mg/m^2 IV injection/infusion weekly on Days 1, 8, 15 and 22 of Cycle 1, then every 2 weeks on Days 1 and 15 of Cycle 2 and every 4 weeks on Day 1 of Cycle 3 and onward.

    Investigational medicinal product name
    Intrathecal Hydrocortisone (HC)
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Concentrate for solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Subjects received intrathecal HC 8 mg for age 1- <2 years, 10 mg for age 2- <3 years, 12 mg for age 3- <9 years and 15 mg for >=9 years on Cycle 1 Days 8, 15, 22, 28 and Cycles 2 and later Day 1 of each cycle.

    Investigational medicinal product name
    Intrathecal methotrexate
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Concentrate for solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Subjects received intrathecal methotrexate 8 mg for age 1- <2 years, 10 mg for age 2- <3 years, 12 mg for age 3- <9 years and 15 mg for >=9 years on Day 1 of Cycle 1 and 2 onwards.

    Investigational medicinal product name
    Intrathecal Cytarabine (ARA-C)
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Concentrate for solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Subjects received intrathecal ARA-C 16 mg for age 1- <2 years, 20 mg for age 2- <3 years, 24 mg for age 3- <9 years and 30 mg for >=9 years on Cycle 1 Days 8, 15, 22, 28 and Cycles 2 and later Day 1 of each cycle.

    Investigational medicinal product name
    Prednisone
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet, Oral liquid, Oral suspension
    Routes of administration
    Oral use
    Dosage and administration details
    Subjects received prednisone 40 mg/m^2 orally daily on Days 1 to 28 of Cycle 1 and then on Days 1 to 5 of Cycle 2 and onward.

    Arm title
    Cohort 2: T-Cell ALL (1-17 Years)
    Arm description
    Subjects with relapsed/refractory T-cell ALL in C1 received intrathecal MTX 8mg:1- <2Y,10mg:2- <3Y, 12mg:3- <9Y and 15mg:>=9Y on C1 D1(all) each C (CNS negative);for CNS positive,with MTX,HC/ARA-C was used per local standard practice; daratumumab 16mg/kg IV infusion weekly on D1,8,15 and 22;doxorubicin 60mg/m^2 IV once on D1;vincristine 1.5mg/m^2 IV injection/infusion weekly on D1,8,15 and 22;prednisone 40mg/m^2 orally daily on D1-28;peg-asparaginase 25000 units per square meter(U/m^2) as intramuscular(IM) injection/IV infusion on D2,16. In C2, subjects received intrathecal MTX 8mg:1- <2Y, 10mg:2- <3Y, 12mg:3- <9Y and 15mg:>=9 Y on C2 D2,15(CNS negative); for CNS positive, with MTX,HC/ARA-C was used per local standard practice; daratumumab 16mg/kg IV infusion weekly on D1,8,15 and 22;MTX 5g/m^2 as IV once on D2, cyclophosphamide IV 1g/m^2 once on D15;cytarabine 75mg/m^2 IV/subcutaneous(SC) on D16-19 and D23-26;6-mercaptopurine60mg/m^2 orally daily on D15-28 (max. duration:2.9months).
    Arm type
    Experimental

    Investigational medicinal product name
    Daratumumab
    Investigational medicinal product code
    Other name
    JNJ-54767414
    Pharmaceutical forms
    Concentrate for solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Subjects received daratumumab 16 mg/kg IV weekly for 4 doses on Days 1, 8, 15, and 22 during cycle 1 and 2.

    Investigational medicinal product name
    Doxorubicin
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Concentrate for solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Subjects received doxorubicin 60 mg/m^2 IV once on Day 1 during cycle 1 alone.

    Investigational medicinal product name
    Vincristine
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Concentrate for solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Subjects received vincristine 1.5 mg/m^2 as IV injection/infusion weekly on Days 1, 8, 15 and 22 during cycle 1 alone.

    Investigational medicinal product name
    Prednisone
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet, Oral liquid, Oral suspension
    Routes of administration
    Oral use
    Dosage and administration details
    Subjects received prednisone 40 mg/m^2 orally daily on Days 1 to 28 during cycle 1 alone.

    Investigational medicinal product name
    Methotrexate (MTX)
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Concentrate for solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Subjects received MTX 5 grams per square meter (g/m^2) as IV once on Day 2 during cycle 2 alone.

    Investigational medicinal product name
    Cyclophosphamide
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Concentrate for solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Subjects received cyclophosphamide IV 1 g/m^2 once on Day 15 during cycle 2 alone.

    Investigational medicinal product name
    Cytarabine
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Concentrate for solution for infusion
    Routes of administration
    Intravenous use, Subcutaneous use
    Dosage and administration details
    Subjects received cytarabine 75 mg/m^2 either IV or subcutaneously on Days 16 to 19 and 23 to 26 during cycle 2 alone.

    Investigational medicinal product name
    6-mercaptopurine
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Subjects received 6-mercaptopurine 60 mg/m^2 orally daily for 14 doses on Days 15 to 28 during cycle 2 alone.

    Investigational medicinal product name
    Intrathecal methotrexate
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Concentrate for solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Subjects received intrathecal methotrexate 8 mg for age 1- <2 years, 10 mg for age 2- <3 years, 12 mg for age 3- <9 years and 15 mg for >=9 years on Days 1 (all subjects), 15 and 22 (CNS negative subjects) during Cycle 1 and on Days 2 and 15 (CNS negative subjects) during Cycle 2.

    Investigational medicinal product name
    Intrathecal Hydrocortisone (HC)
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Concentrate for solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Subjects received intrathecal HC 8 mg for age 1- <2 years, 10 mg for age 2- <3 years, 12 mg for age 3- <9 years and 15 mg for >=9 years on Cycle 1 Days 8, 15, 22, 28 and on Days 2 and 15 of Cycle 2.

    Investigational medicinal product name
    Intrathecal Cytarabine (ARA-C)
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Concentrate for solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Subjects received intrathecal ARA-C 16 mg for age 1- <2 years, 20 mg for age 2- <3 years, 24 mg for age 3- <9 years and 30 mg for >=9 years on Cycle 1 Days 8, 15, 22, 28 and on Days 2 and 15 of Cycle 2.

    Investigational medicinal product name
    Peg-asparaginase
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Concentrate for solution for infusion
    Routes of administration
    Intravenous use, Intramuscular and intravenous use
    Dosage and administration details
    Subject received peg-asparaginase 25000 U/m^2 as IM injection/IV infusion on D2 and 16 during Cycle 1.

    Arm title
    Cohort 2: T-Cell ALL (18-30 Years)
    Arm description
    Subjects with relapsed/refractory T-cell ALL in C1 received intrathecal MTX 8mg:1- <2 Y, 10mg:2- <3 Y, 12mg:3- <9 Y and 15mg:>=9 Y on C1 D1(all) and on C1 D15 and 22 (CNS negative); for CNS positive, with MTX,HC/ARA-C was used per local standard practice; daratumumab 16mg/kg IV infusion weekly on D1,8,15 and 22;doxorubicin 60mg/m^2 IV once on D1; vincristine 1.5mg/m^2 IV injection/infusion weekly on D1,8,15 and 22; prednisone 40mg/m^2 orally daily on D1-28 and peg-asparaginase 25000 U/m^2 as IM injection/IV infusion on D2 and 16. In C2, subjects received intrathecal MTX 8mg:1- <2 Y, 10mg:2- <3 Y, 12mg:3- <9 Y and 15mg:>=9 Y on C2 D2,15(CNS negative); for CNS positive, with MTX, HC/ARA-C was used per local standard practice; daratumumab 16mg/kg IV infusion weekly on D1,8,15 and 22; MTX 5g/m^2 as IV once on D2, cyclophosphamide 1g/m^2 once on D15; cytarabine 75mg/m^2 IV/SC on D16 to 19 and D23 to 26 and 6-mercaptopurine 60mg/m^2 orally daily on D15 to 28 (maximum duration:2.1 months).
    Arm type
    Experimental

    Investigational medicinal product name
    Daratumumab
    Investigational medicinal product code
    Other name
    JNJ-54767414
    Pharmaceutical forms
    Concentrate for solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Subjects received daratumumab 16 mg/kg IV weekly for 4 doses on Days 1, 8, 15, and 22 during cycle 1 and 2.

    Investigational medicinal product name
    Doxorubicin
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Concentrate for solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Subjects received doxorubicin 60 mg/m^2 IV once on Day 1 during cycle 1 alone.

    Investigational medicinal product name
    MTX
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Concentrate for solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Subjects received MTX 5 g/m^2 as IV once on Day 2 during cycle 2 alone.

    Investigational medicinal product name
    Prednisone
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet, Oral liquid, Oral suspension
    Routes of administration
    Oral use
    Dosage and administration details
    Subjects received prednisone 40 mg/m^2 orally daily on Days 1 to 28 during cycle 1 alone.

    Investigational medicinal product name
    Vincristine
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Concentrate for solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Subjects received vincristine 1.5 mg/m^2 as IV injection/infusion weekly on Days 1, 8, 15 and 22 during cycle 1 alone.

    Investigational medicinal product name
    Cyclophosphamide
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Concentrate for solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Subjects received cyclophosphamide IV 1 g/m^2 once on Day 15 during cycle 2 alone.

    Investigational medicinal product name
    Cytarabine
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Concentrate for solution for infusion
    Routes of administration
    Subcutaneous use, Intravenous use
    Dosage and administration details
    Subjects received cytarabine 75 mg/m^2 either IV or subcutaneously on Days 16 to 19 and 23 to 26 during cycle 2 alone.

    Investigational medicinal product name
    6-mercaptopurine
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Subjects received 6-mercaptopurine 60 mg/m^2 orally daily for 14 doses on Days 15 to 28 during cycle 2 alone.

    Investigational medicinal product name
    Intrathecal methotrexate
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Concentrate for solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Subjects received intrathecal methotrexate 8 mg for age 1- <2 years, 10 mg for age 2- <3 years, 12 mg for age 3- <9 years and 15 mg for >=9 years on Days 1 (all subjects), 15 and 22 (CNS negative subjects) during Cycle 1 and on Days 2 and 15 (CNS negative subjects) during Cycle 2.

    Investigational medicinal product name
    Intrathecal Hydrocortisone (HC)
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Concentrate for solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Subjects received intrathecal HC 8 mg for age 1- <2 years, 10 mg for age 2- <3 years, 12 mg for age 3- <9 years and 15 mg for >=9 years on Cycle 1 Days 8, 15, 22, 28 and on Days 2 and 15 of Cycle 2.

    Investigational medicinal product name
    Intrathecal Cytarabine (ARA-C)
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Concentrate for solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Subjects received intrathecal ARA-C 16 mg for age 1- <2 years, 20 mg for age 2- <3 years, 24 mg for age 3- <9 years and 30 mg for >=9 years on Cycle 1 Days 8, 15, 22, 28 and on Days 2 and 15 of Cycle 2.

    Investigational medicinal product name
    Peg-asparaginase
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Concentrate for solution for infusion
    Routes of administration
    Intramuscular and intravenous use
    Dosage and administration details
    Subject received peg-asparaginase 25000 U/m^2 as IM injection/IV infusion on D2 and 16 during Cycle 1.

