Download PDF

Clinical Trial Results:
A Phase 2 Randomized Open-label Study of MEDI-551 in Adults With Relapsed or Refractory DLBCL

Summary
EudraCT number	2011-002565-38
Trial protocol	DE CZ ES HU IT PL
Global end of trial date	17 Jul 2016

Results information
Results version number	v1(current)
This version publication date	21 Feb 2018
First version publication date	21 Feb 2018
Other versions

Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information

Collapse all Expand all

Trial information

Top of page

Sponsor protocol code

CD-ON-MEDI-551-1088

ISRCTN number

US NCT number

NCT01453205

WHO universal trial number (UTN)

Sponsor organisation name

MedImmune, LLC

Sponsor organisation address

One MedImmune Way, Gaithersburg, United States, MD 20878

Public contact

AstraZeneca, AstraZeneca Clinical Study Information Center,, +1 18772409479, information.center@astrazenca.com

Scientific contact

AstraZeneca, AstraZeneca Clinical Study Information Center,, +1 18772409479, information.center@astrazeneca.com

Is trial part of an agreed paediatric investigation plan (PIP)

Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?

Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?

Analysis stage

Final

Date of interim/final analysis

17 Jul 2016

Is this the analysis of the primary completion data?

Global end of trial reached?

Yes

Global end of trial date

17 Jul 2016

Was the trial ended prematurely?

Main objective of the trial

The primary objective of this study was to evaluate the overall response rate (ORR), including partial response (PR) and complete response (CR), of participants treated with MEDI-551 when used in combination with ifosfamide-carboplatin-etoposide (ICE) or dexamethasone-cytarabine-cisplatin (DHAP) versus rituximab in combination with ICE or DHAP in participants with relapsed or refractory diffuse large B-cell lymphoma (DLBCL).

Protection of trial subjects

The conduct of this clinical study met all local and regulatory requirements. The study was conducted in accordance with the ethical principles that have their origin in the Declaration of Helsinki and are consistent with International Conference on Harmonization guideline: Good Clinical Practice and applicable regulatory requirements. Participants signed informed consent form and could withdraw from the study at any time without any disadvantage and without having to provide a reason for this decision. Only investigators qualified by training and experience were selected as appropriate experts to investigate the study drug.

Background therapy

Evidence for comparator

Actual start date of recruitment

27 Feb 2012

Long term follow-up planned

Independent data monitoring committee (IDMC) involvement?

Number of subjects enrolled per country

Country: Number of subjects enrolled

United States: 84

Country: Number of subjects enrolled

Canada: 8

Country: Number of subjects enrolled

Czech Republic: 7

Country: Number of subjects enrolled

France: 13

Country: Number of subjects enrolled

Germany: 4

Country: Number of subjects enrolled

Hungary: 11

Country: Number of subjects enrolled

Israel: 7

Country: Number of subjects enrolled

Poland: 13

Country: Number of subjects enrolled

Russian Federation: 8

Country: Number of subjects enrolled

Spain: 25

Country: Number of subjects enrolled

Turkey: 7

Worldwide total number of subjects

187

EEA total number of subjects

Number of subjects enrolled per age group

In utero

Preterm newborn - gestational age < 37 wk

Newborns (0-27 days)

Infants and toddlers (28 days-23 months)

Children (2-11 years)

Adolescents (12-17 years)

Adults (18-64 years)

138

From 65 to 84 years

85 years and over

Subject disposition

Top of page

Recruitment details

The study was conducted from 27Feb2012 to 17Jun2016.

Screening details

A total of 256 participants were screened, of which 187 participants were randomized in the study.

Period 1 title

Overall Study (overall period)

Is this the baseline period?

Yes

Allocation method

Randomised - controlled

Blinding used

Not blinded

Are arms mutually exclusive

Yes

Rituximab+ ICE/DHAP

Arm description

Participants received Rituximab in combination with ifosfamide + carboplatin + etoposide (ICE) or dexamethasone + cisplatin + cytarabine (DHAP) for 3 cycles (21-day cycles) and were followed until end of the study (36 months after the date of randomization for last participant, or date the sponsor stops the trial, whichever occurs first). Rituximab (375 mg/m^2) was administered intravenous (IV) on 2 days before the start of Cycle 1 and on Day 1 of each cycle. After completion of rituximab, IV infusion of ICE as: ifosfamide 5 g/ m^2 continuously for 24 hours with mesna on Day 2; carboplatin AUC=5 mg/mL x min (800 mg maximum) on Day 2; etoposide 100 mg/ m^2 on Days 1, 2, and 3 in 21-day cycles. After completion of rituximab, IV infusion of DHAP as: dexamethasone 40 mg on Days 1, 2, 3, and 4; cisplatin 100 mg/m^2 continuously for 24 hours on Day 1; cytarabine 2 g/m^2 in 3-hour infusion repeated after 12 hours (2 doses) on Day 2 in 21-day cycles.

Arm type

Active comparator

Investigational medicinal product name

Rituximab

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

Rituximab (375 mg/m^2) was administered intravenous (IV) on 2 days before the start of Cycle 1 and on Day 1 of each cycle.

MEDI-551 2 mg/kg + ICE/DHAP

Arm description

Participants received MEDI-551 (2 mg/kg) in combination with ICE or DHAP for 3 cycles (21-day cycles) and were followed until end of the study (36 months after the date of randomization for last participant, or date the sponsor stops the trial, whichever occurs first). MEDI-551 (2 mg/kg) was administered IV on 7 days before the start of Cycle 1 and on Day 1 of each cycle. After completion of MEDI-551, IV infusion of ICE as: ifosfamide 5 g/ m^2 continuously for 24 hours with mesna on Day 2; carboplatin AUC=5 mg/mL x min (800 mg maximum) on Day 2; etoposide 100 mg/ m^2 on Days 1, 2, and 3 in 21-day cycles. After completion of MEDI-551, IV infusion of DHAP as: dexamethasone 40 mg on Days 1, 2, 3, and 4; cisplatin 100 mg/m^2 continuously for 24 hours on Day 1; cytarabine 2 g/m^2 in 3-hour infusion repeated after 12 hours (2 doses) on Day 2 in 21-day cycles.

Arm type

Experimental

Investigational medicinal product name

MEDI-551 2 mg/kg

Investigational medicinal product code

Other name

Inebilizumab

Pharmaceutical forms

Solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

MEDI-551 (2 mg/kg) was administered IV on 7 days before the start of Cycle 1 and on Day 1 of each cycle.

MEDI-551 4 mg/kg + ICE/DHAP

Arm description

Participants received MEDI-551 (4 mg/kg) in combination with ICE or DHAP for 3 cycles (21-day cycles) and were followed until end of the study (36 months after the date of randomization for last participant, or date the sponsor stops the trial, whichever occurs first). MEDI-551 (4 mg/kg) was administered IV on 7 days before the start of Cycle 1 and on Day 1 of each cycle. After completion of MEDI-551, IV infusion of ICE as: ifosfamide 5 g/ m^2 continuously for 24 hours with mesna on Day 2; carboplatin AUC=5 mg/mL x min (800 mg maximum) on Day 2; etoposide 100 mg/ m^2 on Days 1, 2, and 3 in 21-day cycles. After completion of MEDI-551, IV infusion of DHAP as: dexamethasone 40 mg on Days 1, 2, 3, and 4; cisplatin 100 mg/m^2 continuously for 24 hours on Day 1; cytarabine 2 g/m^2 in 3-hour infusion repeated after 12 hours (2 doses) on Day 2 in 21-day cycles.

Arm type

Experimental

Investigational medicinal product name

MEDI-551 4 mg/kg

Investigational medicinal product code

Other name

Inebilizumab

Pharmaceutical forms

Solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

MEDI-551 (4 mg/kg) was administered IV on 7 days before the start of Cycle 1 and on Day 1 of each cycle.

Number of subjects in period 1	Rituximab+ ICE/DHAP	MEDI-551 2 mg/kg + ICE/DHAP	MEDI-551 4 mg/kg + ICE/DHAP
Started	80	52	55
Completed	0	0	1
Not completed	80	52	54
Adverse event, serious fatal	24	22	18
Consent withdrawn by subject	8	3	-
Unspecified	45	27	35
Lost to follow-up	3	-	1

Baseline characteristics

Top of page

Reporting group title

Rituximab+ ICE/DHAP

Reporting group description

Reporting group title

MEDI-551 2 mg/kg + ICE/DHAP

Reporting group description

Reporting group title

MEDI-551 4 mg/kg + ICE/DHAP

Reporting group description

Reporting group values	Rituximab+ ICE/DHAP	MEDI-551 2 mg/kg + ICE/DHAP	MEDI-551 4 mg/kg + ICE/DHAP	Total
Number of subjects	80	52	55	187
Age Categorical
Units: Subjects
< 65 YEARS	60	35	43	138
>= 65 YEARS	20	17	12	49
Age Continuous
Units: YEARS
arithmetic mean (standard deviation)	56.4 ± 12.3	56.9 ± 11.4	55.9 ± 11.6	-
Gender, Male/Female
Units: Subjects
Female	35	19	24	78
Male	45	33	31	109

Subject analysis set title

MEDI-551

Subject analysis set type

Sub-group analysis

Subject analysis set description

Participants were received MEDI-551 2 mg/kg or 4 mg/kg by IV infusion. Recommended MEDI-551 dose was selected based on the DMC reviews. As there is no data available for the 107 participants presented for the endpoint accepted dose of MEDI-551, I have included the arbitrary value of '99999' for Age continuous field (arithmetic mean and the standard deviation).

