Safety and Efficacy of Venetoclax, Cytarabine and Metformin (VenCM) for Relapsed-Refractory and Induction-Ineligible Acute Myeloid Leukemia (VenCM)

Safety and Efficacy of Venetoclax, Cytarabine and Metformin (VenCM) for Relapsed-Refractory and Induction-Ineligible Acute Myeloid Leukemia: Multicenter, Phase 2, Clinical Trial

Phase 2 clinical trial to evaluate the combination of venetoclax, cytarabine and metformin in relapsed-refractory and induction ineligible acute myeloid leukemia.

Study Overview

• Status: Recruiting
• Conditions: Acute Myeloid Leukemia
• Intervention / Treatment: Drug: Venetoclax; Drug: Cytarabine Injection; Drug: Metformin

Detailed Description

Subjects will be included voluntarily after informed consent. Diagnosis of AML in accordance with the WHO classification and determination of inegibility to induction therapy or refractory or relapsed disease after initial treatment.

• Study Type: Interventional
• Enrollment (Estimated): 100
• Phase: Phase 2

Contacts and Locations

Study Locations

• Brazil
  • Belem, Brazil
    • Not yet recruiting
    • Hospital Ophir Loyola
    • Contact: Thiago Carneiro, MD, PhD
  • Curitiba, Brazil
    • Not yet recruiting
    • Hospital de Clínicas da UFPR
    • Contact: Elenaide Nunes, MD, PhD
  • Florianopolis, Brazil
    • Not yet recruiting
    • Hospital Universitario Polydoro Ernani de Sao Thiago
    • Contact: Giovanna Steffenello, MD, MSc
  • Jaú, Brazil
    • Recruiting
    • Hospital Amaral Carvalho
    • Contact: Ederson Mattos, MD; Phone Number: +55 (14) 3602-1200; Email: edersonmattos@amaralcarvalho.org.br
  • Joinville, Brazil
    • Recruiting
    • Hospital Municipal São José
    • Contact: Marcelo Lacerda, MD, PhD; Phone Number: +55 (47) 3441-6600; Email: marcelo.lacerda@univille.br

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Diagnosis of AML in accordance with the World Health Organization criteria.
• Ineligibility for induction chemotherapy due to age (≥ 70 years) or, for patients 18 to 74 years of age, ECOG-PS 2 or 3, creatinine clearance below 60 mL/min/1,73m², left ventricular ejection fraction ≤ 50%.
• Projected life expectancy of at least 12 weeks.
• Not requiring supplemental oxygen or substitutive renal therapy.
• Female participants must be either postmenopausal, surgically sterile or practicing at least one protocol specified method of birth control starting at Study Day 1 through at least 180 days after the last dose of study drug.
• Male participants must agree, from Study Day 1 through at least 180 days after the last dose of study drug, to practice protocol specified methods of contraception and to refrain from sperm donation from initial study drug administration through at least 180 days after the last dose of study drug.
• Participant must voluntarily sign and date an informed consent form, approved by an Independent Ethics Committee (IEC)/Institutional Review Board (IRB), prior to the initiation of any screening or study-specific procedures.

Exclusion Criteria:

• Diagnosis of acute promyelocytic leukemia (APL).
• Known central nervous system (CNS) involvement with AML.
• Known human immunodeficiency virus (HIV) infection, hepatitis B virus (HBV), or hepatitis C virus (HCV) infection, or other active viral, bacterial or fungal infection requiring treatment.
• History of other malignancies prior to study entry, with the exception of non-melanoma skin cancer.
• Chronic Liver Disease and Cirrhosis with a class B or C Child-Pugh score.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: VenCM; Venetoclax, Cytarabine, Metformin

Drug: Venetoclax; Venetoclax, PO (tablet), 200 - 400mg, once-daily, 10 days per cycle (cycle 1), 5 days per cycle (cycle 2 and subsequent cycles).; Drug: Cytarabine Injection; Cytarabine, Subcutaneous injection, 10 - 100mg per square meter, once-daily, 10 days per cycle (cycle 1), 5 days per cycle (cycle 2 and subsequent cycles).; Drug: Metformin; Metformin, PO (tablet), 850mg, three times a day, 10 days per cycle (cycle 1), 5 days per cycle (cycle 2 and subsequent cycles).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival (OS)	Overall survival is defined as the time from patient inclusion to the date of death, using Kaplan-Meier methodology.	12 months and 24 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Composite Complete Response Rate (CCR)	Percentage of participants with complete remission (CR) or complete remission with partial (CRh) or incomplete blood count recovery (CRi) at any time during the study as assessed by the investigator. Response was based on physical examination, bone marrow results and hematology values according to the revised guidelines by the 2022 European LeukemiaNet AML Diagnosis and Treatment Recommendations.	12 months and 24 months
Negative Measurable Residual Disease (MRD) Rate	Percentage of participants with CR, CRh or CRi with negative measurable residual disease (MRD) as assessed by the investigator, in accordance with ELN recommendations, defined as having less than 10-³ residual blasts per leukocyte measured in the bone marrow.	12 months and 24 months

Collaborators and Investigators

• Sponsor: Hospital Municipal São José
• Collaborators: Hospital de Clínicas da UFPR. Curitiba, PR, Brazil; Hospital Ophir Loyola. Belem, PA, Brazil; Hospital Universitario Polydoro Ernani de São Thiago. Florianopolis, SC, Brazil; Hospital Amaral Carvalho. Jau, SP, Brazil

Study record dates

Study Major Dates

• Study Start (Actual): December 1, 2023
• Primary Completion (Estimated): July 1, 2026
• Study Completion (Estimated): July 1, 2028

Study Registration Dates

• First Submitted: July 31, 2024
• First Submitted That Met QC Criteria: July 31, 2024
• First Posted (Estimated): August 5, 2024

Study Record Updates

• Last Update Posted (Estimated): August 5, 2024
• Last Update Submitted That Met QC Criteria: July 31, 2024
• Last Verified: July 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Hypoglycemic Agents; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Venetoclax; Metformin; Cytarabine
• Other Study ID Numbers: VenCM-001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No