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    Clinical Trial Results:
    Clinical Evaluation of 506U78 in Japanese Patients with Relapsed or Refractory T-cell Acute Lymphoblastic Leukemia or T-cell Lymphoblastic Lymphoma

    Summary
    EudraCT number
    		 2015-004902-41
    Trial protocol
    		 Outside EU/EEA  
    Global end of trial date
    15 Jul 2009

    Results information
    Results version number
    		 v1(current)
    This version publication date
    29 Jan 2017
    First version publication date
    29 Jan 2017
    Other versions

    Trial information

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    Trial identification
    Sponsor protocol code
    PGA105446
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 -
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    GlaxoSmithKline
    Sponsor organisation address
    980 Great West Road, Brentford, Middlesex, United Kingdom,
    Public contact
    GSK Response Center, GlaxoSmithKline, 1 866-435-7343,
    Scientific contact
    GSK Response Center, GlaxoSmithKline, 1 866-435-7343,
    Paediatric regulatory details
    Is trial part of an agreed paediatric investigation plan (PIP)
    No
    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
    16 Nov 2009
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    15 Jul 2009
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    To evaluate the safety and tolerability of nelarabine administered to Japanese participants with T-cell acute lymphoblastic leukemia (T-ALL) or T-cell lymphoblastic lymphoma (T-LBL) as a 2-hour intravenous infusion on a Day 1, 3 and 5 schedule for adult participants and as a 1-hour infusion on a Days 1-5 schedule for pediatric participants. To determine the plasma pharmacokinetic (PK) profiles of nelarabine and 9-beta-D-arabinofuranosyl guanine (ara-G) when nelarabine is administered on these schedules. To determine intracellular ara-G triphosphate (ara-GTP) concentrations when nelarabine is administered on these schedules.
    Protection of trial subjects
    Not Applicable
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    30 Aug 2006
    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
    Japan: 13
    Worldwide total number of subjects
    13
    EEA total number of subjects
    0
    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)
    5
    Adolescents (12-17 years)
    5
    Adults (18-64 years)
    3
    From 65 to 84 years
    0
    85 years and over
    0

    Subject disposition

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    Recruitment
    Recruitment details
    		 -

    Pre-assignment
    Screening details
    		 Participants with relapsed or refractory T-cell acute lymphoblastic leukemia (T-ALL) or T-cell lymphoblastic lymphoma (T-LBL), who had adequate function of major organ systems and Eastern Cooperative Oncology Group scale of Performance Status (ECOG-PS) score <=2 were enrolled in the study.

    Period 1
    Period 1 title
    Overall study (overall period)
    Is this the baseline period?
    		 Yes
    Allocation method
    Non-randomised - controlled
    Blinding used
    		 Not blinded

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Adult
    Arm description
    		 Adult participants received nelarabine 1000 milligrams (mg)/square meter (m^2) in the first cycle and nelarabine 1500 mg/m^2 in the second cycle and subsequent cycles in Cohort 1. Another group (Cohort 2) of adult participants received nelarabine 1500 mg/m^2 through all treatment cycles.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Nelarabine
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Infusion
    Routes of administration
    Intravenous drip use
    Dosage and administration details
    Nelarabine infusion 1000 milligrams (mg)/square meter (m^2) or 1500 mg/m^2 for adult participants and 400 mg/m^2 or 650 mg/m^2 for pediatric participants

    Arm title
    		 Pediatric (Cohorts 1 and 2)
    Arm description
    		 Pediatric participants received nelarabine 400 mg/m^2 in the first cycle and nelarabine 650 mg/m^2 in the second cycle and subsequent cycles in Cohort 1. Another group (Cohort 2) of pediatric participants received nelarabine 650 mg/m^2 through all treatment cycles.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Nelarabine
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Infusion
    Routes of administration
    Intravenous drip use
    Dosage and administration details
    Nelarabine infusion 1000 milligrams (mg)/square meter (m^2) or 1500 mg/m^2 for adult participants and 400 mg/m^2 or 650 mg/m^2 for pediatric participants