Subject analysis sets values	MEDI-551
Number of subjects	107
Age Categorical
Units: Subjects
< 65 YEARS
>= 65 YEARS
Age Continuous
Units: YEARS
arithmetic mean (standard deviation)	56.4 ± 11.8
Gender, Male/Female
Units: Subjects
Female
Male

End points

Top of page

Reporting group title

Rituximab+ ICE/DHAP

Reporting group description

Reporting group title

MEDI-551 2 mg/kg + ICE/DHAP

Reporting group description

Reporting group title

MEDI-551 4 mg/kg + ICE/DHAP

Reporting group description

Subject analysis set title

MEDI-551

Subject analysis set type

Sub-group analysis

Subject analysis set description

Primary: Objective Response Rate (ORR)

Top of page

End point title

Objective Response Rate (ORR)

End point description

Objective Response Rate, defined as the proportion of participants with a best response of complete response (disappearance of all evidence of disease) or partial response (regression of measurable disease and no new sites) according to the International Working Group criteria. The analysis for this end point was based on Intent-To-Treat (ITT) population, which included all participants who were randomized into the study.

End point type

Primary

End point timeframe

From treatment administration (Day1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)

End point values	Rituximab+ ICE/DHAP	MEDI-551 2 mg/kg + ICE/DHAP	MEDI-551 4 mg/kg + ICE/DHAP
Number of subjects analysed	80	52	55
Units: Percentage of participants
number (confidence interval 95%)	47.5 (36.2 to 59.0)	46.2 (32.2 to 60.5)	43.6 (30.3 to 57.7)

Statistical Analysis 1

Comparison groups

Rituximab+ ICE/DHAP v MEDI-551 4 mg/kg + ICE/DHAP

Number of subjects included in analysis

135

Analysis specification

Pre-specified

Analysis type

P-value

= 0.5543

Method

Cochran-Mantel-Haenszel

Confidence interval

Secondary: Progression-Free Survival (PFS)

Top of page

End point title

Progression-Free Survival (PFS)

End point description

Progression-free survival (PFS) is defined as the time from randomization until the first documentation of disease progression or death due to any cause, whichever occurs first. PFS (months) = (Date of PD/death or censoring – Date of randomization + 1) / (365.25/12). The analysis for this end point was based on ITT population, which included all participants who were randomized into the study.

End point type

Secondary

End point timeframe

From treatment administration (Day1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)

End point values	Rituximab+ ICE/DHAP	MEDI-551 2 mg/kg + ICE/DHAP	MEDI-551 4 mg/kg + ICE/DHAP
Number of subjects analysed	80	52	55
Units: months
median (full range (min-max))	6.1 (0.0 to 39.2)	6.6 (0.0 to 31.3)	7.7 (0 to 14.8)

Rituximab vs Inebilizumab 4 mg/kg

Comparison groups

Rituximab+ ICE/DHAP v MEDI-551 4 mg/kg + ICE/DHAP

Number of subjects included in analysis

135

Analysis specification

Pre-specified

Analysis type

P-value

= 0.8567

Method

Logrank

Confidence interval

Secondary: Event-Free Survival (EFS)

Top of page

End point title

Event-Free Survival (EFS)

End point description

Event-Free Survival (EFS) is defined as the time from randomization until the first documentation of EFS events which include disease progression, initiation of alternative antitumor treatment or death due to any cause, whichever occurs first. EFS (months) = (Date of EFS or censoring – Date of randomization + 1) / (365.25/12). The analysis for this end point was based on ITT population, which included all participants who were randomized into the study.

End point type

Secondary

End point timeframe

From treatment administration (Day1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)

End point values	Rituximab+ ICE/DHAP	MEDI-551 2 mg/kg + ICE/DHAP	MEDI-551 4 mg/kg + ICE/DHAP
Number of subjects analysed	80	52	55
Units: months
median (full range (min-max))	4.7 (0.0 to 39.2)	4.2 (0.0 to 31.3)	5.9 (0.0 to 14.8)

Rituximab vs Inebilizumab 4 mg/kg

Comparison groups

Rituximab+ ICE/DHAP v MEDI-551 4 mg/kg + ICE/DHAP

Number of subjects included in analysis

135

Analysis specification

Pre-specified

Analysis type

P-value

= 0.7412

Method

Logrank

Confidence interval

Secondary: Overall Survival (OS)

Top of page

End point title

Overall Survival (OS)

End point description

Overall survival defined as the time from randomization until death due to any cause. OS (months) = (Date of death or censoring – Date of randomization + 1) / (365.25/12). The analysis for this end point was based on ITT population, which included all participants who were randomized into the study. '99999' indicates value was not estimable.

End point type

Secondary

End point timeframe

From treatment administration (Day1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)

End point values	Rituximab+ ICE/DHAP	MEDI-551 2 mg/kg + ICE/DHAP	MEDI-551 4 mg/kg + ICE/DHAP
Number of subjects analysed	80	52	55
Units: months
median (confidence interval 95%)	99999 (15.6 to 99999)	99999 (14.2 to 99999)	23.0 (12.8 to 99999)

Rituximab vs Inebilizumab 4 mg/kg

Comparison groups

Rituximab+ ICE/DHAP v MEDI-551 4 mg/kg + ICE/DHAP

Number of subjects included in analysis

135

Analysis specification

Pre-specified

Analysis type

P-value

= 0.9996

Method

Logrank

Confidence interval

Secondary: Time to Progression (TTP)

Top of page

End point title

Time to Progression (TTP)

End point description

Time to Progression (TTP) defined as the time from randomization until the first documentation of disease progression. TTP (months) = (Date of PD or censoring – Date of randomization + 1) / (365.25/12). The analysis for this end point was based on ITT population, which included all participants who were randomized into the study.

End point type

Secondary

End point timeframe

From treatment administration (Day1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)

End point values	Rituximab+ ICE/DHAP	MEDI-551 2 mg/kg + ICE/DHAP	MEDI-551 4 mg/kg + ICE/DHAP
Number of subjects analysed	80	52	55
Units: months
median (full range (min-max))	4.9 (0.0 to 11.1)	4.2 (0.0 to 31.3)	5.9 (0.0 to 14.0)

Rituximab vs Inebilizumab 4 mg/kg

Comparison groups

Rituximab+ ICE/DHAP v MEDI-551 4 mg/kg + ICE/DHAP

Number of subjects included in analysis

135

Analysis specification

Pre-specified

Analysis type

P-value

= 0.1686

Method

Logrank

Confidence interval

Secondary: Time to Response (TTR)

Top of page

End point title

Time to Response (TTR)

End point description

Time to response (TTR) defined as the time from randomization until the first documentation of disease response. Only participants who have achieved objective response (confirmed CR or confirmed PR) assessed by investigator were evaluated for TTR. TTR (months) = (Date of first disease response – Date of randomization + 1) / (365.25/12). The analysis for this end point was based on ITT population, which included all participants who were randomized into the study.

End point type

Secondary

End point timeframe

From treatment administration (Day1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)

End point values	Rituximab+ ICE/DHAP	MEDI-551 2 mg/kg + ICE/DHAP	MEDI-551 4 mg/kg + ICE/DHAP
Number of subjects analysed	42	32	30
Units: months
median (full range (min-max))	1.7 (0.9 to 3.8)	2.3 (1.5 to 3.4)	2.3 (1.6 to 6.0)

No statistical analyses for this end point

Secondary: Duration of Response (DR)

Top of page

End point title

Duration of Response (DR)

End point description

Duration of Response (DR) defined as time from start of first documented objective response (confirmed Complete Response [CR] or confirmed Partial Response [PR]) to first documented disease progression. Only participants who have achieved objective response assessed by investigator were evaluated. DR calculated as (months) = (Date of PD or censoring – Date of first disease response + 1)/ (365.25/12). The analysis for this end point was based on ITT population, which included all participants who were randomized into the study. '99999' indicates value was not estimable.

