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

Myeloproliferative Neoplasm Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05074355
• Other study ID #: VAAMP
• Secondary ID: 21-5928
• Status: Recruiting
• Phase: Phase 2
• Start date: November 8, 2023
• Est. completion date: December 31, 2025

Study information

• Verified date: February 2024
• Source: University Health Network, Toronto
• Contact: Vikas Gupta, M.D.
• Phone: 416-946-2885
• Email: vikas.gupta[@]uhn.ca
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Recruiting
• Enrollment: 40
• Est. completion date: December 31, 2025
• Est. primary completion date: May 16, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Myeloproliferative Disorders
• Myeloproliferative Neoplasm
• Neoplasms

Intervention

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.
• 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.

Locations

Country	Name	City	State
Canada	Princess Margaret Cancer Centre	Toronto	Ontario

Sponsors (1)

Lead Sponsor	Collaborator
University Health Network, Toronto

Country where clinical trial is conducted

Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Proportion of participants achieving complete remission (CR).		3 years
Primary	Proportion of participants achieving complete remission with incomplete hematologic recovery (CRi).		3 years
Primary	Proportion of participants achieving reversion to chronic myeloproliferative neoplasm (CMPN).		3 years
Secondary	Average number of days from the first dose of azacytidine and venetoclax to the date of death.		3 years
Secondary	Average number of days from CR until relapse.		3 years
Secondary	Average number of days from CRi until relapse.		3 years
Secondary	Average number of days from CMPN until relapse.		3 years
Secondary	The proportion of patients proceeding to allogeneic stem cell transplantation in those eligible for transplantation.		3 years