    Arm title
    Cohort 2: T-Cell LL (1-30 Years)
    Arm description
    Subjects with relapsed/refractory T-cell LL in C1 received intrathecal MTX 8mg:1- <2 Y, 10mg:2- <3 Y, 12mg:3- <9 Y and 15mg:>=9 Y on C1 D1(all) and on C1 D15 and 22 (CNS negative); for CNS positive, with MTX,HC/ARA-C was used per local standard practice; daratumumab 16mg/kg IV infusion weekly on D1,8,15 and 22;doxorubicin 60mg/m^2 IV once on D1; vincristine 1.5mg/m^2 IV injection/infusion weekly on D1,8,15 and 22; prednisone 40mg/m^2 orally daily on D1-28 and peg-asparaginase 25000 U/m^2 as IM injection/IV infusion on D2 and 16. In C2, subjects received intrathecal MTX 8mg:1- <2 Y, 10mg:2- <3 Y, 12mg:3- <9 Y and 15mg:>=9 Y on C2 D2,15(CNS negative); for CNS positive, with MTX, HC/ARA-C was used per local standard practice; daratumumab 16mg/kg IV infusion weekly on D1,8,15 and 22; MTX 5g/m^2 as IV once on D2, cyclophosphamide 1g/m^2 once on D15; cytarabine 75mg/m^2 IV/SC on D16 to 19 and D23 to 26 and 6-mercaptopurine 60mg/m^2 orally daily on D15 to 28 (maximum duration:2.1 months).
    Arm type
    Experimental

    Investigational medicinal product name
    Daratumumab
    Investigational medicinal product code
    Other name
    JNJ-54767414
    Pharmaceutical forms
    Concentrate for solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Subjects received daratumumab 16 mg/kg IV weekly for 4 doses on Days 1, 8, 15, and 22 during cycle 1 and 2.

    Investigational medicinal product name
    Doxorubicin
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Concentrate for solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Subjects received doxorubicin 60 mg/m^2 IV once on Day 1 during cycle 1 alone.

    Investigational medicinal product name
    Vincristine
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Concentrate for solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Subjects received vincristine 1.5 mg/m^2 as IV injection/infusion weekly on Days 1, 8, 15 and 22 during cycle 1 alone.

    Investigational medicinal product name
    Prednisone
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet, Oral liquid, Oral suspension
    Routes of administration
    Oral use
    Dosage and administration details
    Subjects received prednisone 40 mg/m^2 orally daily on Days 1 to 28 during cycle 1 alone.

    Investigational medicinal product name
    MTX
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Concentrate for solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Subjects received MTX 5 g/m^2 as IV once on Day 2 during cycle 2 alone.

    Investigational medicinal product name
    Cyclophosphamide
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Concentrate for solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Subjects received cyclophosphamide IV 1 g/m^2 once on Day 15 during cycle 2 alone.

    Investigational medicinal product name
    Intrathecal methotrexate
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Concentrate for solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Subjects received intrathecal methotrexate 8 mg for age 1- <2 years, 10 mg for age 2- <3 years, 12 mg for age 3- <9 years and 15 mg for >=9 years on Days 1 (all subjects), 15 and 22 (CNS negative subjects) during Cycle 1 and on Days 2 and 15 (CNS negative subjects) during Cycle 2.

    Investigational medicinal product name
    6-mercaptopurine
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Subjects received 6-mercaptopurine 60 mg/m^2 orally daily for 14 doses on Days 15 to 28 during cycle 2 alone.

    Investigational medicinal product name
    Cytarabine
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Concentrate for solution for infusion
    Routes of administration
    Subcutaneous use, Intravenous use
    Dosage and administration details
    Subjects received cytarabine 75 mg/m^2 either IV or subcutaneously on Days 16 to 19 and 23 to 26 during cycle 2 alone.

    Investigational medicinal product name
    Intrathecal Hydrocortisone (HC)
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Concentrate for solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Subjects received intrathecal HC 8 mg for age 1- <2 years, 10 mg for age 2- <3 years, 12 mg for age 3- <9 years and 15 mg for >=9 years on Cycle 1 Days 8, 15, 22, 28 and on Days 2 and 15 of Cycle 2.

    Investigational medicinal product name
    Intrathecal Cytarabine (ARA-C)
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Concentrate for solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Subjects received intrathecal ARA-C 16 mg for age 1- <2 years, 20 mg for age 2- <3 years, 24 mg for age 3- <9 years and 30 mg for >=9 years on Cycle 1 Days 8, 15, 22, 28 and on Days 2 and 15 of Cycle 2.

    Investigational medicinal product name
    Peg-asparaginase
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Concentrate for solution for infusion
    Routes of administration
    Intramuscular and intravenous use
    Dosage and administration details
    Subject received peg-asparaginase 25000 U/m^2 as IM injection/IV infusion on D2 and 16 during Cycle 1.

    Number of subjects in period 1
    Cohort 1: B-cell acute lymphoblastic leukemia(ALL) (1-17Years) Cohort 2: T-Cell ALL (1-17 Years) Cohort 2: T-Cell ALL (18-30 Years) Cohort 2: T-Cell LL (1-30 Years)
    Started
    7
    24
    5
    10
    Completed
    7
    24
    4
    10
    Not completed
    0
    0
    1
    0
         Consent withdrawn by subject
    -
    -
    1
    -

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Cohort 1: B-cell acute lymphoblastic leukemia(ALL) (1-17Years)
    Reporting group description
    Subjects with relapsed/refractory B-cell ALL received intrathecal methotrexate (MTX) 8milligrams(mg):1-less than(<)2 years (y), 10mg:2- <3 Y, 12mg:3- <9 Y and 15 mg:greater than or equal to(>=) 9 Y on Cycle(C) 1 Day(D) 1(all) and C2 and later D1 each C (CNS negative); for CNS positive, with MTX, hydrocortisone(HC)/cytarabine(ARA-C) was used per local standard practice; daratumumab 16 milligrams per kilogram (mg/kg) as intravenous(IV) infusion weekly on D1,8,15 and 22 of C1 and 2 then every 2 weeks on D1,15 of C3 to 6 and every 4 weeks on D1 of C7 and onward;vincristine 1.5 milligrams per square meter(mg/m^2) IV once weekly on D1,8,15 and 22 of C1, then every 2 weeks on D1 and 15 of C2 and every 4 weeks on D1 of C3 and onward;prednisone 40mg/m^2 once daily on D1 to 28 of C1 and on D1 to 5 of C2 onward. Subjects received treatment until disease progression, unacceptable toxicity, or proceeding hematopoietic stem cell transplant after CR whichever came first(maximum duration:2.3 months).

    Reporting group title
    Cohort 2: T-Cell ALL (1-17 Years)
    Reporting group description
    Subjects with relapsed/refractory T-cell ALL in C1 received intrathecal MTX 8mg:1- <2Y,10mg:2- <3Y, 12mg:3- <9Y and 15mg:>=9Y on C1 D1(all) each C (CNS negative);for CNS positive,with MTX,HC/ARA-C was used per local standard practice; daratumumab 16mg/kg IV infusion weekly on D1,8,15 and 22;doxorubicin 60mg/m^2 IV once on D1;vincristine 1.5mg/m^2 IV injection/infusion weekly on D1,8,15 and 22;prednisone 40mg/m^2 orally daily on D1-28;peg-asparaginase 25000 units per square meter(U/m^2) as intramuscular(IM) injection/IV infusion on D2,16. In C2, subjects received intrathecal MTX 8mg:1- <2Y, 10mg:2- <3Y, 12mg:3- <9Y and 15mg:>=9 Y on C2 D2,15(CNS negative); for CNS positive, with MTX,HC/ARA-C was used per local standard practice; daratumumab 16mg/kg IV infusion weekly on D1,8,15 and 22;MTX 5g/m^2 as IV once on D2, cyclophosphamide IV 1g/m^2 once on D15;cytarabine 75mg/m^2 IV/subcutaneous(SC) on D16-19 and D23-26;6-mercaptopurine60mg/m^2 orally daily on D15-28 (max. duration:2.9months).

    Reporting group title
    Cohort 2: T-Cell ALL (18-30 Years)
    Reporting group description
    Subjects with relapsed/refractory T-cell ALL in C1 received intrathecal MTX 8mg:1- <2 Y, 10mg:2- <3 Y, 12mg:3- <9 Y and 15mg:>=9 Y on C1 D1(all) and on C1 D15 and 22 (CNS negative); for CNS positive, with MTX,HC/ARA-C was used per local standard practice; daratumumab 16mg/kg IV infusion weekly on D1,8,15 and 22;doxorubicin 60mg/m^2 IV once on D1; vincristine 1.5mg/m^2 IV injection/infusion weekly on D1,8,15 and 22; prednisone 40mg/m^2 orally daily on D1-28 and peg-asparaginase 25000 U/m^2 as IM injection/IV infusion on D2 and 16. In C2, subjects received intrathecal MTX 8mg:1- <2 Y, 10mg:2- <3 Y, 12mg:3- <9 Y and 15mg:>=9 Y on C2 D2,15(CNS negative); for CNS positive, with MTX, HC/ARA-C was used per local standard practice; daratumumab 16mg/kg IV infusion weekly on D1,8,15 and 22; MTX 5g/m^2 as IV once on D2, cyclophosphamide 1g/m^2 once on D15; cytarabine 75mg/m^2 IV/SC on D16 to 19 and D23 to 26 and 6-mercaptopurine 60mg/m^2 orally daily on D15 to 28 (maximum duration:2.1 months).

    Reporting group title
    Cohort 2: T-Cell LL (1-30 Years)
    Reporting group description
    Subjects with relapsed/refractory T-cell LL in C1 received intrathecal MTX 8mg:1- <2 Y, 10mg:2- <3 Y, 12mg:3- <9 Y and 15mg:>=9 Y on C1 D1(all) and on C1 D15 and 22 (CNS negative); for CNS positive, with MTX,HC/ARA-C was used per local standard practice; daratumumab 16mg/kg IV infusion weekly on D1,8,15 and 22;doxorubicin 60mg/m^2 IV once on D1; vincristine 1.5mg/m^2 IV injection/infusion weekly on D1,8,15 and 22; prednisone 40mg/m^2 orally daily on D1-28 and peg-asparaginase 25000 U/m^2 as IM injection/IV infusion on D2 and 16. In C2, subjects received intrathecal MTX 8mg:1- <2 Y, 10mg:2- <3 Y, 12mg:3- <9 Y and 15mg:>=9 Y on C2 D2,15(CNS negative); for CNS positive, with MTX, HC/ARA-C was used per local standard practice; daratumumab 16mg/kg IV infusion weekly on D1,8,15 and 22; MTX 5g/m^2 as IV once on D2, cyclophosphamide 1g/m^2 once on D15; cytarabine 75mg/m^2 IV/SC on D16 to 19 and D23 to 26 and 6-mercaptopurine 60mg/m^2 orally daily on D15 to 28 (maximum duration:2.1 months).

    Reporting group values
    Cohort 1: B-cell acute lymphoblastic leukemia(ALL) (1-17Years) Cohort 2: T-Cell ALL (1-17 Years) Cohort 2: T-Cell ALL (18-30 Years) Cohort 2: T-Cell LL (1-30 Years) Total
    Number of subjects
    7 24 5 10 46
    Title for AgeCategorical
    Units: subjects
        Children (2-11 years)
    5 16 0 3 24
        Adolescents (12-17 years)
    2 8 0 5 15
        Adults (18-64 years)
    0 0 5 2 7
        From 65 to 84 years
    0 0 0 0 0
        85 years and over
    0 0 0 0 0
    Title for AgeContinuous
    Units: years
        arithmetic mean (standard deviation)
    8.1 ± 5.01 9.8 ± 4.17 22.2 ± 2.77 13.5 ± 5.68 -
    Title for Gender
    Units: subjects
        Female
    4 10 0 1 15
        Male
    3 14 5 9 31

    End points

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    End points reporting groups
    Reporting group title
    Cohort 1: B-cell acute lymphoblastic leukemia(ALL) (1-17Years)
    Reporting group description
    Subjects with relapsed/refractory B-cell ALL received intrathecal methotrexate (MTX) 8milligrams(mg):1-less than(<)2 years (y), 10mg:2- <3 Y, 12mg:3- <9 Y and 15 mg:greater than or equal to(>=) 9 Y on Cycle(C) 1 Day(D) 1(all) and C2 and later D1 each C (CNS negative); for CNS positive, with MTX, hydrocortisone(HC)/cytarabine(ARA-C) was used per local standard practice; daratumumab 16 milligrams per kilogram (mg/kg) as intravenous(IV) infusion weekly on D1,8,15 and 22 of C1 and 2 then every 2 weeks on D1,15 of C3 to 6 and every 4 weeks on D1 of C7 and onward;vincristine 1.5 milligrams per square meter(mg/m^2) IV once weekly on D1,8,15 and 22 of C1, then every 2 weeks on D1 and 15 of C2 and every 4 weeks on D1 of C3 and onward;prednisone 40mg/m^2 once daily on D1 to 28 of C1 and on D1 to 5 of C2 onward. Subjects received treatment until disease progression, unacceptable toxicity, or proceeding hematopoietic stem cell transplant after CR whichever came first(maximum duration:2.3 months).