End point type

Secondary

End point timeframe

From treatment administration (Day1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)

End point values	Rituximab+ ICE/DHAP	MEDI-551 2 mg/kg + ICE/DHAP	MEDI-551 4 mg/kg + ICE/DHAP
Number of subjects analysed	42	32	30
Units: months
median (confidence interval 95%)	99999 (4.9 to 99999)	7.1 (4.1 to 99999)	7.9 (4.6 to 12.2)

No statistical analyses for this end point

Secondary: Number of Participants with Best Overall Response Assessed by Blinded Independent Central Review (BICR)

Top of page

End point title

Number of Participants with Best Overall Response Assessed by Blinded Independent Central Review (BICR)

End point description

The best overall response was calculated, based upon the disease assessments recorded during the study visits, and summarized with the number of participants for the following categories: complete response (CR), partial response (PR), stable disease (SD), progessive disease (PD), and not evaluable (NE). The analysis for this end point was based on ITT population, which included all participants who were randomized into the study.

End point type

Secondary

End point timeframe

From treatment administration (Day1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)

End point values	Rituximab+ ICE/DHAP	MEDI-551 2 mg/kg + ICE/DHAP	MEDI-551 4 mg/kg + ICE/DHAP
Number of subjects analysed	80	52	55
Units: Number of particpants
COMPLETE RESPONSE (CR)	20	6	12
PARTIAL RESPONSE (PR)	18	18	12
STABLE DISEASE (SD)	17	12	14
PROGRESSIVE DISEASE (PD)	5	5	5
UNKNOWN	20	11	12

No statistical analyses for this end point

Secondary: Acceptable Dose of MEDI-551

Top of page

End point title

Acceptable Dose of MEDI-551

End point description

Acceptable dose for MEDI-551 was evaluated based on the benefit-risk analysis. The analysis for this end point was based on all participants who were randomized into the study and received MEDI-551.

End point type

Secondary

End point timeframe

After the administration of the first dose of MEDI-551(7 days before the Cycle 1) to last dose of MEDI-551 (Cycle 3 Day 1) (each cycle of 21 days)

End point values	MEDI-551
Number of subjects analysed	107
Units: milligram per kilogram (mg/kg)	4

No statistical analyses for this end point

Secondary: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs)

Top of page

End point title

Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs)

End point description

An Adverse Event (AE) is any unfavourable and unintended signs, symptoms, or diseases temporally associated with use of study drug, whether or not considered related to study drug. SAE is any AE that resulted in death, inpatient hospitalization or prolongation of existing hospitalization, persistent or significant disability or incapacity, life-threatening, a congenital anomaly/birth defect, or an important medical event. TEAEs are defined as AEs present at baseline that worsened in intensity after administration of study drug, or events absent at baseline that emerged after administration of study drug, up to 90 days after the end of treatment (EOT). The analysis for this end point was based on safety population, which included all participants who received any study treatment.

End point type

Secondary

End point timeframe

From treatment administration (Day1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)

End point values	Rituximab+ ICE/DHAP	MEDI-551 2 mg/kg + ICE/DHAP	MEDI-551 4 mg/kg + ICE/DHAP
Number of subjects analysed	79	52	54
Units: Number of participants
TEAEs	78	51	52
TESAEs	33	25	27

No statistical analyses for this end point

Secondary: Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Hematology/Coagulation Laboratory Results

Top of page

End point title

Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Hematology/Coagulation Laboratory Results

End point description

An abnormal laboratory finding that was judged by the investigator to be medically significant was reported as an AE. TEAEs were defined as events present at baseline that worsened in intensity after administration of inebilizumab, or events absent at baseline that emerged after administration of inebilizumab, for the period extending to 90 days after the EOT. The analysis for this end point was based on safety population, which included all participants who received any study treatment.

End point type

Secondary

End point timeframe

From treatment administration (Day1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)

End point values	Rituximab+ ICE/DHAP	MEDI-551 2 mg/kg + ICE/DHAP	MEDI-551 4 mg/kg + ICE/DHAP
Number of subjects analysed	79	52	54
Units: Number of participants
Anaemia	47	32	33
Febrile neutropenia	16	9	12
Granulocytopenia	3	0	2
Leukopenia	9	6	10
Lymphopenia	4	2	3
Neutropenia	30	15	20
Pancytopenia	2	0	3
Thromobocytopenia	49	24	29
Activated partial thromboplastin time prolonged	0	2	0
Blood immunoglobulin g decreased	0	1	0
Blood immunoglobulin m decreased	0	1	0
Haemoglobin decreased	0	1	0
Immunoglobulins decreased	0	1	0
Lymphocyte count decreased	9	4	3
Neutrophil count decreased	7	6	8
Platelet count decreased	12	8	10
Platelet count increased	0	1	0
White blood cell count decreased	6	5	6

No statistical analyses for this end point

Secondary: Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Chemistry Laboratory Results (include Urinalysis)

Top of page

End point title

Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Chemistry Laboratory Results (include Urinalysis)

End point description

An abnormal laboratory findings that was judged by the investigator to be medically significant was reported as an AE. TEAEs were defined as events present at baseline that worsened in intensity after administration of inebilizumab, or events absent at baseline that emerged after administration of inebilizumab, for the period extending to 90 days after the end of study treatment. The analysis for this end point was based on safety population, which included all participants who received any study treatment.

End point type

Secondary

End point timeframe

From treatment administration (Day1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)

End point values	Rituximab+ ICE/DHAP	MEDI-551 2 mg/kg + ICE/DHAP	MEDI-551 4 mg/kg + ICE/DHAP
Number of subjects analysed	79	52	54
Units: Number of participants
Hyperbilirubinaemia	1	0	0
Hypernatraemia	3	1	1
Hyperphosphataemia	0	0	2
Hypertriglyerideaemia	1	0	0
Hyperuricaemia	5	4	1
Hypoalbuminaemia	3	4	3
Hypocalcaemia	11	6	7
Hypoglycaemia	1	1	1
Hypokalaemia	24	13	14
Hypomagnesaemia	17	6	11
Hyponatraemia	8	2	2
Hypophosphataemia	4	3	3
Hypoproteinaemia	0	0	1
Alanine aminotransferase increased	7	2	4
Aspartate aminotransferase increased	5	2	6
Blood alkaline phosphatase increased	2	0	1
Blood bicarbonate decreased	1	0	0
Blood bilirubin increased	1	1	1
Blood chloride increased	0	1	0
Blood creatinine increased	10	5	7
Blood lactate dehydrogenase increased	2	1	1
Blood magnesium decreased	2	0	0
Blood potassium decreased	2	0	0
Blood uric acid decreased	0	1	0
Blood uric acid increased	1	1	0
Gamma-glutamyltransferase increased	9	3	3
Hepatic enzyme increased	1	0	1
Protein total decreased	0	1	1
Transaminases increased	1	2	0
Dysuria	2	1	3
Hematuria	2	3	0
Glucose urine present	0	1	1
Proteinuria	0	1	1
Urine sodium increased	0	0	1
Calcium deficiency	0	0	1
Electrolyte imbalance	2	0	0
Hypercalcaemia	2	1	0
Hyperglycaemia	12	9	2
Hyperkalaemia	2	2	1
Hypermagnesaemia	3	2	0

No statistical analyses for this end point

Secondary: Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Vital Signs and ECG Abnormalities

Top of page

End point title

Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Vital Signs and ECG Abnormalities

End point description

Vital signs included parameters such as heart rate, blood pressure, temperature, and respiratory rate. An abnormal vital signs and ECG findings that was judged by the investigator to be medically significant was reported an AE. TEAEs were defined as events present at baseline that worsened in intensity after administration of inebilizumab, or events absent at baseline that emerged after administration of inebilizumab, for the period extending to 90 days after the end of study treatment. The analysis for this end point was based on safety population, which included all participants who received any study treatment.

End point type

Secondary

End point timeframe

From treatment administration (Day1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)

End point values	Rituximab+ ICE/DHAP	MEDI-551 2 mg/kg + ICE/DHAP	MEDI-551 4 mg/kg + ICE/DHAP
Number of subjects analysed	79	52	54
Units: Number of participants
Arrhythmia	0	0	2
Atrial fibrillation	1	1	2
Bradycardia	3	1	2
Extrasystoles	0	1	0
Palpitations	2	1	0
Sinus arrhythmia	0	0	1
Sinus bradycardia	1	2	1
Systolic dysfunction	0	0	1
Tachycardia	3	1	2
Pyrexia	17	14	11
Blood pressure increased	0	0	1
Carbon dioxide decreased	1	0	0
Electrocardiogram abnormal	0	0	1
Electrocardiogram QT prolonged	0	2	2
Heart rate irregular	1	0	0
Weight decreased	0	1	1
Weight increased	1	0	1
Dyspnoea	11	7	8
Dyspnoea exertional	0	3	1
Hypertension	5	2	3
Hypotension	10	4	8

No statistical analyses for this end point

Secondary: Number of Participants who Developed Detectable MEDI-551 Anti-drug Antibodies

Top of page

End point title

Number of Participants who Developed Detectable MEDI-551 Anti-drug Antibodies ^[1]

End point description

A participant was considered ADA-positive across the study if they had a positive reading (titer of 50 or higher) at any time point during the study. The analysis for this end point was based on safety population, which included all participants who received any study treatment.