    Arm title
    		 Pediatric (Cohort 3)
    Arm description
    		 Pediatric participants received nelarabine 650 mg/m^2 through all treatment cycles.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Nelarabine
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Infusion
    Routes of administration
    Intravenous drip use
    Dosage and administration details
    Nelarabine infusion 1000 milligrams (mg)/square meter (m^2) or 1500 mg/m^2 for adult participants and 400 mg/m^2 or 650 mg/m^2 for pediatric participants

    Number of subjects in period 1
    		Adult Pediatric (Cohorts 1 and 2) Pediatric (Cohort 3)
    Started
    7
    4
    2
    Completed
    2
    0
    0
    Not completed
    5
    4
    2
         Other reason
    3
    2
    2
         Lack of efficacy
    2
    2
    -

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Adult
    Reporting group description
    		 Adult participants received nelarabine 1000 milligrams (mg)/square meter (m^2) in the first cycle and nelarabine 1500 mg/m^2 in the second cycle and subsequent cycles in Cohort 1. Another group (Cohort 2) of adult participants received nelarabine 1500 mg/m^2 through all treatment cycles.

    Reporting group title
    Pediatric (Cohorts 1 and 2)
    Reporting group description
    		 Pediatric participants received nelarabine 400 mg/m^2 in the first cycle and nelarabine 650 mg/m^2 in the second cycle and subsequent cycles in Cohort 1. Another group (Cohort 2) of pediatric participants received nelarabine 650 mg/m^2 through all treatment cycles.

    Reporting group title
    Pediatric (Cohort 3)
    Reporting group description
    		 Pediatric participants received nelarabine 650 mg/m^2 through all treatment cycles.

    Reporting group values
    		 Adult Pediatric (Cohorts 1 and 2) Pediatric (Cohort 3) Total
    Number of subjects
    		 7 4 2
    Age categorical
    Units: Subjects
    Age continuous
    Units: years
        arithmetic mean (standard deviation)
    		 24.1 ( 12.58 ) 6.3 ( 3.77 ) 9.5 ( 3.54 ) -
    Gender categorical
    Units:
        Female
    		 1 1 0 2
        Male
    		 6 3 2 11
    Race, Customized
    Units: Subjects
        Asian-Japanese
    		 7 4 2 13

    End points

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    End points reporting groups
    Reporting group title
    Adult
    Reporting group description
    		 Adult participants received nelarabine 1000 milligrams (mg)/square meter (m^2) in the first cycle and nelarabine 1500 mg/m^2 in the second cycle and subsequent cycles in Cohort 1. Another group (Cohort 2) of adult participants received nelarabine 1500 mg/m^2 through all treatment cycles.

    Reporting group title
    Pediatric (Cohorts 1 and 2)
    Reporting group description
    		 Pediatric participants received nelarabine 400 mg/m^2 in the first cycle and nelarabine 650 mg/m^2 in the second cycle and subsequent cycles in Cohort 1. Another group (Cohort 2) of pediatric participants received nelarabine 650 mg/m^2 through all treatment cycles.

    Reporting group title
    Pediatric (Cohort 3)
    Reporting group description
    		 Pediatric participants received nelarabine 650 mg/m^2 through all treatment cycles.

    Subject analysis set title
    Adult 1000 mg/m^2
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    Adult participants who received nelarabine 1000 mg/m^2 in the study

    Subject analysis set title
    Adult 1500 mg/m^2
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    Adult participants who received nelarabine 1500 mg/m^2 in the study

