T-cell Type Acute Leukemia-PrecursorPhase 2ISLAYNCT02999633
Safety and Efficacy of Isatuximab in Lymphoblastic Leukemia
A Phase 2 study testing Isatuximab SAR650984, dexamethasone and acetaminophen in people with T-cell Type Acute Leukemia-Precursor and T-lymphoblastic Lymphoma/Leukaemia, run by Sanofi at 17 sites in 7 countries.
Trial 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). Read more about this study
- Who is it for?
- Ages 16 years and older
- Conditions the study is for
- T-cell Type Acute Leukemia-Precursor, T-lymphoblastic Lymphoma/Leukaemia
- What is being tested?
- Isatuximab SAR650984, dexamethasone and acetaminophen
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 14 participants
- Where
- 17 sitesin 7 countries
- Study dates
- 8 Mar 2017to 14 Nov 2017
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 16 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
Trial locations and contacts
17 sites in 7 countries.
17 sites in 7 countries
France4 sites
Investigational Site Number 2500005
Nantes, 44093
Investigational Site Number 2500001
Paris, 75475
Investigational Site Number 2500004
Pessac, 33600
Investigational Site Number 2500002
Pierre-Bénite, 69310
United States3 sites
Investigational Site Number 8400002
Atlanta, Georgia, 30342
Investigational Site Number 8400003
Hackensack, New Jersey, 07601
Investigational Site Number 8400001
Houston, Texas, 77030
Hungary3 sites
Investigational Site Number 3480001
Budapest, 1083
Investigational Site Number 3480003
Budapest, 1097
Investigational Site Number 3480002
Debrecen, 4032
Russia3 sites
Investigational Site Number 6430003
Moscow, 117198
Investigational Site Number 6430004
Moscow, 125167
Investigational Site Number 6430001
Moscow, 129301
Italy2 sites
Investigational Site Number 3800001
Bergamo, 24127
Investigational Site Number 3800004
Brescia, 25123
About this study
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)
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.
Read the 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.
- Being tested
- Isatuximab SAR650984, dexamethasone, acetaminophen, ranitidine, diphenhydramine
- Medical subject headings
- Precursor T-Cell Lymphoblastic Leukemia-Lymphoma, Leukemia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Isatuximab SAR650984Drug
Pharmaceutical form:solution Route of administration: intravenous
dexamethasoneDrug
Pharmaceutical form:pills Route of administration: oral
dexamethasoneDrug
Pharmaceutical form:solution Route of administration: intravenous
acetaminophenDrug
Pharmaceutical form:pills Route of administration: oral
ranitidineDrug
Pharmaceutical form:solution Route of administration: intravenous
diphenhydramineDrug
Pharmaceutical form:solution Route of administration: intravenous
| Study group | Role | What they receive |
|---|---|---|
| Isatuximab | Experimental | 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). Receives: Drug: Isatuximab SAR650984; Drug: dexamethasone; Drug: acetaminophen; Drug: ranitidine; Drug: diphenhydramine |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Baseline until disease progression or death (maximum duration: 12.1 weeks)
Secondary outcomes (4)
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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: Baseline until death or study cut-off (maximum duration: 12.1 weeks)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Dec 2016 (estimated)
- Study start8 Mar 2017
- Primary completion14 Nov 2017
- Study completion14 Nov 2017
Why it 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
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for T-cell Type Acute Leukemia-PrecursorStudies of the same condition, open and under way.
- More trials run by SanofiThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 14 participants (actual)
Sponsor and investigators
- Lead sponsor
- Sanofi
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Clinical Sciences & Operations, Study director, Sanofi
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02999633
- Sponsor's protocol ID
- ACT14596
- Other IDs
- 2016-002739-14, U1111-1179-5294, 2016
- Acronym
- ISLAY
- Status last verified
- Mar 2022
- First submitted
- 19 Dec 2016
- Last updated
- 21 Mar 2022
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: 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
Publications
Brillac C, Semiond D, Oprea C, Baruchel A, Zwaan CM, Nguyen L. Selection of isatuximab dosing regimen in pediatric patients with leukemia using population pharmacokinetics. Cancer Chemother Pharmacol. 2025 Dec 3;95(1):116. doi: 10.1007/s00280-025-04832-2.
PubMed 41331127Wang 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.
PubMed 34376579
Study at a glance
From the registry record, last updated by the sponsor on 21 Mar 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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)
- ClinicalTrials.gov ID
- NCT02999633
- Acronym / sponsor ID
- ISLAY / ACT14596
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason 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
- Enrolment
- 14 participants (actual)
- Lead sponsor
- SanofiIndustry (pharma, biotech, devices)
- Study start
- 8 Mar 2017 (actual)
- Primary completion
- 14 Nov 2017 (actual)
- Study completion
- 14 Nov 2017 (actual)
- First posted
- 21 Dec 2016 (estimated)
- Results
- Posted 18 Jan 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Isatuximab | Experimental | Drug: Isatuximab SAR650984, Drug: dexamethasone, Drug: acetaminophen, Drug: ranitidine, Drug: diphenhydramineParticipants 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). |
Who may qualify
- Ages
- 16 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (4 listed)
- 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.
Key exclusion criteria (5 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Isatuximab SAR650984Pharmaceutical form:solution Route of administration: intravenous | Drug | Isatuximab |
| dexamethasonePharmaceutical form:pills Route of administration: oral | Drug | Isatuximab |
| dexamethasonePharmaceutical form:solution Route of administration: intravenous | Drug | Isatuximab |
| acetaminophenPharmaceutical form:pills Route of administration: oral | Drug | Isatuximab |
| ranitidinePharmaceutical form:solution Route of administration: intravenous | Drug | Isatuximab |
| diphenhydraminePharmaceutical form:solution Route of administration: intravenous | Drug | Isatuximab |
Primary outcome
Percentage of Participants With Objective Response
Time frame: 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.
4 secondary outcomes
Duration of Response (DOR)
Time frame: Baseline until disease progression or death (maximum duration: 12.1 weeks)
Progression Free Survival (PFS)
Time frame: Baseline until disease progression or death (maximum duration: 12.1 weeks)
Overall Survival (OS)
Time frame: Baseline until death (maximum duration: 12.1 weeks)
Number of Participants With Minimal Residual Disease (MRD)
Time frame: Baseline until death or study cut-off (maximum duration: 12.1 weeks)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Mar 2022.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 41331127Brillac C, Semiond D, Oprea C, Baruchel A, Zwaan CM, Nguyen L. Selection of isatuximab dosing regimen in pediatric patients with leukemia using population pharmacokinetics. Cancer Chemother Pharmacol. 2025 Dec 3;95(1):116. doi: 10.1007/s00280-025-04832-2.
- Derived from this study: PubMed 34376579Wang 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.
- Individual participant dataSharing planned: Yes. 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
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Clinical Sciences & Operations study director
Sanofi
17 sites in 7 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Isatuximab SAR650984, dexamethasone and acetaminophen in people with T-cell Type Acute Leukemia-Precursor and T-lymphoblastic Lymphoma/Leukaemia, run by Sanofi at 17 sites in 7 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 21 Mar 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 17 sites in France, United States, Hungary, Russia, Italy and 2 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 18 Jan 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Percentage of Participants With Objective Response (time frame: Baseline until disease progression or death (maximum duration: 12.1 weeks)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02999633, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Mar 2022.