End point type

Secondary

End point timeframe

7 days before the start of Cycle 1, Day 1 of each subsequent Cycle, EOT, and post EOT on Days 30, 60, 90 and 270 (up to 36 months from the randomization of last participant)

Notes
[1] - 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 end point is related to MEDI-551. Therefore, it is applicable for “MEDI-551 2 mg/kg + ICE/DHAP” and “MEDI-551 4 mg/kg + ICE/DHAP” arms only.

End point values	MEDI-551 2 mg/kg + ICE/DHAP	MEDI-551 4 mg/kg + ICE/DHAP
Number of subjects analysed	52	54
Units: Number of participants	1	0

No statistical analyses for this end point

Secondary: Mean Serum Concentration of MEDI-551

Top of page

End point title

Mean Serum Concentration of MEDI-551 ^[2]

End point description

The mean serum concentration of MEDI-551 were observed. Participants who received MEDI-551 were analysed for this end point. Here, "n" is number of participants analysed at this time point.

End point type

Secondary

End point timeframe

Cycle 1 Day -7 Post dose, pre-dose and postdose on Day 1, post-dose on Days 4, 8, 15 of Cycle 1, pre-dose and postdose on Day 1 of Cycle 2 and Cycle 3

Notes
[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 end point is related to MEDI-551. Therefore, it is applicable for “MEDI-551 2 mg/kg + ICE/DHAP” and “MEDI-551 4 mg/kg + ICE/DHAP” arms only.

End point values	MEDI-551 2 mg/kg + ICE/DHAP	MEDI-551 4 mg/kg + ICE/DHAP
Number of subjects analysed	52	54
Units: mcg/mL
arithmetic mean (standard deviation)
Cycle 1 Day-7 Post Dose (n= 46, 50)	47.0 ± 23.7	83.8 ± 21.9
Cycle 1 Day 1 Pre Dose (n= 46, 52)	16.7 ± 5.81	33.1 ± 16.3
Cycle 1 Day 1 Post Dose (n= 46, 51)	64.8 ± 26.4	116 ± 41.3
Cycle 1 Day 4 (n= 43, 45)	38.8 ± 14.6	71.9 ± 23.0
Cycle 1 Day 8 (n= 44, 48)	30.6 ± 9.69	69.3 ± 25.1
Cycle 1 Day 15 (n= 40, 43)	19.4 ± 6.19	44.7 ± 25.0
Cycle 2 Day 1 Pre Dose (n= 40, 44)	15.0 ± 5.45	30.9 ± 14.3
Cycle 2 Day 1 Post Dose (n= 40, 43)	52.3 ± 18.7	112 ± 32.6
Cycle 3 Day 1 Pre Dose (n= 26, 26)	14.0 ± 6.50	36.4 ± 18.7
Cycle 3 Day 1 Post Dose (n= 25, 25)	52.4 ± 16.9	116 ± 30.9

No statistical analyses for this end point

Secondary: Half-life (T1/2) of MEDI-551

Top of page

End point title

Half-life (T1/2) of MEDI-551 ^[3]

End point description

Terminal elimination half-life (T1/2) is the time required for half of the drug to be eliminated from the serum. Participants who received MEDI-551 were analysed for this end point. Here, "n" is number of participants analysed at this time point.

End point type

Secondary

End point timeframe

Cycle 1 and EOT (Day 21 of Cycle 3 [each cycle of 21 days] or earlier cycles if treatment stopped before Cycle 3)

Notes
[3] - 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 end point is related to MEDI-551. Therefore, it is applicable for “MEDI-551 2 mg/kg + ICE/DHAP” and “MEDI-551 4 mg/kg + ICE/DHAP” arms only.

End point values	MEDI-551 2 mg/kg + ICE/DHAP	MEDI-551 4 mg/kg + ICE/DHAP
Number of subjects analysed	52	54
Units: Day
arithmetic mean (standard deviation)
Cycle 1 n= (36, 43)	14.4 ± 5.09	16.5 ± 10.5
End of Treatment n= (9,17)	18.9 ± 4.34	20.2 ± 5.73

No statistical analyses for this end point

Adverse events

Top of page

Timeframe for reporting adverse events

From treatment administration (Day1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)

Adverse event reporting additional description

AE were reported for safety population, which included all participants who received any study treatment.

Assessment type

Systematic

Dictionary name

MedDRA

Dictionary version

19.0

Reporting group title

Rituximab+ ICE/DHAP

Reporting group description

Reporting group title

MEDI-551 4 mg/kg + ICE/DHAP

Reporting group description

Participants received MEDI-551 (4 mg/kg) in combination with ICE or DHAP for 3 cycles (21-day cycles) and were followed until end of the study (36 months after the date of randomization for last participant, or date the sponsor stops the trial, whichever occurs first). MEDI-551 (4 mg/kg) was administered IV on 7 days before the start of Cycle 1 and on Day 1 of each cycle. After completion of MEDI-551, IV infusion of ICE as: ifosfamide 5 g/ m^2 continuously for 24 hours with mesna on Day 2; carboplatin AUC=5 mg/mL x min (800 mg maximum) on Day 2; etoposide 100 mg/ m^2 on Days 1, 2, and 3 in 21-day cycles. After completion of Inebilizumab, IV infusion of DHAP as: dexamethasone 40 mg on Days 1, 2, 3, and 4; cisplatin 100 mg/m^2 continuously for 24 hours on Day 1; cytarabine 2 g/m^2 in 3-hour infusion repeated after 12 hours (2 doses) on Day 2 in 21-day cycles.

Reporting group title

MEDI-551 2 mg/kg + ICE/DHAP

Reporting group description

Participants received MEDI-551 (2 mg/kg) in combination with ICE or DHAP for 3 cycles (21-day cycles) and were followed until end of the study (36 months after the date of randomization for last participant, or date the sponsor stops the trial, whichever occurs first). MEDI-551 (2 mg/kg) was administered IV on 7 days before the start of Cycle 1 and on Day 1 of each cycle. After completion of MEDI-551, IV infusion of ICE as: ifosfamide 5 g/ m^2 continuously for 24 hours with mesna on Day 2; carboplatin AUC=5 mg/mL x min (800 mg maximum) on Day 2; etoposide 100 mg/ m^2 on Days 1, 2, and 3 in 21-day cycles. After completion of Inebilizumab, IV infusion of DHAP as: dexamethasone 40 mg on Days 1, 2, 3, and 4; cisplatin 100 mg/m^2 continuously for 24 hours on Day 1; cytarabine 2 g/m^2 in 3-hour infusion repeated after 12 hours (2 doses) on Day 2 in 21-day cycles.

