Study of Venetoclax and Azacitidine in Advanced BCR-ABL Negative Myeloproliferative Neoplasms
Phase 2
Recruiting
- Conditions
- Myeloproliferative Neoplasm
- Interventions
- Registration Number
- NCT05074355
- Lead Sponsor
- University Health Network, Toronto
- 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.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 40
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 & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Azacitidine and Venetoclax Azacitidine 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. Azacitidine and Venetoclax 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.
- Primary Outcome Measures
Name Time Method Proportion of participants achieving complete remission (CR). 3 years Proportion of participants achieving reversion to chronic myeloproliferative neoplasm (CMPN). 3 years Proportion of participants achieving complete remission with incomplete hematologic recovery (CRi). 3 years
- Secondary Outcome Measures
Name Time Method Average number of days from CMPN until relapse. 3 years Average number of days from CR until relapse. 3 years The proportion of patients proceeding to allogeneic stem cell transplantation in those eligible for transplantation. 3 years Average number of days from CRi until relapse. 3 years Average number of days from the first dose of azacytidine and venetoclax to the date of death. 3 years
Trial Locations
- Locations (1)
Princess Margaret Cancer Centre
🇨🇦Toronto, Ontario, Canada