Study of Venetoclax and Azacitidine in Advanced BCR-ABL Negative Myeloproliferative Neoplasms

NCT05074355 | Recruiting Phase 2 DMC

• 2 other identifiers: VAAMP21-5928
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

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

Outcome Measures

Primary Outcomes (3)

• Proportion of participants achieving complete remission (CR).

  3 years

• Proportion of participants achieving complete remission with incomplete hematologic recovery (CRi).

  3 years

• Proportion of participants achieving reversion to chronic myeloproliferative neoplasm (CMPN).

  3 years

Secondary Outcomes (5)

• Average number of days from the first dose of azacytidine and venetoclax to the date of death.

  3 years

• Average number of days from CR until relapse.

  3 years

• Average number of days from CRi until relapse.

  3 years

• Average number of days from CMPN until relapse.

  3 years

• The proportion of patients proceeding to allogeneic stem cell transplantation in those eligible for transplantation.

  3 years

Study Arms (1)

Azacitidine and Venetoclax

EXPERIMENTAL

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 * Participants have not responded to the study drugs will be withdrawn from the study.

Drug: Azacitidine; Drug: Venetoclax

Interventions

Azacitidine DRUG

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.

Azacitidine and Venetoclax

Venetoclax DRUG

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.

Azacitidine and Venetoclax

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• University Health Network, Toronto: lead

Study Sites (1)

Princess Margaret Cancer Centre

Toronto, Ontario, M5G 2M9, Canada

RECRUITING

MeSH Terms

Conditions

Myeloproliferative Disorders

Interventions

Azacitidine; venetoclax

Condition Hierarchy (Ancestors)

Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Aza Compounds; Organic Chemicals; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides

Study Officials

• Vikas Gupta, M.D.

  Princess Margaret Cancer Centre

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Vikas Gupta, M.D.

CONTACT

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

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 29, 2021
• First Posted: October 12, 2021
• Study Start: November 8, 2023
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2026
• Last Updated: December 18, 2025

Record last verified: 2025-12

Locations

CA (1)