Serious adverse events	Rituximab+ ICE/DHAP	MEDI-551 4 mg/kg + ICE/DHAP	MEDI-551 2 mg/kg + ICE/DHAP
Total subjects affected by serious adverse events
subjects affected / exposed	33 / 79 (41.77%)	27 / 54 (50.00%)	25 / 52 (48.08%)
number of deaths (all causes)	24	18	22
number of deaths resulting from adverse events
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Central nervous system lymphoma
subjects affected / exposed	1 / 79 (1.27%)	0 / 54 (0.00%)	1 / 52 (1.92%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 1
Tumour haemorrhage
subjects affected / exposed	1 / 79 (1.27%)	0 / 54 (0.00%)	0 / 52 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Vascular disorders
Hypotension
subjects affected / exposed	0 / 79 (0.00%)	0 / 54 (0.00%)	1 / 52 (1.92%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Thrombophlebitis
subjects affected / exposed	0 / 79 (0.00%)	0 / 54 (0.00%)	1 / 52 (1.92%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
General disorders and administration site conditions
Death
subjects affected / exposed	0 / 79 (0.00%)	0 / 54 (0.00%)	1 / 52 (1.92%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 1
Fatigue
subjects affected / exposed	0 / 79 (0.00%)	0 / 54 (0.00%)	1 / 52 (1.92%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
General physical health deterioration
subjects affected / exposed	1 / 79 (1.27%)	0 / 54 (0.00%)	1 / 52 (1.92%)
occurrences causally related to treatment / all	0 / 1	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 1	0 / 0	0 / 0
Multiple organ dysfunction syndrome
subjects affected / exposed	1 / 79 (1.27%)	0 / 54 (0.00%)	0 / 52 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Pyrexia
subjects affected / exposed	1 / 79 (1.27%)	2 / 54 (3.70%)	2 / 52 (3.85%)
occurrences causally related to treatment / all	0 / 1	0 / 2	1 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Respiratory, thoracic and mediastinal disorders
Acute pulmonary oedema
subjects affected / exposed	1 / 79 (1.27%)	0 / 54 (0.00%)	0 / 52 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Acute respiratory failure
subjects affected / exposed	0 / 79 (0.00%)	1 / 54 (1.85%)	0 / 52 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Dyspnoea
subjects affected / exposed	0 / 79 (0.00%)	1 / 54 (1.85%)	0 / 52 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Laryngeal inflammation
subjects affected / exposed	1 / 79 (1.27%)	0 / 54 (0.00%)	0 / 52 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Pleural effusion
subjects affected / exposed	0 / 79 (0.00%)	2 / 54 (3.70%)	2 / 52 (3.85%)
occurrences causally related to treatment / all	0 / 0	0 / 2	1 / 3
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Pleurisy
subjects affected / exposed	1 / 79 (1.27%)	0 / 54 (0.00%)	0 / 52 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Pneumonitis
subjects affected / exposed	0 / 79 (0.00%)	1 / 54 (1.85%)	0 / 52 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	1 / 1	0 / 0
Pneumothorax
subjects affected / exposed	1 / 79 (1.27%)	0 / 54 (0.00%)	0 / 52 (0.00%)
occurrences causally related to treatment / all	1 / 3	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 1	0 / 0	0 / 0
Pulmonary embolism
subjects affected / exposed	0 / 79 (0.00%)	1 / 54 (1.85%)	0 / 52 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Pulmonary oedema
subjects affected / exposed	0 / 79 (0.00%)	0 / 54 (0.00%)	1 / 52 (1.92%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Respiratory failure
subjects affected / exposed	1 / 79 (1.27%)	1 / 54 (1.85%)	0 / 52 (0.00%)
occurrences causally related to treatment / all	0 / 1	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 1	0 / 0	0 / 0
Psychiatric disorders
Confusional state
subjects affected / exposed	0 / 79 (0.00%)	1 / 54 (1.85%)	0 / 52 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Depression
subjects affected / exposed	0 / 79 (0.00%)	0 / 54 (0.00%)	1 / 52 (1.92%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Mental status changes
subjects affected / exposed	1 / 79 (1.27%)	0 / 54 (0.00%)	0 / 52 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Suicidal ideation
subjects affected / exposed	1 / 79 (1.27%)	0 / 54 (0.00%)	0 / 52 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Investigations
Blood creatinine increased
subjects affected / exposed	0 / 79 (0.00%)	0 / 54 (0.00%)	1 / 52 (1.92%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Neutrophil count decreased
subjects affected / exposed	0 / 79 (0.00%)	0 / 54 (0.00%)	1 / 52 (1.92%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
White blood cell count decreased
subjects affected / exposed	0 / 79 (0.00%)	0 / 54 (0.00%)	1 / 52 (1.92%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Injury, poisoning and procedural complications
Overdose
subjects affected / exposed	0 / 79 (0.00%)	0 / 54 (0.00%)	1 / 52 (1.92%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Spinal fracture
subjects affected / exposed	0 / 79 (0.00%)	0 / 54 (0.00%)	1 / 52 (1.92%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Toxicity to various agents
subjects affected / exposed	1 / 79 (1.27%)	1 / 54 (1.85%)	0 / 52 (0.00%)
occurrences causally related to treatment / all	1 / 1	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Cardiac disorders
Acute myocardial infarction
subjects affected / exposed	0 / 79 (0.00%)	1 / 54 (1.85%)	0 / 52 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Angina pectoris
subjects affected / exposed	0 / 79 (0.00%)	1 / 54 (1.85%)	0 / 52 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Atrial fibrillation
subjects affected / exposed	0 / 79 (0.00%)	0 / 54 (0.00%)	1 / 52 (1.92%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Cardiac failure
subjects affected / exposed	1 / 79 (1.27%)	0 / 54 (0.00%)	0 / 52 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Cardiac failure congestive
subjects affected / exposed	0 / 79 (0.00%)	1 / 54 (1.85%)	0 / 52 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Nervous system disorders
Coma hepatic
subjects affected / exposed	0 / 79 (0.00%)	0 / 54 (0.00%)	1 / 52 (1.92%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 1
Dizziness
subjects affected / exposed	1 / 79 (1.27%)	0 / 54 (0.00%)	0 / 52 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Encephalopathy
subjects affected / exposed	0 / 79 (0.00%)	1 / 54 (1.85%)	0 / 52 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Headache
subjects affected / exposed	1 / 79 (1.27%)	1 / 54 (1.85%)	0 / 52 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Memory impairment
subjects affected / exposed	0 / 79 (0.00%)	0 / 54 (0.00%)	1 / 52 (1.92%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Seizure
subjects affected / exposed	0 / 79 (0.00%)	1 / 54 (1.85%)	0 / 52 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Somnolence
subjects affected / exposed	0 / 79 (0.00%)	0 / 54 (0.00%)	1 / 52 (1.92%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Syncope
subjects affected / exposed	0 / 79 (0.00%)	0 / 54 (0.00%)	2 / 52 (3.85%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Blood and lymphatic system disorders
Anaemia
subjects affected / exposed	0 / 79 (0.00%)	0 / 54 (0.00%)	1 / 52 (1.92%)
occurrences causally related to treatment / all	0 / 0	0 / 0	2 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Disseminated intravascular coagulation
subjects affected / exposed	1 / 79 (1.27%)	0 / 54 (0.00%)	0 / 52 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Febrile bone marrow aplasia
subjects affected / exposed	0 / 79 (0.00%)	0 / 54 (0.00%)	1 / 52 (1.92%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Febrile neutropenia
subjects affected / exposed	11 / 79 (13.92%)	9 / 54 (16.67%)	8 / 52 (15.38%)
occurrences causally related to treatment / all	8 / 11	10 / 10	9 / 10
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Leukopenia
subjects affected / exposed	1 / 79 (1.27%)	0 / 54 (0.00%)	0 / 52 (0.00%)
occurrences causally related to treatment / all	1 / 2	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Lymphadenopathy
subjects affected / exposed	0 / 79 (0.00%)	0 / 54 (0.00%)	1 / 52 (1.92%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Neutropenia
subjects affected / exposed	4 / 79 (5.06%)	3 / 54 (5.56%)	1 / 52 (1.92%)
occurrences causally related to treatment / all	4 / 5	2 / 3	2 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Pancytopenia
subjects affected / exposed	1 / 79 (1.27%)	1 / 54 (1.85%)	0 / 52 (0.00%)
occurrences causally related to treatment / all	1 / 1	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Thrombocytopenia
subjects affected / exposed	5 / 79 (6.33%)	1 / 54 (1.85%)	0 / 52 (0.00%)
occurrences causally related to treatment / all	6 / 7	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Thrombotic microangiopathy
subjects affected / exposed	0 / 79 (0.00%)	1 / 54 (1.85%)	0 / 52 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 1	0 / 0
Ear and labyrinth disorders
Vertigo
subjects affected / exposed	1 / 79 (1.27%)	0 / 54 (0.00%)	0 / 52 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Gastrointestinal disorders
Gastritis
subjects affected / exposed	1 / 79 (1.27%)	0 / 54 (0.00%)	0 / 52 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Nausea
subjects affected / exposed	1 / 79 (1.27%)	1 / 54 (1.85%)	1 / 52 (1.92%)
occurrences causally related to treatment / all	0 / 1	1 / 1	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Neutropenic colitis
subjects affected / exposed	1 / 79 (1.27%)	0 / 54 (0.00%)	0 / 52 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Obstruction gastric
subjects affected / exposed	1 / 79 (1.27%)	0 / 54 (0.00%)	0 / 52 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Vomiting
subjects affected / exposed	2 / 79 (2.53%)	0 / 54 (0.00%)	1 / 52 (1.92%)
occurrences causally related to treatment / all	2 / 2	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Renal and urinary disorders
Acute kidney injury
subjects affected / exposed	3 / 79 (3.80%)	2 / 54 (3.70%)	3 / 52 (5.77%)
occurrences causally related to treatment / all	3 / 3	1 / 2	2 / 3
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Nephropathy toxic
subjects affected / exposed	1 / 79 (1.27%)	0 / 54 (0.00%)	0 / 52 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Renal failure
subjects affected / exposed	1 / 79 (1.27%)	2 / 54 (3.70%)	1 / 52 (1.92%)
occurrences causally related to treatment / all	1 / 1	3 / 3	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Musculoskeletal and connective tissue disorders
Back pain
subjects affected / exposed	0 / 79 (0.00%)	0 / 54 (0.00%)	1 / 52 (1.92%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Bone pain
subjects affected / exposed	1 / 79 (1.27%)	0 / 54 (0.00%)	0 / 52 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Musculoskeletal chest pain
subjects affected / exposed	0 / 79 (0.00%)	1 / 54 (1.85%)	0 / 52 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Infections and infestations
Bacteraemia
subjects affected / exposed	0 / 79 (0.00%)	1 / 54 (1.85%)	0 / 52 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Bacterial sepsis
subjects affected / exposed	0 / 79 (0.00%)	0 / 54 (0.00%)	1 / 52 (1.92%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Cellulitis
subjects affected / exposed	0 / 79 (0.00%)	0 / 54 (0.00%)	1 / 52 (1.92%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Clostridium difficile colitis
subjects affected / exposed	0 / 79 (0.00%)	1 / 54 (1.85%)	0 / 52 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Cystitis viral
subjects affected / exposed	1 / 79 (1.27%)	0 / 54 (0.00%)	0 / 52 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Device related infection
subjects affected / exposed	1 / 79 (1.27%)	1 / 54 (1.85%)	1 / 52 (1.92%)
occurrences causally related to treatment / all	0 / 1	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Enterobacter sepsis
subjects affected / exposed	1 / 79 (1.27%)	0 / 54 (0.00%)	0 / 52 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Escherichia sepsis
subjects affected / exposed	1 / 79 (1.27%)	0 / 54 (0.00%)	0 / 52 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Herpes zoster
subjects affected / exposed	0 / 79 (0.00%)	0 / 54 (0.00%)	1 / 52 (1.92%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Pneumonia
subjects affected / exposed	3 / 79 (3.80%)	1 / 54 (1.85%)	0 / 52 (0.00%)
occurrences causally related to treatment / all	2 / 4	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 1	0 / 0	0 / 0
Respiratory tract infection
subjects affected / exposed	0 / 79 (0.00%)	0 / 54 (0.00%)	1 / 52 (1.92%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Sepsis
subjects affected / exposed	3 / 79 (3.80%)	4 / 54 (7.41%)	1 / 52 (1.92%)
occurrences causally related to treatment / all	0 / 3	5 / 5	0 / 1
deaths causally related to treatment / all	0 / 2	2 / 2	0 / 0
Septic shock
subjects affected / exposed	1 / 79 (1.27%)	0 / 54 (0.00%)	1 / 52 (1.92%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 1
deaths causally related to treatment / all	1 / 1	0 / 0	0 / 1
Staphylococcal sepsis
subjects affected / exposed	0 / 79 (0.00%)	0 / 54 (0.00%)	1 / 52 (1.92%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Urinary tract infection
subjects affected / exposed	0 / 79 (0.00%)	0 / 54 (0.00%)	1 / 52 (1.92%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Metabolism and nutrition disorders
Decreased appetite
subjects affected / exposed	0 / 79 (0.00%)	0 / 54 (0.00%)	1 / 52 (1.92%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Dehydration
subjects affected / exposed	0 / 79 (0.00%)	1 / 54 (1.85%)	1 / 52 (1.92%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Hyperglycaemia
subjects affected / exposed	0 / 79 (0.00%)	0 / 54 (0.00%)	1 / 52 (1.92%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Hypokalaemia
subjects affected / exposed	0 / 79 (0.00%)	0 / 54 (0.00%)	1 / 52 (1.92%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Hyponatraemia
subjects affected / exposed	1 / 79 (1.27%)	1 / 54 (1.85%)	0 / 52 (0.00%)
occurrences causally related to treatment / all	1 / 1	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Tumour lysis syndrome
subjects affected / exposed	0 / 79 (0.00%)	1 / 54 (1.85%)	2 / 52 (3.85%)
occurrences causally related to treatment / all	0 / 0	1 / 1	1 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 1

