T-cell Type Acute Leukemia-Precursor, T-lymphoblastic Lymphoma/Leukaemia
Conditions
Brief summary
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
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.
Interventions
Pharmaceutical form:solution Route of administration: intravenous
DRUGdexamethasone
Pharmaceutical form:pills Route of administration: oral
DRUGacetaminophen
Pharmaceutical form:pills Route of administration: oral
DRUGranitidine
Pharmaceutical form:solution Route of administration: intravenous
DRUGdiphenhydramine
Pharmaceutical form:solution Route of administration: intravenous
Sponsors
Sanofi
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
16 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Objective Response | Baseline until disease progression or death (maximum duration: 12.1 weeks) | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Duration of Response (DOR) | Baseline until disease progression or death (maximum duration: 12.1 weeks) | 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. |
| Progression Free Survival (PFS) | Baseline until disease progression or death (maximum duration: 12.1 weeks) | 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. |
| Overall Survival (OS) | Baseline until death (maximum duration: 12.1 weeks) | 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. |
| Number of Participants With Minimal Residual Disease (MRD) | Baseline until death or study cut-off (maximum duration: 12.1 weeks) | 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. |
Countries
Finland, France, Hungary, Italy, Lithuania, Russia, United States
Participant flow
Recruitment details
The study was conducted in 6 countries. A total of 16 participants were screened of those 2 participants failed screening: 1 participant for evidence of ongoing infection and 1 participant for not meeting the criterion for relapsed or refractory T-acute lymphoblastic leukemia (ALL)/T-lymphoblastic lymphoma (LBL).
Pre-assignment details
The first participant was enrolled on 14 March 2017. A total of 14 participants were enrolled to receive isatuximab. The study was early terminated on 08 Nov 2017 due to an unsatisfactory benefit/risk ratio.
Participants by arm
| Arm | Count |
|---|---|
| Isatuximab Participants received intravenous administration of isatuximab at a dose of 20 mg/kg at Day 1, 8, 15 and 22 of each Cycle (up to 2 treatment cycles, each cycle 28 days). | 14 |
| Total | 14 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 2 |
| Overall Study | Progressive disease | 12 |
Baseline characteristics
| Characteristic | Isatuximab |
|---|---|
| Age, Continuous | 41.36 years STANDARD_DEVIATION 19.3 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 8 Participants |
| Race (NIH/OMB) White | 6 Participants |
| Sex: Female, Male Female | 2 Participants |
| Sex: Female, Male Male | 12 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 6 / 14 |
| other Total, other adverse events | 12 / 14 |
| serious Total, serious adverse events | 10 / 14 |
Outcome results
Primary
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.
Time frame: Baseline until disease progression or death (maximum duration: 12.1 weeks)
Population: Safety analysis set included all participants who received at least 1 dose of isatuximab.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Isatuximab | Percentage of Participants With Objective Response | 0 percentage of participants |
Secondary
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.
Time frame: Baseline until disease progression or death (maximum duration: 12.1 weeks)
Population: The outcome measure was not analyzed due to lack of objective response. There was no specific additional data collected for the analysis of DOR as this outcome measure was to be derived using time point responses and death information that were collected and analyzed as part of primary and safety outcome measures, respectively.
Secondary
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.
Time frame: Baseline until death or study cut-off (maximum duration: 12.1 weeks)
Population: Data for this outcome measure was not collected and analyzed because no participant achieved CR or CRi.
Secondary
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.
Time frame: Baseline until death (maximum duration: 12.1 weeks)
Population: This outcome measure was not analyzed because overall survival data were not collected.
Secondary
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.
Time frame: Baseline until disease progression or death (maximum duration: 12.1 weeks)
Population: This outcome measure was not analyzed because disease progression data were not collected.