NCT05342584 · Montefiore Medical Center
Venetoclax Plus Intensive Chemotherapy in AML and Advanced MDS
(Venetoclax AML)
What this study is about
This is a Phase 1b, where both patients and doctors know the treatment given study evaluating Venetoclax in combination with intensive induction and consolidation chemotherapy in previously untreated, adult patients with acute myeloid leukemia.
View original scientific description
This is a Phase 1b, open-label study evaluating Venetoclax in combination with intensive induction and consolidation chemotherapy in previously untreated, adult patients with acute myeloid leukemia. In Part 1, the dose escalation phase, the safety and tolerability of the combination with Venetoclax at different doses and duration will inform the appropriate dose(s) and regimen(s) for Part 2. In Part 2, the dose expansion phase, a maximum of 28 additional patients will be randomized 1:1 to the MTD determined in Part 1 and the starting dose (assuming the MTD is not the starting dose), to further evaluate the safety and efficacy of the study drug combination.
Interventions
DRUG
Venetoclax Oral Tablet
Given PO
DRUG
Daunorubicin
Given IV
DRUG
Cytarabine
Given IV
Primary outcome measures
Frequency and Severity of all Adverse Events (AEs) and Serious Adverse Events (SAEs)
Time frame: Through study completion, up to 6 years
The number and percentage of patients with SAEs and AEs, including AEs leading to dose modifications or discontinuations, will be summarized.
Frequency and Severity of AEs and SAEs by Age Group
Time frame: Through study completion, up to 6 years
The number and percentage of patients with SAEs and AEs, including AEs leading to dose modifications or discontinuations, will be summarized by age group.
Frequency and Severity of AEs and SAEs by Dose Level
Time frame: Through study completion, up to 6 years
The number and percentage of patients with SAEs and AEs, including AEs leading to dose modifications or discontinuations, will be summarized by dose level.
Rate of Non-Hematologic Dose Limiting Toxicities (DLTs)
Time frame: Up to 28 days during induction and 1st consolidation cycle
The rate of non-hematologic DLTs will be monitored. Non-hematologic DLTs will be defined as any Grade 3 or higher non-hematologic events occurring during the first cycle (i.e., the first 28 days) that are at least possibly attributable to Venetoclax unless the event is clearly due to extraneous causes or disease progression, confirmed Hy's law case, with the exceptions outlined in Section 4.5.1 of the study protocol. The number/percentage of patients non-hematologic DLTs will be summarized. 90% Confidence Intervals will be estimated using the Clopper-Pearson method with all available data at the Maximum Tolerated Dose (MTD) and, if relevant, for the dose level below.
Rate of Hematologic Dose Limiting Toxicities (DLTs)
Time frame: Up to 42 days during induction and 1st consolidation cycle
The rate of hematologic DLTs will be monitored. Hematologic DLT is defined as Grade ≥ 3 neutropenia and/or thrombocytopenia with no greater than 5% marrow blasts lasting for 6 weeks or more after the start of a course unless the delay in count recovery is due to another identifiable factor, such as documented myelosuppressive infection. Anemia will not be considered for the definition of DLT. The number/percentage of patients with hematologic DLTs will be summarized. 90% Confidence Intervals will be estimated using the Clopper-Pearson method with all available data at the MTD and, if relevant, for the dose level below.
The Number/Percentage of Patients with Dose Modifications
Time frame: During the 3 days of chemotherapy administration
The number/percentage of patients with dose modifications, as prescribed in the protocol for the 400mg and 200mg dosage, will be summarized. It should be noted that the only relevant dose modifications apply to consolidation cycles with intermediate dose cytarabine and specifically the older group cohort.
Maximum tolerated dose of Venetoclax in combination with Daunorubicin and Cytarabine
Time frame: During induction phase, up to 14 days
To determine a safe and tolerable dose of Venetoclax in combination with Daunorubicin and Cytarabine during the induction phase.
Maximum tolerated dose of Venetoclax in combination with high dose Cytarabine
Time frame: During consolidation phase, up to 7 days
To determine a safe and tolerable dose of Venetoclax in combination high dose of Cytarabine during the consolidation phase.
Who can participate
This study lists these criteria on ClinicalTrials.gov. A study coordinator reviews eligibility during screening — this page does not determine whether you qualify.
Inclusion criteria
- New diagnosis of AML by WHO criteria. Patients with higher risk MDS (R-IPSS\>3.5) and 10% blasts or more, or proliferative (WBC ≥ 13 x 10⁹/L) CMML-2 are also eligible at the discretion of the PI. Patients having received any prior hypomethylating agent with or without BCL2 inhibitor therapy for MDS/AML are also eligible at the discretion of the PI
- Patients ≥ 18 to ≤ 75 years.
- Eastern Cooperative Oncology Group (ECOG) Performance Status of ≤ 2
- Adequate renal function including creatinine clearance \> 30 mL/min based on the Cockcroft Gault equation.
- Adequate hepatic function including total bilirubin \< 1.5x ULN unless increase is due to Gilbert's disease or leukemic involvement, and AST and/or ALT \< 3x ULN unless considered due to leukemic involvement
- Ability to understand and provide signed informed consent
- Male subjects must agree to refrain from unprotected sex and sperm donation from initial study drug administration until 90 days after the last dose of study drug.
Exclusion criteria
- Patients with t(15;17) karyotypic abnormality or acute promyelocytic leukemia (FAB class M3-AML)
- Subject has known active CNS involvement with AML
- Patients with New York Heart Association (NYHA) Class III or IV congestive heart failure or LVEF \<45% by echocardiogram or multi-gated acquisition (MUGA) scan
- Patients with a history of myocardial infarction within the last 6 months or unstable / uncontrolled angina pectoris or history of severe and/or uncontrolled ventricular arrhythmias
- Patients with uncontrolled infection with human immunodeficiency virus (HIV) or active Hepatitis B or C
- Patients with known dysphagia, short-gut syndrome, or other conditions that would affect the ingestion or gastrointestinal absorption of drugs administered orally.
- Subject has any other significant medical or psychiatric history that in the opinion of the investigator would adversely affect participation in this study.
- Subject has a white blood cell count \> 25 x 10⁹/L. (Note: Hydroxyurea and/or cytarabine (up to 2 g/m\^2 is permitted to meet this criterion.)
- Nursing women, women of childbearing potential (WOCBP) with positive urine pregnancy test, or women of childbearing potential who are not willing to maintain adequate contraception. Appropriate method(s) of contraception include oral or injectable hormonal birth control, IUD, and double barrier methods (for example a condom in combination with a spermicide).
Where
- The Bronx, New York
Collaborators
AbbVie, Dana-Farber Cancer Institute
Related conditions & keywords
Frequently asked questions
What is a clinical trial?
A clinical trial is a research study that tests new medical treatments, drugs, devices, or procedures to determine their safety and effectiveness. Trials are carefully designed and monitored to protect participants while advancing medical knowledge.
Is it safe to participate?
Clinical trials follow strict safety guidelines and ethical standards. Trials must be reviewed and approved, and participants are closely monitored by medical professionals throughout the study. You can withdraw at any time if you choose.
Will I be compensated?
Many clinical trials offer compensation for your time, travel expenses, and inconvenience. The specific compensation varies by study and will be discussed during the screening process. All study-related medical care is typically provided at no cost to participants.
Will I receive a placebo instead of treatment?
When effective treatment exists, participants typically receive either the standard treatment plus the study intervention, or the standard treatment plus placebo. You would not be denied effective care. Placebos are primarily used when no proven treatment is available, or in addition to standard care. Your trial consent form will clearly explain what treatments you may receive.
Can I leave a trial if I change my mind?
Absolutely. Participation in clinical trials is completely voluntary. You have the right to withdraw from the study at any time, for any reason, without penalty or loss of benefits to which you are otherwise entitled.
How long does a clinical trial last?
Trial duration varies widely depending on the study design and purpose. Some trials last just a few weeks, while others may continue for months or years. The study coordinator will provide specific timeline information during your screening call.
Data: ClinicalTrials.gov · synced Jan 8, 2026 · Source of record for eligibility and locations