    Reporting group title
    Cohort 2: T-Cell ALL (1-17 Years)
    Reporting group description
    Subjects with relapsed/refractory T-cell ALL in C1 received intrathecal MTX 8mg:1- <2Y,10mg:2- <3Y, 12mg:3- <9Y and 15mg:>=9Y on C1 D1(all) each C (CNS negative);for CNS positive,with MTX,HC/ARA-C was used per local standard practice; daratumumab 16mg/kg IV infusion weekly on D1,8,15 and 22;doxorubicin 60mg/m^2 IV once on D1;vincristine 1.5mg/m^2 IV injection/infusion weekly on D1,8,15 and 22;prednisone 40mg/m^2 orally daily on D1-28;peg-asparaginase 25000 units per square meter(U/m^2) as intramuscular(IM) injection/IV infusion on D2,16. In C2, subjects received intrathecal MTX 8mg:1- <2Y, 10mg:2- <3Y, 12mg:3- <9Y and 15mg:>=9 Y on C2 D2,15(CNS negative); for CNS positive, with MTX,HC/ARA-C was used per local standard practice; daratumumab 16mg/kg IV infusion weekly on D1,8,15 and 22;MTX 5g/m^2 as IV once on D2, cyclophosphamide IV 1g/m^2 once on D15;cytarabine 75mg/m^2 IV/subcutaneous(SC) on D16-19 and D23-26;6-mercaptopurine60mg/m^2 orally daily on D15-28 (max. duration:2.9months).

    Reporting group title
    Cohort 2: T-Cell ALL (18-30 Years)
    Reporting group description
    Subjects with relapsed/refractory T-cell ALL in C1 received intrathecal MTX 8mg:1- <2 Y, 10mg:2- <3 Y, 12mg:3- <9 Y and 15mg:>=9 Y on C1 D1(all) and on C1 D15 and 22 (CNS negative); for CNS positive, with MTX,HC/ARA-C was used per local standard practice; daratumumab 16mg/kg IV infusion weekly on D1,8,15 and 22;doxorubicin 60mg/m^2 IV once on D1; vincristine 1.5mg/m^2 IV injection/infusion weekly on D1,8,15 and 22; prednisone 40mg/m^2 orally daily on D1-28 and peg-asparaginase 25000 U/m^2 as IM injection/IV infusion on D2 and 16. In C2, subjects received intrathecal MTX 8mg:1- <2 Y, 10mg:2- <3 Y, 12mg:3- <9 Y and 15mg:>=9 Y on C2 D2,15(CNS negative); for CNS positive, with MTX, HC/ARA-C was used per local standard practice; daratumumab 16mg/kg IV infusion weekly on D1,8,15 and 22; MTX 5g/m^2 as IV once on D2, cyclophosphamide 1g/m^2 once on D15; cytarabine 75mg/m^2 IV/SC on D16 to 19 and D23 to 26 and 6-mercaptopurine 60mg/m^2 orally daily on D15 to 28 (maximum duration:2.1 months).

    Reporting group title
    Cohort 2: T-Cell LL (1-30 Years)
    Reporting group description
    Subjects with relapsed/refractory T-cell LL in C1 received intrathecal MTX 8mg:1- <2 Y, 10mg:2- <3 Y, 12mg:3- <9 Y and 15mg:>=9 Y on C1 D1(all) and on C1 D15 and 22 (CNS negative); for CNS positive, with MTX,HC/ARA-C was used per local standard practice; daratumumab 16mg/kg IV infusion weekly on D1,8,15 and 22;doxorubicin 60mg/m^2 IV once on D1; vincristine 1.5mg/m^2 IV injection/infusion weekly on D1,8,15 and 22; prednisone 40mg/m^2 orally daily on D1-28 and peg-asparaginase 25000 U/m^2 as IM injection/IV infusion on D2 and 16. In C2, subjects received intrathecal MTX 8mg:1- <2 Y, 10mg:2- <3 Y, 12mg:3- <9 Y and 15mg:>=9 Y on C2 D2,15(CNS negative); for CNS positive, with MTX, HC/ARA-C was used per local standard practice; daratumumab 16mg/kg IV infusion weekly on D1,8,15 and 22; MTX 5g/m^2 as IV once on D2, cyclophosphamide 1g/m^2 once on D15; cytarabine 75mg/m^2 IV/SC on D16 to 19 and D23 to 26 and 6-mercaptopurine 60mg/m^2 orally daily on D15 to 28 (maximum duration:2.1 months).

    Primary: Percentage of Subjects with Complete Response (CR) for B-cell Acute Lymphoblastic Leukemia (ALL)

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    End point title
    Percentage of Subjects with Complete Response (CR) for B-cell Acute Lymphoblastic Leukemia (ALL) [1] [2]
    End point description
    Complete response based on the modified National Comprehensive Cancer Network (NCCN) criteria is defined as: less than 5 percent (%) blasts in the bone marrow; no evidence of circulating blasts or extramedullary disease; full recovery of peripheral blood counts: platelets greater than (>)100*10^9 cells/liter (L) and absolute neutrophil count (ANC) >1.0*10^9 cells/L. The all treated analysis set included all enrolled subjects who received at least 1 dose of daratumumab. This endpoint was planned to be analysed for specified arm only as pre specified in protocol.
    End point type
    Primary
    End point timeframe
    Up to 2 cycles (each cycle of 28-days)
    Notes
    [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: No inferential statistics was planned for this primary endpoint.
    [2] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: This endpoint was planned to be analysed for specified arms only.
    End point values
    Cohort 1: B-cell acute lymphoblastic leukemia(ALL) (1-17Years)
    Number of subjects analysed
    7
    Units: Percentage of Subjects
        number (confidence interval 90%)
    0 (0 to 0)
    No statistical analyses for this end point

    Primary: Percentage of Subjects with CR for T-cell ALL 

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    End point title
    Percentage of Subjects with CR for T-cell ALL  [3] [4]
    End point description
    CR based on the modified NCCN criteria is defined as: less than 5% blasts in the bone marrow; no evidence of circulating blasts or extramedullary disease; full recovery of peripheral blood counts: platelets >100*10^9 cell/L and ANC >1.0*10^9 cell/L. The all treated analysis set included all enrolled subjects who received at least 1 dose of daratumumab. This endpoint was planned to be analysed for specified arm only as pre specified in protocol.
    End point type
    Primary
    End point timeframe
    End of Cycle 1 (ie., up to 28 days)
    Notes
    [3] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: No inferential statistics was planned for this primary endpoint.
    [4] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: This endpoint was planned to be analysed for specified arms only.
    End point values
    Cohort 2: T-Cell ALL (1-17 Years) Cohort 2: T-Cell ALL (18-30 Years) Cohort 2: T-Cell LL (1-30 Years)
    Number of subjects analysed
    24
    5
    10
    Units: Percentage of subjects
        number (confidence interval 90%)
    41.7 (24.6 to 60.3)
    60.0 (18.9 to 92.4)
    30.0 (8.7 to 60.7)
    No statistical analyses for this end point

    Secondary: Overall Response Rate (ORR)

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    End point title
    Overall Response Rate (ORR)
    End point description
    ORR is defined as percentage of ALL subjects who achieved CR with only partial hematological recovery (CRi) according to NCCN criteria. Per NCCN criteria, CR for ALL is defined as: Less than 5 % blasts in the bone marrow; no evidence of circulating blasts or extramedullary disease; full recovery of peripheral blood counts: Platelets >100 x10^9 cell/L and ANC >1.0x10^9 cell/L; CRi for ALL: less than 5% blasts in the bone marrow; no evidence of circulating blasts or extramedullary disease; partial recovery of peripheral blood counts not meeting criteria for CR. For LL subjects, ORR was defined as the percentage of subjects who achieved CR or partial response (PR) during or after treatment administration but prior to the start of subsequent anti-cancer therapy or allogenic hematopoietic stem cell transplant (HSCT). The all treated analysis set included all enrolled subjects who received at least 1 dose of daratumumab.
    End point type
    Secondary
    End point timeframe
    Up to 4 years 4 months
    End point values
    Cohort 1: B-cell acute lymphoblastic leukemia(ALL) (1-17Years) Cohort 2: T-Cell ALL (1-17 Years) Cohort 2: T-Cell ALL (18-30 Years) Cohort 2: T-Cell LL (1-30 Years)
    Number of subjects analysed
    7
    24
    5
    10
    Units: Percentage of subjects
        number (confidence interval 90%)
    14.3 (0.7 to 52.1)
    83.3 (65.8 to 94.1)
    80.0 (34.3 to 99.0)
    50.0 (22.2 to 77.8)
    No statistical analyses for this end point

    Secondary: Event Free Survival (EFS)

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    End point title
    Event Free Survival (EFS)
    End point description
    EFS is defined as the time (in months) from the date of first treatment to the first documented treatment failure (that is [ie], disease progression) or date of relapse from CR or death due to any cause, whichever occurs first. Per NCCN criteria, relapse from CR is defined as: reappearance of leukemia blasts in the peripheral blood or >5% blasts in the bone marrow; reappearance of extramedullary disease or new extramedullary disease. Progressive disease: increase of at least 25% in the absolute number of circulating peripheral or bone marrow blasts, or development of new extramedullary disease. Kaplan-Meier method was used for the analysis. The all treated analysis set included all enrolled subjects who received at least 1 dose of daratumumab. Here,'99999' indicates that data were not evaluable due to less number of subjects with events.
    End point type
    Secondary
    End point timeframe
    Up to 4 years 4 months
    End point values
    Cohort 1: B-cell acute lymphoblastic leukemia(ALL) (1-17Years) Cohort 2: T-Cell ALL (1-17 Years) Cohort 2: T-Cell ALL (18-30 Years) Cohort 2: T-Cell LL (1-30 Years)
    Number of subjects analysed
    7
    24
    5
    10
    Units: Months
        median (confidence interval 90%)
    1.1 (0.9 to 2.1)
    8.9 (5.3 to 99999)
    10.3 (2.6 to 99999)
    2.9 (1.3 to 4.9)
    No statistical analyses for this end point

    Secondary: Relapse-free Survival (RFS)

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    End point title
    Relapse-free Survival (RFS)
    End point description
    RFS is defined as the time (in months) from CR to relapse from CR or disease progression or death due to any cause, whichever occurs first. Per NCCN criteria, relapse from CR is defined as: reappearance of leukemia blasts in the peripheral blood or >5% blasts in the bone marrow, or reappearance of extramedullary disease or new extramedullary disease. Progressive disease: increase of at least 25% in absolute number of circulating peripheral or bone marrow blasts, or development of new extramedullary disease. Kaplan-Meier method was used for analysis. The response evaluable analysis set included all enrolled subjects who received at least 1 dose of daratumumab and had at least 1 adequate post-baseline disease assessment. Here, 'N' (number of subject analysed) signifies all treated who achieved a complete response. Here,'99999' indicate that data were not evaluable due to less number of subjects with events.
    End point type
    Secondary
    End point timeframe
    Up to 4 years 4 months
    End point values
    Cohort 1: B-cell acute lymphoblastic leukemia(ALL) (1-17Years) Cohort 2: T-Cell ALL (1-17 Years) Cohort 2: T-Cell ALL (18-30 Years) Cohort 2: T-Cell LL (1-30 Years)
    Number of subjects analysed
    0 [5]
    12
    3
    4
    Units: Months
        median (confidence interval 90%)
    ( to )
    19.4 (5.3 to 99999)
    9.4 (3.6 to 99999)
    99999 (1.8 to 99999)
    Notes
    [5] - RFS was not evaluable for this arm as no subjects achieved CR.
    No statistical analyses for this end point

