Combining venetoclax and azacitidine for advanced myeloproliferative neoplasms

Venetoclax and Azacitidine Combination Therapy for Patients With Accelerated or Blast Phase BCR-ABL Negative Myeloproliferative Neoplasm (VAAMP)

This study is testing if combining two drugs, venetoclax and azacitidine, can help people with advanced blood cancers feel better and manage their disease.

Quick facts

• Phase: PHASE2
• Study type: Interventional
• Enrollment: 40 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: University Health Network, Toronto (other)
• Locations: 1 site (Toronto, Ontario)
• Trial ID: NCT05074355 on ClinicalTrials.gov

What this trial studies

This study evaluates the safety and efficacy of a combination of azacitidine and venetoclax in patients with advanced BCR-ABL negative myeloproliferative neoplasms. Participants will undergo a safety run-in period followed by two stages to assess their response to the treatment. The study aims to determine if this drug combination can effectively manage the disease in patients who have progressed to accelerated or blast phases. All participants will receive both drugs throughout the study.

Who should consider this trial

Good fit: Ideal candidates include individuals diagnosed with BCR-ABL negative myeloproliferative neoplasms who have progressed to accelerated or blast phases.

Not a fit: Patients who have previously received treatment with venetoclax, azacitidine, or other hypomethylating agents may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a new therapeutic option for patients with advanced myeloproliferative neoplasms.

How similar studies have performed: Other studies have explored similar drug combinations in hematological malignancies, showing promising results, but this specific combination is novel.

Eligibility criteria

Inclusion Criteria:

* Ability to voluntarily provide written informed consent.
* Documented diagnosis per World Health Organization (WHO) 2016 criteria of BCR-ABL negative myeloproliferative neoplasms (MPN).
* Documented MPN transformation to accelerated phase (AP) or blast phase (BP) without prior blast reduction therapy for their AP/BP disease.
* Eastern Cooperative Oncology Group (ECOG) performance status 0-2.
* Adequate organ function.
* Must practice at least one reliable method of birth-control starting at least on cycle 1 day 1 until at least 90 days after the last dose of study drug.
* Female participants of childbearing potential must have a negative serum pregnancy test within 14 days prior to cycle 1 day 1.

Exclusion Criteria:

* History of allogeneic stem cell transplant for MPN.
* Previous treatment with venetoclax, navitoclax, azacytidine or other hypomethylating agents (HMA).
* White blood cell count \>25 x 10\^9/L.
* Current enrollment in another interventional study.
* Presence of any active uncontrolled infection such as bacterial or fungal infections progressing despite adequate antimicrobial treatment.
* Myocardial infarction in the preceding 3 months.
* Active human immunodeficiency virus (HIV), hepatitis B (HBV), hepatitis C (HCV) infection.
* History of active malignancy in the previous 2 years.
* Any psychiatric illness or social circumstances or significant co-morbid conditions that may compromise study participation.
* Pregnant or breastfeeding women.
* Patients with known central nervous system (CNS) involvement with acute myeloid leukemia (AML) or CNS extramedullary hematopoiesis.
* Patients with t (15;17)
* Patients who have received strong and/or moderate CYP3A inducers within 7 days prior to the initiation of study treatment.
* Active COVID-19 infection.
* History of prior blast-reduction therapy for AP/BP-MPN.
* Preceding history MDS, chronic myelomonocytic leukemia (CMML), and other myelodysplastic syndromes (MDS)/MPN overlap syndromes.

Where this trial is running

Toronto, Ontario

• Princess Margaret Cancer Centre — Toronto, Ontario, Canada (RECRUITING)

Study contacts

• Principal investigator: Vikas Gupta, M.D. — Princess Margaret Cancer Centre
• Study coordinator: Vikas Gupta, M.D.

Conditions: Myeloproliferative Neoplasm