    Primary: Best overall response with bone marrow involvement

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    End point title
    		 Best overall response with bone marrow involvement [1] [2]
    End point description
    The best overall response was assessed from the overall response (Complete Response (CR), CR with/without hematologic recovery (CR*), Partial Response (PR), and treatment failure) throughout the study. Efficacy Population: all participants with evaluable efficacy data at screening and at least one post-dose assessment time (that is, who are evaluable for disease state). Only participants with available data were analyzed.
    End point type
    Primary
    End point timeframe
    Up to approximately 5 months
    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: There are no statistical data to report.
    [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 is only reporting on a subset of the arms that are contained in the baseline period.
    End point values
    		 Adult Pediatric (Cohorts 1 and 2)
    Number of subjects analysed
    4 [3]
    4
    Units: Participants
        CR
    1
    2
        CR*
    0
    0
        PR
    0
    0
        Treatment failure
    2
    2
        Missing
    1
    0
    Notes
    [3] - Efficacy Population
    No statistical analyses for this end point

    Primary: Best overall response without bone marrow involvement

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    End point title
    		 Best overall response without bone marrow involvement [4] [5]
    End point description
    The best overall response was assessed from the overall response (Complete Response (CR), Partial Response (PR), Stable Disease (SD), and Progressive Disease (PD)) throughout the study. Efficacy Population: all participants with evaluable efficacy data at screening and at least one post-dose assessment time (that is, who are evaluable for disease state). Only participants with available data were analyzed.
    End point type
    Primary
    End point timeframe
    Up to approximately 5 months
    Notes
    [4] - 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: There are no statistical data to report.
    [5] - 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 is only reporting on a subset of the arms that are contained in the baseline period.
    End point values
    		 Adult Pediatric (Cohorts 1 and 2)
    Number of subjects analysed
    3 [6]
    0 [7]
    Units: Participants
        CR
    0
        PR
    0
        SD
    2
        PD
    1
    Notes
    [6] - Efficacy Population
    [7] - Participants were not analyzed as data were not available.
    No statistical analyses for this end point

    Primary: Number of participants with response with bone marrow involvement

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    End point title
    		 Number of participants with response with bone marrow involvement [8] [9]
    End point description
    Response is defined as participants with CR, CR*, or PR. Only participants with available data were analyzed.
    End point type
    Primary
    End point timeframe
    Up to approximately 5 months
    Notes
    [8] - 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: There are no statistical data to report.
    [9] - 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 is only reporting on a subset of the arms that are contained in the baseline period.
    End point values
    		 Adult Pediatric (Cohorts 1 and 2)
    Number of subjects analysed
    4 [10]
    4
    Units: Participants
    1
    2
    Notes
    [10] - Efficacy Population
    No statistical analyses for this end point

    Primary: Number of Participants with response without bone marrow involvement

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    End point title
    		 Number of Participants with response without bone marrow involvement [11] [12]
    End point description
    Response is defined as number of participants with CR or PR. Only participants with available data were analyzed.
    End point type
    Primary
    End point timeframe
    Up to approximately 5 months
    Notes
    [11] - 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: There are no statistical data to report.
    [12] - 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 is only reporting on a subset of the arms that are contained in the baseline period.
    End point values
    		 Adult Pediatric (Cohorts 1 and 2)
    Number of subjects analysed
    3 [13]
    0 [14]
    Units: Participants
    0
    Notes
    [13] - Efficacy Population
    [14] - Participants were not analyzed as data were not available.
    No statistical analyses for this end point

    Primary: Number of participants with response with or without bone marrow involvement

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    End point title
    		 Number of participants with response with or without bone marrow involvement [15] [16]
    End point description
    Response is defined as number of participants with CR, CR*, or PR.
    End point type
    Primary
    End point timeframe
    Up to approximately 5 months
    Notes
    [15] - 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: There are no statistical data to report.
    [16] - 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 is only reporting on a subset of the arms that are contained in the baseline period.
    End point values
    		 Adult Pediatric (Cohorts 1 and 2)
    Number of subjects analysed
    7 [17]
    4
    Units: Participants
    1
    2
    Notes
    [17] - Efficacy Population
    No statistical analyses for this end point

    Primary: Pharmacokinetic (PK) parameters of plasma nelarabine: area under the plasma concentration-time curve (AUC) from time zero to the last measurable concentration (AUC0-t) and AUC from time zero to infinity (AUC0-infinity)