    Secondary: Overall Survival (OS) 

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    End point title
    Overall Survival (OS) 
    End point description
    OS is defined as the time (in months) from the date of first study drug administration to the date of death due to any cause. Kaplan-Meier method was used for the analysis. Subjects who died after consent withdrawal were considered as having an OS event. If the subject was alive or the survival status was unknown, then the subject’s data were censored at the last known alive date. The all treated analysis set included all enrolled subjects who received at least 1 dose of daratumumab. Here,'99999' indicates that data were not evaluable due to less number of subjects with events.
    End point type
    Secondary
    End point timeframe
    Up to 4 years 4 months
    End point values
    Cohort 1: B-cell acute lymphoblastic leukemia(ALL) (1-17Years) Cohort 2: T-Cell ALL (1-17 Years) Cohort 2: T-Cell ALL (18-30 Years) Cohort 2: T-Cell LL (1-30 Years)
    Number of subjects analysed
    7
    24
    5
    10
    Units: Months
        median (confidence interval 90%)
    3.2 (1.0 to 3.6)
    10.9 (6.7 to 99999)
    12.0 (4.5 to 99999)
    4.9 (1.7 to 5.6)
    No statistical analyses for this end point

    Secondary: Minimal Residual Disease (MRD) Negative Rate

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    End point title
    Minimal Residual Disease (MRD) Negative Rate
    End point description
    MRD negative rate was defined as the percentage of subjects who were considered MRD negative after MRD testing by bone marrow aspirate at any timepoint after first study treatment administration and before disease progression or starting subsequent anti-cancer therapy or allogeneic HSCT. MRD negative is defined as <0.01% abnormal population counts to nucleated mononuclear cells when measured by flow cytometry. The all treated analysis set included all enrolled subjects who received at least 1 dose of daratumumab.
    End point type
    Secondary
    End point timeframe
    Up to 4 years 4 months
    End point values
    Cohort 1: B-cell acute lymphoblastic leukemia(ALL) (1-17Years) Cohort 2: T-Cell ALL (1-17 Years) Cohort 2: T-Cell ALL (18-30 Years) Cohort 2: T-Cell LL (1-30 Years)
    Number of subjects analysed
    7
    24
    5
    10
    Units: Percentage of subjects
        number (confidence interval 90%)
    0 (0 to 0)
    45.8 (28.2 to 64.2)
    20.0 (1.0 to 65.7)
    50.0 (22.2 to 77.8)
    No statistical analyses for this end point

    Secondary: Percentage of Subjects who Received an Allogeneic Hematopoietic Stem Cell Transplant (HSCT)

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    End point title
    Percentage of Subjects who Received an Allogeneic Hematopoietic Stem Cell Transplant (HSCT)
    End point description
    Percentage of subjects who received an allogeneic HSCT after treatment with daratumumab were assessed. The allogeneic HSCT rate was defined as the percentage of subjects who received an allogeneic HSCT after treatment with daratumumab. The all treated analysis set included all enrolled subjects who received at least 1 dose of daratumumab.
    End point type
    Secondary
    End point timeframe
    Up to 4 years 4 months
    End point values
    Cohort 1: B-cell acute lymphoblastic leukemia(ALL) (1-17Years) Cohort 2: T-Cell ALL (1-17 Years) Cohort 2: T-Cell ALL (18-30 Years) Cohort 2: T-Cell LL (1-30 Years)
    Number of subjects analysed
    7
    24
    5
    10
    Units: Percentage of subject
        number (confidence interval 90%)
    14.3 (0.7 to 52.1)
    75.0 (56.5 to 88.5)
    60.0 (18.9 to 92.4)
    30.0 (8.7 to 60.7)
    No statistical analyses for this end point

    Secondary: Maximum Observed Serum Concentration (Cmax) of Daratumumab

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    End point title
    Maximum Observed Serum Concentration (Cmax) of Daratumumab
    End point description
    Cmax is defined as maximum observed serum concentration. The serum pharmacokinetics (PK) evaluable analysis set included all enrolled subjects who received at least 1 dose of daratumumab and provided at least 1 post-infusion blood sample for serum daratumumab concentrations. Here, follow-up indicated 8 week post treatment. EOI: End of infusion.
    End point type
    Secondary
    End point timeframe
    B-cell ALL: Predose and EOI on Day 1 of Cycles 1 and 2, EOT and follow-up; T-cell ALL: Predose and EOI on Day 1 of Cycles 1 and 2, Cycle 2 Day 22, EOT and follow-up
    End point values
    Cohort 1: B-cell acute lymphoblastic leukemia(ALL) (1-17Years) Cohort 2: T-Cell ALL (1-17 Years) Cohort 2: T-Cell ALL (18-30 Years) Cohort 2: T-Cell LL (1-30 Years)
    Number of subjects analysed
    7
    24
    5
    10
    Units: Micrograms per millilitre (mcg/mL)
        arithmetic mean (standard deviation)
    494 ± 184
    763 ± 185
    501 ± 347
    758 ± 157
    No statistical analyses for this end point

    Secondary: Minimum Observed Serum Concentration (Cmin) of Daratumumab

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    End point title
    Minimum Observed Serum Concentration (Cmin) of Daratumumab
    End point description
    Cmin is defined as minimum observed serum concentration. The serum PK evaluable analysis set included all enrolled subjects who received at least 1 dose of daratumumab and provided at least 1 post-infusion blood sample for serum daratumumab concentrations. Here, follow-up indicated 8 week post treatment.
    End point type
    Secondary
    End point timeframe
    B-cell ALL: Predose and EOI on Day 1 of Cycles 1 and 2, EOT and follow-up; T-cell ALL: Predose and EOI on Day 1 of Cycles 1 and 2, Cycle 2 Day 22, EOT and follow-up
    End point values
    Cohort 1: B-cell acute lymphoblastic leukemia(ALL) (1-17Years) Cohort 2: T-Cell ALL (1-17 Years) Cohort 2: T-Cell ALL (18-30 Years) Cohort 2: T-Cell LL (1-30 Years)
    Number of subjects analysed
    7
    24
    5
    10
    Units: mcg/mL
        arithmetic mean (standard deviation)
    172 ± 115
    369 ± 105
    172 ± 177
    365 ± 204
    No statistical analyses for this end point

    Secondary: Number of Subjects with Anti-daratumumab Antibody

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    End point title
    Number of Subjects with Anti-daratumumab Antibody
    End point description
    Number of subjects with anti-daratumumab antibody was reported. The immunogenicity evaluable analysis set included all enrolled subjects who received at least 1 dose of daratumumab and had at least 1 post-infusion sample for detection of anti-daratumumab antibodies.
    End point type
    Secondary
    End point timeframe
    Up to 4 years 4 months
    End point values
    Cohort 1: B-cell acute lymphoblastic leukemia(ALL) (1-17Years) Cohort 2: T-Cell ALL (1-17 Years) Cohort 2: T-Cell ALL (18-30 Years) Cohort 2: T-Cell LL (1-30 Years)
    Number of subjects analysed
    5
    22
    5
    9
    Units: Subjects
    0
    0
    0
    0
    No statistical analyses for this end point

    Secondary: Concentration of Daratumumab in Cerebrospinal Fluid (CSF) 

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    End point title
    Concentration of Daratumumab in Cerebrospinal Fluid (CSF) 
    End point description
    Concentration of daratumumab in CSF was reported. The CSF PK evaluable analysis set included all enrolled subjects who received at least 1 dose of daratumumab and provided at least 1 post-infusion CSF sample for daratumumab concentrations. Here, 'N' (number of subject analysed) signifies number of subjects who were evaluable for this endpoint and 'n' (number analysed) represent number of subjects evaluable for specified timepoints. Here,'99999' indicates that data was not calculated due to the lower limit of quantification (LLOQ) limit in timepoint cycle 1: Day 1 predose and due to the less number of subject in timepoints cycle 1: Day 15 predose and cycle 2: Days 2, 15 predose.
    End point type
    Secondary
    End point timeframe
    Cohort 1: Cycle 1 and 2: Day 1 pre-dose; Cohort 2: Cycle 1 Day 1 and 15: pre-dose and Cycel 2 Day 2 and Day 15: pre-dose
    End point values
    Cohort 1: B-cell acute lymphoblastic leukemia(ALL) (1-17Years) Cohort 2: T-Cell ALL (1-17 Years) Cohort 2: T-Cell ALL (18-30 Years) Cohort 2: T-Cell LL (1-30 Years)
    Number of subjects analysed
    3
    21
    5
    10
    Units: mcg/mL
    arithmetic mean (standard deviation)
        Cycle 1: Day 1 predose (n=3, 18, 3, 10)
    99999 ± 99999
    99999 ± 99999
    99999 ± 99999
    99999 ± 99999
        Cycle 1: Day 15 predose (n=0, 21, 5, 10)
    99999 ± 99999
    0.907 ± 1.96
    0.319 ± 0.203
    0.456 ± 0.280
        Cycle 2: Day 1 predose (n=3, 0, 0, 0)
    0.573 ± 0.545
    99999 ± 99999
    99999 ± 99999
    99999 ± 99999
        Cycle 2: Day 2 predose (n=0, 14, 3, 5)
    99999 ± 99999
    0.915 ± 0.916
    0.296 ± 0.191
    1.23 ± 0.728
        Cycle 2: Day 15 predose (n=0, 16, 1, 5)
    99999 ± 99999
    0.934 ± 0.549
    0.163 ± 99999
    1.06 ± 0.282
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    From baseline up to 4 years 4 months
    Adverse event reporting additional description
    The safety analysis set included all enrolled subjects who received at least 1 dose of daratumumab.
    Assessment type
    Non-systematic
    Dictionary used for adverse event reporting
    Dictionary name
    MedDRA
    Dictionary version
    25.0
    Reporting groups
    Reporting group title
    Cohort 1: B-Cell ALL (1-17 Years)
    Reporting group description
    Subjects aged 1 year to 17 years with relapsed/refractory B-cell acute lymphoblastic leukemia (ALL) received daratumumab 16 milligrams per kilogram (mg/kg) as intravenous (IV) infusion weekly on Days 1, 8, 15 and 22 of Cycles 1 and 2 then every 2 weeks on Days 1 and 15 of Cycle 3 to 6 and every 4 weeks on Day 1 of Cycle 7 and onward; vincristine 1.5 milligrams per square meter (mg/m^2) as IV injection/infusion weekly on Days 1, 8, 15 and 22 of Cycle 1, then every 2 weeks on Days 1 and 15 of Cycle 2 and every 4 weeks on Day 1 of Cycle 3 and onward; prednisone 40 mg/m^2 orally daily on Days 1 to 28 of Cycle 1 and then on Days 1 to 5 of Cycle 2 and onward. Subjects received study drugs until disease progression, unacceptable toxicity, or achievement of complete response (CR) followed by hematopoietic stem cell transplant (HSCT), whichever occurred first (maximum duration: 2.3 months).

    Reporting group title
    Cohort 2: T-Cell LL (1-30 Years)
    Reporting group description
    Subjects with relapsed/refractory T-cell LL in C1 received intrathecal MTX 8mg:1- <2 Y, 10mg:2- <3 Y, 12mg:3- <9 Y and 15mg:>=9 Y on C1 D1(all) and on C1 D15 and 22 (CNS negative); for CNS positive, with MTX,HC/ARA-C was used per local standard practice; daratumumab 16mg/kg IV infusion weekly on D1,8,15 and 22;doxorubicin 60mg/m^2 IV once on D1; vincristine 1.5mg/m^2 IV injection/infusion weekly on D1,8,15 and 22; prednisone 40mg/m^2 orally daily on D1-28 and peg-asparaginase 25000 U/m^2 as IM injection/IV infusion on D2 and 16. In C2, subjects received intrathecal MTX 8mg:1- <2 Y, 10mg:2- <3 Y, 12mg:3- <9 Y and 15mg:>=9 Y on C2 D2,15(CNS negative); for CNS positive, with MTX, HC/ARA-C was used per local standard practice; daratumumab 16mg/kg IV infusion weekly on D1,8,15 and 22; MTX 5g/m^2 as IV once on D2, cyclophosphamide 1g/m^2 once on D15; cytarabine 75mg/m^2 IV/SC on D16 to 19 and D23 to 26 and 6-mercaptopurine 60mg/m^2 orally daily on D15 to 28 (maximum duration:2.1 months).

    Reporting group title
    Cohort 2: T-Cell ALL (18-30 Years)
    Reporting group description
    Subjects with relapsed/refractory T-cell ALL in C1 received intrathecal MTX 8mg:1- <2 Y, 10mg:2- <3 Y, 12mg:3- <9 Y and 15mg:>=9 Y on C1 D1(all) and on C1 D15 and 22 (CNS negative); for CNS positive, with MTX,HC/ARA-C was used per local standard practice; daratumumab 16mg/kg IV infusion weekly on D1,8,15 and 22;doxorubicin 60mg/m^2 IV once on D1; vincristine 1.5mg/m^2 IV injection/infusion weekly on D1,8,15 and 22; prednisone 40mg/m^2 orally daily on D1-28 and peg-asparaginase 25000 U/m^2 as IM injection/IV infusion on D2 and 16. In C2, subjects received intrathecal MTX 8mg:1- <2 Y, 10mg:2- <3 Y, 12mg:3- <9 Y and 15mg:>=9 Y on C2 D2,15(CNS negative); for CNS positive, with MTX, HC/ARA-C was used per local standard practice; daratumumab 16mg/kg IV infusion weekly on D1,8,15 and 22; MTX 5g/m^2 as IV once on D2, cyclophosphamide 1g/m^2 once on D15; cytarabine 75mg/m^2 IV/SC on D16 to 19 and D23 to 26 and 6-mercaptopurine 60mg/m^2 orally daily on D15 to 28 (maximum duration:2.1 months).

    Reporting group title
    Cohort 2: T-Cell ALL (1-17 Years)
    Reporting group description
    Subjects with relapsed/refractory T-cell ALL in C1 received intrathecal MTX 8mg:1- <2Y,10mg:2- <3Y, 12mg:3- <9Y and 15mg:>=9Y on C1 D1(all) each C (CNS negative);for CNS positive,with MTX,HC/ARA-C was used per local standard practice; daratumumab 16mg/kg IV infusion weekly on D1,8,15 and 22;doxorubicin 60mg/m^2 IV once on D1;vincristine 1.5mg/m^2 IV injection/infusion weekly on D1,8,15 and 22;prednisone 40mg/m^2 orally daily on D1-28;peg-asparaginase 25000 units per square meter(U/m^2) as intramuscular(IM) injection/IV infusion on D2,16. In C2, subjects received intrathecal MTX 8mg:1- <2Y, 10mg:2- <3Y, 12mg:3- <9Y and 15mg:>=9 Y on C2 D2,15(CNS negative); for CNS positive, with MTX,HC/ARA-C was used per local standard practice; daratumumab 16mg/kg IV infusion weekly on D1,8,15 and 22;MTX 5g/m^2 as IV once on D2, cyclophosphamide IV 1g/m^2 once on D15;cytarabine 75mg/m^2 IV/subcutaneous(SC) on D16-19 and D23-26;6-mercaptopurine60mg/m^2 orally daily on D15-28 (max. duration:2.1months).

