Combining Venetoclax with chemotherapy for treating acute myeloid leukemia and advanced MDS
Phase 1B Study of Venetoclax in Combination With Standard Intensive Chemotherapy With Daunorubicin Plus Cytarabine Followed by High-Dose Cytarabine in Adult Patients With Newly Diagnosed Acute Myeloid Leukemia and Advanced Myelodysplastic Syndrome
This study is testing if combining the drug Venetoclax with chemotherapy can help adults with newly diagnosed acute myeloid leukemia and advanced myelodysplastic syndromes feel better and live longer.
Quick facts
| Phase | Phase 1 |
|---|---|
| Study type | Interventional |
| Enrollment | 99 (estimated) |
| Ages | 18 Years to 75 Years |
| Sex | All |
| Sponsor | Montefiore Medical Center Academic / other |
| Drugs / interventions | chemotherapy |
| Locations | 1 site (The Bronx, New York) |
| Trial ID | NCT05342584 on ClinicalTrials.gov |
What this trial studies
This Phase 1b clinical trial evaluates the safety and tolerability of Venetoclax in combination with intensive chemotherapy for adults with newly diagnosed acute myeloid leukemia (AML) and advanced myelodysplastic syndromes (MDS). The study consists of two parts: a dose escalation phase to determine the maximum tolerated dose (MTD) of the drug combination, followed by a dose expansion phase to further assess safety and efficacy. Patients will be monitored for various response parameters, including overall survival and event-free survival, as well as the eradication of leukemia stem cells. The trial aims to provide insights into the effectiveness of this combination therapy in treating these aggressive blood cancers.
Who should consider this trial
Good fit: Ideal candidates are adults aged 18 to 75 with a new diagnosis of AML or higher risk MDS.
Not a fit: Patients with prior treatment for AML or MDS, or those with significant comorbidities affecting their ability to tolerate chemotherapy may not benefit from this study.
Why it matters
Potential benefit: If successful, this treatment could improve survival rates and outcomes for patients with acute myeloid leukemia and advanced myelodysplastic syndromes.
How similar studies have performed: Other studies have shown promising results with similar combinations of Venetoclax and chemotherapy, indicating potential for success in this approach.
Eligibility criteria
Show full inclusion / exclusion criteria
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 this trial is running
The Bronx, New York
- Montefiore Einstein Cancer Center and Children's Hospital at Montefiore (CHAM) — The Bronx, New York, United States (Recruiting)
Study contacts
- Principal investigator: Ioannis Mantzaris, MD — Montefiore Medical Center
- Study coordinator: Ioannis Mantzaris, MD
- Email: imantzar@montefiore.org
- Phone: 718-920-4826
How to participate
- Review the eligibility criteria above with your treating physician.
- Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
- Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.