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
Overview
- Phase
- Phase 2
- Intervention
- Daratumumab
- Conditions
- Precursor Cell Lymphoblastic Leukemia-Lymphoma
- Sponsor
- Janssen Research & Development, LLC
- Enrollment
- 47
- Locations
- 53
- Primary Endpoint
- Cohort 2: Percentage of Participants With Complete Response (CR) for T-cell ALL
- Status
- Completed
- Last Updated
- 11 months ago
Overview
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.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Documented acute lymphoblastic leukemia (ALL) or lymphoblastic lymphoma (LL) as defined by the criteria below:
- •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.
- •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:
- •Hemoglobin (\>=) 7.5 gram per deciliter (g/dL) (\[\>=\] 5 millimole per liter \[mmol/L\]; prior red blood cell \[RBC\] transfusion is permitted)
- •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:
- •Alanine aminotransferase level less than or equal to (\<=) 2.5\* the upper limit of normal (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:
- •Evidence of dyspnea at rest or oxygen saturation (\<=) 94 percent (%).
- •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:
Arms & Interventions
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.
Intervention: Daratumumab
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.
Intervention: Vincristine
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.
Intervention: Prednisone
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.
Intervention: Daratumumab
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.
Intervention: Vincristine
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.
Intervention: Prednisone
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.
Intervention: Doxorubicin
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.
Intervention: Peg-asparaginase
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.
Intervention: Cyclophosphamide
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.
Intervention: Cytarabine
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.
Intervention: 6-mercaptopurine
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.
Intervention: Methotrexate
Outcomes
Primary Outcomes
Cohort 2: Percentage of Participants With Complete Response (CR) for T-cell ALL
Time Frame: End of Cycle 1 (that is, up to 28 days)
Complete response based on the modified NCCN criteria was 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 cells/L and ANC \>1.0\*10\^9 cells/L. This outcome measure was planned to be analyzed for specified arms only.
Cohort 1: Percentage of Participants With Complete Response (CR) for B-cell Acute Lymphoblastic Leukemia (ALL)
Time Frame: Up to 2 cycles, that is, up to 56 days (each cycle of 28-days)
Complete response based on the modified National Comprehensive Cancer Network (NCCN) criteria was defined as: less than 5 percent (%) blasts in the bone marrow; no evidence of circulating blasts or extramedullary disease; full recovery of peripheral blood counts: platelets greater than (\>)100\*10\^9 cells/liter (L) and absolute neutrophil count (ANC) \>1.0\*10\^9 cells/L. This outcome measure was planned to be analyzed for specified arm only.
Secondary Outcomes
- Overall Response Rate (ORR)(Up to 4 years 4 months)
- Event-free Survival (EFS)(Up to 4 years 4 months)
- Relapse-free Survival (RFS)(Up to 4 years 4 months)
- Concentration of Daratumumab in Cerebrospinal Fluid (CSF)(Pre-dose on Cohort 1: Cycles 1 and 2: Day 1; Cohort 2: Cycle 1 Day 1 and Day 15 and Cycle 2 Day 2 and Day 15)
- Overall Survival (OS)(Up to 4 years 4 months)
- Number of Participants With Anti-daratumumab Antibodies(Up to 4 years 4 months)
- Minimum Observed Serum Concentration (Cmin) of Daratumumab(Cohort 1: B-cell ALL: Predose on Day 1 of Cycle 2; Cohort 2: T-cell ALL (1-17 years): Predose on Day 22 of Cycle 2; Cohort 2: T-cell ALL (18-30 years): Predose on Day 1 of Cycle 2; Cohort 2: T-cell LL (1-30 years): Predose on Day 22 of Cycle 2)
- Minimal Residual Disease (MRD) Negative Rate(Up to 4 years 4 months)
- Maximum Observed Serum Concentration (Cmax) of Daratumumab(Cohort 1: B-cell ALL: End of infusion (EOI) on Day 1 of Cycle 2; Cohort 2: T-cell ALL (1-17 years): EOI on Day 22 of Cycle 2; Cohort 2: T-cell ALL (18-30 years): EOI on Day 1 of Cycle 2; Cohort 2: T-cell LL (1-30 years): EOI on Day 22 of Cycle 2)
- Percentage of Participants Who Received an Allogeneic Hematopoietic Stem Cell Transplant (HSCT)(Up to 4 years 4 months)