Clinical Trials /

Phase I/II Trial of S64315 Plus Azacitidine in Acute Myeloid Leukaemia

NCT04629443

Description:

The purpose of this study is to assess the safety, tolerability and clinical activity of the combination S64315 with azacitidine in patients with acute myeloid leukaemia.

Related Conditions:
  • Acute Myeloid Leukemia
Recruiting Status:

Not yet recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Phase I/II Trial of S64315 Plus Azacitidine in Acute Myeloid Leukaemia
  • Official Title: Phase I/II, International, Multicentre, Open-label, Non-randomised, Non-comparative, Study Evaluating the Safety, Tolerability and Clinical Activity of Intravenously Administered S64315, a Selective Mcl-1 Inhibitor, in Combination With Azacitidine in Patients With Acute Myeloid Leukaemia (AML)

Clinical Trial IDs

  • ORG STUDY ID: CL1-64315-004
  • SECONDARY ID: 2019-004896-38
  • NCT ID: NCT04629443

Conditions

  • Acute Myeloid Leukaemia

Interventions

DrugSynonymsArms
S 64315 (also referred as MIK665) and azacitidineS64315 (also referred as MIK665) with azacitidine

Purpose

The purpose of this study is to assess the safety, tolerability and clinical activity of the combination S64315 with azacitidine in patients with acute myeloid leukaemia.

Trial Arms

NameTypeDescriptionInterventions
S64315 (also referred as MIK665) with azacitidineExperimental
  • S 64315 (also referred as MIK665) and azacitidine

Eligibility Criteria

        Inclusion Criteria:

          1. Patients aged ≥ 18 years

          2. Patients with cytologically confirmed and documented de novo, secondary or
             therapy-related AML as defined by World Health Organization 2016 classification
             (Arber, 2016) excluding acute promyelocytic leukaemia (APL, French American-British M3
             classification) with: relapsed or refractory disease and without established
             alternative therapy, or secondary to MyeloDysplastic Syndrome and without established
             alternative therapy or, newly diagnosed AML, not previously treated for AML and who
             are not candidate for intensive chemotherapy due to age or comorbidities.

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

          4. Adequate haematological, renal and hepatic functions based on the last assessment
             performed within 7 days prior to the first Investigational Medicinal Product
             administration.

        Exclusion Criteria:

          1. Previous myeloproliferative syndrome (MPS).

          2. Patient previously treated with hypomethylating agents (HMAs) such as azacitidine or
             decitabine, during dose escalation phase I part.

          3. Patients previously treated with any Mcl-1 inhibitor.

          4. Patients who have not recovered from toxicity of previous anticancer therapy,
             including Grade ≥ 2 toxicity (except alopecia of any grade) according to the National
             Cancer Institute Common Terminology Criteria for Adverse Event (NCI CTCAE) version
             5.0, prior to the first IMP administration.

        5-Severe or uncontrolled active acute or chronic infection.

        6-Uncontrolled hepatitis B or C infection.

        7-Known carriers of HIV antibodies, history of significant liver disease, active acute or
        chronic pancreatitis, active central nervous system disease.

        8-Troponin (I or T) > ULN (Upper Limit of reference range).

        9-Clinically significant cardiac dysfunction (including New York Heart Association class
        ≥II heart failure, Left Ventricular Ejection Fraction (LVEF) < 50% as assessed by
        echocardiography (ECHO) or Multi-Gated Acquisition (MUGA) scan).

        10-QT prolongation defined as QTc (QT interval corrected for heart rate) interval
        (corrected with Fridericia's formula) > 450 ms for males and > 470 ms for females, obtained
        from triplicate 12-lead ECG.

        11-Any factors that increase the risk of QTc prolongation or risk of arrhythmic events such
        as heart failure, hypokalaemia, congenital long QT syndrome, family history of long QT
        syndrome or unexplained sudden death under 40 years of age.

        12-Uncontrolled arterial hypertension (systolic blood pressure (SBP) > 150 mmHg or
        diastolic blood pressure (DBP) > 95 mmHg).
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Dose Limiting Toxicity (DLT) (Phase I - dose escalation)
Time Frame:Day -13 to Cycle 1 Day 28 (each cycle is 28 days)
Safety Issue:
Description:Incidence of DLTs starting from the Lead-In Dose period to the end of the first cycle of treatment of S64315 in combination with azacitidine.

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 European LeukemiaNet 2017 criteria (Phase I - dose escalation)
Measure:Pharmacokinetic profile of S64315 administered in combination with Azacitidine in plasma: Area Under the Curve (AUC) (Phase I - dose escalation)
Time Frame:At Day -13, Cycle 1 Day 1, Cycle 1 Day 2, Cycle 1 Day 3, Cycle 1 Day 5, Cycle 1 Day 7 and Cycle 1 Day 9 (each cycle is 28 days)
Safety Issue:
Description:
Measure:Pharmacokinetic profile of S64315 administered in combination with Azacitidine in plasma: maximum Concentration (Cmax) (Phase I - dose escalation)
Time Frame:At Day -13, Cycle 1 Day 1, Cycle 1 Day 2, Cycle 1 Day 3, Cycle 1 Day 5, Cycle 1 Day 7 and Cycle 1 Day 9 (each cycle is 28 days)
Safety Issue:
Description:

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Institut de Recherches Internationales Servier

Trial Keywords

  • Acute Myeloid Leukaemia
  • Oncology
  • Mcl-1 inhibitor
  • Azacitidine
  • Combination
  • Phase I/II
  • International
  • Safety
  • Maximum tolerated dose

Last Updated

November 16, 2020