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Safety and Efficacy of Isatuximab in Lymphoblastic Leukemia (ISLAY)

Primary Purpose

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

Status
Terminated
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
Isatuximab SAR650984
dexamethasone
dexamethasone
acetaminophen
ranitidine
diphenhydramine
Sponsored by
Sanofi
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for T-cell Type Acute Leukemia-Precursor

Eligibility Criteria

16 Years - undefined (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Investigational Site Number 8400002
  • Investigational Site Number 8400003
  • Investigational Site Number 8400001
  • Investigational Site Number 2460001
  • Investigational Site Number 2500005
  • Investigational Site Number 2500001
  • Investigational Site Number 2500004
  • Investigational Site Number 2500002
  • Investigational Site Number 3480001
  • Investigational Site Number 3480003
  • Investigational Site Number 3480002
  • Investigational Site Number 3800001
  • Investigational Site Number 3800004
  • Investigational Site Number 4400001
  • Investigational Site Number 6430003
  • Investigational Site Number 6430004
  • Investigational Site Number 6430001

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Isatuximab

Arm Description

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).

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.
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.
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.
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.

Full Information

First Posted
December 19, 2016
Last Updated
March 10, 2022
Sponsor
Sanofi
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1. Study Identification

Unique Protocol Identification Number
NCT02999633
Brief Title
Safety and Efficacy of Isatuximab in Lymphoblastic Leukemia
Acronym
ISLAY
Official Title
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)
Study Type
Interventional

2. Study Status

Record Verification Date
March 2022
Overall Recruitment Status
Terminated
Why Stopped
Due to an unsatisfactory benefit/risk ratio, as specified in & 14.8.1 of the protocol, Sanofi decided to stop enrollment and terminate ACT14596 prematurely
Study Start Date
March 8, 2017 (Actual)
Primary Completion Date
November 14, 2017 (Actual)
Study Completion Date
November 14, 2017 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Sanofi

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
T-cell Type Acute Leukemia-Precursor, T-lymphoblastic Lymphoma/Leukaemia

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
14 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Isatuximab
Arm Type
Experimental
Arm Description
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).
Intervention Type
Drug
Intervention Name(s)
Isatuximab SAR650984
Intervention Description
Pharmaceutical form:solution Route of administration: intravenous
Intervention Type
Drug
Intervention Name(s)
dexamethasone
Intervention Description
Pharmaceutical form:pills Route of administration: oral
Intervention Type
Drug
Intervention Name(s)
dexamethasone
Intervention Description
Pharmaceutical form:solution Route of administration: intravenous
Intervention Type
Drug
Intervention Name(s)
acetaminophen
Intervention Description
Pharmaceutical form:pills Route of administration: oral
Intervention Type
Drug
Intervention Name(s)
ranitidine
Intervention Description
Pharmaceutical form:solution Route of administration: intravenous
Intervention Type
Drug
Intervention Name(s)
diphenhydramine
Intervention Description
Pharmaceutical form:solution Route of administration: intravenous
Primary Outcome Measure Information:
Title
Percentage of Participants With Objective Response
Description
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)
Secondary Outcome Measure Information:
Title
Duration of Response (DOR)
Description
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)
Title
Progression Free Survival (PFS)
Description
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)
Title
Overall Survival (OS)
Description
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)
Title
Number of Participants With Minimal Residual Disease (MRD)
Description
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)

10. Eligibility

Sex
All
Minimum Age & Unit of Time
16 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Clinical Sciences & Operations
Organizational Affiliation
Sanofi
Official's Role
Study Director
Facility Information:
Facility Name
Investigational Site Number 8400002
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30342
Country
United States
Facility Name
Investigational Site Number 8400003
City
Hackensack
State/Province
New Jersey
ZIP/Postal Code
07601
Country
United States
Facility Name
Investigational Site Number 8400001
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Facility Name
Investigational Site Number 2460001
City
Helsinki
ZIP/Postal Code
00029
Country
Finland
Facility Name
Investigational Site Number 2500005
City
Nantes Cedex 01
ZIP/Postal Code
44093
Country
France
Facility Name
Investigational Site Number 2500001
City
Paris Cedex 10
ZIP/Postal Code
75475
Country
France
Facility Name
Investigational Site Number 2500004
City
Pessac
ZIP/Postal Code
33600
Country
France
Facility Name
Investigational Site Number 2500002
City
Pierre Benite
ZIP/Postal Code
69310
Country
France
Facility Name
Investigational Site Number 3480001
City
Budapest
ZIP/Postal Code
1083
Country
Hungary
Facility Name
Investigational Site Number 3480003
City
Budapest
ZIP/Postal Code
1097
Country
Hungary
Facility Name
Investigational Site Number 3480002
City
Debrecen
ZIP/Postal Code
4032
Country
Hungary
Facility Name
Investigational Site Number 3800001
City
Bergamo
ZIP/Postal Code
24127
Country
Italy
Facility Name
Investigational Site Number 3800004
City
Brescia
ZIP/Postal Code
25123
Country
Italy
Facility Name
Investigational Site Number 4400001
City
Vilnius
ZIP/Postal Code
08661
Country
Lithuania
Facility Name
Investigational Site Number 6430003
City
Moscow
ZIP/Postal Code
117198
Country
Russian Federation
Facility Name
Investigational Site Number 6430004
City
Moscow
ZIP/Postal Code
125167
Country
Russian Federation
Facility Name
Investigational Site Number 6430001
City
Moscow
ZIP/Postal Code
129301
Country
Russian Federation

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing Plan Description
Qualified researchers may request access to patient level data and related study documents including the clinical study report, study protocol with any amendments, blank case report form, statistical analysis plan, and dataset specifications. Patient level data will be anonymized and study documents will be redacted to protect the privacy of trial participants. Further details on Sanofi's data sharing criteria, eligible studies, and process for requesting access can be found at: https://vivli.org
Citations:
PubMed Identifier
34376579
Citation
Wang A, Song Z, Zheng G, Nicolazzi C, Fromm JR, Shehu E, Srinivasan S, Chen X, Zhu C, Blondel MC, Adrian FJ. Evaluation of Preclinical Activity of Isatuximab in Patients with Acute Lymphoblastic Leukemia. Mol Cancer Ther. 2021 Oct;20(10):1916-1925. doi: 10.1158/1535-7163.MCT-21-0058. Epub 2021 Aug 10.
Results Reference
derived

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Safety and Efficacy of Isatuximab in Lymphoblastic Leukemia

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