Clinical trial NCT05074355: 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
Overall status: RECRUITING
Phase: PHASE2
Conditions: Myeloproliferative Neoplasm
Lead sponsor: University Health Network, Toronto
Sponsor class: OTHER
First posted: 2021-10-12
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Proportion of participants achieving complete remission (CR).
timeFrame: 3 years
measure: Proportion of participants achieving complete remission with incomplete hematologic recovery (CRi).
timeFrame: 3 years
measure: Proportion of participants achieving reversion to chronic myeloproliferative neoplasm (CMPN).
timeFrame: 3 years
Secondary outcomes:
measure: Average number of days from the first dose of azacytidine and venetoclax to the date of death.
timeFrame: 3 years
measure: Average number of days from CR until relapse.
timeFrame: 3 years
measure: Average number of days from CRi until relapse.
timeFrame: 3 years
measure: Average number of days from CMPN until relapse.
timeFrame: 3 years
measure: The proportion of patients proceeding to allogeneic stem cell transplantation in those eligible for transplantation.
timeFrame: 3 years
Other outcomes:
Locations:
city: Toronto
country: Canada
facility: Princess Margaret Cancer Centre
state: Ontario
Study officials:
affiliation: Princess Margaret Cancer Centre
name: Vikas Gupta, M.D.
role: PRINCIPAL_INVESTIGATOR
References: