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A Study to Evaluate the Efficacy and Safety of Daratumumab in Pediatric and Young Adult Participants Greater Than or Equal to (>=)1 and Less Than or Equal to (<=) 30 Years of Age With Relapsed/Refractory Precursor B-cell or T-cell Acute Lymphoblastic Leukemia or Lymphoblastic Lymphoma

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ClinicalTrials.gov Identifier: NCT03384654
Recruitment Status : Recruiting
First Posted : December 27, 2017
Last Update Posted : April 24, 2020
Sponsor:
Information provided by (Responsible Party):
Janssen Research & Development, LLC

Tracking Information
First Submitted Date  ICMJE December 20, 2017
First Posted Date  ICMJE December 27, 2017
Last Update Posted Date April 24, 2020
Actual Study Start Date  ICMJE May 14, 2018
Estimated Primary Completion Date October 5, 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: December 20, 2017)
  • Percentage of Participants with Complete Response (CR) for B-cell Acute Lymphoblastic Leukemia (ALL) [ Time Frame: Within 2 cycles (each cycle of 28-days) ]
    Complete response based on the modified National Comprehensive Cancer Network (NCCN) criteria is defined as: Less than 5 percent (%) blasts in the bone marrow; No evidence of circulating blasts or extramedullary disease; Full recovery of peripheral blood counts: Platelets greater than (>)100*10^9/liter (L) and absolute neutrophil count (ANC) >1.0*10^9/L.
  • Percentage of Participants with Complete Response (CR) for T-cell ALL [ Time Frame: End of Cycle 1 (each cycle of 28 days) ]
    Complete response based on the modified NCCN criteria is defined as: Less than 5% blasts in the bone marrow; No evidence of circulating blasts or extramedullary disease; Full recovery of peripheral blood counts: Platelets >100*10^9/L and ANC >1.0*10^9/L.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: October 3, 2018)
  • Overall Response Rate (ORR) [ Time Frame: approximately 3 years ]
    ORR is defined as percentage of participants who achieve CR or complete response with only partial hematological recovery (CRi) according to NCCN criteria. NCCN criteria for CR: Less than 5 % blasts in the bone marrow; No evidence of circulating blasts or extramedullary disease; Full recovery of peripheral blood counts: Platelets (>)100 x10^9/L and ANC >1.0x10^9/L; CRi: Less than 5% blasts in the bone marrow; No evidence of circulating blasts or extramedullary disease; Partial recovery of peripheral blood counts not meeting criteria for CR.
  • Event-Free Survival (EFS) [ Time Frame: approximately 3 years ]
    EFS is defined as the time from the date of first treatment to the first documented treatment failure (that is [ie], disease progression) or date of relapse from CR or death due to any cause, whichever occurs first. Progressive disease: increase of at least 25% in the absolute number of circulating peripheral or bone marrow blasts, or development of new extramedullary disease.
  • Relapse-Free Survival (RFS) [ Time Frame: approximately 3 years ]
    RFS is defined as the time from CR to relapse from CR or death due to any cause, whichever occurs first. Relapse from CR is defined as: Reappearance of leukemia blasts in the peripheral blood or more than (>) 5% blasts in the bone marrow; Reappearance of extramedullary disease or new extramedullary disease.
  • Overall Survival (OS) [ Time Frame: approximately 3 years ]
    OS is defined as the time from the date of first treatment to the date of death due to any cause.
  • Percentage of Participants who are Minimal Residual Disease (MRD) Negative [ Time Frame: approximately 3 years ]
    Percentage of participants who are MRD negative will be assessed. MRD negative is defined as less than (<) 0.01% abnormal population counts to nucleated mononuclear cells when measured by flow.
  • Percentage of Participants who Receive an Allogeneic Hematopoietic Stem Cell Transplant (HSCT) [ Time Frame: approximately 3 years ]
    The percentage of participants who received an allogeneic HSCT after treatment with daratumumab will be assessed.
  • Maximum Observed Plasma Concentration (Cmax) of Daratumumab [ Time Frame: Cohort 1 Cycles 1-9 (each cycle is 28 days); Cohort 2 Cycles 1-2 (each cycle is 28 days) ]
    The Cmax is the maximum observed plasma concentration.
  • Minimum Observed Plasma Concentration (Cmin) of Daratumumab [ Time Frame: Cohort 1 Cycles 1-9 (each cycle is 28 days); Cohort 2 Cycles 1-2 (each cycle is 28 days) ]
    The Cmin is the minimum observed plasma concentration.
  • Number of Participants with Anti-Daratumumab Antibodies [ Time Frame: approximately 3 years ]
    The incidence of anti-daratumumab antibodies will be assessed as number of participant with anti-daratumumab antibodies.
  • Concentration of Daratumumab in Cerebrospinal Fluid (CSF) [ Time Frame: Cohort 1 Cycles 1-9 (each cycle is 28 days); Cohort 2 Cycles 1-2 (each cycle is 28 days) ]
    Concentration of daratumumab in CSF will be assessed.
Original Secondary Outcome Measures  ICMJE
 (submitted: December 20, 2017)
  • Overall Response Rate (ORR) [ Time Frame: approximately 3 years ]
    ORR is defined as percentage of participants who achieve CR or complete response with only partial hematological recovery (CRi) according to NCCN criteria. NCCN criteria for CR: Less than 5 % blasts in the bone marrow; No evidence of circulating blasts or extramedullary disease; Full recovery of peripheral blood counts: Platelets (>)100 x10^9/L and ANC >1.0x10^9/L; CRi: Less than 5% blasts in the bone marrow; No evidence of circulating blasts or extramedullary disease; Partial recovery of peripheral blood counts not meeting criteria for CR.
  • Event-Free Survival (EFS) [ Time Frame: approximately 3 years ]
    EFS is defined as the time from the date of first treatment to the first documented treatment failure (that is [ie], disease progression) or date of relapse from CR or death due to any cause, whichever occurs first. Progressive disease: increase of at least 25% in the absolute number of circulating peripheral or bone marrow blasts, or development of new extramedullary disease.
