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

December 11, 2025 updated by: University Health Network, Toronto

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

Status

Indicates the current recruitment status or the expanded access status.
Recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
40

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

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

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

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

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
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

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Time Frame
Proportion of participants achieving complete remission (CR).
Time Frame: 3 years
3 years
Proportion of participants achieving complete remission with incomplete hematologic recovery (CRi).
Time Frame: 3 years
3 years
Proportion of participants achieving reversion to chronic myeloproliferative neoplasm (CMPN).
Time Frame: 3 years
3 years

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Time Frame
Average number of days from the first dose of azacytidine and venetoclax to the date of death.
Time Frame: 3 years
3 years
Average number of days from CR until relapse.
Time Frame: 3 years
3 years
Average number of days from CRi until relapse.
Time Frame: 3 years
3 years
Average number of days from CMPN until relapse.
Time Frame: 3 years
3 years
The proportion of patients proceeding to allogeneic stem cell transplantation in those eligible for transplantation.
Time Frame: 3 years
3 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
University Health Network, Toronto

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Vikas Gupta, M.D., Princess Margaret Cancer Centre

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
November 8, 2023

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
December 31, 2026

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
December 31, 2026

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
September 29, 2021

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
September 29, 2021

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
October 12, 2021

Study Record Updates

Last Update Posted (Estimated)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
December 18, 2025

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
December 11, 2025

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
December 1, 2025

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant 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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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