Frequency threshold for reporting non-serious adverse events: 2%

Non-serious adverse events	Rituximab+ ICE/DHAP	MEDI-551 4 mg/kg + ICE/DHAP	MEDI-551 2 mg/kg + ICE/DHAP
Total subjects affected by non serious adverse events
subjects affected / exposed	78 / 79 (98.73%)	52 / 54 (96.30%)	49 / 52 (94.23%)
Vascular disorders
Hypertension
subjects affected / exposed	5 / 79 (6.33%)	3 / 54 (5.56%)	2 / 52 (3.85%)
occurrences all number	9	10	2
Hypotension
subjects affected / exposed	10 / 79 (12.66%)	8 / 54 (14.81%)	3 / 52 (5.77%)
occurrences all number	12	9	4
General disorders and administration site conditions
Asthenia
subjects affected / exposed	9 / 79 (11.39%)	11 / 54 (20.37%)	12 / 52 (23.08%)
occurrences all number	12	15	21
Chills
subjects affected / exposed	6 / 79 (7.59%)	2 / 54 (3.70%)	1 / 52 (1.92%)
occurrences all number	9	2	1
Fatigue
subjects affected / exposed	22 / 79 (27.85%)	15 / 54 (27.78%)	20 / 52 (38.46%)
occurrences all number	32	20	33
Mucosal inflammation
subjects affected / exposed	7 / 79 (8.86%)	3 / 54 (5.56%)	3 / 52 (5.77%)
occurrences all number	7	5	3
Oedema
subjects affected / exposed	5 / 79 (6.33%)	2 / 54 (3.70%)	1 / 52 (1.92%)
occurrences all number	6	2	2
Oedema peripheral
subjects affected / exposed	10 / 79 (12.66%)	5 / 54 (9.26%)	6 / 52 (11.54%)
occurrences all number	12	7	9
Pyrexia
subjects affected / exposed	17 / 79 (21.52%)	9 / 54 (16.67%)	12 / 52 (23.08%)
occurrences all number	24	10	16
Respiratory, thoracic and mediastinal disorders
Cough
subjects affected / exposed	10 / 79 (12.66%)	8 / 54 (14.81%)	9 / 52 (17.31%)
occurrences all number	12	8	12
Dyspnoea
subjects affected / exposed	11 / 79 (13.92%)	7 / 54 (12.96%)	7 / 52 (13.46%)
occurrences all number	15	8	11
Dyspnoea exertional
subjects affected / exposed	0 / 79 (0.00%)	1 / 54 (1.85%)	3 / 52 (5.77%)
occurrences all number	0	2	3
Epistaxis
subjects affected / exposed	5 / 79 (6.33%)	1 / 54 (1.85%)	3 / 52 (5.77%)
occurrences all number	5	1	5
Hiccups
subjects affected / exposed	2 / 79 (2.53%)	2 / 54 (3.70%)	3 / 52 (5.77%)
occurrences all number	2	3	3
Oropharyngeal pain
subjects affected / exposed	6 / 79 (7.59%)	4 / 54 (7.41%)	0 / 52 (0.00%)
occurrences all number	7	4	0
Pleural effusion
subjects affected / exposed	5 / 79 (6.33%)	2 / 54 (3.70%)	0 / 52 (0.00%)
occurrences all number	5	2	0
Pulmonary embolism
subjects affected / exposed	2 / 79 (2.53%)	2 / 54 (3.70%)	0 / 52 (0.00%)
occurrences all number	2	2	0
Rhinorrhoea
subjects affected / exposed	6 / 79 (7.59%)	1 / 54 (1.85%)	2 / 52 (3.85%)
occurrences all number	6	1	2
Psychiatric disorders
Anxiety
subjects affected / exposed	7 / 79 (8.86%)	2 / 54 (3.70%)	5 / 52 (9.62%)
occurrences all number	8	2	5
Confusional state
subjects affected / exposed	3 / 79 (3.80%)	3 / 54 (5.56%)	1 / 52 (1.92%)
occurrences all number	3	4	1
Insomnia
subjects affected / exposed	8 / 79 (10.13%)	8 / 54 (14.81%)	4 / 52 (7.69%)
occurrences all number	9	8	4
Investigations
Alanine aminotransferase increased
subjects affected / exposed	7 / 79 (8.86%)	4 / 54 (7.41%)	2 / 52 (3.85%)
occurrences all number	13	7	2
Aspartate aminotransferase increased
subjects affected / exposed	5 / 79 (6.33%)	6 / 54 (11.11%)	2 / 52 (3.85%)
occurrences all number	11	13	2
Blood creatinine increased
subjects affected / exposed	10 / 79 (12.66%)	7 / 54 (12.96%)	5 / 52 (9.62%)
occurrences all number	17	17	8
Blood lactate dehydrogenase increased
subjects affected / exposed	2 / 79 (2.53%)	1 / 54 (1.85%)	1 / 52 (1.92%)
occurrences all number	2	1	1
Electrocardiogram qt prolonged
subjects affected / exposed	0 / 79 (0.00%)	2 / 54 (3.70%)	2 / 52 (3.85%)
occurrences all number	0	2	2
Gamma-glutamyltransferase increased
subjects affected / exposed	9 / 79 (11.39%)	3 / 54 (5.56%)	3 / 52 (5.77%)
occurrences all number	15	4	8
Lymphocyte count decreased
subjects affected / exposed	9 / 79 (11.39%)	3 / 54 (5.56%)	4 / 52 (7.69%)
occurrences all number	27	7	13
Neutrophil count decreased
subjects affected / exposed	7 / 79 (8.86%)	8 / 54 (14.81%)	5 / 52 (9.62%)
occurrences all number	8	16	8
Platelet count decreased
subjects affected / exposed	12 / 79 (15.19%)	10 / 54 (18.52%)	8 / 52 (15.38%)
occurrences all number	31	23	38
White blood cell count decreased
subjects affected / exposed	6 / 79 (7.59%)	6 / 54 (11.11%)	4 / 52 (7.69%)
occurrences all number	13	22	9
Injury, poisoning and procedural complications
Infusion related reaction
subjects affected / exposed	11 / 79 (13.92%)	6 / 54 (11.11%)	7 / 52 (13.46%)
occurrences all number	32	6	9
Cardiac disorders
Atrial fibrillation
subjects affected / exposed	1 / 79 (1.27%)	2 / 54 (3.70%)	1 / 52 (1.92%)
occurrences all number	1	2	1
Bradycardia
subjects affected / exposed	3 / 79 (3.80%)	2 / 54 (3.70%)	1 / 52 (1.92%)
occurrences all number	3	2	1
Sinus bradycardia
subjects affected / exposed	1 / 79 (1.27%)	1 / 54 (1.85%)	2 / 52 (3.85%)
occurrences all number	1	1	3
Tachycardia
subjects affected / exposed	3 / 79 (3.80%)	2 / 54 (3.70%)	1 / 52 (1.92%)
occurrences all number	3	3	1
Nervous system disorders
Dizziness
subjects affected / exposed	11 / 79 (13.92%)	7 / 54 (12.96%)	8 / 52 (15.38%)
occurrences all number	12	9	10
Dysgeusia
subjects affected / exposed	3 / 79 (3.80%)	3 / 54 (5.56%)	5 / 52 (9.62%)
occurrences all number	3	3	5
Headache
subjects affected / exposed	14 / 79 (17.72%)	8 / 54 (14.81%)	7 / 52 (13.46%)
occurrences all number	19	10	7
Neuropathy peripheral
subjects affected / exposed	5 / 79 (6.33%)	2 / 54 (3.70%)	2 / 52 (3.85%)
occurrences all number	5	3	2
Presyncope
subjects affected / exposed	3 / 79 (3.80%)	1 / 54 (1.85%)	1 / 52 (1.92%)
occurrences all number	3	1	1
Syncope
subjects affected / exposed	2 / 79 (2.53%)	2 / 54 (3.70%)	2 / 52 (3.85%)
occurrences all number	3	2	2
Blood and lymphatic system disorders
Anaemia
subjects affected / exposed	47 / 79 (59.49%)	33 / 54 (61.11%)	32 / 52 (61.54%)
occurrences all number	113	111	87
Febrile neutropenia
subjects affected / exposed	6 / 79 (7.59%)	3 / 54 (5.56%)	2 / 52 (3.85%)
occurrences all number	6	4	2
Granulocytopenia
subjects affected / exposed	3 / 79 (3.80%)	2 / 54 (3.70%)	0 / 52 (0.00%)
occurrences all number	5	4	0
Leukopenia
subjects affected / exposed	8 / 79 (10.13%)	10 / 54 (18.52%)	6 / 52 (11.54%)
occurrences all number	10	31	8
Lymphopenia
subjects affected / exposed	4 / 79 (5.06%)	3 / 54 (5.56%)	2 / 52 (3.85%)
occurrences all number	22	4	18
Neutropenia
subjects affected / exposed	27 / 79 (34.18%)	18 / 54 (33.33%)	15 / 52 (28.85%)
occurrences all number	50	45	30
Thrombocytopenia
subjects affected / exposed	47 / 79 (59.49%)	28 / 54 (51.85%)	24 / 52 (46.15%)
occurrences all number	172	114	71
Ear and labyrinth disorders
Tinnitus
subjects affected / exposed	4 / 79 (5.06%)	3 / 54 (5.56%)	0 / 52 (0.00%)