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    End point title
    		 Pharmacokinetic (PK) parameters of plasma nelarabine: area under the plasma concentration-time curve (AUC) from time zero to the last measurable concentration (AUC0-t) and AUC from time zero to infinity (AUC0-infinity) [18]
    End point description
    Blood samples were collected during the specified time points on Day 1 and the nelarabine concentrations were assessed in plasma. Nelarabine PK parameters were derived by PK analysis using nelarabine concentrations. PK Population: all participants with evaluable PK data.
    End point type
    Primary
    End point timeframe
    Pre-dose, and 0.0, 0.25, 0.5, 1, 2, 3, 5, 7, 10, and 22 hours post-dose on Day 1 and Day 5 (22 hours post-dose on Day 5 was optional)
    Notes
    [18] - 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: There are no statistical data to report.
    End point values
    		 Adult 1000 mg/m^2 Adult 1500 mg/m^2
    Number of subjects analysed
    3 [19]
    6
    Units: hour*micromole per liter
    geometric mean (confidence interval 95%)
        AUC0-t
    36.09 (8.34 to 156.14)
    32.75 (17.35 to 61.83)
        AUC0-infinity
    36.27 (8.44 to 155.83)
    32.97 (17.5 to 62.12)
    Notes
    [19] - PK Population
    No statistical analyses for this end point

    Primary: PK parameters of plasma nelarabine: maximum observed plasma concentration (Cmax)

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    End point title
    		 PK parameters of plasma nelarabine: maximum observed plasma concentration (Cmax) [20]
    End point description
    Blood samples were collected during the specified time points on Day 1 and the nelarabine concentrations were assessed in plasma. Nelarabine PK parameters were derived by PK analysis using nelarabine concentrations.
    End point type
    Primary
    End point timeframe
    Pre-dose, and 0.0, 0.25, 0.5, 1, 2, 3, 5, 7, 10, and 22 hours post-dose on Day 1 and Day 5 (22 hours post-dose on Day 5 was optional)
    Notes
    [20] - 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: There are no statistical data to report.
    End point values
    		 Adult 1000 mg/m^2 Adult 1500 mg/m^2
    Number of subjects analysed
    3 [21]
    6
    Units: micromole per liter
        geometric mean (confidence interval 95%)
    28.3229 (6.8186 to 117.6465)
    26.2848 (14.1822 to 48.7152)
    Notes
    [21] - PK Population
    No statistical analyses for this end point

    Primary: PK parameters of plasma nelarabine: time for Cmax (tmax)

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    End point title
    		 PK parameters of plasma nelarabine: time for Cmax (tmax) [22]
    End point description
    Blood samples were collected during the specified time points on Day 1 and the nelarabine concentrations were assessed in plasma. Nelarabine PK parameters were derived by PK analysis using nelarabine concentrations.
    End point type
    Primary
    End point timeframe
    Pre-dose, and 0.0, 0.25, 0.5, 1, 2, 3, 5, 7, 10, and 22 hours post-dose on Day 1 and Day 5 (22 hours post-dose on Day 5 was optional)
    Notes
    [22] - 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: There are no statistical data to report.
    End point values
    		 Adult 1000 mg/m^2 Adult 1500 mg/m^2
    Number of subjects analysed
    3 [23]
    6
    Units: hours
        median (full range (min-max))
    2 (2 to 2)
    2.04 (2 to 2.2)
    Notes
    [23] - PK Population
    No statistical analyses for this end point

    Primary: PK parameters of plasma nelarabine: half-life (t1/2)

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    End point title
    		 PK parameters of plasma nelarabine: half-life (t1/2) [24]
    End point description
    Blood samples were collected during the specified time points on Day 1 and the nelarabine concentrations were assessed in plasma. Nelarabine PK parameters were derived by PK analysis using nelarabine concentrations.
    End point type
    Primary
    End point timeframe
    Pre-dose, and 0.0, 0.25, 0.5, 1, 2, 3, 5, 7, 10, and 22 hours post-dose on Day 1 and Day 5 (22 hours post-dose on Day 5 was optional)
    Notes
    [24] - 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: There are no statistical data to report.
    End point values
    		 Adult 1000 mg/m^2 Adult 1500 mg/m^2
    Number of subjects analysed
    3 [25]
    6
    Units: hours
        geometric mean (confidence interval 95%)
    0.3043 (0.1579 to 0.5865)
    0.2324 (0.1607 to 0.3361)
    Notes
    [25] - PK Population
    No statistical analyses for this end point

    Primary: PK parameters of plasma nelarabine: clearance (CL)

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    End point title
    		 PK parameters of plasma nelarabine: clearance (CL) [26]
    End point description
    Blood samples were collected during the specified time points on Day 1 and the nelarabine concentrations were assessed in plasma. Nelarabine PK parameters were derived by PK analysis using nelarabine concentrations.
    End point type
    Primary
    End point timeframe
    Predose, and 0.0, 0.25, 0.5, 1, 2, 3, 5, 7, 10, and 22 hours post-dose on Day 1 and Day 5 (22 hours post-dose on Day 5 was optional)
    Notes
    [26] - 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: There are no statistical data to report.
    End point values
    		 Adult 1000 mg/m^2 Adult 1500 mg/m^2
    Number of subjects analysed
    3 [27]
    6
    Units: Liters per hour
        geometric mean (confidence interval 95%)
    148.26 (37.75 to 582.36)
    243.99 (133.57 to 445.7)
    Notes
    [27] - PK Population
    No statistical analyses for this end point

    Primary: PK parameters of plasma nelarabine: steady state volume of distribution (Vss)

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    End point title
    		 PK parameters of plasma nelarabine: steady state volume of distribution (Vss) [28]
    End point description
    Blood samples were collected during the specified time points on Day 1 and the nelarabine concentrations were assessed in plasma. Nelarabine PK parameters were derived by PK analysis using nelarabine concentrations.
    End point type
    Primary
    End point timeframe
    Predose, and 0.0, 0.25, 0.5, 1, 2, 3, 5, 7, 10, and 22 hours post-dose on Day 1 and Day 5 (22 hours post-dose on Day 5 was optional)
    Notes
    [28] - 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: There are no statistical data to report.
    End point values
    		 Adult 1000 mg/m^2 Adult 1500 mg/m^2
    Number of subjects analysed
    3 [29]
    6
    Units: Liters
        geometric mean (confidence interval 95%)
    65.08 (30.73 to 137.85)
    81.8 (57.19 to 116.99)
    Notes
    [29] - PK Population
    No statistical analyses for this end point

    Primary: PK parameters of plasma 9-beta-D-arabinofuranosyl guanine (ara-G): AUC0-t and AUC0-infinity

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    End point title
    		 PK parameters of plasma 9-beta-D-arabinofuranosyl guanine (ara-G): AUC0-t and AUC0-infinity [30]
    End point description
    Blood samples were collected during the specified time points on Day 1 and the ara-G concentrations were assessed in plasma. PK parameters for ara-G were derived by PK analysis using ara-G concentrations.
    End point type
    Primary
    End point timeframe
    Predose, and 0.0, 0.25, 0.5, 1, 2, 3, 5, 7, 10, and 22 hours post-dose on Day 1 and Day 5 (22 hours post-dose on Day 5 was optional)
    Notes
    [30] - 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: There are no statistical data to report.
    End point values
    		 Adult 1000 mg/m^2 Adult 1500 mg/m^2
    Number of subjects analysed
    3 [31]
    6
    Units: hour*micromole per liter
    geometric mean (confidence interval 95%)
        AUC0-t
    436.96 (259.24 to 736.53)
    616.42 (389.17 to 976.36)
        AUC0-infinity
    440.73 (263 to 738.56)
    622.54 (390.78 to 991.76)
    Notes
    [31] - PK Population
    No statistical analyses for this end point

