Phase I/II Trial of S65487 Plus Azacitidine in Acute Myeloid Leukemia

NCT ID: NCT04742101

Last Updated: 2025-04-11

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 57 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-03-10
• Study Completion Date: 2025-12-30

Brief Summary

The purpose of this study is to assess the safety, tolerability and clinical activity of the combination S65487 with azacitidine in patients with acute myeloid leukaemia.

Detailed Description

The study is designed in two parts: A dose escalation phase I part, and a dose expansion phase II part with an additional potential expansion cohort.

During dose escalation of S65487 in combination with azacitidine, only S65487 agent dose will escalate and a DDI (Drug-Drug interaction) assessment between S65487 and posaconazole (antifungal drug) will be performed. A ramp-up dose of S65487 will be administered on the first two days of cycle 1, then the full dose of S65487 will be administered for the remainder of cycle 1. Each treatment cycle is 28 days.

For the expansion phase, the dose will be the RP2D (Recommended Phase 2 Dose) determined during phase I part. An additional potential expansion cohort will be included if there is more than one promising dose/schedule candidate.

Conditions

Acute Myeloid Leukemia

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

S65487 with azacitidine

Group Type: EXPERIMENTAL

S65487 and azacitidine

Intervention Type: DRUG

Treatment cycle of combination of S65487 and azacitidine during 4 weeks. Two administration schedules are set up. S65487 will be administered via intravenous (IV) infusion. Azacitidine will be administered via either subcutaneous (SC) or Intravenous (IV) infusion according to local practices.

Interventions

S65487 and azacitidine

Treatment cycle of combination of S65487 and azacitidine during 4 weeks. Two administration schedules are set up. S65487 will be administered via intravenous (IV) infusion. Azacitidine will be administered via either subcutaneous (SC) or Intravenous (IV) infusion according to local practices.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Male or female participant aged ≥ 18 years old
• Participants with cytologically confirmed and documented treatment naïve, de novo or secondary AML defined by WHO 2016 classification (Arber, 2016). Secondary AML includes:

• Previous myelodysplastic syndrome transformed
• 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
• Participants not eligible for standard induction chemotherapy

• Aged ≥ 75 years old
• Or Age ≥18 years with at least one of the following comorbidities:

• 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
• Other contraindication(s) to anthracycline therapy (must be documented)
• Other comorbidity that the Investigator judges as incompatible with intensive remission induction chemotherapy, which must be documented
• ECOG (Eastern Cooperative Oncology Group) performance status should be (criterion should be rechecked at inclusion visit) ECOG ≤ 2.
• Written informed consent obtained prior any study-specific procedure as described in section 13.3 of the protocol.
• Adequate renal and hepatic function
• Circulating White Blood Cell Count (WBC count) < 25*109 G/L (with or without use of hydroxycarbamide/leukapheresis)
• Serum potassium, serum calcium, serum phosphates, serum magnesium within normal limits with or without supplementation.

Exclusion Criteria

• Major surgery within 3 weeks prior to the first IMP administration, or participants who have not recovered from side effects of the surgery
• Any radiotherapy within 3 weeks before the first IMP administration,
• 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
• Acute promyelocytic leukemia (APL, French-American-British M3 classification)
• 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 3, 2019 for Acute Myeloid Leukemia
• Treatment with hypomethylating agents (decitabine/azacitidine) or Venetoclax for AHD (antecedent hematologic disorders) in the 3 months prior to the first IMP intake

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

ADIR, a Servier Group company

INDUSTRY

Sponsor Role: collaborator

Institut de Recherches Internationales Servier

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Institut Gustave Roussy

Villejuif, , France

Semmelweis Egyetem Belgyógyászati és Onkológiai Klinika Klinikai Farmakológiai Részleg

Budapest, , Hungary

Narodowy Instytut Onkologii im. M. Sklodowskiej-Curie Klinika Transplantacji Szpiku i Onkohematologii pokoj 4.041 ul. Wybrzeze Armii Krajowej 15

Gliwice, , Poland

Seoul National University Hospital - Department of Hematology-Oncology

Seoul, , South Korea

Samsung Medical Center - Division of Hematology-Oncology

Seoul, , South Korea

Hospital 12 de Octubre Servicio de Hematología

Madrid, , Spain

C. Universidad de Navarra Servicio de Hematologia

Pamplona, , Spain

H. Universitario La Fe Servicio de Hematologia

Valencia, , Spain

Western General Hospital

Edinburgh, , United Kingdom

University College London - Hospitals NHS Foundation Trust

London, , United Kingdom

The Christie NHS foundation Trust

Manchester, , United Kingdom

Countries

France; Hungary; Poland; South Korea; Spain; United Kingdom

References

Pierola AA, De Botton S, Jan JH, Campbell V, O'Nions J, Calbacho M, Ervin-Hayes AL, Keagle K, Maillard A, Beneton M, Romagnoli M, Broniscer A. Trial in Progress: An Open Label Phase I/II, Multicenter Study Evaluating Safety, Pharmacokinetics and Efficacy of S65487, a BCL-2 Inhibitor Combined with Azacitidine in Adults with Previously Untreated Acute Myeloid Leukemia Ineligible for Intensive Treatment. Blood. 2023 Nov 2;142(Supplement 1):1555. doi: https://doi.org/10.1182/blood-2023-180795

Reference Type: BACKGROUND

Study Documents

Document Type: Individual Participant Data Set

View Document

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Document Type: Informed Consent Form

View Document

Document Type: Clinical Study Report

View Document

Document Type: Study-level clinical trial data

View Document

Related Links

https://clinicaltrials.servier.com/

Find Results on Servier Clinical Trial Data website

Other Identifiers

2020-003061-19

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

CL1-65487-003

Identifier Type: -

Identifier Source: org_study_id