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

NCT ID: NCT03594955

Last Updated: 2022-05-24

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 7 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-10-24
• Study Completion Date: 2021-02-06

Brief Summary

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.

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.

Conditions

Leukaemia

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

SAR440234

Intervention Type: DRUG

Pharmaceutical form:lyophilisate to be resuspended in solution Route of administration: intravenous

Interventions

SAR440234

Pharmaceutical form:lyophilisate to be resuspended in solution Route of administration: intravenous

Intervention Type: DRUG

Eligibility Criteria

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.

• Minimum Eligible Age: 16 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Sanofi

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Clinical Sciences & Operations

Role: STUDY_DIRECTOR

Sanofi

Locations

Investigational Site Number 8400001

Houston, Texas, United States

Investigational Site Number 2500004

Marseille, , France

Investigational Site Number 2500001

Paris, , France

Investigational Site Number 2500003

Villejuif, , France

Countries

United States; France

References

Gerard E, Zohar S, Thai HT, Lorenzato C, Riviere MK, Ursino M. Bayesian dose regimen assessment in early phase oncology incorporating pharmacokinetics and pharmacodynamics. Biometrics. 2022 Mar;78(1):300-312. doi: 10.1111/biom.13433. Epub 2021 Feb 18.

Reference Type: DERIVED

PMID: 33527351 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

2017-004148-39

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

U1111-1197-8041

Identifier Type: OTHER

Identifier Source: secondary_id

TED15138

Identifier Type: -

Identifier Source: org_study_id