Acute Myeloid Leukemia
Conditions
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.
Interventions
DRUGVenetoclax
Venetoclax, PO (tablet), 200 - 400mg, once-daily, 10 days per cycle (cycle 1), 5 days per cycle (cycle 2 and subsequent cycles).
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).
DRUGMetformin
Metformin, PO (tablet), 850mg, three times a day, 10 days per cycle (cycle 1), 5 days per cycle (cycle 2 and subsequent cycles).
Sponsors
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
Hospital Municipal São José
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Cohort 1: Newly diagnosed, induction-ineligible AML patients Cohort 2: Relapsed-refractory AML patients
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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) Rate | 12 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. |
Countries
Brazil
Outcome results
None listed