    Serious adverse events
    Cohort 1: B-Cell ALL (1-17 Years) Cohort 2: T-Cell LL (1-30 Years) Cohort 2: T-Cell ALL (18-30 Years) Cohort 2: T-Cell ALL (1-17 Years)
    Total subjects affected by serious adverse events
         subjects affected / exposed
    3 / 7 (42.86%)
    7 / 10 (70.00%)
    4 / 5 (80.00%)
    16 / 24 (66.67%)
         number of deaths (all causes)
    3
    6
    2
    11
         number of deaths resulting from adverse events
    Investigations
    Alanine Aminotransferase Increased
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 10 (0.00%)
    0 / 5 (0.00%)
    1 / 24 (4.17%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Aspartate Aminotransferase Increased
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 10 (0.00%)
    0 / 5 (0.00%)
    1 / 24 (4.17%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Blood Lactic Acid Increased
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 10 (0.00%)
    0 / 5 (0.00%)
    1 / 24 (4.17%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    2 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gamma-Glutamyltransferase Increased
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 10 (0.00%)
    0 / 5 (0.00%)
    1 / 24 (4.17%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pseudomonas Test Positive
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 10 (0.00%)
    0 / 5 (0.00%)
    1 / 24 (4.17%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Staphylococcus Test Positive
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 10 (0.00%)
    0 / 5 (0.00%)
    1 / 24 (4.17%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Weight Decreased
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 10 (0.00%)
    1 / 5 (20.00%)
    0 / 24 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Vascular disorders
    Hypotension
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 10 (0.00%)
    0 / 5 (0.00%)
    1 / 24 (4.17%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    2 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Nervous system disorders
    Brain Oedema
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 10 (0.00%)
    0 / 5 (0.00%)
    1 / 24 (4.17%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    Depressed Level of Consciousness
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 10 (0.00%)
    0 / 5 (0.00%)
    1 / 24 (4.17%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Dysarthria
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 10 (0.00%)
    0 / 5 (0.00%)
    1 / 24 (4.17%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Peripheral Motor Neuropathy
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 10 (10.00%)
    0 / 5 (0.00%)
    0 / 24 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Leukoencephalopathy
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 10 (10.00%)
    0 / 5 (0.00%)
    0 / 24 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Posterior Reversible Encephalopathy Syndrome
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 10 (10.00%)
    0 / 5 (0.00%)
    0 / 24 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Peripheral Nerve Palsy
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 10 (10.00%)
    0 / 5 (0.00%)
    0 / 24 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Seizure
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 10 (10.00%)
    0 / 5 (0.00%)
    0 / 24 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Tremor
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 10 (0.00%)
    0 / 5 (0.00%)
    1 / 24 (4.17%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Blood and lymphatic system disorders
    Febrile Neutropenia
         subjects affected / exposed
    3 / 7 (42.86%)
    2 / 10 (20.00%)
    1 / 5 (20.00%)
    6 / 24 (25.00%)
         occurrences causally related to treatment / all
    0 / 3
    4 / 4
    0 / 1
    6 / 9
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Neutropenia
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 10 (0.00%)
    0 / 5 (0.00%)
    2 / 24 (8.33%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    2 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Thrombocytopenia
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 10 (0.00%)
    1 / 5 (20.00%)
    0 / 24 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    General disorders and administration site conditions
    Death
         subjects affected / exposed
    1 / 7 (14.29%)
    0 / 10 (0.00%)
    0 / 5 (0.00%)
    0 / 24 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    Mucosal Inflammation
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 10 (0.00%)
    0 / 5 (0.00%)
    1 / 24 (4.17%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    General Physical Health Deterioration
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 10 (0.00%)
    0 / 5 (0.00%)
    1 / 24 (4.17%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    Multiple Organ Dysfunction Syndrome
         subjects affected / exposed
    1 / 7 (14.29%)
    0 / 10 (0.00%)
    0 / 5 (0.00%)
    0 / 24 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    Pain
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 10 (0.00%)
    1 / 5 (20.00%)
    0 / 24 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pyrexia
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 10 (10.00%)
    1 / 5 (20.00%)
    7 / 24 (29.17%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    2 / 9
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Anal Fistula
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 10 (0.00%)
    0 / 5 (0.00%)
    1 / 24 (4.17%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Diarrhoea
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 10 (0.00%)
    0 / 5 (0.00%)
    2 / 24 (8.33%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastritis
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 10 (0.00%)
    0 / 5 (0.00%)
    1 / 24 (4.17%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Proctalgia
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 10 (0.00%)
    0 / 5 (0.00%)
    1 / 24 (4.17%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Stomatitis
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 10 (0.00%)
    1 / 5 (20.00%)
    1 / 24 (4.17%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Vomiting
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 10 (0.00%)
    0 / 5 (0.00%)
    1 / 24 (4.17%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hepatobiliary disorders
    Hepatic Failure
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 10 (0.00%)
    0 / 5 (0.00%)
    1 / 24 (4.17%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    Hyperbilirubinaemia
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 10 (0.00%)
    0 / 5 (0.00%)
    3 / 24 (12.50%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Pharyngeal Inflammation
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 10 (10.00%)
    0 / 5 (0.00%)
    0 / 24 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pleural Effusion
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 10 (10.00%)
    0 / 5 (0.00%)
    0 / 24 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    Respiratory Distress
         subjects affected / exposed
    1 / 7 (14.29%)
    0 / 10 (0.00%)
    0 / 5 (0.00%)
    1 / 24 (4.17%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Psychiatric disorders
    Delirium
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 10 (0.00%)
    1 / 5 (20.00%)
    0 / 24 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Psychotic Disorder
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 10 (0.00%)
    1 / 5 (20.00%)
    0 / 24 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Renal and urinary disorders
    Acute Kidney Injury
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 10 (10.00%)
    1 / 5 (20.00%)
    0 / 24 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Infections and infestations
    Arthritis Bacterial
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 10 (10.00%)
    0 / 5 (0.00%)
    0 / 24 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Bacteraemia
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 10 (0.00%)
    0 / 5 (0.00%)
    1 / 24 (4.17%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Campylobacter Infection
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 10 (10.00%)
    0 / 5 (0.00%)
    0 / 24 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Candida Infection
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 10 (0.00%)
    0 / 5 (0.00%)
    1 / 24 (4.17%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cellulitis
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 10 (0.00%)
    1 / 5 (20.00%)
    1 / 24 (4.17%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Enterobacter Bacteraemia
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 10 (0.00%)
    0 / 5 (0.00%)
    1 / 24 (4.17%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Enterocolitis Infectious
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 10 (0.00%)
    0 / 5 (0.00%)
    1 / 24 (4.17%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Mucormycosis
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 10 (0.00%)
    0 / 5 (0.00%)
    1 / 24 (4.17%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pseudomonas Infection
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 10 (0.00%)
    0 / 5 (0.00%)
    1 / 24 (4.17%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Respiratory Syncytial Virus Infection
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 10 (0.00%)
    0 / 5 (0.00%)
    1 / 24 (4.17%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Sepsis
         subjects affected / exposed
    1 / 7 (14.29%)
    0 / 10 (0.00%)
    0 / 5 (0.00%)
    1 / 24 (4.17%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Septic Shock
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 10 (0.00%)
    1 / 5 (20.00%)
    2 / 24 (8.33%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
    1 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Staphylococcal Infection
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 10 (10.00%)
    0 / 5 (0.00%)
    0 / 24 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Metabolism and nutrition disorders
    Decreased Appetite
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 10 (0.00%)
    1 / 5 (20.00%)
    0 / 24 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    Cohort 1: B-Cell ALL (1-17 Years) Cohort 2: T-Cell LL (1-30 Years) Cohort 2: T-Cell ALL (18-30 Years) Cohort 2: T-Cell ALL (1-17 Years)
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    7 / 7 (100.00%)
    10 / 10 (100.00%)
    5 / 5 (100.00%)
    24 / 24 (100.00%)
    Vascular disorders
    Hypertension
         subjects affected / exposed
    2 / 7 (28.57%)
    4 / 10 (40.00%)
    1 / 5 (20.00%)
    5 / 24 (20.83%)
         occurrences all number
    2
    5
    1
    6
    Flushing
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 10 (10.00%)
    0 / 5 (0.00%)
    1 / 24 (4.17%)
         occurrences all number
    0
    1
    0
    1
    Superficial Vein Thrombosis
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 10 (0.00%)
    1 / 5 (20.00%)
    0 / 24 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Hypotension
         subjects affected / exposed
    0 / 7 (0.00%)
    2 / 10 (20.00%)
    1 / 5 (20.00%)
    2 / 24 (8.33%)
         occurrences all number
    0
    4
    2
    2
    Thrombophlebitis
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 10 (0.00%)
    1 / 5 (20.00%)
    0 / 24 (0.00%)
         occurrences all number
    0
    0
    1
    0
    General disorders and administration site conditions
    Asthenia
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 10 (0.00%)
    0 / 5 (0.00%)
    2 / 24 (8.33%)
         occurrences all number
    0
    0
    0
    2
    Catheter Site Haematoma
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 10 (0.00%)
    2 / 5 (40.00%)
    0 / 24 (0.00%)
         occurrences all number
    0
    0
    2
    0
    Chills
         subjects affected / exposed
    1 / 7 (14.29%)
    1 / 10 (10.00%)
    1 / 5 (20.00%)
    0 / 24 (0.00%)
         occurrences all number
    1
    1
    1
    0
    Fatigue
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 10 (10.00%)
    3 / 5 (60.00%)
    3 / 24 (12.50%)
         occurrences all number
    0
    1
    3
    5
    Face Oedema
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 10 (0.00%)
    0 / 5 (0.00%)
    2 / 24 (8.33%)
         occurrences all number
    0
    0
    0
    4
    Injection Site Bruising
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 10 (10.00%)
    0 / 5 (0.00%)
    0 / 24 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Generalised Oedema
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 10 (0.00%)
    0 / 5 (0.00%)
    3 / 24 (12.50%)
         occurrences all number
    0
    0
    0
    3
    Localised Oedema
         subjects affected / exposed
    0 / 7 (0.00%)
    2 / 10 (20.00%)
    0 / 5 (0.00%)
    1 / 24 (4.17%)
         occurrences all number
    0
    2
    0
    1
    Pyrexia
         subjects affected / exposed
    4 / 7 (57.14%)
    7 / 10 (70.00%)
    3 / 5 (60.00%)
    13 / 24 (54.17%)
         occurrences all number
    10
    12
    12
    26
    Oedema Peripheral
         subjects affected / exposed
    0 / 7 (0.00%)
    3 / 10 (30.00%)
    0 / 5 (0.00%)
    4 / 24 (16.67%)
         occurrences all number
    0
    3
    0
    5
    Non-Cardiac Chest Pain
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 10 (0.00%)
    0 / 5 (0.00%)
    2 / 24 (8.33%)
         occurrences all number
    0
    0
    0
    2
    Vascular Device Occlusion
         subjects affected / exposed
    1 / 7 (14.29%)
    0 / 10 (0.00%)
    0 / 5 (0.00%)
    0 / 24 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Immune system disorders
    Drug Hypersensitivity
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 10 (10.00%)
    0 / 5 (0.00%)
    0 / 24 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Hypogammaglobulinaemia
         subjects affected / exposed
    1 / 7 (14.29%)
    3 / 10 (30.00%)
    0 / 5 (0.00%)
    1 / 24 (4.17%)
         occurrences all number
    1
    3
    0
    2
    Social circumstances
    Menopause
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 10 (10.00%)
    0 / 5 (0.00%)
    0 / 24 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Reproductive system and breast disorders
    Balanoposthitis
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 10 (10.00%)
    0 / 5 (0.00%)
    0 / 24 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Pelvic Pain
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 10 (0.00%)
    1 / 5 (20.00%)
    0 / 24 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Respiratory, thoracic and mediastinal disorders
    Allergic Cough
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 10 (10.00%)
    0 / 5 (0.00%)
    1 / 24 (4.17%)
         occurrences all number
    0
    1
    0
    1
    Atelectasis
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 10 (0.00%)
    1 / 5 (20.00%)
    0 / 24 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Bronchospasm
         subjects affected / exposed
    1 / 7 (14.29%)
    1 / 10 (10.00%)
    0 / 5 (0.00%)
    1 / 24 (4.17%)
         occurrences all number
    1
    1
    0
    1
    Dyspnoea
         subjects affected / exposed
    1 / 7 (14.29%)
    3 / 10 (30.00%)
    2 / 5 (40.00%)
    1 / 24 (4.17%)
         occurrences all number
    1
    3
    2
    1
    Cough
         subjects affected / exposed
    3 / 7 (42.86%)
    5 / 10 (50.00%)
    0 / 5 (0.00%)
    7 / 24 (29.17%)
         occurrences all number