  • Relapse-Free Survival (RFS) [ Time Frame: approximately 3 years ]
    RFS is defined as the time from CR to relapse from CR or death due to any cause, whichever occurs first. Relapse from CR is defined as: Reappearance of leukemia blasts in the peripheral blood or more than (>) 5% blasts in the bone marrow; Reappearance of extramedullary disease or new extramedullary disease.
  • Overall Survival (OS) [ Time Frame: approximately 3 years ]
    OS is defined as the time from the date of first treatment to the date of death due to any cause.
  • Percentage of Participants who are Minimal Residual Disease (MRD) Negative [ Time Frame: approximately 3 years ]
    Percentage of participants who are MRD negative will be assessed. MRD negative is defined as less than (<) 0.01% abnormal population counts to total event counts when measured by flow.
  • Percentage of Participants who Receive an Allogeneic Hematopoietic Stem Cell Transplant (HSCT) [ Time Frame: approximately 3 years ]
    The percentage of participants who received an allogeneic HSCT after treatment with daratumumab will be assessed.
  • Maximum Observed Plasma Concentration (Cmax) of Daratumumab [ Time Frame: Cohort 1 Cycles 1-9; Cohort 2 Cycles 1-2 ]
    The Cmax is the maximum observed plasma concentration.
  • Minimum Observed Plasma Concentration (Cmin) of Daratumumab [ Time Frame: Cohort 1 Cycles 1-9; Cohort 2 Cycles 1-2 ]
    The Cmin is the minimum observed plasma concentration.
  • Number of Participants with Anti-Daratumumab Antibodies [ Time Frame: approximately 3 years ]
    The incidence of anti-daratumumab antibodies will be assessed as number of participant with anti-daratumumab antibodies.
  • Concentration of Daratumumab in Cerebrospinal Fluid (CSF) [ Time Frame: Cohort 1 Cycles 1-9; Cohort 2 Cycles 1-2 ]
    Concentration of daratumumab in CSF will be assessed.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Study to Evaluate the Efficacy and Safety of Daratumumab in Pediatric and Young Adult Participants Greater Than or Equal to (>=)1 and Less Than or Equal to (<=) 30 Years of Age With Relapsed/Refractory Precursor B-cell or T-cell Acute Lymphoblastic Leukemia or Lymphoblastic Lymphoma
Official Title  ICMJE An Open-label, Multicenter, Phase 2 Study Evaluating the Efficacy and Safety of Daratumumab in Pediatric and Young Adult Subjects >=1 and <=30 Years of Age With Relapsed/Refractory Precursor B-cell or T-cell Acute Lymphoblastic Leukemia or Lymphoblastic Lymphoma
Brief Summary The purpose of this study is to evaluate the efficacy of daratumumab in addition to standard chemotherapy in pediatric participants with relapsed/refractory B-cell acute lymphoblastic leukemia (ALL)/lymphoblastic lymphoma (LL) and T-cell ALL/LL as measured by the complete response (CR) rate.
Detailed Description Screening for eligible participants will be performed within 21 days before administration of the study drug. Participants with B-cell ALL/LL will receive treatment until disease progression, unacceptable toxicity or achievement of CR followed by hematopoietic stem cell transplant (HSCT). Participants with T cell ALL/LL will receive treatment for up to 2 cycles. If disease progression is confirmed, then the participant will discontinue study treatment, complete the End of Treatment Visit, and enter the Posttreatment Period. For those participants who discontinue study drug prior to disease progression, disease evaluations will continue to be performed every 8 weeks until subsequent anticancer therapy is initiated.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Precursor Cell Lymphoblastic Leukemia-Lymphoma
Intervention  ICMJE
  • Drug: Daratumumab
    Participant will receive daratumumab 16 milligram per kilogram (mg/kg) in cohort 1 and cohort 2.
  • Drug: Vincristine
    Participant will receive vincristine 1.5 milligram per meter square (mg/m^2) in cohort 1 and cohort 2.
  • Drug: Prednisone
    Participant will receive prednisone 40 mg/m^2 in cohort 1 and cohort 2.
  • Drug: Doxorubicin
    Participant will receive doxorubicin 60 mg/m^2 in cohort 2.
  • Biological: Peg-asparaginase
    Participant will receive peg-asparaginase 2500 units per meter square (U/m^2) in cohort 2.
  • Drug: Cyclophosphamide
    Participant will receive cyclophosphamide 1 gram per meter square (g/m^2) once in cohort 2.
  • Drug: Cytarabine
    Participant will receive cytarabine 75 mg/m^2 in cohort 2.
  • Drug: 6-mercaptopurine
    Participant will receive 6-mercaptopurine 60 mg/m^2 orally daily in cohort 2.
  • Drug: Methotrexate
    Participant will receive methotrexate 5 g/m^2 intravenously (IV) in cohort 2.
Study Arms  ICMJE
  • Experimental: Cohort 1: B-Cell Acute Lymphoblastic Leukemia (ALL)/LL
    Cohort 1 will include participants with B cell ALL/LL in second or greater relapse or refractory to at least 2 prior induction regimens. Participant will receive daratumumab in combination with vincristine and prednisone.
    Interventions:
    • Drug: Daratumumab
    • Drug: Vincristine
    • Drug: Prednisone
  • Experimental: Cohort 2: T-Cell ALL/LL
    Cohort 2 will include participants with T-cell ALL/LL in first relapse or refractory to at least 1 prior induction/consolidation regimen. Participant will receive daratumumab in combination with vincristine, prednisone, doxorubicin and peg-asparaginase in Cycle 1 and daratumumab in combination with cyclophosphamide, cytarabine, 6- mercaptopurine and methotrexate in Cycle 2.
    Interventions:
    • Drug: Daratumumab
    • Drug: Vincristine
    • Drug: Prednisone
    • Drug: Doxorubicin
    • Biological: Peg-asparaginase
    • Drug: Cyclophosphamide
    • Drug: Cytarabine
    • Drug: 6-mercaptopurine
    • Drug: Methotrexate
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: November 7, 2019)
32
Original Estimated Enrollment  ICMJE
 (submitted: December 20, 2017)
69
Estimated Study Completion Date  ICMJE August 20, 2021
Estimated Primary Completion Date October 5, 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Documented acute lymphoblastic leukemia (ALL) or lymphoblastic lymphoma (LL) as defined by the criteria below:

