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

NCT04742101 | Active Not Recruiting Phase 1

• 2 other identifiers: CL1-65487-0032020-003061-19
• Study Type: interventional
• Target: 57
• Locations: 6 countries
• Sites: 11

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.

Conditions

Acute Myeloid Leukemia

Keywords

Acute Myeloid Leukemia; Dose escalation; Phase I/II; Azacitidine; Combination; Oncology

Outcome Measures

Primary Outcomes (3)

• Dose Limiting Toxicity (DLT) (phase I part)

  DLT assessment at the end of cycle 1

  Through the end of first cycle (each cycle is 28 days)

• Adverse Event (phase I part)

  AE recording throughout the study evaluated according to CTCAE v5.0, dose interruptions, reductions, and intensity

  Through study completion, an average of 3 years ans 5 months

• Complete Remission (CR) rate (phase II part)

  CR rate is defined as the proportion of subjects who achieve complete response. Response is evaluated based on the "'Diagnosis and management of AML in adults: 2022 ELN recommendations from an international expert panel" (Döhner, 2022).

  Through study completion, up to 3 years and 5 months

Secondary Outcomes (4)

• PharmacoKinetics - maximum Concentration at the End of the infusion (Cinf) (phase I and phase II parts)

  Cycle 1 Day 1, Cycle 1 Day 8, Cycle 1 Day 15 (schedule 1, first two cohorts), Cycle 2 Day 8 (from Cohort 3), or Day 15 (first two cohorts)(each cycle is 28 days)

• PharmacoKinetics - Area Under the Curve (AUC) (phase I and phase II parts)

  Cycle 1 Day 8 to Day 9, Cycle 2 Day 8 to Day 9 (from cohort 3), or Day 15 to Day 16 (first two cohorts)(each cycle is 28 days)

• Assessment of anti-leukemic activity of S65487 combined to azacitidine (phase I and phase II parts)

  Through study completion, an average of 3 years and 5 months

• Assessment of anti-leukemic activity of S65487 combined to azacitidine (phase I and phase II parts)

  Through study completion, an average of 3 years and 5 months

Study Arms (1)

S65487 with azacitidine

EXPERIMENTAL

Drug: S65487 and azacitidine

Interventions

S65487 and azacitidine 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.

S65487 with azacitidine

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• Institut de Recherches Internationales Servier: lead
• ADIR, a Servier Group company: collaborator

Study Sites (11)

Institut Gustave Roussy

Villejuif, 94805, France

Location

Semmelweis Egyetem Belgyógyászati és Onkológiai Klinika Klinikai Farmakológiai Részleg

Budapest, H-1083, Hungary

Location

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

Gliwice, 44-102, Poland

Location

Seoul National University Hospital - Department of Hematology-Oncology

Seoul, 03080, South Korea

Location

Samsung Medical Center - Division of Hematology-Oncology

Seoul, 06351, South Korea

Location

Hospital 12 de Octubre Servicio de Hematología

Madrid, 28041, Spain

Location

C. Universidad de Navarra Servicio de Hematologia

Pamplona, 31008, Spain

Location

H. Universitario La Fe Servicio de Hematologia

Valencia, 46026, Spain

Location

Western General Hospital

Edinburgh, EH4 2XU, United Kingdom

Location

University College London - Hospitals NHS Foundation Trust

London, NW1 2PG, United Kingdom

Location

The Christie NHS foundation Trust

Manchester, M20 4BX, United Kingdom

Location

Related Publications (1)

• 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

  BACKGROUND

Related Links

• Find Results on Servier Clinical Trial Data website

MeSH Terms

Conditions

Leukemia, Myeloid, Acute; Neoplasms

Interventions

Azacitidine

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Hematologic Diseases; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Aza Compounds; Organic Chemicals; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 14, 2020
• First Posted: February 5, 2021
• Study Start: March 10, 2021
• Primary Completion: December 30, 2025
• Study Completion: December 30, 2025
• Last Updated: April 11, 2025

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: After Marketing Authorisation in EEA or US if the study is used for the approval.
• Access Criteria: Researchers should register on Servier Data Portal and fill in the research proposal form. This form in four parts should be fully documented. The Research Proposal Form will not be reviewed until all mandatory fields are completed.

Locations

KR (2); FR (1); PL (1); ES (3); HU (1); GB (3)