Safety and Efficacy of Isatuximab in Lymphoblastic Leukemia

Study Overview
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Brief Summary
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Primary Objective: To evaluate the efficacy of isatuximab. Secondary Objectives: To evaluate the safety profile of isatuximab. To evaluate the duration of response (DOR). To evaluate progression free survival (PFS) and overall survival (OS). To evaluate the pharmacokinetics (PK) of isatuximab in participants with T-ALL or T-LBL. To evaluate immunogenicity of isatuximab in participants with T-ALL or T-LBL. To assess minimal residual disease (MRD) and correlate it with clinical outcome.

Detailed Description
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The study duration per participant included a 3-week screening period, an approximately 1 year of treatment period or until disease progression or discontinuation for any other reason, and a follow-up period of at least 30 days after the last investigational medicinal product administration.

Official Title
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Phase 2, Safety and Efficacy Study of Isatuximab, an Anti-CD38 Monoclonal Antibody, Administered by Intravenous (IV) Infusion in Patients With Relapsed or Refractory T-acute Lymphoblastic Leukemia (T-ALL) or T-lymphoblastic Lymphoma (T-LBL)

Conditions
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T-cell Type Acute Leukemia-Precursor, T-lymphoblastic Lymphoma/Leukaemia

Intervention / Treatment
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* Drug: Isatuximab SAR650984
* Drug: dexamethasone
* Drug: dexamethasone
* Drug: acetaminophen
* Drug: ranitidine
* Drug: diphenhydramine


Participation Criteria
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Eligibility Criteria
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Inclusion criteria : Participants must had a known diagnosis of acute lymphoblastic leukemia (ALL) of T cell origin, including T-LBL and T-ALL with extramedullary involvement at relapse confirmed by biopsy. Participants must be previously treated for T-ALL or T-LBL and have relapsed or are refractory to most recent treatment. Participants in first relapse were be eligible regardless of the first remission duration. Participants must had been previously exposed to nelarabine in countries where this drug is available (unless due to a contraindication to its use or administrative issue). No more than 3 prior salvage therapies. Exclusion criteria: Prior treatment with immunotherapy/investigational agents within 3 weeks, chemotherapy within 2 weeks of study treatment. Must have recovered from acute toxicity before first study treatment administration. Prior stem cell transplant within 4 months and/or evidence of active systemic Graft versus Host Disease and/or immunosuppressive therapy for Graft versus Host Disease within 1 week before the first study treatment administration. Clinical evidence of active central nervous system (CNS) leukemia. T-ALL with testicular involvement alone. The above information was not intended to contain all considerations relevant to a participant's potential participation in a clinical trial.

Ages Eligible for Study
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Minimum Age: 16 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Isatuximab<br>Participants received intravenous administration of isatuximab at a dose of 20 milligrams/kilogram (mg/kg) at Day 1, 8, 15 and 22 of each Cycle (up to 2 treatment cycles, each cycle 28 days). | Drug: Isatuximab SAR650984<br>* Pharmaceutical form:solution Route of administration: intravenous<br>Drug: dexamethasone<br>* Pharmaceutical form:pills Route of administration: oral<br>Drug: dexamethasone<br>* Pharmaceutical form:solution Route of administration: intravenous<br>Drug: acetaminophen<br>* Pharmaceutical form:pills Route of administration: oral<br>Drug: ranitidine<br>* Pharmaceutical form:solution Route of administration: intravenous<br>Drug: diphenhydramine<br>* Pharmaceutical form:solution Route of administration: intravenous<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Objective Response | Objective response was defined as percentage of participants with complete response (CR) or with complete response with incomplete peripheral recovery (CRi) as per National Comprehensive Cancer Network (NCCN) guidelines. CR was defined as no circulating blasts or extramedullary disease, no lymphadenopathy, splenomegaly, skin/gum infiltration/testicular mass/central nervous system involvement, trilineage hematopoiesis and less than 5 percentage blasts, absolute neutrophil count (ANC) greater than 1000 per micro liter, platelets less than 100 000 per micro liter, no recurrence for 4 weeks. CRi meet all criteria for complete response except platelet count and/or ANC. | Baseline until disease progression or death (maximum duration: 12.1 weeks) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Duration of Response (DOR) | DOR defined as time (in days) from date of first response until date of first documented progressive disease (PD) or death (from any cause), whichever came first. Progressive disease as per NCCN guidelines was defined as increase of at least 25 percentage (%) in the absolute number of circulating or bone marrow blasts or development of extramedullary disease. | Baseline until disease progression or death (maximum duration: 12.1 weeks) | 
| Progression Free Survival (PFS) | PFS was defined as the time interval (in days) from the date of first study drug administration to the date of first observation of PD or death due to any cause, whichever came first. PD as per NCCN guidelines was defined as increase of at least 25% in the absolute number of circulating or bone marrow blasts or development of extramedullary disease. | Baseline until disease progression or death (maximum duration: 12.1 weeks) | 
| Overall Survival (OS) | Overall Survival was defined as the time interval from the date of first study drug administration to the date of death due to any cause. | Baseline until death (maximum duration: 12.1 weeks) | 
| Number of Participants With Minimal Residual Disease (MRD) | Presence of MRD was measured by sequencing and/or flow cytometry in participants achieving CR and CRi. CR was defined as no circulating blasts or extramedullary disease, no lymphadenopathy, splenomegaly, skin/gum infiltration/testicular mass/central nervous system involvement, trilineage hematopoiesis and less than 5 percentage blasts, ANC greater than 1000 per micro liter, platelets less than 100 000 per micro liter, no recurrence for 4 weeks. Complete response with incomplete blood count recovery meet all criteria for complete response except platelet count and/or ANC. | Baseline until death or study cut-off (maximum duration: 12.1 weeks) |