First in Human Testing of Dose-escalation of SAR440234 in Patients With Acute Myeloid Leukemia, Acute Lymphoid Leukemia and Myelodysplastic Syndrome

May 3, 2022 updated by: Sanofi

An Open-label, First-in-human, Dose Escalation Study of SAR440234 Administered as Single Agent by Intravenous Infusion in Patients With Relapsed or Refractory Acute Myeloid Leukemia (R/R AML), B-cell Acute Lymphoblastic Leukemia (B-ALL), or High Risk Myelodysplasia (HR-MDS)

Primary Objective:

  • Dose escalation: To determine the maximum tolerated dose (MTD) of SAR440234 administered as a single agent in participants with relapsed or refractory acute myeloid leukemia (R/R AML), high risk myelodysplastic syndrome (HR-MDS), or B-cell acute lymphoblastic leukemia (B-ALL), and determine the recommended phase 2 dose (RP2D) for the subsequent Expansion part.
  • Expansion part: To assess the activity of single agent SAR440234 at the RP2D in participants with R/R AML or HR-MDS.

Secondary Objective:

  • To characterize the safety profile including cumulative adverse drug reactions.
  • To evaluate the potential immunogenicity of SAR440234.
  • To assess any preliminary evidence of hematologic response in the Dose Escalation Part.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Terminated

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

The duration of the study for the participants included a period for screening of up to 14 days. The cycle duration was 42 days. Participants continued study treatment as long as clinical benefit was possible or until disease progression, unacceptable adverse reaction, participant's decision to stop treatment, or other reason of discontinuation. After study treatment discontinuation participants returned to the study site 30 days after the last administration of SAR440234 for end of treatment assessments. Participants without documented disease progression at the end of a treatment visit who had not yet started treatment with another anti-cancer therapy would proceed with monthly follow-up visits until initiation of another anti-cancer therapy, disease progression, or study cut-off date, whichever came first.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
7

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • France
      • Marseille, France, 13273
        • Investigational Site Number 2500004
      • Paris Cedex 10, France, 75010
        • Investigational Site Number 2500001
      • Villejuif Cedex, France, 94805
        • Investigational Site Number 2500003
  • United States
    • Texas
      • Houston, Texas, United States, 77030
        • Investigational Site Number 8400001

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

16 years and older (Child, Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion criteria:

  • Confirmed diagnosis of Acute Myeloblastic leukemia (AML) (except acute promyelocytic leukemia), or myelodysplastic syndrome (MDS) with a risk category of intermediate or higher. Participants must had exhausted available treatment options and might not be eligible for any treatment known to provide clinical benefit.
  • Participants with AML must had relapsed or refractory disease that had been resistant to available therapies.
  • Participants with B-ALL (B acute lymphoid leukemia) in second or subsequent relapse: should had completed previously greater than or equal to (>=) 1 cycle of a salvage regimen. Participants must had exhausted available treatment options and must not be eligible for any treatment known to provide clinical benefit.
  • Participants with HR-MDS (high risk myelodysplastic syndrome) must have greater than (>) 10 percentage blasts in the bone marrow at the time of enrollment and fit one of the following categories: Not eligible for induction therapy and having completed >=2 cycles of therapy or not eligible for allogeneic stem cell transplant and had completed >=1 course of induction therapy.
  • Signed written informed consent.

Exclusion criteria:

  • Aged less than 16 years old.
  • Eastern Cooperative Oncology Group (ECOG) performance status >2.
  • Participants with inadequate biological tests.
  • White blood cell count > 30,000 per cubic millimeter.
  • History of active or chronic autoimmune conditions that had required or requires therapy.
  • Graft-versus-host disease following allogeneic stem cell transplantation required treatment with more than 10 milligrams (mg) of oral prednisone or equivalent daily. The stem cell transplant and/or donor lymphocyte infusion should had been performed more than 3 months before study treatment start.
  • Second primary malignancy that required active therapy. Adjuvant hormonal therapy was allowed.
  • Previous treatment with radiotherapy or immunotherapeutic agents in the 4 weeks prior to investigational medicinal product (IMP) administration.
  • Previous treatment with any other investigational agent in the 4 weeks prior to IMP administration.
  • Receiving, at the time of first IMP administration, of concurrent steroids >10 mg per day of oral prednisone or the equivalent for >=3 months.
  • Requirement for tocilizumab for any other diagnosis.
  • Evidence of active central nervous system leukemia at the time of enrollment.
  • Acquired immunodeficiency syndrome (AIDS-related illnesses) or human immunodeficiency virus disease requiring antiretroviral treatment or had active Hepatitis B viral infection or Hepatitis C viral infection.
  • Women of childbearing potential, male with a partner of childbearing potential who did not agree to use effective methods of birth control.
  • Any clinically significant, uncontrolled medical conditions that, in the Investigator's opinion, would expose excessive risk to the participant or may interfere with compliance or interpretation of the study results.

