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

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

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.

Study Overview

• Status: Recruiting
• Conditions: Myeloproliferative Neoplasm
• Intervention / Treatment: Drug: Azacitidine; Drug: Venetoclax

Detailed Description

All participants in this study will receive azacitidine and venetoclax.

This study will be done in multiple stages:

Safety Run-In Period - 7 participants will receive the study drugs to ensure that the combination is safe and tolerable.

Stage 1 - About 15 participants will receive the study drugs and will be evaluated to see whether they respond to the study drugs.

Stage 2 - If enough participants in Stage 1 respond to the study drugs, then Stage 2 will begin. During this stage, an additional 25 participants will take part in the study to further see if participants respond to the study drugs.

• Study Type: Interventional
• Enrollment (Estimated): 40
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Vikas Gupta, M.D.; Phone Number: 416-946-2885; Email: vikas.gupta@uhn.ca

Study Locations

• Canada
  • Ontario
    • Toronto, Ontario, Canada, M5G 2M9
      • Recruiting
      • Princess Margaret Cancer Centre
      • Contact: Vikas Gupta, M.D.; Phone Number: 416-946-2885
      • Principal Investigator: Vikas Gupta, M.D.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

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.

Drug: 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.; Drug: 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
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 Outcome Measures

Outcome Measure	Time Frame
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

Collaborators and Investigators

• Sponsor: University Health Network, Toronto
• Investigators: Principal Investigator: Vikas Gupta, M.D., Princess Margaret Cancer Centre

Study record dates

Study Major Dates

• Study Start (Actual): November 8, 2023
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2026

Study Registration Dates

• First Submitted: September 29, 2021
• First Submitted That Met QC Criteria: September 29, 2021
• First Posted (Actual): October 12, 2021

Study Record Updates

• Last Update Posted (Estimated): December 18, 2025
• Last Update Submitted That Met QC Criteria: December 11, 2025
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Hematologic Diseases; Bone Marrow Diseases; Hemic and Lymphatic Diseases; Myeloproliferative Disorders; Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleic Acids, Nucleotides, and Nucleosides; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Aza Compounds; Nucleosides; Ribonucleosides; Azacitidine; venetoclax
• Other Study ID Numbers: VAAMP; 21-5928 (Other Identifier: University Health Network)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No