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

NCT03594955

Description:

Primary Objective: - Dose escalation: To determine the maximum tolerated dose (MTD) of SAR440234 administered as a single agent in patients with R/R AML (relapsed or refractory acute myeloid leukemia), HR-MDS (high risk myelodysplastic syndrome), or B-ALL (B-cell acute lymphoblastic leukemia), 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 patients 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.

Related Conditions:
  • Acute Myeloid Leukemia
  • B-Cell Acute Lymphoblastic Leukemia
  • Myelodysplastic Syndromes
Recruiting Status:

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: First in Human Testing of Dose-escalation of SAR440234 in Patients With Acute Myeloid Leukemia, Acute Lymphoid Leukemia and Myelodysplastic Syndrome
  • Official Title: 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)

Clinical Trial IDs

  • ORG STUDY ID: TED15138
  • SECONDARY ID: 2017-004148-39
  • SECONDARY ID: U1111-1197-8041
  • NCT ID: NCT03594955

Conditions

  • Leukaemia

Interventions

DrugSynonymsArms
SAR440234SAR440234

Purpose

Primary Objective: - Dose escalation: To determine the maximum tolerated dose (MTD) of SAR440234 administered as a single agent in patients with R/R AML (relapsed or refractory acute myeloid leukemia), HR-MDS (high risk myelodysplastic syndrome), or B-ALL (B-cell acute lymphoblastic leukemia), 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 patients 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 patients will include a period for screening of up to 14
      days. The cycle duration is 42 days. Patients will continue study treatment as long as
      clinical benefit is possible or until disease progression, unacceptable adverse reaction,
      patient's decision to stop treatment, or other reason of discontinuation. After study
      treatment discontinuation patients will return to the study site 30 days after the last
      administration of SAR440234 for end of treatment assessments. Patients without documented
      disease progression at the end of a treatment visit who have not yet started treatment with
      another anti-cancer therapy will proceed with monthly follow-up visits until initiation of
      another anti-cancer therapy, disease progression, or study cut-off date, whichever comes
      first.
    

Trial Arms

NameTypeDescriptionInterventions
SAR440234ExperimentalSAR440234 as weekly intravenous injection; a cycle is defined as 6 weeks of study treatment; (Additionally infusion on day 4 is planned for dose level ≥ 3). One dose escalation scheme will be used. Treatment may be continued as long as it is clinically beneficial.
  • SAR440234

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. Patients must have exhausted available treatment options and must not be
             eligible for any treatment known to provide clinical benefit.

          -  Patients with AML must have relapsed or refractory disease that has been resistant to
             available therapies.

          -  Patients with B-ALL (B acute lymphoid leukemia) in second or subsequent relapse:
             should have completed previously ≥1 cycle of a salvage regimen. Patients must have
             exhausted available treatment options and must not be eligible for any treatment known
             to provide clinical benefit.

          -  Patients with HR-MDS (high risk myelodysplastic syndrome) must have >10% 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 having completed ≥1 course of
             induction therapy.

          -  Signed written informed consent.

        Exclusion criteria:

          -  Age <16 years old.

          -  Eastern Cooperative Oncology Group (ECOG) performance status >2.

          -  Patients with inadequate biological tests.

          -  White blood cell count > 30,000/mm3

          -  History of active or chronic autoimmune conditions that has required or requires
             therapy.

          -  Graft-versus-host disease following allogeneic stem cell transplantation requiring
             treatment with more than 10 mg of oral prednisone or equivalent daily. The stem cell
             transplant and/or donor lymphocyte infusion should have been performed more than 3
             months before study treatment start.

          -  Second primary malignancy that requires active therapy. Adjuvant hormonal therapy is
             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/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 HIV (human
             immunodeficiency virus) disease requiring antiretroviral treatment or having active
             Hepatitis B viral infection or Hepatitis C viral infection.

          -  Women of childbearing potential, male with a partner of childbearing potential who do
             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 patient or may interfere
             with compliance or interpretation of the study results.

        The above information is not intended to contain all considerations relevant to a patient's
        potential participation in a clinical trial.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:16 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Incidence of Dose-limiting toxicities (DLTs)
Time Frame:Baseline to Day 42
Safety Issue:
Description:Incidence of DLTs observed, using NCI-CTCAE v4.03 or 2014 NCI Consensus Guidelines for cytokine release syndrome, during the first 42 days following the first administration of IMP in the first cycle of treatment.

Secondary Outcome Measures

Measure:Adverse events
Time Frame:Baseline to 30 days after last study treatment administration
Safety Issue:
Description:Number of adverse events.
Measure:Preliminary Anti-leukemia Activity
Time Frame:Baseline to approximately 3 months after the last entered patient
Safety Issue:
Description:Preliminary anti-leukemia activity as defined by IWG for MDS or AML or National Comprehensive Cancer Network (NCCN) for B-ALL. (Dose escalation part).
Measure:Immunogenicity of SAR440234
Time Frame:Baseline to approximately 3 months after the last entered patient
Safety Issue:
Description:Anti-SAR440234 Antibodies (ADA) incidence is defined as the proportion of patients found to either have treatment induced ADA or boosted their pre-existing ADA response during the study.

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Sanofi

Last Updated

February 18, 2020