The above information was not intended to contain all considerations relevant to a participant's potential participation in a clinical trial.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: SAR440234
SAR440234 was administered as intravenous infusion once weekly for 6 weeks per Cycle. Per plan, participants were to receive first 2 to 3 doses as Lead-in doses followed by a fixed dose until the end of treatment or unless the dose needs to be decreased for safety reasons. Due to early study termination, all participants received only 1 treatment cycle at a dose of 1 nanogram per kilogram (ng/kg) once weekly.
Drug: SAR440234
Pharmaceutical form:lyophilisate to be resuspended in solution Route of administration: intravenous

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Dose Escalation Part: Number of Participants With Dose Limiting Toxicities (DLTs)
Time Frame: Cycle 1 (42 days)
DLTs: occurrence of any of following related to investigational medicinal product (IMP): Any grade (G) greater than or equal to (>=) 3 nonhematological adverse events (AE); G4 hematological toxicities (bone marrow hypocellularity, decreased neutrophils, febrile neutropenia, decreased platelet count and anemia) as defined in national cancer institute common terminology criteria for adverse events (NCI-CTCAE, v4.03); G3 or G4 cytokine release syndrome (CRS) (G1: fever, nausea, fatigue, headache, myalgias and malaise; G2: oxygen requirement less than [<] 40 percent (%); G3: oxygen requirement greater than [>] 40% ; G4: life-threatening symptoms, requirement for mechanical ventilation, organ toxicity, G5: death) graded by NCI Consensus Guidelines; Grade 2 CRS for >48 hours or <48 hours before IMP; any treatment-emergent AE of potential significance and IMP-related adverse reaction lasted >2 weeks with failure to recover to baseline or improve to Grade less than or equal to (<=1).
Cycle 1 (42 days)
Dose Escalation Part: Number of Participants With Allergic Reactions/Hypersensitivity and Cytokine Release Syndrome/Acute Infusion Reactions
Time Frame: First IMP administration (Day 1) up to last dose of IMP + 30 days (i.e., up to 72 days)
In this outcome measure, number of participants with allergic reactions or hypersensitivity and CRS or acute infusion reactions is reported. CRS is a nonantigen specific toxicity that occurs as result of potent immune activation mediated by large, rapid release of cytokines into blood from immune cells affected by IMP. Grading and management of CRS was based on National Cancer Institute (NCI) Consensus Guidelines 2014. Allergic/Hypersensitivity reactions or acute infusion reactions are defined as disorder characterized by adverse local/general response from exposure to allergen; graded by NCI CTCAE v4.03.
First IMP administration (Day 1) up to last dose of IMP + 30 days (i.e., up to 72 days)
Expansion Part: Percentage of Participants With Overall Response (OR) Per International Working Group (IWG) Criteria
Time Frame: From the date of first IMP administration until disease progression or death, whichever came earlier (up to 42 days)
Response: assessed by IWG 2003 recommendations for acute myeloid leukemia (AML) and revised 2000 criteria for myelodysplastic syndrome (MDS). MDS - OR: complete remission (CR)/marrow CR/partial remission (PR), CR: repeat bone marrow show <5% myeloblasts and peripheral blood evaluations lasting >=2 months hemoglobin (>11 grams per deciliter), neutrophils 1500 per cubic millimeter (mm^3), platelets >=100000/mm^3, blasts 0% and no dysplasia, PR: all CR criteria except blasts decreased by >=50% over pretreatment or less advanced than pretreatment. AML - OR:CR/CR with incomplete hematological recovery(CRi)/PR, CR:absolute neutrophil count (ANC) >=1000 per microliter (mcL), platelets >=100000/mcL, <5% blast cells in bone marrow; auer rods should not be detectable; no platelet/whole blood transfusions for 7 days prior hematology test. CRi:all criteria of CR except platelets and/or ANC. PR:all CR criteria except blasts decreased by >=50% over pretreatment or less advanced than pretreatment.
From the date of first IMP administration until disease progression or death, whichever came earlier (up to 42 days)
Expansion Part: Duration of Response (DOR)
Time Frame: From 1st documentation of response to date of first documentation of disease progression or death, whichever came earlier (up to 42 days)
DOR: time from first tumor assessment at which the overall response was recorded as CR, marrow CR, or PR (MDS) and CR/CRi (AML) until documented progressive disease (PD) determined by IWG criteria, or death from any cause, whichever occurred first. Per IWG criteria, relapse was defined as reappearance of blasts in blood or bone marrow (>5%) or in any extramedullary site after a CR. CR:<= 5% myeloblasts in bone marrow with no evidence of persistent dysplasia; peripheral blood showing hemoglobin>=11g/dL. Marrow CR: no circulating blasts, <5% blast, absolute neutrophil count >1000/mcL, platelets >100000/mcL, no recurrence for 4 weeks. CRi: meet all criteria for CR except platelet count and/or ANC. PR: all CR criteria except blasts decreased by >=50% over pretreatment or less advanced than pretreatment. Progression: at least 50% decrease from maximum remission/response in granulocytes/platelets; reduction in Hgb by >=2 g/dL; transfusion dependence.
From 1st documentation of response to date of first documentation of disease progression or death, whichever came earlier (up to 42 days)
Expansion Part: Number of Participants With Disease-free Survival
Time Frame: First IMP administration to date of first documentation of disease progression or relapse or death, whichever came earlier (up to 42 days)
Disease-free survival was defined as the time from date of first administration of study intervention until the earliest of any of the following: date of death or date of first response assessment confirming relapse or date of final response assessment which fails to confirm response whichever occurred first.
First IMP administration to date of first documentation of disease progression or relapse or death, whichever came earlier (up to 42 days)

