Phase I Dose Escalation Study of Intravenously Administered S64315 in Combination With Orally Administered Venetoclax in Patients With Acute Myeloid Leukaemia.
- Conditions
- Acute Myeloid Leukaemia
- Interventions
- Combination Product: S 64315 (also referred as MIK665) and venetoclax
- Registration Number
- NCT03672695
- Lead Sponsor
- Institut de Recherches Internationales Servier
- Brief Summary
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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 37
-
Male or female aged ≥ 18 years;
-
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
-
Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2
-
Able to comply with study procedures
-
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
-
Adequate hepatic function within 7 days before the inclusion of the patient defined as:
- AST and ALT ≤ 1.5 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
- Participant already enrolled and treated in the study
- Pregnancy, breastfeeding or possibility of becoming pregnant during the study
- 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
- 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).
- Known carriers of HIV antibodies
- Known history of significant liver disease
- Uncontrolled hepatitis B or C infection
- Known active acute or chronic pancreatitis
- History of myocardial infarction (MI), unstable angina pectoris, coronary artery bypass graft (CABG) within 6 months prior to starting study treatment
- Any factors that could increase the risk of QTc prolongation or risk of arrhythmic events.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Initial Schedule - S64315 low dose and venetoclax high dose administered in combination S 64315 (also referred as MIK665) and venetoclax - Initial Schedule - S64315 medium dose and venetoclax medium dose administered in combination S 64315 (also referred as MIK665) and venetoclax - Initial Schedule - S64315 medium dose and venetoclax low dose administered in combination S 64315 (also referred as MIK665) and venetoclax - Initial Schedule - S64315 high dose and venetoclax medium dose administered in combination S 64315 (also referred as MIK665) and venetoclax - Initial Schedule - S64315 medium dose and venetoclax high dose administered in combination S 64315 (also referred as MIK665) and venetoclax - Alternative Schedule - Venetoclax medium dose administered with no S64315 S 64315 (also referred as MIK665) and venetoclax - Alternative Schedule - S64315 medium dose and venetoclax medium dose administered in combination S 64315 (also referred as MIK665) and venetoclax - Alternative Schedule - S64315 high dose and venetoclax low dose administered in combination S 64315 (also referred as MIK665) and venetoclax -
- Primary Outcome Measures
Name Time Method Incidence and severity of AEs Through study completion, an average of 6 months. Number of participants with dose reductions "will be measured and reported in the Outcome Measure results data table. Through study completion, an average of 6 months. Incidence and severity of SAEs Through study completion, an average of 6 months. Dose intensity Through study completion, an average of 6 months. Incidence of Dose Limiting Toxicity (DLTs) At the end of cycle 1 (each cycle is 21 or 28 days). Number of participants with dose interruptions "will be measured and reported in the Outcome Measure results data table. Through study completion, an average of 6 months.
- Secondary Outcome Measures
Name Time Method Pharmacokinetic profile of S64315 administered in combination with Venetoclax in plasma: Area Under the Curve (AUC) From Day 1 of cycle 1 to the end of cycle 2 (each cycle is 21 or 28 days). Pharmacokinetic profile of S64315 administered in combination with Venetoclax in plasma: Concentration at the end of infusion (Cinf) From Day 1 of cycle 1 to the end of cycle 2 (each cycle is 21 or 28 days). Pharmacokinetic profile of S64315 administered in combination with Venetoclax in plasma: terminal half-life (t½z) From Day 1 of cycle 1 to the end of cycle 2 (each cycle is 21 or 28 days). Anti-leukemic activity Through study completion, an average of 6 months. Using blood, bone marrow aspirate and medullary biopsy if available according to ELN 2017 criteria
Trial Locations
- Locations (7)
Smilow Cancer Hospital at Yale
🇺🇸New Haven, Connecticut, United States
The University of Texas MD Anderson Cancer Center, Houston, TX
🇺🇸Houston, Texas, United States
Peter MacCallum cancer centrer
🇦🇺Melbourne, Australia
The Alfred Hospital Department of Haematology
🇦🇺Victoria Park, Australia
Institut Paoli-Calmettes
🇫🇷Marseille, France
Hopital Saint-Antoine
🇫🇷Paris, France
Institut Universitaire du Cancer Toulouse - Oncopole
🇫🇷Toulouse, France