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

Официальное название

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

Обзор

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.

Подробное описание

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.

Вмешательства

• Препарат 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.
• Препарат 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.

Первичные конечные точки

• Proportion of participants achieving complete remission (CR). [Срок оценки: 3 years]
• Proportion of participants achieving complete remission with incomplete hematologic recovery (CRi). [Срок оценки: 3 years]
• Proportion of participants achieving reversion to chronic myeloproliferative neoplasm (CMPN). [Срок оценки: 3 years]

Вторичные конечные точки (5)

• Average number of days from the first dose of azacytidine and venetoclax to the date of death. [Срок оценки: 3 years]
• Average number of days from CR until relapse. [Срок оценки: 3 years]
• Average number of days from CRi until relapse. [Срок оценки: 3 years]
• Average number of days from CMPN until relapse. [Срок оценки: 3 years]
• The proportion of patients proceeding to allogeneic stem cell transplantation in those eligible for transplantation. [Срок оценки: 3 years]

Критерии участия

Критерии включения

• 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.

Критерии исключения

• 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.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Не применимо

Модель

Одна группа

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Канада · 1 центр

• Princess Margaret Cancer Centre — Toronto

Идентификаторы

NCT: NCT05074355 · VAAMP · 21-5928

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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