    Primary: PK parameters of plasma ara-G: Cmax

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    End point title
    		 PK parameters of plasma ara-G: Cmax [32]
    End point description
    Blood samples were collected during the specified time points on Day 1 and the ara-G concentrations were assessed in plasma. PK parameters for ara-G were derived by PK analysis using ara-G concentrations.
    End point type
    Primary
    End point timeframe
    Predose, and 0.0, 0.25, 0.5, 1, 2, 3, 5, 7, 10, and 22 hours post-dose on Day 1 and Day 5 (22 hours post-dose on Day 5 was optional)
    Notes
    [32] - 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: There are no statistical data to report.
    End point values
    		 Adult 1000 mg/m^2 Adult 1500 mg/m^2
    Number of subjects analysed
    3 [33]
    6
    Units: micromole per liter
        geometric mean (confidence interval 95%)
    86.9682 (65.1873 to 116.0267)
    131.7519 (108.5299 to 159.9427)
    Notes
    [33] - PK Population
    No statistical analyses for this end point

    Primary: PK parameters of plasma ara-G: tmax

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    End point title
    		 PK parameters of plasma ara-G: tmax [34]
    End point description
    Blood samples were collected during the specified time points on Day 1 and the ara-G concentrations were assessed in plasma. PK parameters for ara-G were derived by PK analysis using ara-G concentrations.
    End point type
    Primary
    End point timeframe
    Predose, and 0.0, 0.25, 0.5, 1, 2, 3, 5, 7, 10, and 22 hours post-dose on Day 1 and Day 5 (22 hours post-dose on Day 5 was optional)
    Notes
    [34] - 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: There are no statistical data to report.
    End point values
    		 Adult 1000 mg/m^2 Adult 1500 mg/m^2
    Number of subjects analysed
    3 [35]
    6
    Units: hours
        median (full range (min-max))
    2 (2 to 2)
    2.105 (2 to 2.25)
    Notes
    [35] - PK Population
    No statistical analyses for this end point

    Primary: PK parameters of plasma ara-G: half-life (t1/2)

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    End point title
    		 PK parameters of plasma ara-G: half-life (t1/2) [36]
    End point description
    Blood samples were collected during the specified time points on Day 1 and the ara-G concentrations were assessed in plasma. PK parameters for ara-G were derived by PK analysis using ara-G concentrations.
    End point type
    Primary
    End point timeframe
    Predose, and 0.0, 0.25, 0.5, 1, 2, 3, 5, 7, 10, and 22 hours post-dose on Day 1 and Day 5 (22 hours post-dose on Day 5 was optional)
    Notes
    [36] - 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: There are no statistical data to report.
    End point values
    		 Adult 1000 mg/m^2 Adult 1500 mg/m^2
    Number of subjects analysed
    3 [37]
    6
    Units: hours
        geometric mean (confidence interval 95%)
    3.5417 (2.8113 to 4.4619)
    2.9758 (2.1055 to 4.2059)
    Notes
    [37] - PK population
    No statistical analyses for this end point

    Primary: PK parameters of plasma ara-G: apparent total clearance (CL/F)

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    End point title
    		 PK parameters of plasma ara-G: apparent total clearance (CL/F) [38]
    End point description
    Blood samples were collected during the specified time points on Day 1 and the ara-G concentrations were assessed in plasma. PK parameters for ara-G were derived by PK analysis using ara-G concentrations.
    End point type
    Primary
    End point timeframe
    Predose, and 0.0, 0.25, 0.5, 1, 2, 3, 5, 7, 10, and 22 hours post-dose on Day 1 and Day 5 (22 hours post-dose on Day 5 was optional)
    Notes
    [38] - 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: There are no statistical data to report.
    End point values
    		 Adult 1000 mg/m^2 Adult 1500 mg/m^2
    Number of subjects analysed
    3 [39]
    6
    Units: Liters per hour
        geometric mean (confidence interval 95%)
    12.2 (7.72 to 19.3)
    12.92 (8.23 to 20.29)
    Notes
    [39] - PK Population
    No statistical analyses for this end point

    Primary: PK parameters of plasma ara-G: steady state apparent volume of distribution (Vss/F)