    4
    5
    0
    10
    Choking
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 10 (10.00%)
    0 / 5 (0.00%)
    0 / 24 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Epistaxis
         subjects affected / exposed
    0 / 7 (0.00%)
    2 / 10 (20.00%)
    1 / 5 (20.00%)
    6 / 24 (25.00%)
         occurrences all number
    0
    2
    1
    6
    Nasal Mucosal Disorder
         subjects affected / exposed
    1 / 7 (14.29%)
    0 / 10 (0.00%)
    0 / 5 (0.00%)
    0 / 24 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Nasal Congestion
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 10 (10.00%)
    1 / 5 (20.00%)
    0 / 24 (0.00%)
         occurrences all number
    0
    1
    1
    0
    Hypoxia
         subjects affected / exposed
    2 / 7 (28.57%)
    0 / 10 (0.00%)
    3 / 5 (60.00%)
    4 / 24 (16.67%)
         occurrences all number
    2
    0
    4
    6
    Oropharyngeal Pain
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 10 (10.00%)
    1 / 5 (20.00%)
    1 / 24 (4.17%)
         occurrences all number
    0
    1
    1
    1
    Pleural Effusion
         subjects affected / exposed
    0 / 7 (0.00%)
    2 / 10 (20.00%)
    1 / 5 (20.00%)
    2 / 24 (8.33%)
         occurrences all number
    0
    2
    2
    2
    Pharyngeal Enanthema
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 10 (10.00%)
    0 / 5 (0.00%)
    0 / 24 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Pleuritic Pain
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 10 (0.00%)
    1 / 5 (20.00%)
    0 / 24 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Pulmonary Oedema
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 10 (0.00%)
    1 / 5 (20.00%)
    0 / 24 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Rhinorrhoea
         subjects affected / exposed
    0 / 7 (0.00%)
    2 / 10 (20.00%)
    0 / 5 (0.00%)
    2 / 24 (8.33%)
         occurrences all number
    0
    3
    0
    3
    Rhinitis Allergic
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 10 (10.00%)
    0 / 5 (0.00%)
    1 / 24 (4.17%)
         occurrences all number
    0
    1
    0
    1
    Sneezing
         subjects affected / exposed
    1 / 7 (14.29%)
    0 / 10 (0.00%)
    0 / 5 (0.00%)
    1 / 24 (4.17%)
         occurrences all number
    1
    0
    0
    1
    Wheezing
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 10 (0.00%)
    1 / 5 (20.00%)
    1 / 24 (4.17%)
         occurrences all number
    0
    0
    1
    1
    Psychiatric disorders
    Anxiety
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 10 (10.00%)
    0 / 5 (0.00%)
    2 / 24 (8.33%)
         occurrences all number
    0
    1
    0
    2
    Insomnia
         subjects affected / exposed
    1 / 7 (14.29%)
    2 / 10 (20.00%)
    1 / 5 (20.00%)
    2 / 24 (8.33%)
         occurrences all number
    1
    2
    1
    3
    Product issues
    Device Occlusion
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 10 (0.00%)
    1 / 5 (20.00%)
    0 / 24 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Investigations
    Activated Partial Thromboplastin Time Prolonged
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 10 (0.00%)
    1 / 5 (20.00%)
    0 / 24 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Alanine Aminotransferase Increased
         subjects affected / exposed
    3 / 7 (42.86%)
    5 / 10 (50.00%)
    3 / 5 (60.00%)
    9 / 24 (37.50%)
         occurrences all number
    6
    23
    8
    41
    Blood Alkaline Phosphatase Increased
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 10 (0.00%)
    4 / 5 (80.00%)
    0 / 24 (0.00%)
         occurrences all number
    0
    0
    8
    0
    Aspartate Aminotransferase Increased
         subjects affected / exposed
    2 / 7 (28.57%)
    5 / 10 (50.00%)
    3 / 5 (60.00%)
    4 / 24 (16.67%)
         occurrences all number
    2
    11
    7
    21
    Antithrombin Iii Decreased
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 10 (0.00%)
    1 / 5 (20.00%)
    0 / 24 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Ammonia Increased
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 10 (0.00%)
    1 / 5 (20.00%)
    0 / 24 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Blood Lactate Dehydrogenase Increased
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 10 (0.00%)
    0 / 5 (0.00%)
    2 / 24 (8.33%)
         occurrences all number
    0
    0
    0
    2
    Electrocardiogram QT Prolonged
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 10 (10.00%)
    1 / 5 (20.00%)
    0 / 24 (0.00%)
         occurrences all number
    0
    1
    1
    0
    Gamma-Glutamyltransferase Increased
         subjects affected / exposed
    1 / 7 (14.29%)
    4 / 10 (40.00%)
    1 / 5 (20.00%)
    3 / 24 (12.50%)
         occurrences all number
    1
    15
    1
    15
    Blood Fibrinogen Decreased
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 10 (0.00%)
    2 / 5 (40.00%)
    3 / 24 (12.50%)
         occurrences all number
    0
    0
    2
    10
    Interleukin Level Increased
         subjects affected / exposed
    1 / 7 (14.29%)
    0 / 10 (0.00%)
    0 / 5 (0.00%)
    0 / 24 (0.00%)
         occurrences all number
    1
    0
    0
    0
    International Normalised Ratio Increased
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 10 (0.00%)
    1 / 5 (20.00%)
    0 / 24 (0.00%)
         occurrences all number
    0
    0
    2
    0
    Lipase Increased
         subjects affected / exposed
    0 / 7 (0.00%)
    4 / 10 (40.00%)
    2 / 5 (40.00%)
    1 / 24 (4.17%)
         occurrences all number
    0
    14
    4
    1
    Urine Output Decreased
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 10 (10.00%)
    0 / 5 (0.00%)
    0 / 24 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Weight Decreased
         subjects affected / exposed
    1 / 7 (14.29%)
    1 / 10 (10.00%)
    2 / 5 (40.00%)
    3 / 24 (12.50%)
         occurrences all number
    1
    3
    3
    4
    Weight Increased
         subjects affected / exposed
    2 / 7 (28.57%)
    0 / 10 (0.00%)
    0 / 5 (0.00%)
    0 / 24 (0.00%)
         occurrences all number
    2
    0
    0
    0
    Injury, poisoning and procedural complications
    Accidental Overdose
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 10 (10.00%)
    0 / 5 (0.00%)
    0 / 24 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Wound Complication
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 10 (0.00%)
    1 / 5 (20.00%)
    0 / 24 (0.00%)
         occurrences all number
    0
    0
    2
    0
    Wound
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 10 (10.00%)
    0 / 5 (0.00%)
    0 / 24 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Cardiac disorders
    Cardiac Failure
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 10 (0.00%)
    1 / 5 (20.00%)
    0 / 24 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Sinus Bradycardia
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 10 (10.00%)
    0 / 5 (0.00%)
    2 / 24 (8.33%)
         occurrences all number
    0
    2
    0
    2
    Sinus Tachycardia
         subjects affected / exposed
    2 / 7 (28.57%)
    1 / 10 (10.00%)
    1 / 5 (20.00%)
    3 / 24 (12.50%)
         occurrences all number
    4
    1
    1
    5
    Tachycardia
         subjects affected / exposed
    0 / 7 (0.00%)
    2 / 10 (20.00%)
    1 / 5 (20.00%)
    1 / 24 (4.17%)
         occurrences all number
    0
    2
    1
    1
    Nervous system disorders
    Depressed Level of Consciousness
         subjects affected / exposed
    1 / 7 (14.29%)
    0 / 10 (0.00%)
    0 / 5 (0.00%)
    0 / 24 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Dizziness
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 10 (0.00%)
    0 / 5 (0.00%)
    3 / 24 (12.50%)
         occurrences all number
    0
    0
    0
    4
    Facial Paralysis
         subjects affected / exposed
    1 / 7 (14.29%)
    0 / 10 (0.00%)
    0 / 5 (0.00%)
    0 / 24 (0.00%)
         occurrences all number
    2
    0
    0
    0
    Encephalopathy
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 10 (10.00%)
    0 / 5 (0.00%)
    0 / 24 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Dysarthria
         subjects affected / exposed
    1 / 7 (14.29%)
    0 / 10 (0.00%)
    0 / 5 (0.00%)
    0 / 24 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Headache
         subjects affected / exposed
    2 / 7 (28.57%)
    4 / 10 (40.00%)
    2 / 5 (40.00%)
    11 / 24 (45.83%)
         occurrences all number
    2
    4
    2
    18
    Peripheral Motor Neuropathy
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 10 (10.00%)
    0 / 5 (0.00%)
    1 / 24 (4.17%)
         occurrences all number
    0
    1
    0
    1
    Peripheral Sensory Neuropathy
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 10 (10.00%)
    1 / 5 (20.00%)
    4 / 24 (16.67%)
         occurrences all number
    0
    1
    1
    5
    Somnolence
         subjects affected / exposed
    1 / 7 (14.29%)
    0 / 10 (0.00%)
    0 / 5 (0.00%)
    1 / 24 (4.17%)
         occurrences all number
    1
    0
    0
    1
    Seizure
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 10 (10.00%)
    0 / 5 (0.00%)
    0 / 24 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Tremor
         subjects affected / exposed
    0 / 7 (0.00%)
    2 / 10 (20.00%)
    0 / 5 (0.00%)
    1 / 24 (4.17%)
         occurrences all number
    0
    2
    0
    1
    Blood and lymphatic system disorders
    Febrile Neutropenia
         subjects affected / exposed
    2 / 7 (28.57%)
    4 / 10 (40.00%)
    2 / 5 (40.00%)
    7 / 24 (29.17%)
         occurrences all number
    2
    4
    4
    12
    Anaemia
         subjects affected / exposed
    4 / 7 (57.14%)
    10 / 10 (100.00%)
    2 / 5 (40.00%)
    16 / 24 (66.67%)
         occurrences all number
    13
    49
    5
    109
    Hypocoagulable State
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 10 (10.00%)
    0 / 5 (0.00%)
    0 / 24 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Lymph Node Pain
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 10 (10.00%)
    0 / 5 (0.00%)
    0 / 24 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Leukopenia
         subjects affected / exposed
    3 / 7 (42.86%)
    5 / 10 (50.00%)
    1 / 5 (20.00%)
    9 / 24 (37.50%)
         occurrences all number
    6
    50
    5
    46
    Lymphocytosis
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 10 (0.00%)
    1 / 5 (20.00%)
    0 / 24 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Lymphopenia
         subjects affected / exposed
    1 / 7 (14.29%)
    1 / 10 (10.00%)
    1 / 5 (20.00%)
    5 / 24 (20.83%)
         occurrences all number
    1
    2
    1
    12
    Neutropenia
         subjects affected / exposed
    2 / 7 (28.57%)
    6 / 10 (60.00%)
    2 / 5 (40.00%)
    15 / 24 (62.50%)
         occurrences all number
    2
    36
    6
    86
    Thrombocytopenia
         subjects affected / exposed
    2 / 7 (28.57%)
    9 / 10 (90.00%)
    3 / 5 (60.00%)
    18 / 24 (75.00%)
         occurrences all number
    10
    71
    11
    111
    Ear and labyrinth disorders
    Ear Pain
         subjects affected / exposed
    1 / 7 (14.29%)
    0 / 10 (0.00%)
    0 / 5 (0.00%)
    0 / 24 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Eye disorders
    Eye Oedema
         subjects affected / exposed
    1 / 7 (14.29%)
    0 / 10 (0.00%)
    0 / 5 (0.00%)
    0 / 24 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Eye Pruritus
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 10 (0.00%)
    0 / 5 (0.00%)
    2 / 24 (8.33%)
         occurrences all number
    0
    0
    0
    2
    Vision Blurred
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 10 (0.00%)
    0 / 5 (0.00%)
    3 / 24 (12.50%)
         occurrences all number
    0
    0
    0
    3
    Visual Acuity Reduced
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 10 (10.00%)
    0 / 5 (0.00%)
    0 / 24 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Gastrointestinal disorders
    Abdominal Pain Upper
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 10 (0.00%)
    1 / 5 (20.00%)
    3 / 24 (12.50%)
         occurrences all number
    0
    0
    1
    4
    Abdominal Pain
         subjects affected / exposed
    2 / 7 (28.57%)
    4 / 10 (40.00%)
    3 / 5 (60.00%)
    12 / 24 (50.00%)
         occurrences all number
    3
    4
    3
    37
    Anal Fissure
         subjects affected / exposed
    1 / 7 (14.29%)
    0 / 10 (0.00%)
    0 / 5 (0.00%)
    3 / 24 (12.50%)
         occurrences all number
    1
    0
    0
    3
    Anal Fistula
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 10 (0.00%)
    1 / 5 (20.00%)
    1 / 24 (4.17%)
         occurrences all number
    0
    0
    1
    1
    Anal Inflammation
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 10 (0.00%)
    0 / 5 (0.00%)
    3 / 24 (12.50%)
         occurrences all number
    0
    0
    0
    4
    Ascites
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 10 (0.00%)
    0 / 5 (0.00%)
    3 / 24 (12.50%)
         occurrences all number
    0
    0
    0
    4
    Colitis
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 10 (0.00%)
    0 / 5 (0.00%)
    3 / 24 (12.50%)
         occurrences all number
    0
    0
    0
    3
    Diarrhoea
         subjects affected / exposed
    2 / 7 (28.57%)
    3 / 10 (30.00%)
    1 / 5 (20.00%)
    7 / 24 (29.17%)
         occurrences all number
    2
    4
    1
    10
    Constipation
         subjects affected / exposed
    2 / 7 (28.57%)
    2 / 10 (20.00%)
    4 / 5 (80.00%)
    6 / 24 (25.00%)
         occurrences all number
    2
    2
    6
    6
    Dysphagia
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 10 (0.00%)
    1 / 5 (20.00%)
    0 / 24 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Dyspepsia
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 10 (10.00%)
    0 / 5 (0.00%)
    2 / 24 (8.33%)
         occurrences all number
    0
    1
    0
    2
    Gastrointestinal Haemorrhage
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 10 (0.00%)
    1 / 5 (20.00%)
    1 / 24 (4.17%)
         occurrences all number
    0
    0
    1
    1
    Gingival Bleeding
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 10 (0.00%)
    1 / 5 (20.00%)
    0 / 24 (0.00%)
         occurrences all number
    0
    0
    2
    0
    Gastrooesophageal Reflux Disease
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 10 (0.00%)
    0 / 5 (0.00%)
    2 / 24 (8.33%)
         occurrences all number
    0
    0
    0
    2
    Haematochezia
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 10 (10.00%)
    0 / 5 (0.00%)
    1 / 24 (4.17%)
         occurrences all number
    0
    1
    0
    1
    Haemorrhoidal Haemorrhage
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 10 (10.00%)
    0 / 5 (0.00%)
    0 / 24 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Haemorrhoids
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 10 (0.00%)
    1 / 5 (20.00%)
    2 / 24 (8.33%)
         occurrences all number
    0
    0
    2
    2
    Nausea
         subjects affected / exposed
    0 / 7 (0.00%)
    4 / 10 (40.00%)
    2 / 5 (40.00%)
    11 / 24 (45.83%)
         occurrences all number
    0
    5
    2
    17
    Lip Dry
         subjects affected / exposed
    1 / 7 (14.29%)
    0 / 10 (0.00%)
    0 / 5 (0.00%)
    0 / 24 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Odynophagia
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 10 (0.00%)
    1 / 5 (20.00%)
    0 / 24 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Pancreatitis
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 10 (10.00%)
