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

Primary Purpose

Myeloproliferative Neoplasm

Status
Not yet recruiting
Phase
Phase 2
Locations
Canada
Study Type
Interventional
Intervention
Azacitidine
Venetoclax
Sponsored by
University Health Network, Toronto
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Myeloproliferative Neoplasm

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Princess Margaret Cancer Centre

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Azacitidine and Venetoclax

Arm Description

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.

Outcomes

Primary Outcome Measures

Proportion of participants achieving complete remission (CR).
Proportion of participants achieving complete remission with incomplete hematologic recovery (CRi).
Proportion of participants achieving reversion to chronic myeloproliferative neoplasm (CMPN).

Secondary Outcome Measures

Average number of days from the first dose of azacytidine and venetoclax to the date of death.
Average number of days from CR until relapse.
Average number of days from CRi until relapse.
Average number of days from CMPN until relapse.
The proportion of patients proceeding to allogeneic stem cell transplantation in those eligible for transplantation.

Full Information

First Posted
September 29, 2021
Last Updated
June 15, 2023
Sponsor
University Health Network, Toronto
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1. Study Identification

Unique Protocol Identification Number
NCT05074355
Brief Title
Study of Venetoclax and Azacitidine in Advanced BCR-ABL Negative Myeloproliferative Neoplasms
Official Title
Venetoclax and Azacitidine Combination Therapy for Patients With Accelerated or Blast Phase BCR-ABL Negative Myeloproliferative Neoplasm (VAAMP)
Study Type
Interventional

2. Study Status

Record Verification Date
June 2023
Overall Recruitment Status
Not yet recruiting
Study Start Date
September 16, 2023 (Anticipated)
Primary Completion Date
May 16, 2024 (Anticipated)
Study Completion Date
May 16, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University Health Network, Toronto

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. 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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Myeloproliferative Neoplasm

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
40 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Azacitidine and Venetoclax
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Azacitidine
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
Venetoclax
Intervention Description
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 Information:
Title
Proportion of participants achieving complete remission (CR).
Time Frame
3 years
Title
Proportion of participants achieving complete remission with incomplete hematologic recovery (CRi).
Time Frame
3 years
Title
Proportion of participants achieving reversion to chronic myeloproliferative neoplasm (CMPN).
Time Frame
3 years
Secondary Outcome Measure Information:
Title
Average number of days from the first dose of azacytidine and venetoclax to the date of death.
Time Frame
3 years
Title
Average number of days from CR until relapse.
Time Frame
3 years
Title
Average number of days from CRi until relapse.
Time Frame
3 years
Title
Average number of days from CMPN until relapse.
Time Frame
3 years
Title
The proportion of patients proceeding to allogeneic stem cell transplantation in those eligible for transplantation.
Time Frame
3 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Vikas Gupta, M.D.
Phone
416-946-2885
Email
vikas.gupta@uhn.ca
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Vikas Gupta, M.D.
Organizational Affiliation
Princess Margaret Cancer Centre
Official's Role
Principal Investigator
Facility Information:
Facility Name
Princess Margaret Cancer Centre
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M5G 2M9
Country
Canada
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Vikas Gupta, M.D.
Phone
416-946-2885
First Name & Middle Initial & Last Name & Degree
Vikas Gupta, M.D.

12. IPD Sharing Statement

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

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