Previously untreated Acute Myeloid Leukemia (AML) MedDRA version: 21.0 Level: LLT Classification code 10000886 Term: Acute myeloid leukemia System Organ Class: 100000004864
Conditions
Sponsors
Institut de Recherches Internationales Servier
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Male or female participant aged = 18 years old according to section 5.1.2 2. Participants with cytologically confirmed and documented treatment naïve, de novo or secondary AML defined by WHO 2016 classification (Arber, 2016). Secondary AML includes: a. Previous myelodysplastic syndrome transformed b. AML due to exposure to potentially leukemogenic therapies or agents (e.g. radiation therapy, alkylating agents, topoisomerase II inhibitors) with the primary malignancy in remission for at least 3 years 3. Participants not eligible for standard induction chemotherapy a. Aged = 75 years old b. Or Age =18 years with at least one of the following comorbidities: i. Clinically significant heart or lung comorbidities, as reflected by at least one of: - Lung diffusing capacity for carbon monoxide (DLCO) =65% of expected - Forced expiratory volume in 1 second (FEV1) =65% of expected ii. Other contraindication(s) to anthracycline therapy (must be documented) iii. Other comorbidity that the Investigator judges as incompatible with intensive remission induction chemotherapy, which must be documented 4. ECOG (Eastern Cooperative Oncology Group) performance status should be (criterion should be rechecked at inclusion visit) ECOG = 2. 5. Written informed consent obtained prior any study-specific procedure as described in section 13.3 of the protocol. 6. Adequate renal and hepatic function 7. Circulating White Blood Cell Count (WBC count) =65 years) yes F.1.3.1 Number of subjects for this age range 73
Exclusion criteria
Exclusion criteria: 9. Major surgery within 3 weeks prior to the first IMP administration, or participants who have not recovered from side effects of the surgery 10. Any radiotherapy within 3 weeks before the first IMP administration, 11. Allogenic stem cell transplant within 3 months before the first IMP administration and/or participants with active Graft-versus-host disease within 3 months before the first IMP administration and/or participants who still receive immunosuppressive treatment within 3 months before the first IMP administration and/or participant who receive donor lymphocyte infusion (DLI) within 3 months before the first IMP administration 12. Acute promyelocytic leukemia (APL, French-American-British M3 classification) 13. Favorable risk cytogenetics such as t(8;21), inv(16) or t(16;16) or t(15;17) as per the National Comprehensive Cancer Network (NCCN) Guidelines Version 2, 2016 for Acute Myeloid Leukemia 14. Treatment with hypomethylating agents (decitabine/azacitidine) or Venetoclax for AHD (antecedent hematologic disorders) in the 3 months prior to the first IMP intake
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Phase I: To determine the safety profile and tolerability of S65487 combined to azacitidine (including Dose Limiting Toxicity (DLT) and Maximum Tolerated Dose (MTD)) To determine the Recommended Phase II Dose (RP2D) of S65487 combined to azacitidine Phase II: To assess the efficacy of S65487 combined to azacitidine ;Secondary Objective: Phase I: To determine the PK profile of S65487 and azacitidine administered in combination To assess the anti-leukemic activity of S65487 combined to azacitidine Phase II: To assess anti-leukemic activity of S65487 combined to azacitidine To evaluate the depth and the duration of response Safety profile and tolerability of S65487 in combination with azacitidine To determine the PK profile of S65487 and azacitidine administered in combination;Primary end point(s): Phase I: DLT assessment at the end of cycle 1 AE recording throughout the study evaluated according to CTCAE v5.0, dose interruptions, reductions, and intensity Vitals signs, Laboratory tests, ECG Phase II: CR rate: Complete Remission (CR) rate.;Timepoint(s) of evaluation of this end point: All along the study | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): For phase I: PK parameters of S65487, azacitidine and potential metabolite(s) or co-administered drugs or potential endogenous substrates of enzymes or transporters of interest if applicable will be determined in plasma (e.g. Cinf, tinf, AUClast, tlast, Clast, AUC, t½, z, CL and Vss) CR rate: Complete Response (CR) rate, CR rate by initiation of cycle 2 (CR2), Overall response rate (ORR), CRi rate: Complete Response rate with incomplete blood recovery, Duration of Response (DOR), Event Free Survival (EFS), Progression Free Survival (PFS), Overall Survival (OS), time to first response Antileukemic activity assessment using blood, bone marrow aspirate and medullary biopsies if available according to ELN 2017 response criteria;Timepoint(s) of evaluation of this end point: All along the study | — |
Countries
Belgium, France, Hungary, Korea, Republic of, Spain, United Kingdom
Contacts
Public ContactClinical Studies Department
Institut de Recherches Internationales Servier
Outcome results
None listed