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

Sponsor
University Health Network, Toronto (Other)
Overall Status
Not yet recruiting
CT.gov ID
NCT05074355
Collaborator
(none)
40
1
1
24
1.7

Study Details

Study Description

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.

Condition or Disease Intervention/Treatment Phase
Phase 2

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 Design

Study Type:
Interventional
Anticipated Enrollment :
40 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
Venetoclax and Azacitidine Combination Therapy for Patients With Accelerated or Blast Phase BCR-ABL Negative Myeloproliferative Neoplasm (VAAMP)
Anticipated Study Start Date :
May 16, 2022
Anticipated Primary Completion Date :
May 16, 2024
Anticipated Study Completion Date :
May 16, 2024

Arms and Interventions

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.

Outcome Measures

Primary Outcome Measures

  1. Proportion of participants achieving complete remission (CR). [3 years]

  2. Proportion of participants achieving complete remission with incomplete hematologic recovery (CRi). [3 years]

  3. Proportion of participants achieving reversion to chronic myeloproliferative neoplasm (CMPN). [3 years]

Secondary Outcome Measures

  1. Average number of days from the first dose of azacytidine and venetoclax to the date of death. [3 years]

  2. Average number of days from CR until relapse. [3 years]

  3. Average number of days from CRi until relapse. [3 years]

  4. Average number of days from CMPN until relapse. [3 years]

  5. The proportion of patients proceeding to allogeneic stem cell transplantation in those eligible for transplantation. [3 years]

Eligibility Criteria

Criteria

Ages Eligible for Study:
18 Years and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
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.

Contacts and Locations

Locations

Site City State Country Postal Code
1 Princess Margaret Cancer Centre Toronto Ontario Canada M5G 2M9

Sponsors and Collaborators

  • University Health Network, Toronto

Investigators

  • Principal Investigator: Vikas Gupta, M.D., Princess Margaret Cancer Centre

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.
Responsible Party:
University Health Network, Toronto
ClinicalTrials.gov Identifier:
NCT05074355
Other Study ID Numbers:
  • VAAMP
  • 21-5928
First Posted:
Oct 12, 2021
Last Update Posted:
Apr 20, 2022
Last Verified:
Apr 1, 2022
Studies a U.S. FDA-regulated Drug Product:
No
Studies a U.S. FDA-regulated Device Product:
No
Additional relevant MeSH terms:

Study Results

No Results Posted as of Apr 20, 2022