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

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ClinicalTrials.gov Identifier: NCT04742101
Recruitment Status : Recruiting
First Posted : February 5, 2021
Last Update Posted : May 5, 2021
Sponsor:
Collaborator:
ADIR, a Servier Group company
Information provided by (Responsible Party):
Servier ( Institut de Recherches Internationales Servier )

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.

Condition or disease Intervention/treatment Phase
Acute Myeloid Leukemia Drug: S65487 and azacitidine Phase 1 Phase 2

Detailed Description:

The study is designed in two parts: A single arm dose escalation phase I part and dose expansion phase II part.

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.

For the expansion phase, Ramp up dose and full dose will be the RP2D (Recommended Phase 2 Dose) determined during phase I part

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 81 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase I / II, Open Label, Dose Escalation Part (Phase I) Followed by Noncomparative Expansion Part (Phase II), Multi-centre Study, Evaluating Safety, Pharmacokinetics and Efficacy of S65487, a Bcl2 Inhibitor Combined With Azacitidine in Adult Patients With Previously Untreated Acute Myeloid Leukemia Not Eligible for Intensive Treatment
Actual Study Start Date : March 10, 2021
Estimated Primary Completion Date : March 2024
Estimated Study Completion Date : March 2024


Arm Intervention/treatment
Experimental: S65487 with azacitidine Drug: S65487 and azacitidine
Treatment cycle of combination of S65487 and azacitidine during 4 weeks. S65487 will be administered via intravenous (IV) infusion. Azacitidine will be administered via either subcutaneous (SC) or Intravenous (IV) infusion according to local practices.




Primary Outcome Measures :
  1. Dose Limiting Toxicity (DLT) [ Time Frame: From Ramp-up period (day 4 or day 3 before the first cycle) to the end of first cycle (each cycle is 28 days) ]
    DLT assessment at the end of cycle 1

  2. Adverse Event [ Time Frame: Through study completion, an average of 3 years ans 5 months ]
    AE recording throughout the study evaluated according to CTCAE v5.0, dose interruptions, reductions, and intensity


Secondary Outcome Measures :
  1. PharmacoKinetics - maximum Concentration at the End of the infusion (Cinf) [ Time Frame: Cycle 1 (each cycle is 28 days) Day 1, Cycle 1 Day 8, Cycle 1 Day 15 ]
    PK parameters of S65487, azacitidine and potential metabolite(s)

  2. PharmacoKinetics - Area Under the Curve (AUC) [ Time Frame: Ramp-up (day 4 or day 3 before the first cycle), Cycle 1(each cycle is 28 days) Day 1, Cycle 1 Day 8, Cycle 1 Day 9, Cycle 1 Day 15 and each Day 1 for following cycles ]
    PK parameters of S65487, azacitidine and potential metabolite(s)

  3. Assessment of anti-leukemic activity of S65487 combined to azacitidine [ Time Frame: Through study completion, an average of 3 years ans 5 months ]
    Complete Response rate

  4. Assessment of anti-leukemic activity of S65487 combined to azacitidine [ Time Frame: Through study completion, an average of 3 years and 5 months ]
    Progression Free Survival



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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 2, 2016 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04742101


Locations
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France
Institut Gustave Roussy Not yet recruiting
Villejuif, France, 94805
Korea, Republic of
Seoul National University Hospital - Department of Hematology-Oncology Not yet recruiting
Seoul, Korea, Republic of, 03080
Samsung Medical Center - Division of Hematology-Oncology Not yet recruiting
Seoul, Korea, Republic of, 06351
Spain
Hospital 12 de Octubre Servicio de Hematología Not yet recruiting
Madrid, Spain, 28041
C. Universidad de Navarra Servicio de Hematologia Recruiting
Pamplona, Spain, 31008
Contact: Ana Alfonso    0034 948 255 400 ext 5801    aalfonso@unav.es   
H. Universitario La Fe Servicio de Hematologia Not yet recruiting
Valencia, Spain, 46026
United Kingdom
Western General Hospital Not yet recruiting
Edinburgh, United Kingdom, EH4 2XU
University College London - Hospitals NHS Foundation Trust Not yet recruiting
London, United Kingdom, NW1 2PG
Sponsors and Collaborators
Institut de Recherches Internationales Servier
ADIR, a Servier Group company
Additional Information:
Study Data/Documents: Individual Participant Data Set  This link exits the ClinicalTrials.gov site

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Responsible Party: Institut de Recherches Internationales Servier
ClinicalTrials.gov Identifier: NCT04742101    
Other Study ID Numbers: CL1-65487-003
2020-003061-19 ( EudraCT Number )
First Posted: February 5, 2021    Key Record Dates
Last Update Posted: May 5, 2021
Last Verified: April 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description:

Qualified scientific and medical researchers can request access to anonymized patient-level and study-level clinical trial data.

Access can be requested for all interventional clinical studies:

  • used for Marketing Authorization (MA) of medicines and new indications approved after 1 January 2014 in the European Economic Area (EEA) or the United States (US).
  • where Servier is the Marketing Authorization Holder (MAH). The date of the first MA of the new medicine (or the new indication) in one of the EEA Member States will be considered for this scope.

In addition, access can be requested for all interventional clinical studies in patients:

  • sponsored by Servier
  • with a first patient enrolled as of 1 January 2004 onwards
  • for New Chemical Entity or New Biological Entity (new pharmaceutical form excluded) for which development has been terminated before any Marketing authorization (MA) approval.
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Informed Consent Form (ICF)
Clinical Study Report (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.
URL: https://clinicaltrials.servier.com/

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Servier ( Institut de Recherches Internationales Servier ):
Acute Myeloid Leukemia
Dose escalation
Phase I/II
Azacitidine
Combination
Oncology
Additional relevant MeSH terms:
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Leukemia
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Neoplasms by Histologic Type
Neoplasms
Azacitidine
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Enzyme Inhibitors