Venetoclax and Azacitidine Combination Therapy for Patients With Accelerated or Blast Phase BCR-ABL Negative Myeloproliferative Neoplasm (VAAMP)
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 40
- 试验地点
- 2
- 主要终点
- Proportion of participants achieving complete remission (CR).
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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-
- •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.
排除标准
- •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.
研究组 & 干预措施
Azacitidine and 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.
干预措施: Azacitidine (Drug)
Azacitidine and 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.
干预措施: Venetoclax (Drug)
结局指标
主要结局
Proportion of participants achieving complete remission (CR).
时间窗: 3 years
Proportion of participants achieving reversion to chronic myeloproliferative neoplasm (CMPN).
时间窗: 3 years
Proportion of participants achieving complete remission with incomplete hematologic recovery (CRi).
时间窗: 3 years
次要结局
- 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)