Recruiting
Phase 2

Venetoclax & Azacitidine

Sponsor:

University Health Network, Toronto

Code:

NCT05074355

Conditions

Myeloproliferative Neoplasm

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Interventions

Azacitidine

Venetoclax

Study Details

Brief summary:

The purpose of this research study is to look at how safe and useful a drug called azacitidine in combination with a drug called venetoclax, is in people with accelerated or blast phase BRC-ABL negative myeloproliferative neoplasms.

Conditions

Myeloproliferative Neoplasm

Study ID

NCT05074355

Start date

Nov 8, 2023

Status verified date

Jul, 2026

Completion date

Dec 31, 2026

Anticipated

Primary completion date

Dec 31, 2026

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

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.

Study Design

Enrollment

40 participants

Anticipated

Intervention Model

Single group

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: Azacitidine and Venetoclax

A treatment cycle is 28 days long.

Azacitidine will be given by injection under the skin, once a day, for the first 6 days of every cycle.

Venetoclax will be given orally, once a day, as follows at the discretion of their study doctors:

Cycle 1:

  • Day 1 - 100 mg
  • Day 2 - 200 mg
  • Days 3 to 28 - 400 mg

Cycle 2:

  • Participants with a response to the study drugs will continue taking 400 mg from Days 1 to 21, with no study drug from Days 22 to 28 during Cycle 2.
  • Participants who have not yet responded to the study drugs will continue taking 400 mg from Days 1 to 28 during Cycle 2.

Cycle 3 and subsequent cycles:

  • Participants with a response to the study drugs will continue to take 400 mg from Days 1 to 21, with no study drug from Days 22 to 28.
  • Participants whose disease has not worsened will continue taking 400 mg from Days 1 to 28.
  • Participants have not responded to the study drugs will be withdrawn from the study.

Interventions

Azacitidine

Azacitidine is a hypomethylating agent that works by activating certain genes in the body to help cells mature and to kill abnormal bone marrow cells.

Venetoclax

Venetoclax is a drug that blocks a protein called B-cell lymphoma (BCL2) protein from working. BCL2 is a protein that helps control whether a cell lives or dies and is thought to help cancer cells to live. Blocking BCL2 is believed to help kill cancer cells.

Primary outcome measure

  • Proportion of participants achieving complete remission (CR). [ Time Frame: 3 years ]
  • Proportion of participants achieving complete remission with incomplete hematologic recovery (CRi). [ Time Frame: 3 years ]
  • Proportion of participants achieving reversion to chronic myeloproliferative neoplasm (CMPN). [ Time Frame: 3 years ]

Central Contacts and Locations

Central contacts

Vikas Gupta, M.D.

416-946-2885vikas.gupta@uhn.ca

Locations

Princess Margaret Cancer Centre

Recruiting

Toronto, Ontario, Canada, M5G 2M9

Contacts

Vikas Gupta, M.D.

416-946-2885

Principal Investigator:

Vikas Gupta, M.D.

More Information

Sponsor

University Health Network, Toronto

Last update posted

Jul 6, 2026

Last verified

Jul, 2026

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-10. This information was provided to ClinicalTrials.gov by University Health Network, Toronto on 2026-07-06.