    1. B-cell cohort: Stage 1; ALL in second or greater relapse or refractory to 2 prior induction regimens with greater than or equal to (>=) 5 percent (%) blasts in the bone marrow and aged 1 to less than (<) 18 years. Stage 2; ALL in second or greater relapse or refractory to 2 prior induction regimens with (>=) 5% blasts in the bone marrow and aged 1 to 30 years. LL in second or greater relapse or refractory to 2 prior induction regimens and biopsy proven and with evidence of measurable disease by radiologic criteria and aged 1 to 30 years.
    2. T-cell cohort: Stage 1; ALL in first relapse or refractory to 1 prior induction/consolidation regimen with (>=) 5% blasts in the bone marrow and aged 1 to <18 years. Stage 2; ALL in first relapse or refractory to 1 prior induction/consolidation regimen with (>=) 5% blasts in the bone marrow and aged 1 to 30 years. LL in first relapse or refractory to 1 prior induction/consolidation regimen biopsy proven and with evidence of measurable disease by radiologic criteria and aged 1 to 30 years
  • Performance status greater than or equal to (>=) 70 by Lansky scale (for participants less than [<] 16 years of age) or Karnofsky scale (for participants [>=] 16 years of age)
  • Adequate hematology laboratory values at Cycle 1 Day 1 pre-dosing defined as follows:

