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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

NCT03384654

Description:

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.

Related Conditions:
  • B-Cell Acute Lymphoblastic Leukemia
  • B-Cell Lymphoblastic Lymphoma
  • T-Cell Acute Lymphoblastic Leukemia
  • T-Cell Lymphoblastic Lymphoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: 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: 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

Clinical Trial IDs

  • ORG STUDY ID: CR108432
  • SECONDARY ID: 2017-003377-34
  • SECONDARY ID: 54767414ALL2005
  • NCT ID: NCT03384654

Conditions

  • Precursor Cell Lymphoblastic Leukemia-Lymphoma

Interventions

DrugSynonymsArms
DaratumumabCohort 1: B-Cell Acute Lymphoblastic Leukemia (ALL)/LL
VincristineCohort 1: B-Cell Acute Lymphoblastic Leukemia (ALL)/LL
PrednisoneCohort 1: B-Cell Acute Lymphoblastic Leukemia (ALL)/LL
DoxorubicinCohort 2: T-Cell ALL/LL
Peg-asparaginaseCohort 2: T-Cell ALL/LL
CyclophosphamideCohort 2: T-Cell ALL/LL
CytarabineCohort 2: T-Cell ALL/LL
6-mercaptopurineCohort 2: T-Cell ALL/LL
MethotrexateCohort 2: T-Cell ALL/LL

Purpose

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.
    

Trial Arms

NameTypeDescriptionInterventions
Cohort 1: B-Cell Acute Lymphoblastic Leukemia (ALL)/LLExperimentalCohort 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.
  • Daratumumab
  • Vincristine
  • Prednisone
Cohort 2: T-Cell ALL/LLExperimentalCohort 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.
  • Daratumumab
  • Vincristine
  • Prednisone
  • Doxorubicin
  • Peg-asparaginase
  • Cyclophosphamide
  • Cytarabine
  • 6-mercaptopurine
  • Methotrexate

Eligibility Criteria

        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)
      
Maximum Eligible Age:30 Years
Minimum Eligible Age:1 Year
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Percentage of Participants with Complete Response (CR) for B-cell Acute Lymphoblastic Leukemia (ALL)
Time Frame:Within 2 cycles (each cycle of 28-days)
Safety Issue:
Description:Complete response based on the modified National Comprehensive Cancer Network (NCCN) criteria is defined as: Less than 5 percent (%) blasts in the bone marrow; No evidence of circulating blasts or extramedullary disease; Full recovery of peripheral blood counts: Platelets greater than (>)100*10^9/liter (L) and absolute neutrophil count (ANC) >1.0*10^9/L.

Secondary Outcome Measures

Measure:Overall Response Rate (ORR)
Time Frame:approximately 3 years
Safety Issue:
Description: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.
Measure:Event-Free Survival (EFS)
Time Frame:approximately 3 years
Safety Issue:
Description: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.
Measure:Relapse-Free Survival (RFS)
Time Frame:approximately 3 years
Safety Issue:
Description: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.
Measure:Overall Survival (OS)
Time Frame:approximately 3 years
Safety Issue:
Description:OS is defined as the time from the date of first treatment to the date of death due to any cause.
Measure:Percentage of Participants who are Minimal Residual Disease (MRD) Negative
Time Frame:approximately 3 years
Safety Issue:
Description: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.
Measure:Percentage of Participants who Receive an Allogeneic Hematopoietic Stem Cell Transplant (HSCT)
Time Frame:approximately 3 years
Safety Issue:
Description:The percentage of participants who received an allogeneic HSCT after treatment with daratumumab will be assessed.
Measure: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)
Safety Issue:
Description:The Cmax is the maximum observed plasma concentration.
Measure: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)
Safety Issue:
Description:The Cmin is the minimum observed plasma concentration.
Measure:Number of Participants with Anti-Daratumumab Antibodies
Time Frame:approximately 3 years
Safety Issue:
Description:The incidence of anti-daratumumab antibodies will be assessed as number of participant with anti-daratumumab antibodies.
Measure: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)
Safety Issue:
Description:Concentration of daratumumab in CSF will be assessed.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Janssen Research & Development, LLC

Last Updated

February 27, 2020