occurrences all number	4	3	0
Eye disorders
Dry eye
subjects affected / exposed	4 / 79 (5.06%)	0 / 54 (0.00%)	1 / 52 (1.92%)
occurrences all number	4	0	1
Vision blurred
subjects affected / exposed	2 / 79 (2.53%)	1 / 54 (1.85%)	1 / 52 (1.92%)
occurrences all number	2	1	1
Gastrointestinal disorders
Abdominal pain
subjects affected / exposed	4 / 79 (5.06%)	2 / 54 (3.70%)	6 / 52 (11.54%)
occurrences all number	5	3	9
Abdominal pain upper
subjects affected / exposed	5 / 79 (6.33%)	4 / 54 (7.41%)	2 / 52 (3.85%)
occurrences all number	5	4	2
Constipation
subjects affected / exposed	23 / 79 (29.11%)	18 / 54 (33.33%)	17 / 52 (32.69%)
occurrences all number	38	27	23
Diarrhoea
subjects affected / exposed	19 / 79 (24.05%)	13 / 54 (24.07%)	15 / 52 (28.85%)
occurrences all number	26	16	17
Dry mouth
subjects affected / exposed	4 / 79 (5.06%)	0 / 54 (0.00%)	1 / 52 (1.92%)
occurrences all number	4	0	1
Dyspepsia
subjects affected / exposed	4 / 79 (5.06%)	1 / 54 (1.85%)	1 / 52 (1.92%)
occurrences all number	4	1	1
Gastrooesophageal reflux disease
subjects affected / exposed	6 / 79 (7.59%)	5 / 54 (9.26%)	0 / 52 (0.00%)
occurrences all number	8	5	0
Haemorrhoids
subjects affected / exposed	4 / 79 (5.06%)	1 / 54 (1.85%)	2 / 52 (3.85%)
occurrences all number	4	1	2
Nausea
subjects affected / exposed	43 / 79 (54.43%)	25 / 54 (46.30%)	23 / 52 (44.23%)
occurrences all number	75	42	45
Oral pain
subjects affected / exposed	2 / 79 (2.53%)	2 / 54 (3.70%)	0 / 52 (0.00%)
occurrences all number	2	2	0
Stomatitis
subjects affected / exposed	5 / 79 (6.33%)	0 / 54 (0.00%)	2 / 52 (3.85%)
occurrences all number	5	0	2
Vomiting
subjects affected / exposed	26 / 79 (32.91%)	14 / 54 (25.93%)	14 / 52 (26.92%)
occurrences all number	37	21	28
Skin and subcutaneous tissue disorders
Alopecia
subjects affected / exposed	6 / 79 (7.59%)	8 / 54 (14.81%)	5 / 52 (9.62%)
occurrences all number	7	8	7
Night sweats
subjects affected / exposed	2 / 79 (2.53%)	4 / 54 (7.41%)	1 / 52 (1.92%)
occurrences all number	3	4	1
Petechiae
subjects affected / exposed	4 / 79 (5.06%)	1 / 54 (1.85%)	2 / 52 (3.85%)
occurrences all number	5	1	2
Pruritus
subjects affected / exposed	3 / 79 (3.80%)	1 / 54 (1.85%)	1 / 52 (1.92%)
occurrences all number	3	1	1
Rash
subjects affected / exposed	3 / 79 (3.80%)	6 / 54 (11.11%)	0 / 52 (0.00%)
occurrences all number	4	8	0
Renal and urinary disorders
Acute kidney injury
subjects affected / exposed	1 / 79 (1.27%)	4 / 54 (7.41%)	3 / 52 (5.77%)
occurrences all number	4	5	5
Dysuria
subjects affected / exposed	2 / 79 (2.53%)	3 / 54 (5.56%)	1 / 52 (1.92%)
occurrences all number	2	3	3
Haematuria
subjects affected / exposed	2 / 79 (2.53%)	0 / 54 (0.00%)	3 / 52 (5.77%)
occurrences all number	3	0	3
Pollakiuria
subjects affected / exposed	4 / 79 (5.06%)	0 / 54 (0.00%)	1 / 52 (1.92%)
occurrences all number	4	0	2
Renal failure
subjects affected / exposed	3 / 79 (3.80%)	1 / 54 (1.85%)	0 / 52 (0.00%)
occurrences all number	4	1	0
Musculoskeletal and connective tissue disorders
Arthralgia
subjects affected / exposed	4 / 79 (5.06%)	1 / 54 (1.85%)	4 / 52 (7.69%)
occurrences all number	4	2	5
Back pain
subjects affected / exposed	12 / 79 (15.19%)	4 / 54 (7.41%)	2 / 52 (3.85%)
occurrences all number	15	4	2
Bone pain
subjects affected / exposed	7 / 79 (8.86%)	7 / 54 (12.96%)	8 / 52 (15.38%)
occurrences all number	8	9	9
Muscle spasms
subjects affected / exposed	3 / 79 (3.80%)	0 / 54 (0.00%)	1 / 52 (1.92%)
occurrences all number	4	0	1
Muscular weakness
subjects affected / exposed	1 / 79 (1.27%)	3 / 54 (5.56%)	4 / 52 (7.69%)
occurrences all number	1	3	4
Musculoskeletal chest pain
subjects affected / exposed	3 / 79 (3.80%)	0 / 54 (0.00%)	2 / 52 (3.85%)
occurrences all number	4	0	2
Myalgia
subjects affected / exposed	6 / 79 (7.59%)	1 / 54 (1.85%)	4 / 52 (7.69%)
occurrences all number	7	1	8
Neck pain
subjects affected / exposed	3 / 79 (3.80%)	0 / 54 (0.00%)	3 / 52 (5.77%)
occurrences all number	3	0	3
Pain in extremity
subjects affected / exposed	6 / 79 (7.59%)	1 / 54 (1.85%)	2 / 52 (3.85%)
occurrences all number	6	1	5
Infections and infestations
Oral candidiasis
subjects affected / exposed	1 / 79 (1.27%)	1 / 54 (1.85%)	2 / 52 (3.85%)
occurrences all number	1	1	2
Oral herpes
subjects affected / exposed	4 / 79 (5.06%)	0 / 54 (0.00%)	2 / 52 (3.85%)
occurrences all number	5	0	2
Pneumonia
subjects affected / exposed	2 / 79 (2.53%)	2 / 54 (3.70%)	0 / 52 (0.00%)
occurrences all number	2	2	0
Rhinitis
subjects affected / exposed	2 / 79 (2.53%)	1 / 54 (1.85%)	2 / 52 (3.85%)
occurrences all number	2	1	2
Upper respiratory tract infection
subjects affected / exposed	1 / 79 (1.27%)	0 / 54 (0.00%)	3 / 52 (5.77%)
occurrences all number	1	0	3
Urinary tract infection
subjects affected / exposed	7 / 79 (8.86%)	3 / 54 (5.56%)	3 / 52 (5.77%)
occurrences all number	10	3	3
Metabolism and nutrition disorders
Decreased appetite
subjects affected / exposed	12 / 79 (15.19%)	8 / 54 (14.81%)	7 / 52 (13.46%)
occurrences all number	14	11	7
Dehydration
subjects affected / exposed	1 / 79 (1.27%)	0 / 54 (0.00%)	3 / 52 (5.77%)
occurrences all number	1	0	3
Fluid overload
subjects affected / exposed	2 / 79 (2.53%)	1 / 54 (1.85%)	1 / 52 (1.92%)
occurrences all number	2	1	1
Hyperglycaemia
subjects affected / exposed	12 / 79 (15.19%)	2 / 54 (3.70%)	8 / 52 (15.38%)
occurrences all number	23	4	22
Hyperkalaemia
subjects affected / exposed	2 / 79 (2.53%)	1 / 54 (1.85%)	2 / 52 (3.85%)
occurrences all number	2	1	2
Hypermagnesaemia
subjects affected / exposed	3 / 79 (3.80%)	0 / 54 (0.00%)	2 / 52 (3.85%)
occurrences all number	5	0	2
Hypernatraemia
subjects affected / exposed	3 / 79 (3.80%)	1 / 54 (1.85%)	1 / 52 (1.92%)
occurrences all number	3	1	1
Hyperuricaemia
subjects affected / exposed	5 / 79 (6.33%)	1 / 54 (1.85%)	4 / 52 (7.69%)
occurrences all number	6	1	5
Hypoalbuminaemia
subjects affected / exposed	3 / 79 (3.80%)	3 / 54 (5.56%)	4 / 52 (7.69%)
occurrences all number	3	3	4
Hypocalcaemia
subjects affected / exposed	11 / 79 (13.92%)	7 / 54 (12.96%)	6 / 52 (11.54%)
occurrences all number	31	8	9
Hypokalaemia
subjects affected / exposed	24 / 79 (30.38%)	14 / 54 (25.93%)	13 / 52 (25.00%)
occurrences all number	50	28	23
Hypomagnesaemia
subjects affected / exposed	17 / 79 (21.52%)	11 / 54 (20.37%)	6 / 52 (11.54%)
occurrences all number	37	19	10
Hyponatraemia
subjects affected / exposed	8 / 79 (10.13%)	2 / 54 (3.70%)	2 / 52 (3.85%)
occurrences all number	11	2	3
Hypophosphataemia
subjects affected / exposed	4 / 79 (5.06%)	3 / 54 (5.56%)	3 / 52 (5.77%)
occurrences all number	10	3	4
Tumour lysis syndrome
subjects affected / exposed	3 / 79 (3.80%)	1 / 54 (1.85%)	0 / 52 (0.00%)
occurrences all number	3	1	0