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    End point title
    		 PK parameters of plasma ara-G: steady state apparent volume of distribution (Vss/F) [40]
    End point description
    Blood samples were collected during the specified time points on Day 1 and the ara-G concentrations were assessed in plasma. PK parameters for ara-G were derived by PK analysis using ara-G concentrations.
    End point type
    Primary
    End point timeframe
    Predose, and 0.0, 0.25, 0.5, 1, 2, 3, 5, 7, 10, and 22 hours post-dose on Day 1 and Day 5 (22 hours post-dose on Day 5 was optional)
    Notes
    [40] - 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: There are no statistical data to report.
    End point values
    		 Adult 1000 mg/m^2 Adult 1500 mg/m^2
    Number of subjects analysed
    3 [41]
    6
    Units: Liters
        geometric mean (confidence interval 95%)
    62.35 (31.32 to 124.15)
    55.48 (41.92 to 73.44)
    Notes
    [41] - PK Population
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    Serious adverse events (SAEs) and non-serious adverse events (AEs) were assessed from Baseline to end of study (approximately 2.5 months).
    Adverse event reporting additional description
    SAEs and non-serious AEs were analyzed in Safety Population, which was defined as all participants who received at least one dose of study medication. Non-serious AEs are presented for if they occurred in more than one patient in any treatment. The # of occurrences information is not available; therefore, the # of occurrences = # participants.
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    9.1
    Reporting groups
    Reporting group title
    Adult
    Reporting group description
    		 Adult participants received nelarabine 1000 milligrams (mg)/square meter (m^2) in the first cycle and nelarabine 1500 mg/m^2 in the second cycle and subsequent cycles in Cohort 1. Another group (Cohort 2) of adult participants received nelarabine 1500 mg/m^2 through all treatment cycles.

    Reporting group title
    Pediatric (Cohorts 1 and 2)
    Reporting group description
    		 Pediatric participants received nelarabine 400 mg/m^2 in the first cycle and nelarabine 650 mg/m^2 in the second cycle and subsequent cycles in Cohort 1. Another group (Cohort 2) of pediatric participants received nelarabine 650 mg/m^2 through all treatment cycles.

    Reporting group title
    Pediatric (Cohort 3)
    Reporting group description
    		 Pediatric participants received nelarabine 650 mg/m^2 through all treatment cycles.

    Serious adverse events
    		 Adult Pediatric (Cohorts 1 and 2) Pediatric (Cohort 3)
    Total subjects affected by serious adverse events
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 4 (25.00%)
    0 / 2 (0.00%)
         number of deaths (all causes)
    0
    0
    0
         number of deaths resulting from adverse events
    Infections and infestations
    Herpes zoster
    alternative dictionary used: MedDRA 12.1
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 4 (25.00%)
    0 / 2 (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
    Frequency threshold for reporting non-serious adverse events: 0%
    Non-serious adverse events
    		 Adult Pediatric (Cohorts 1 and 2) Pediatric (Cohort 3)
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    7 / 7 (100.00%)
    4 / 4 (100.00%)
    2 / 2 (100.00%)
    Investigations
    Lymphocyte count decreased
         subjects affected / exposed
    4 / 7 (57.14%)
    3 / 4 (75.00%)
    1 / 2 (50.00%)
         occurrences all number
    4
    3
    1
    Aspartate aminotransferase increased
         subjects affected / exposed
    4 / 7 (57.14%)
    0 / 4 (0.00%)
    0 / 2 (0.00%)
         occurrences all number
    4
    0
    0
    Alanine aminotransferase increased
         subjects affected / exposed
    4 / 7 (57.14%)
    0 / 4 (0.00%)
    0 / 2 (0.00%)
         occurrences all number
    4
    0
    0
    White blood cell count decreased
         subjects affected / exposed
    3 / 7 (42.86%)
    3 / 4 (75.00%)
    2 / 2 (100.00%)
         occurrences all number
    3
    3
    2
    Haemoglobin decreased
         subjects affected / exposed
    2 / 7 (28.57%)
    3 / 4 (75.00%)
    0 / 2 (0.00%)
         occurrences all number
    2
    3
    0
    Blood urine present
         subjects affected / exposed
    2 / 7 (28.57%)
    3 / 4 (75.00%)
    0 / 2 (0.00%)
         occurrences all number
    2
    3
    0
    Neutrophil count decreased
         subjects affected / exposed
    2 / 7 (28.57%)
    2 / 4 (50.00%)
    1 / 2 (50.00%)
         occurrences all number
    2
    2
    1
    Platelet count decreased
         subjects affected / exposed
    2 / 7 (28.57%)
    0 / 4 (0.00%)
    0 / 2 (0.00%)
         occurrences all number
    2
    0
    0
    Blood alkaline phosphatase increased
         subjects affected / exposed
    2 / 7 (28.57%)
    0 / 4 (0.00%)
    0 / 2 (0.00%)
         occurrences all number
    2
    0
    0
    Blood creatine phosphokinase increased
         subjects affected / exposed
    2 / 7 (28.57%)
    0 / 4 (0.00%)
    0 / 2 (0.00%)
         occurrences all number
    2
    0
    0
    Urobilin urine present
         subjects affected / exposed
    2 / 7 (28.57%)
    0 / 4 (0.00%)
    0 / 2 (0.00%)
         occurrences all number
    2
    0
    0
    Nervous system disorders
    Somnolence
         subjects affected / exposed
    7 / 7 (100.00%)
    0 / 4 (0.00%)
    0 / 2 (0.00%)
         occurrences all number
    7
    0
    0
    Headache
         subjects affected / exposed
    2 / 7 (28.57%)
    0 / 4 (0.00%)
    0 / 2 (0.00%)
         occurrences all number
    2
    0
    0
    General disorders and administration site conditions
    Pyrexia
         subjects affected / exposed
    2 / 7 (28.57%)
    0 / 4 (0.00%)
    0 / 2 (0.00%)
         occurrences all number
    2
    0
    0
    Malaise
         subjects affected / exposed
    2 / 7 (28.57%)
    0 / 4 (0.00%)
    0 / 2 (0.00%)
         occurrences all number
    2
    0
    0
    Gastrointestinal disorders
    Nausea
         subjects affected / exposed
    5 / 7 (71.43%)
    0 / 4 (0.00%)
    0 / 2 (0.00%)
         occurrences all number
    5
    0
    0
    Abdominal pain
         subjects affected / exposed
    3 / 7 (42.86%)
    0 / 4 (0.00%)
    0 / 2 (0.00%)
         occurrences all number
    3
    0
    0
    Diarrhoea
         subjects affected / exposed
    0 / 7 (0.00%)
    2 / 4 (50.00%)
    0 / 2 (0.00%)
         occurrences all number
    0
    2
    0
    Respiratory, thoracic and mediastinal disorders
    Dysphonia
         subjects affected / exposed
    2 / 7 (28.57%)
    0 / 4 (0.00%)
    0 / 2 (0.00%)
         occurrences all number
    2
    0
    0
    Skin and subcutaneous tissue disorders
    Urticaria
         subjects affected / exposed
    2 / 7 (28.57%)
    0 / 4 (0.00%)
    0 / 2 (0.00%)
         occurrences all number
    2
    0
    0
    Rash
         subjects affected / exposed
    0 / 7 (0.00%)
    2 / 4 (50.00%)
    0 / 2 (0.00%)
         occurrences all number
    0
    2
    0
    Infections and infestations
    Gingival swelling
         subjects affected / exposed
    3 / 7 (42.86%)
    0 / 4 (0.00%)
    0 / 2 (0.00%)
         occurrences all number
    3
    0
    0
    Pneumonia
         subjects affected / exposed
    2 / 7 (28.57%)
    0 / 4 (0.00%)
    0 / 2 (0.00%)
         occurrences all number
    2
    0
    0

    More information

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? No

    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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