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Dose Escalation Part: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs)
Time Frame: From Baseline (Day 1) up to last dose of IMP + 30 days (i.e., up to 72 days)
An AE was defined as any untoward medical occurrence in a participant who received study drug and did not necessarily had to have a causal relationship with the treatment. Serious AEs (SAEs) were any untoward medical occurrence that resulted in any of the following outcomes: death, life-threatening, required initial or prolonged in-patient hospitalization, persistent or significant disability/incapacity, congenital anomaly/birth defect, or considered as medically important event. TEAEs were defined as the AEs that developed or worsened or became serious during the TEAE period (defined as the time from the first dose of the IMP to the last dose of IMP + 30 days).
From Baseline (Day 1) up to last dose of IMP + 30 days (i.e., up to 72 days)
Dose Escalation Part: Percentage of Participants With Objective Response Per IWG Criteria
Time Frame: From the date of first IMP administration until disease progression or death, whichever came earlier (up to 42 days)
Objective response was defined as the percentage of participants who had a marrow CR, or PR (MDS) and CR/CRi (AML) per IWG criteria. For MDS, CR: repeat bone marrow show <5% myeloblasts and peripheral blood evaluations lasting >=2 months of hemoglobin (>11 g/dL), neutrophils 1500/mm^3, platelets >=100000/mm^3, blasts 0% and no dysplasia, PR: all CR criteria except blasts decreased by >=50% over pretreatment or less advanced than pretreatment. For AML, CR: ANC >=1000/mcL, platelet count >=100000/mcL, bone marrow should contain <5% blast cells; auer rods should not be detectable; no platelet/whole blood transfusions for 7 days prior to date of hematology assessment. CRi: morphologic complete remission but ANC count might be <1000/mcL or platelet <100000/mcL.
From the date of first IMP administration until disease progression or death, whichever came earlier (up to 42 days)
Immunogenicity: Number of Participants With Treatment-Emergent Anti-drug Antibodies (ADA) Response
Time Frame: From Baseline (Day 1) up to last dose of IMP + 30 days (i.e., up to 72 days)
ADA response categories: 1) Treatment-induced ADA: Participants without pre-existing ADA and without pre-treatment samples and who developed ADAs during the TEAE period. 2) Treatment-boosted ADA: Participant with pre-existing ADAs that was increased at least a 4-fold in titer compared to Baseline during the TEAE period. 2) Treatment-emergent ADA: Participants with at least one treatment-induced/boosted ADA sample. TEAE period was defined as the time from the first dose of the IMP to the last dose of the IMP + 30 days.
From Baseline (Day 1) up to last dose of IMP + 30 days (i.e., up to 72 days)
Pharmacokinetics (PK): Maximum Observed Plasma Concentration (Cmax) of SAR440234
Time Frame: Cycle 1: D 1: SOI, EOI, 1, 2, 5, 7, 24, 48, 72 H post EOI; D 8: SOI, MOI, EOI, 2, 5, 168 H post EOI; D 15: MOI, EOI, 2, 5, 24 H post EOI; D 22: SOI, MOI, EOI, 2, 5, 24, 48, 72, 96, 168 H post EOI; D 29: EOI, 2 H post EOI; D 36: SOI, EOI, 2 H post EOI
Cmax was the maximum observed plasma concentration. Cmax was obtained by a non-compartmental analysis. Here in the time frame, Day = D, start of infusion = SOI, mid of infusion = MOI, end of infusion = EOI and hours = H.
Cycle 1: D 1: SOI, EOI, 1, 2, 5, 7, 24, 48, 72 H post EOI; D 8: SOI, MOI, EOI, 2, 5, 168 H post EOI; D 15: MOI, EOI, 2, 5, 24 H post EOI; D 22: SOI, MOI, EOI, 2, 5, 24, 48, 72, 96, 168 H post EOI; D 29: EOI, 2 H post EOI; D 36: SOI, EOI, 2 H post EOI

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Sanofi

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
October 24, 2018

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
February 6, 2021

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
February 6, 2021

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
July 2, 2018

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
July 19, 2018

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
July 20, 2018

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
May 24, 2022

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
May 3, 2022

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
May 1, 2022

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • TED15138
  • 2017-004148-39 (EudraCT Number)
  • U1111-1197-8041 (Other Identifier: UTN)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

Yes

IPD 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

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

Yes

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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