More information

Top of page

Were there any global substantial amendments to the protocol? Yes

27 Feb 2013

The Protocol was amended to update the exploratory objectives; Randomization plan and schedule of data monitoring committee (DMC) reviews updated; Number of study centers was increased from 50 to 106; Russia, and Israel were added; and Australia was removed, reflecting current strategy for enrolling the study. The choice of ifosfamide-carboplatin-etoposide (ICE) or dexamethasone-cytarabine-cisplatin (DHAP) as the chemotherapy regimen was made for each participant by the investigator as per institutional standard of care; Study-stopping criteria updated; Updated inclusion and exclusion criteria, withdrawal criteria, and specified replacement of participants criteria. Rituximab was added to ICE and DHAP. Updated treatment assignment and treatment regimen to improve study design. Added information related to MEDI-551 preparation and administration, dose modification for toxicity management, and concomitant medication to improve participants safety. The scheduled of procedures was updated.

11 Mar 2014

The minimum dose of methylprednisolone was administered before the first infusion of MEDI-551 was changed from 50 mg to 60 mg (or its equivalent), as this is the standard dose for this purpose; Three additional exploratory objectives were added; The total number of participants to be enrolled was increased from 170 to 180; Inclusion Criteria, exclusion Criteria, withdrawal Criteria, dose modification for toxicity management, permitted concomitant medications, schedule of study procedures were updated.

06 Mar 2015

Previous evaluations of “Full-body fluorodeoxyglucose-positron emission tomography (FDG-PET) scan and chest, abdomen, pelvis, and neck CT scan, unless participant discontinued for progressive disease (PD), tumor measurements, and disease response evaluation” at End of Treatment (+ 14 Days) and Day 60 Post EOT (+/- 7 Days) were changed to evaluation of “Chest, abdomen, pelvis, and neck CT scan, unless participant discontinued for PD” at End of Treatment and Day 90 Post EOT (+/- 14 Days) and evaluation of “Full-body FDG-PET scan (or CT-Pet scan)” at End of Treatment (+ 14 Days). The evaluation of Full-body FDG-PET scan was deleted from Long-term safety evaluations.

Were there any global interruptions to the trial? No

Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.

None reported

Select Country:	Select Age Range:
Select Trial Status:	Select Trial Phase:
Select Gender:
Select Date Range: to
Select Rare Disease:
IMP with orphan designation in the indication
Orphan Designation Number:
Results Status:
Clear advanced search filters

Austria
Belgium
Bulgaria
Croatia
Cyprus
Czechia
Denmark
Estonia
Finland
France
Germany
Greece
Hungary
Iceland
Ireland
Italy
Latvia
Liechtenstein
Lithuania
Luxembourg
Malta
Netherlands
Norway
Poland
Portugal
Romania
Slovakia
Slovenia
Spain
Sweden
United Kingdom
Outside EU/EEA

Clinical trials

Clinical Trial Results: A Phase 2 Randomized Open-label Study of MEDI-551 in Adults With Relapsed or Refractory DLBCL

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Objective Response Rate (ORR)

Primary: Objective Response Rate (ORR)

Secondary: Progression-Free Survival (PFS)

Secondary: Progression-Free Survival (PFS)

Secondary: Event-Free Survival (EFS)

Secondary: Event-Free Survival (EFS)

Secondary: Overall Survival (OS)

Secondary: Overall Survival (OS)

Secondary: Time to Progression (TTP)

Secondary: Time to Progression (TTP)

Secondary: Time to Response (TTR)

Secondary: Time to Response (TTR)

Secondary: Duration of Response (DR)

Secondary: Duration of Response (DR)

Secondary: Number of Participants with Best Overall Response Assessed by Blinded Independent Central Review (BICR)

Secondary: Number of Participants with Best Overall Response Assessed by Blinded Independent Central Review (BICR)

Secondary: Acceptable Dose of MEDI-551

Secondary: Acceptable Dose of MEDI-551

Secondary: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs)

Secondary: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs)

Secondary: Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Hematology/Coagulation Laboratory Results

Secondary: Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Hematology/Coagulation Laboratory Results

Secondary: Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Chemistry Laboratory Results (include Urinalysis)

Secondary: Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Chemistry Laboratory Results (include Urinalysis)

Secondary: Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Vital Signs and ECG Abnormalities

Secondary: Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Vital Signs and ECG Abnormalities

Secondary: Number of Participants who Developed Detectable MEDI-551 Anti-drug Antibodies

Secondary: Number of Participants who Developed Detectable MEDI-551 Anti-drug Antibodies

Secondary: Mean Serum Concentration of MEDI-551

Secondary: Mean Serum Concentration of MEDI-551

Secondary: Half-life (T1/2) of MEDI-551

Secondary: Half-life (T1/2) of MEDI-551

Adverse events

Adverse events

More information

Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

More information

Clinical Trial Results:
A Phase 2 Randomized Open-label Study of MEDI-551 in Adults With Relapsed or Refractory DLBCL