Clinical Trials /

Study of a New Intravenous Drug, Called S65487, in Patients With Acute Myeloid Leukemia, Non Hodgkin Lymphoma or Multiple Myeloma

NCT03755154

Description:

The purpose of this first in human study is to assess safety, tolerability, Pharmacokinetic (PK) and preliminary clinical activity and to estimate the Maximum Tolerated Doses (MTD(s))/ Recommended Phase 2 Doses (RP2D(s)) of S65487 as single agent administered intravenously (i.v.) in adult patients with refractory or relapsed Acute Myeloid Leukemia (AML), Non-Hodgkin Lymphoma (NHL) or Multiple Myeloma (MM).

Related Conditions:
  • Acute Myeloid Leukemia
  • Diffuse Large B-Cell Lymphoma
  • Follicular Lymphoma
  • Mantle Cell Lymphoma
  • Marginal Zone Lymphoma
  • Multiple Myeloma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Study of a New Intravenous Drug, Called S65487, in Patients With Acute Myeloid Leukemia, Non Hodgkin Lymphoma or Multiple Myeloma
  • Official Title: Phase I, Open Label, Non-randomised, Non-comparative, Multi-center Study, Evaluating S65487, a Bcl-2 Inhibitor Intravenously Administered, in Patients With Relapse or Refractory Acute Myeloid Leukemia, Non Hodgkin Lymphoma or Multiple Myeloma

Clinical Trial IDs

  • ORG STUDY ID: CL1-65487-002
  • SECONDARY ID: 2018-004170-97
  • NCT ID: NCT03755154

Conditions

  • Relapse or Refractory Acute Myeloid Leukemia
  • Relapse or Refractory Non-Hodgkin Lymphoma
  • Relapse or Refractory Multiple Myeloma

Interventions

DrugSynonymsArms
S65487S65487

Purpose

The purpose of this first in human study is to assess safety, tolerability, Pharmacokinetic (PK) and preliminary clinical activity and to estimate the Maximum Tolerated Doses (MTD(s))/ Recommended Phase 2 Doses (RP2D(s)) of S65487 as single agent administered intravenously (i.v.) in adult patients with refractory or relapsed Acute Myeloid Leukemia (AML), Non-Hodgkin Lymphoma (NHL) or Multiple Myeloma (MM).

Detailed Description

      This study is designed in two parts: one part for dose escalation, one part for dose
      expansion.The dose escalation part will be followed by expansion part at the MTD(s)/RP2D(s)

      This study will utilize an adaptative Bayesian Logistic Regression model to guide dose
      escalation and estimate the MTD(s) based on the Dose Limiting Toxicity (DLT) relationship(s)
      for S65487 in the indications.
    

Trial Arms

NameTypeDescriptionInterventions
S65487Experimental
  • S65487

Eligibility Criteria

        Inclusion Criteria:

          -  Patients with cytologically confirmed and documented de novo, secondary or
             therapy-related AML, excluding acute promyelocytic leukaemia with relapsed or
             refractory disease without established alternative therapy. Or patients with
             measurable confirmed Multiple Myeloma (IMWG) with relapsed or refractory disease who
             have previously received at least three lines of treatment and without established
             alternative therapy. Or patients with histologically and measurable confirmed Non
             Hodgkin Lymphoma defined as Diffuse Large B cell Lymphoma (DLBCL), Follicular Lymphoma
             (FL), Mantle Cell Lymphoma (MCL), Marginal Zone Lymphoma (MZL), High-Grade B cell
             Lymphoma with relapsed or refractory disease who have received at least two lines of
             therapy (including rituximab) and without established alternative therapy.

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

          -  For NHL and MM patients: haematological function (independent of any growth factor
             support) based on the last assessment performed before inclusion, defined as: absolute
             neutrophil count (ANC) ≥ 1 x 109/L, haemoglobin ≥ 8 g/dL, platelet count ≥ 50 x 109/L.

          -  For AML patients: circulating Blood White Cell count (WBC count) < 25 x 109/L (with or
             without use of hydroxycarbamide) based on the last assessment performed before
             inclusion.

          -  Adequate renal function based on the last assessment performed before inclusion,
             assessed as Glomerular Filtration Rate (GFR) using Modification of Diet in Renal
             Disease (MDRD) Formula.

          -  Adequate hepatic function based on the last assessment performed before inclusion.

        Exclusion Criteria:

          -  Pregnancy, breastfeeding or possibility of becoming pregnant during the study.

          -  Participation in another interventional study at the same time or another
             interventional study requiring investigational treatment intake within 3 weeks or at
             least 5 half-lives (whichever is longer) prior to the first S65487 administration.

          -  Participant already enrolled in the study (informed consent signed) and has received
             at least one dose of S65487.

          -  Patients who have not recovered from toxicity of previous anticancer therapy,
             including grade ≥ 2 non-hematologic toxicity, prior to the first IMP administration
             (including peripheral neurotoxicity). Certain toxicities will not be considered in
             this category (e.g. alopecia).

          -  Patients refractory to a previous treatment with a Bcl-2 inhibitor.

          -  For AML patients : Allogenic stem cell transplant within 3 months before the first IMP
             administration and/or patients who still receive immunosuppressive treatment within 3
             months before the first IMP administration and/or patients with active
             Graft-versus-host disease within 3 months before the first IMP administration and/or
             patient who receive donor lymphocyte infusion (DLI) within 3 months before the first
             IMP administration.

          -  For NHL and MM patients Prior allogenic stem cell transplant before the first IMP
             administration and/or Autologous stem cell transplant within 3 months before the first
             IMP administration.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Incidence of Dose Limiting Toxicity (DLT)
Time Frame:until the end of the first cycle (each cycle is 21days)
Safety Issue:
Description:Safety criterion

Secondary Outcome Measures

Measure:The pharmacokinetic (PK) profile of S65487: Area Under the Curve (AUC)
Time Frame:Cycle 1 Day 1, Cycle 1 Day 2, Cycle 1 Day 8, Cycle 1 Day 9 (one cycle is 21 days)
Safety Issue:
Description:
Measure:PK profile of S65487: Volume of distribution at steady-state (Vss)
Time Frame:Cycle 1 Day 1, Cycle 1 Day 2, Cycle 1 Day 8, Cycle 1 Day 9 (one cycle is 21 days)
Safety Issue:
Description:
Measure:PK profile of S65487: total CLearance (CL)
Time Frame:Cycle 1 Day 1, Cycle 1 Day 2, Cycle 1 Day 8, Cycle 1 Day 9 (one cycle is 21 days)
Safety Issue:
Description:
Measure:PK profile of S65487: terminal half-life (t½z)
Time Frame:Cycle 1 Day 1, Cycle 1 Day 2, Cycle 1 Day 8, Cycle 1 Day 9 (one cycle is 21 days)
Safety Issue:
Description:
Measure:Best Overall Response (BOR)
Time Frame:Through study completion, an average of 6 months
Safety Issue:
Description:Best Response observed during the treatment period
Measure:Overall Response Rate (ORR)
Time Frame:Through study completion, an average of 6 months
Safety Issue:
Description:Proportion of patients in whom a complete response (CR) or a partial response (PR)

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Institut de Recherches Internationales Servier

Trial Keywords

  • Leukemia
  • Lymphoma
  • Myeloma
  • Dose-escalation

Last Updated

January 31, 2020