    1. Hemoglobin (>=) 7.5 gram per deciliter (g/dL) ([>=] 5 millimole per liter [mmol/L]; prior red blood cell [RBC] transfusion is permitted)
    2. Platelet count (>=) 10*10^9 per liter (L) (prior platelet transfusion is permitted)
  • Adequate renal function defined as normal serum creatinine for the participant's age or creatinine clearance or radioisotope glomerular filtration rate (GFR) >= 70 milliliter per minute per 1.73 square meter (mL/min/1.73 m^2) prior to enrollment
  • Adequate liver function prior to enrollment defined as:

    1. Alanine aminotransferase level less than or equal to (<=) 2.5* the upper limit of normal (ULN),
    2. Aspartate aminotransferase level (<=) 2.5* ULN, and
    3. Total bilirubin (<=) 2* ULN or direct bilirubin level (<=) 2.0* ULN

Exclusion Criteria:

  • Received an allogeneic hematopoietic transplant within 3 months of screening
  • Active acute graft-versus-host disease of any grade or chronic graft-versus-host disease of Grade 2 or higher
  • Received immunosuppression post hematopoietic transplant within 1 month of study entry
  • Philadelphia chromosome positive (Ph+) B-cell ALL eligible for tyrosine kinase inhibitor therapy
  • Has either of the following:

    1. Evidence of dyspnea at rest or oxygen saturation (<=) 94 percent (%).
    2. Known moderate or severe persistent asthma within the past 2 years, or uncontrolled asthma of any classification
  • Received an investigational drug, was vaccinated with live attenuated vaccines, or used an invasive investigational medical device within 4 weeks before the planned first dose of study drug, or is currently being treated in an investigational study
  • Known to be seropositive for human immunodeficiency virus (HIV)
  • Any one of the following:

    1. Seropositive for hepatitis B (defined by a positive test for hepatitis B surface antigen [HBsAg]). Participants with resolved infection (ie, participants who are HBsAg negative but positive for antibodies to hepatitis B core antigen [anti-HBc] and/or antibodies to hepatitis B surface antigen [anti-HBs]) must be screened using real-time polymerase chain reaction (PCR) measurement of hepatitis B virus (HBV) deoxyribonucleic acid (DNA) levels. Those who are PCR positive will be excluded
    2. Known to be seropositive for hepatitis C (except in the setting of a sustained virologic response [SVR], defined as aviremia at least 12 weeks after completion of antiviral therapy)
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 1 Year to 30 Years   (Child, Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Study Contact 844-434-4210 JNJ.CT@sylogent.com
Listed Location Countries  ICMJE Belgium,   France,   Germany,   Israel,   Italy,   Netherlands,   Spain,   Sweden,   United Kingdom,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03384654
Other Study ID Numbers  ICMJE CR108432
2017-003377-34 ( EudraCT Number )
54767414ALL2005 ( Other Identifier: Janssen Research & Development, LLC )
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Janssen Research & Development, LLC
Study Sponsor  ICMJE Janssen Research & Development, LLC
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Janssen Research & Development, LLC Clinical Trial Janssen Research & Development, LLC
PRS Account Janssen Research & Development, LLC
Verification Date April 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP