Recruiting
Phase 1

Venetoclax with Chemotherapy

Sponsor:

Montefiore Medical Center

Code:

NCT05342584

Conditions

Acute Myeloid Leukemia

Myelodysplastic Syndromes

Eligibility Criteria

Sex: All

Age: 18 - 70+

Healthy Volunteers: Not accepted

Interventions

Venetoclax Oral Tablet

Daunorubicin

Cytarabine

Study Details

Brief summary:

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.

Conditions

Acute Myeloid Leukemia

Myelodysplastic Syndromes

Study ID

NCT05342584

Start date

May 25, 2022

Status verified date

Jan, 2026

Completion date

Dec, 2028

Anticipated

Primary completion date

Dec, 2028

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 18 - 70+

Healthy Volunteers: Not accepted

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).

Study Design

Enrollment

99 participants

Anticipated

Intervention Model

Single group

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: Venetoclax plus 7+3

see detailed description

Interventions

Venetoclax Oral Tablet

Given PO

Daunorubicin

Given IV

Cytarabine

Given IV

Primary outcome measure

  • Frequency and Severity of all Adverse Events (AEs) and Serious Adverse Events (SAEs) [ Time Frame: Through study completion, up to 6 years ]
  • Frequency and Severity of AEs and SAEs by Age Group [ Time Frame: Through study completion, up to 6 years ]
  • Frequency and Severity of AEs and SAEs by Dose Level [ Time Frame: Through study completion, up to 6 years ]
  • Rate of Non-Hematologic Dose Limiting Toxicities (DLTs) [ Time Frame: Up to 28 days during induction and 1st consolidation cycle ]
  • Rate of Hematologic Dose Limiting Toxicities (DLTs) [ Time Frame: Up to 42 days during induction and 1st consolidation cycle ]
  • The Number/Percentage of Patients with Dose Modifications [ Time Frame: During the 3 days of chemotherapy administration ]
  • Maximum tolerated dose of Venetoclax in combination with Daunorubicin and Cytarabine [ Time Frame: During induction phase, up to 14 days ]
  • Maximum tolerated dose of Venetoclax in combination with high dose Cytarabine [ Time Frame: During consolidation phase, up to 7 days ]

Central Contacts and Locations

Central contacts

Ioannis Mantzaris, MD

718-920-4826imantzar@montefiore.org

Locations

Montefiore Einstein Cancer Center and Children's Hospital at Montefiore (CHAM)

Recruiting

The Bronx, New York, United States, 10467

Contacts

Ioannis Mantzaris, MD

718-920-4826imantzar@montefiore.org

Amit K Verma, MD

718-430-2205

More Information

Sponsor

Montefiore Medical Center

Last update posted

Jan 8, 2026

Last verified

Jan, 2026

Keywords

  • AML
  • MDS
  • Venetoclax
  • Ven
  • 7+3
  • daunorubicin and cytarabine
  • daunorubicin
  • cytarabine

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-10. This information was provided to ClinicalTrials.gov by Montefiore Medical Center on 2026-01-08.