    0 / 5 (0.00%)
    0 / 24 (0.00%)
         occurrences all number
    0
    2
    0
    0
    Oesophagitis
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 10 (0.00%)
    1 / 5 (20.00%)
    0 / 24 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Proctalgia
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 10 (0.00%)
    0 / 5 (0.00%)
    2 / 24 (8.33%)
         occurrences all number
    0
    0
    0
    2
    Vomiting
         subjects affected / exposed
    2 / 7 (28.57%)
    5 / 10 (50.00%)
    2 / 5 (40.00%)
    14 / 24 (58.33%)
         occurrences all number
    3
    10
    3
    28
    Tongue Coated
         subjects affected / exposed
    1 / 7 (14.29%)
    0 / 10 (0.00%)
    0 / 5 (0.00%)
    0 / 24 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Stomatitis
         subjects affected / exposed
    0 / 7 (0.00%)
    7 / 10 (70.00%)
    2 / 5 (40.00%)
    10 / 24 (41.67%)
         occurrences all number
    0
    12
    4
    18
    Hepatobiliary disorders
    Hyperbilirubinaemia
         subjects affected / exposed
    0 / 7 (0.00%)
    4 / 10 (40.00%)
    4 / 5 (80.00%)
    7 / 24 (29.17%)
         occurrences all number
    0
    14
    9
    17
    Hepatomegaly
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 10 (0.00%)
    0 / 5 (0.00%)
    2 / 24 (8.33%)
         occurrences all number
    0
    0
    0
    3
    Hepatic Cytolysis
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 10 (10.00%)
    0 / 5 (0.00%)
    1 / 24 (4.17%)
         occurrences all number
    0
    1
    0
    2
    Skin and subcutaneous tissue disorders
    Acne
         subjects affected / exposed
    1 / 7 (14.29%)
    0 / 10 (0.00%)
    0 / 5 (0.00%)
    0 / 24 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Alopecia
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 10 (10.00%)
    1 / 5 (20.00%)
    2 / 24 (8.33%)
         occurrences all number
    0
    1
    1
    3
    Dermatitis Allergic
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 10 (10.00%)
    0 / 5 (0.00%)
    1 / 24 (4.17%)
         occurrences all number
    0
    1
    0
    1
    Erythema
         subjects affected / exposed
    1 / 7 (14.29%)
    1 / 10 (10.00%)
    0 / 5 (0.00%)
    1 / 24 (4.17%)
         occurrences all number
    1
    1
    0
    1
    Petechiae
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 10 (10.00%)
    0 / 5 (0.00%)
    0 / 24 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Pruritus
         subjects affected / exposed
    1 / 7 (14.29%)
    1 / 10 (10.00%)
    2 / 5 (40.00%)
    2 / 24 (8.33%)
         occurrences all number
    1
    1
    2
    2
    Rash Macular
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 10 (10.00%)
    0 / 5 (0.00%)
    0 / 24 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Rash Erythematous
         subjects affected / exposed
    0 / 7 (0.00%)
    2 / 10 (20.00%)
    0 / 5 (0.00%)
    2 / 24 (8.33%)
         occurrences all number
    0
    3
    0
    2
    Rash
         subjects affected / exposed
    1 / 7 (14.29%)
    2 / 10 (20.00%)
    2 / 5 (40.00%)
    4 / 24 (16.67%)
         occurrences all number
    1
    5
    2
    5
    Rash Maculo-Papular
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 10 (0.00%)
    0 / 5 (0.00%)
    4 / 24 (16.67%)
         occurrences all number
    0
    0
    0
    5
    Rash Papular
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 10 (10.00%)
    0 / 5 (0.00%)
    0 / 24 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Skin Striae
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 10 (0.00%)
    1 / 5 (20.00%)
    0 / 24 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Skin Ulcer
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 10 (10.00%)
    0 / 5 (0.00%)
    0 / 24 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Urticaria
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 10 (0.00%)
    0 / 5 (0.00%)
    4 / 24 (16.67%)
         occurrences all number
    0
    0
    0
    5
    Renal and urinary disorders
    Acute Kidney Injury
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 10 (10.00%)
    1 / 5 (20.00%)
    0 / 24 (0.00%)
         occurrences all number
    0
    2
    1
    0
    Urinary Retention
         subjects affected / exposed
    1 / 7 (14.29%)
    0 / 10 (0.00%)
    0 / 5 (0.00%)
    1 / 24 (4.17%)
         occurrences all number
    1
    0
    0
    1
    Renal Tubular Disorder
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 10 (10.00%)
    0 / 5 (0.00%)
    1 / 24 (4.17%)
         occurrences all number
    0
    1
    0
    1
    Renal Impairment
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 10 (10.00%)
    0 / 5 (0.00%)
    0 / 24 (0.00%)
         occurrences all number
    0
    3
    0
    0
    Endocrine disorders
    Adrenal Insufficiency
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 10 (10.00%)
    1 / 5 (20.00%)
    0 / 24 (0.00%)
         occurrences all number
    0
    1
    1
    0
    Musculoskeletal and connective tissue disorders
    Bone Pain
         subjects affected / exposed
    2 / 7 (28.57%)
    1 / 10 (10.00%)
    0 / 5 (0.00%)
    2 / 24 (8.33%)
         occurrences all number
    2
    1
    0
    3
    Back Pain
         subjects affected / exposed
    1 / 7 (14.29%)
    3 / 10 (30.00%)
    1 / 5 (20.00%)
    2 / 24 (8.33%)
         occurrences all number
    1
    3
    1
    2
    Arthralgia
         subjects affected / exposed
    1 / 7 (14.29%)
    2 / 10 (20.00%)
    1 / 5 (20.00%)
    1 / 24 (4.17%)
         occurrences all number
    1
    3
    4
    2
    Flank Pain
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 10 (0.00%)
    1 / 5 (20.00%)
    0 / 24 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Muscular Weakness
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 10 (0.00%)
    0 / 5 (0.00%)
    2 / 24 (8.33%)
         occurrences all number
    0
    0
    0
    2
    Musculoskeletal Chest Pain
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 10 (10.00%)
    2 / 5 (40.00%)
    0 / 24 (0.00%)
         occurrences all number
    0
    1
    2
    0
    Myalgia
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 10 (0.00%)
    1 / 5 (20.00%)
    2 / 24 (8.33%)
         occurrences all number
    0
    0
    1
    3
    Pain in Extremity
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 10 (10.00%)
    1 / 5 (20.00%)
    4 / 24 (16.67%)
         occurrences all number
    0
    1
    1
    5
    Pain in Jaw
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 10 (10.00%)
    0 / 5 (0.00%)
    2 / 24 (8.33%)
         occurrences all number
    0
    1
    0
    2
    Spinal Pain
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 10 (0.00%)
    1 / 5 (20.00%)
    1 / 24 (4.17%)
         occurrences all number
    0
    0
    1
    1
    Infections and infestations
    Clostridium Difficile Colitis
         subjects affected / exposed
    1 / 7 (14.29%)
    0 / 10 (0.00%)
    0 / 5 (0.00%)
    0 / 24 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Cellulitis
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 10 (10.00%)
    0 / 5 (0.00%)
    1 / 24 (4.17%)
         occurrences all number
    0
    1
    0
    1
    Clostridium Difficile Infection
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 10 (10.00%)
    0 / 5 (0.00%)
    0 / 24 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Conjunctivitis
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 10 (10.00%)
    0 / 5 (0.00%)
    0 / 24 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Device Related Infection
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 10 (0.00%)
    0 / 5 (0.00%)
    2 / 24 (8.33%)
         occurrences all number
    0
    0
    0
    3
    Herpes Simplex
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 10 (10.00%)
    0 / 5 (0.00%)
    0 / 24 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Influenza
         subjects affected / exposed
    1 / 7 (14.29%)
    0 / 10 (0.00%)
    0 / 5 (0.00%)
    0 / 24 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Kidney Infection
         subjects affected / exposed
    1 / 7 (14.29%)
    0 / 10 (0.00%)
    0 / 5 (0.00%)
    0 / 24 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Oral Candidiasis
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 10 (10.00%)
    1 / 5 (20.00%)
    2 / 24 (8.33%)
         occurrences all number
    0
    1
    1
    2
    Otitis Externa
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 10 (0.00%)
    0 / 5 (0.00%)
    2 / 24 (8.33%)
         occurrences all number
    0
    0
    0
    3
    Paronychia
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 10 (10.00%)
    0 / 5 (0.00%)
    0 / 24 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Periorbital Cellulitis
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 10 (10.00%)
    0 / 5 (0.00%)
    0 / 24 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Pneumonia
         subjects affected / exposed
    0 / 7 (0.00%)
    2 / 10 (20.00%)
    0 / 5 (0.00%)
    2 / 24 (8.33%)
         occurrences all number
    0
    2
    0
    2
    Rhinitis
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 10 (0.00%)
    1 / 5 (20.00%)
    0 / 24 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Upper Respiratory Tract Infection
         subjects affected / exposed
    1 / 7 (14.29%)
    0 / 10 (0.00%)
    0 / 5 (0.00%)
    1 / 24 (4.17%)
         occurrences all number
    1
    0
    0
    1
    Splenic Infection Fungal
         subjects affected / exposed
    1 / 7 (14.29%)
    0 / 10 (0.00%)
    0 / 5 (0.00%)
    0 / 24 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Vaginal Infection
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 10 (10.00%)
    0 / 5 (0.00%)
    0 / 24 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Metabolism and nutrition disorders
    Alkalosis
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 10 (10.00%)
    0 / 5 (0.00%)
    0 / 24 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Decreased Appetite
         subjects affected / exposed
    1 / 7 (14.29%)
    1 / 10 (10.00%)
    2 / 5 (40.00%)
    4 / 24 (16.67%)
         occurrences all number
    1
    1
    2
    4
    Dehydration
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 10 (0.00%)
    2 / 5 (40.00%)
    0 / 24 (0.00%)
         occurrences all number
    0
    0
    2
    0
    Hyperammonaemia
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 10 (0.00%)
    1 / 5 (20.00%)
    1 / 24 (4.17%)
         occurrences all number
    0
    0
    1
    1
    Fluid Retention
         subjects affected / exposed
    1 / 7 (14.29%)
    2 / 10 (20.00%)
    0 / 5 (0.00%)
    0 / 24 (0.00%)
         occurrences all number
    2
    3
    0
    0
    Hyperglycaemia
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 10 (10.00%)
    1 / 5 (20.00%)
    5 / 24 (20.83%)
         occurrences all number
    0
    1
    1
    10
    Hyperferritinaemia
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 10 (10.00%)
    0 / 5 (0.00%)
    0 / 24 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Hypercalcaemia
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 10 (10.00%)
    0 / 5 (0.00%)
    0 / 24 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Hyperamylasaemia
         subjects affected / exposed
    0 / 7 (0.00%)
    2 / 10 (20.00%)
    1 / 5 (20.00%)
    1 / 24 (4.17%)
         occurrences all number
    0
    6
    1
    1
    Hyperkalaemia
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 10 (10.00%)
    1 / 5 (20.00%)
    1 / 24 (4.17%)
         occurrences all number
    0
    6
    1
    1
    Hypermagnesaemia
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 10 (10.00%)
    1 / 5 (20.00%)
    0 / 24 (0.00%)
         occurrences all number
    0
    1
    1
    0
    Hypernatraemia
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 10 (10.00%)
    1 / 5 (20.00%)
    0 / 24 (0.00%)
         occurrences all number
    0
    2
    1
    0
    Hyperphosphataemia
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 10 (0.00%)
    1 / 5 (20.00%)
    0 / 24 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Hypertriglyceridaemia
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 10 (10.00%)
    1 / 5 (20.00%)
    3 / 24 (12.50%)
         occurrences all number
    0
    1
    1
    5
    Hyperuricaemia
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 10 (0.00%)
    1 / 5 (20.00%)
    0 / 24 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Hypervolaemia
         subjects affected / exposed
    1 / 7 (14.29%)
    0 / 10 (0.00%)
    0 / 5 (0.00%)
    2 / 24 (8.33%)
         occurrences all number
    1
    0
    0
    2
    Hypoalbuminaemia
         subjects affected / exposed
    0 / 7 (0.00%)
    5 / 10 (50.00%)
    3 / 5 (60.00%)
    12 / 24 (50.00%)
         occurrences all number
    0
    24
    4
    34
    Hypocalcaemia
         subjects affected / exposed
    1 / 7 (14.29%)
    1 / 10 (10.00%)
    2 / 5 (40.00%)
    2 / 24 (8.33%)
         occurrences all number
    1
    5
    4
    9
    Hypoglycaemia
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 10 (10.00%)
    0 / 5 (0.00%)
    0 / 24 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Hypokalaemia
         subjects affected / exposed
    1 / 7 (14.29%)
    3 / 10 (30.00%)
    1 / 5 (20.00%)
    8 / 24 (33.33%)
         occurrences all number
    1
    22
    5
    24
    Hyponatraemia
         subjects affected / exposed
    0 / 7 (0.00%)
    2 / 10 (20.00%)
    4 / 5 (80.00%)
    6 / 24 (25.00%)
         occurrences all number
    0
    2
    5
    7
    Hypomagnesaemia
         subjects affected / exposed
    0 / 7 (0.00%)
    2 / 10 (20.00%)
    1 / 5 (20.00%)
    2 / 24 (8.33%)
         occurrences all number
    0
    2
    1
    2
    Tumour Lysis Syndrome
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 10 (10.00%)
    1 / 5 (20.00%)
    0 / 24 (0.00%)
         occurrences all number
    0
    1
    1
    0
    Malnutrition
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 10 (10.00%)
    0 / 5 (0.00%)
    0 / 24 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Hypophosphataemia
         subjects affected / exposed
    1 / 7 (14.29%)
    2 / 10 (20.00%)
    1 / 5 (20.00%)
    3 / 24 (12.50%)
         occurrences all number
    1
    7
    4
    6
    Vitamin D Deficiency
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 10 (0.00%)
    1 / 5 (20.00%)
    0 / 24 (0.00%)
         occurrences all number
    0
    0
    1
    0

    More information

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    Substantial protocol amendments (globally)

    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    12 Jan 2018
    The purpose of this amendment was to include clarifications for the procedures to be conducted during the follow-up period and the addition of the collection of relevant information from subjects who proceeded to post-treatment, off-study bone marrow transplantation.
    04 Sep 2018
    The purpose of this amenment was to incorporate changes from country-specific amendments and to provide additional details and clarifications regarding study procedures.
    22 Jan 2019
    The purpose of this amendment was to include changes based on the identification of a new important risk (that is, hepatitis B virus [HBV] reactivation): the text for identification of HBV reactivation, testing, and management of subjects with the potential for HBV reactivation was added or modified.

    Interruptions (globally)

    Were there any global interruptions to the trial? No

    Limitations and caveats

    Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.
    None reported
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