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Phase I Study of S64315 Administred Intravenously in Patients With Acute Myeloid Leukaemia or Myelodysplastic Syndrome

NCT02979366

Description:

The CL1-64315-001 study is a phase I, international, multicentre, open-label, non-randomised, non-comparative study. This study is designed in two parts: one part for dose escalation, one part for dose expansion.

Related Conditions:
  • Acute Myeloid Leukemia
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Phase I Study of S64315 Administred Intravenously in Patients With Acute Myeloid Leukaemia or Myelodysplastic Syndrome
  • Official Title: Phase I, International, Multicentre, Open-label, Non-randomised, Non-comparative Study of Intravenously Administered S64315, a Mcl-1 Inhibitor, in Patients With Acute Myeloid Leukaemia (AML) or Myelodysplastic Syndrome (MDS)

Clinical Trial IDs

  • ORG STUDY ID: CL1-64315-001
  • SECONDARY ID: 2016-003768-38
  • NCT ID: NCT02979366

Conditions

  • Acute Myeloid Leukaemia (AML)
  • Myelodysplastic Syndrome (MDS)

Interventions

DrugSynonymsArms
S64315MIK665S64315 (also referred as MIK665)

Purpose

The CL1-64315-001 study is a phase I, international, multicentre, open-label, non-randomised, non-comparative study. This study is designed in two parts: one part for dose escalation, one part for dose expansion.

Trial Arms

NameTypeDescriptionInterventions
S64315 (also referred as MIK665)Experimental
  • S64315

Eligibility Criteria

        Inclusion Criteria:

          -  Male or female aged ≥ 18 years;

          -  Patients with cytologically confirmed and documented de novo, secondary or
             therapy-related AML, excluding acute promyelocytic leukaemia (APL, French-American
             British M3 classification):

               -  with relapsed or refractory disease without established alternative therapy or

               -  secondary to MDS treated at least by hypomethylating agent or

               -  > 65 years not previously treated for AML and who are not candidates for
                  intensive chemotherapy nor candidates for established alternative chemotherapy Or
                  Patients with cytologically confirmed and documented MDS), in relapse or
                  refractory after previous treatment line including at least one hypomethylating
                  agent and have ≥10% bone marrow blasts;

          -  Eastern Cooperative Oncology Group (ECOG) performance status 0 to 2

          -  Circulating white blood cells < 25.1000000000 /L (with or without use of
             hydroxycarbamide).

          -  Adequate renal function defined as:

             • Serum creatinine ≤ 1.5 x ULN (upper normal limit) or calculated creatinine clearance
             (determined by MDRD) > 50 mL/min/1.73m2.

          -  LDH < 2 x ULN

          -  Adequate hepatic function defined as:

               -  AST and ALT ≤ 3 x ULN

               -  Total bilirubin level ≤ 1.5 x ULN, except for patients with known Gilbert's
                  syndrome (confirmed by the UGT1A1 polymorphism analysis), who are excluded if
                  total bilirubin>3.0 x ULN or direct bilirubin > 1.5 x ULN

          -  Serum CK/CPK ≤2.5 x ULN.

        Exclusion Criteria:

          -  Unlikely to cooperate in the study.

          -  Participant already enrolled in the study who has received at least one S64315
             infusion.

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

          -  Participation in another interventional study requiring investigational treatment
             intake within 2 weeks or at least 5 half-lives (whichever is longer) prior to first
             dose of S64315 (participation in non-interventional registries or epidemiological
             studies is allowed).

          -  Presence of ≥ CTCAE grade 2 toxicity (except alopecia of any grade) due to prior
             cancer therapy, according to the National Cancer Institute Common Terminology Criteria
             for Adverse Events (NCI-CTCAE, version 4.03)

          -  Known carriers of HIV antibodies

          -  Known history of significant liver disease

          -  Uncontrolled hepatitis B or C infection

          -  Known active or chronic pancreatitis

          -  History of myocardial infarction (MI), angina pectoris, coronary artery bypass graft
             (CABG) within 6 months prior to starting study treatment.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Incidence of DLTs during the first cycle of treatment with single agent S64315
Time Frame:21-day cycle 1
Safety Issue:
Description:

Secondary Outcome Measures

Measure:Concentration at the end of infusion (C inf) in plasma
Time Frame:D1 and D2 of cycle 1 and 2, D15 and D16 of cycle 1 and D1 from cycle 3 to cycle 6.
Safety Issue:
Description:
Measure:Cumulative amount of a compound excreted in the urine (Ae)
Time Frame:only D1 of cycle 1
Safety Issue:
Description:
Measure:Preliminary efficacy assessment according to Cheson criteria (adapted for each disease)
Time Frame:From first dose until 30 days after the last dose administration
Safety Issue:
Description:
Measure:Time corresponding to end of infusion (tinf/tend) in plasma
Time Frame:D1 and D2 of cycle 1 and 2, D15 and D16 of cycle 1 and D1 from cycle 3 to cycle 6.
Safety Issue:
Description:
Measure:Area under the concentration-time curve from zero (time of drug administration) to tlast (AUC last) in plasma
Time Frame:D1 and D2 of cycle 1 and 2, D15 and D16 of cycle 1 and D1 from cycle 3 to cycle 6.
Safety Issue:
Description:
Measure:Time corresponding to Clast (tlast) in plasma.
Time Frame:D1 and D2 of cycle 1 and 2, D15 and D16 of cycle 1 and D1 from cycle 3 to cycle 6.
Safety Issue:
Description:
Measure:Last quantifiable observed concentration (Clast) in plasma
Time Frame:D1 and D2 of cycle 1 and 2, D15 and D16 of cycle 1 and D1 from cycle 3 to cycle 6.
Safety Issue:
Description:
Measure:Area Under the Curve (AUC) in plasma
Time Frame:D1 and D2 of cycle 1 and 2, D15 and D16 of cycle 1 and D1 from cycle 3 to cycle 6.
Safety Issue:
Description:
Measure:Terminal elimination half-life (t½,z) in plasma
Time Frame:D1 and D2 of cycle 1 and 2, D15 and D16 of cycle 1 and D1 from cycle 3 to cycle 6.
Safety Issue:
Description:
Measure:total Clearance (CL)
Time Frame:D1 and D2 of cycle 1 and 2, D15 and D16 of cycle 1 and D1 from cycle 3 to cycle 6.
Safety Issue:
Description:
Measure:Volume of distribution at steady-state (Vss) in plasma
Time Frame:D1 and D2 of cycle 1 and 2, D15 and D16 of cycle 1 and D1 from cycle 3 to cycle 6.
Safety Issue:
Description:
Measure:Ae expressed as a percentage of the dose (fe) in urine
Time Frame:only D1 of cycle 1
Safety Issue:
Description:
Measure:Renal clearance (CLR)
Time Frame:only D1 of cycle 1
Safety Issue:
Description:

Details

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

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