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Phase I Dose Escalation Study of Intravenously Administered S64315 in Combination With Orally Administered Venetoclax in Patients With Acute Myeloid Leukaemia.

NCT03672695

Description:

The purpose of this study is to determine the safety profile, tolerability and the Recommended Phase 2 Dose of the combination S64315 with venetoclax in patients with Acute Myeloid Leukaemia.

Related Conditions:
  • Acute Myeloid Leukemia
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Phase I Dose Escalation Study of Intravenously Administered S64315 in Combination With Orally Administered Venetoclax in Patients With Acute Myeloid Leukaemia.
  • Official Title: An International Phase Ib Multicentre Study to Characterize the Safety and Tolerability of Intravenously Administered S64315, a Selective Mcl-1 Inhibitor, in Combination With Orally Administered Venetoclax, a Selective Bcl-2 Inhibitor in Patients With Acute Myeloid Leukaemia (AML).

Clinical Trial IDs

  • ORG STUDY ID: CL1-64315-002
  • SECONDARY ID: 2018-001809-88
  • NCT ID: NCT03672695

Conditions

  • Acute Myeloid Leukaemia

Purpose

The purpose of this study is to determine the safety profile, tolerability and the Recommended Phase 2 Dose of the combination S64315 with venetoclax in patients with Acute Myeloid Leukaemia.

Trial Arms

NameTypeDescriptionInterventions
S64315 and venetoclax administered in combinationExperimental

    Eligibility Criteria

            Inclusion Criteria:
    
              1. Male or female aged ≥ 18 years;
    
              2. Patients with cytologically confirmed and documented de novo, secondary or
                 therapy-related AML as defined by World Health Organization (WHO) 2016 classification
                 (Arber, 2016), 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 and without
                      established alternative therapy or
    
                   -  ≥ 65 years not previously treated for AML and who are not candidates for
                      intensive chemotherapy nor candidates for established alternative therapy
    
              3. Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2
    
              4. Able to comply with study procedures
    
              5. Adequate renal function within 7 days before the inclusion of the patient defined as:
    
                 • Serum creatinine ≤ 1.5 x ULN (upper normal limit) or calculated creatinine clearance
                 (determined by MDRD) > 50 mL/min/1.73m2
    
              6. Adequate hepatic function within 7 days before the inclusion of the patient defined
                 as:
    
                   -  AST and ALT ≤ 3 x ULN
    
                   -  Total serum bilirubin level ≤ 1.5 x ULN, except for patients with known Gilbert's
                      syndrome, who are excluded if total bilirubin > 3.0 x ULN or direct bilirubin >
                      1.5 x ULN
    
            Exclusion Criteria:
    
              1. Participant already enrolled and treated in the study
    
              2. Pregnancy, breastfeeding or possibility of becoming pregnant during the study
    
              3. Participation in another interventional study requiring investigational treatment
                 intake at the same time or within 2 weeks or at least 5 halflives (whichever is
                 longer) prior to first dose of IMP (participation in non-interventional registries or
                 epidemiological studies is allowed). In case of biologic agents with a long half life
                 such as CART cells, immune checkpoint antibodies, bispecific antibodies a flat
                 wash-out of 28 days will be acceptable
    
              4. 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 (NCICTCAE, version 4.03).
    
              5. Known carriers of HIV antibodies
    
              6. Known history of significant liver disease
    
              7. Uncontrolled hepatitis B or C infection
    
              8. Known active acute or chronic pancreatitis
    
              9. History of myocardial infarction (MI), unstable 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 Dose Limiting Toxicity (DLTs)
    Time Frame:At the end of cycle 1 (each cycle is 21 or 28 days).
    Safety Issue:
    Description:

    Secondary Outcome Measures

    Measure:Anti-leukemic activity
    Time Frame:Through study completion, an average of 6 months.
    Safety Issue:
    Description:Using blood, bone marrow aspirate and medullary biopsy if available according to ELN 2017 criteria
    Measure:Pharmacokinetic profile of S64315 administered in combination with Venetoclax in plasma: Area Under the Curve (AUC)
    Time Frame:From Day 1 of cycle 1 to the end of cycle 2 (each cycle is 21 or 28 days).
    Safety Issue:
    Description:
    Measure:Pharmacokinetic profile of S64315 administered in combination with Venetoclax in plasma: Concentration at the end of infusion (Cinf)
    Time Frame:From Day 1 of cycle 1 to the end of cycle 2 (each cycle is 21 or 28 days).
    Safety Issue:
    Description:
    Measure:Pharmacokinetic profile of S64315 administered in combination with Venetoclax in plasma: terminal half-life (t½z)
    Time Frame:From Day 1 of cycle 1 to the end of cycle 2 (each cycle is 21 or 28 days).
    Safety Issue:
    Description:

    Details

    Phase:Phase 1
    Primary Purpose:Interventional
    Overall Status:Recruiting
    Lead Sponsor:Servier

    Last Updated