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

Phase 2
Recruiting
Conditions
Acute Myeloid Leukemia
Interventions
Registration Number
NCT06537843
Lead Sponsor
Hospital Municipal São José
Brief Summary

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

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.

Recruitment & Eligibility

Status
RECRUITING
Sex
All
Target Recruitment
100
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 & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
VenCMCytarabine InjectionVenetoclax, Cytarabine, Metformin
VenCMVenetoclaxVenetoclax, Cytarabine, Metformin
VenCMMetforminVenetoclax, Cytarabine, Metformin
Primary Outcome Measures
NameTimeMethod
Overall Survival (OS)12 months and 24 months

Overall survival is defined as the time from patient inclusion to the date of death, using Kaplan-Meier methodology.

Secondary Outcome Measures
NameTimeMethod
Composite Complete Response Rate (CCR)12 months and 24 months

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.

Negative Measurable Residual Disease (MRD) Rate12 months and 24 months

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.

Trial Locations

Locations (5)

Hospital Ophir Loyola

🇧🇷

Belem, Brazil

Hospital de Clínicas da UFPR

🇧🇷

Curitiba, Brazil

Hospital Amaral Carvalho

🇧🇷

Jaú, Brazil

Hospital Universitario Polydoro Ernani de Sao Thiago

🇧🇷

Florianopolis, Brazil

Hospital Municipal Sao Jose

🇧🇷

Joinville, Brazil

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