Discontinuation of Hypomethylating Agent and Venetoclax in Patients With Newly Diagnosed Acute Myeloid Leukemia (AML) Who Have Achieved Negative Measurable Residual Disease (MRD)
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 37
- 试验地点
- 1
- 主要终点
- Rates of Complete Response (CR)/Complete Response with incomplete hematologic recovery (CRi)
研究概览
简要总结
The purpose of this research study is to see if people whose Acute myeloid leukemia (AML) is being successfully treated with azacitidine or decitabine in combination with venetoclax can discontinue this chemotherapy for some period of time after a year of treatment without increasing the likelihood that their AML will return.
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
- •Adults 18 years of age or older at the time of obtaining informed consent.
- •Diagnosed with Acute Myeloid Leukemia (AML) (non-M3) as defined by 2016 World Health Organization (WHO)
- •Eastern Cooperative Group (ECOG) performance status score ≤ 2
- •Currently on frontline therapy with HMA (azacitidine or decitabine)/VEN and achieved Complete Remission (CR)/Complete Remission with incomplete marrow recovery (CRi) with MRD negativity defined as < 0.1% by Multiparameter Flow Cytometry (MFC)
- •Within 12 months of starting HMA (azacitidine or decitabine)/VEN
- •Ineligible for or declined allogeneic hematopoietic cell transplantation (HCT)
- •Ability to understand and the willingness to sign a written informed consent document
- •Must agree to adhere to the study visit schedule and other protocol requirements
- •Patients must be able to provide adequate Bone Marrow (BM) aspirate and biopsy specimens for histopathological and Measurable Residual Disease analysis during the screening procedure
排除标准
- •Use of cytotoxic chemotherapeutic agents, or experimental agents (agents that are not commercially available) for the treatment of AML within 28 days, or 5 half-lives, at the start of the study. Only patients who are receiving frontline HMA (azacitidine or decitabine)/VEN are potentially eligible, but if they had received a course of hydroxyurea prior to achieving CR/CRi, this is allowed.
- •Any serious medical condition or uncontrolled current illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements or will place the subject at unacceptable risk if he/she participates in the study. Controlled infections or other medical conditions on long-term therapy is allowed.
- •Patients who harbored TP53 mutation at diagnosis
- •AML with extramedullary involvement including central nervous system (CNS) involvement, myeloid sarcoma, and leukemia cutis requiring directed therapy at the time of enrollment.
- •Patient is pregnant.
研究组 & 干预措施
Consolidation and Discontinuation
Consolidation: Patient will receive HMA (azacitidine or decitabine)/VEN (venetoclax) as part of standard of care treatment.
At the conclusion of consolidation, if the results of the bone marrow biopsy are a negative Measurable Residual Disease (MRD), patient will continue to Discontinuation.
Discontinuation:
Monthly clinic visits with laboratory assessment and bone marrow biopsies (BMBs) with MRD testing every 3 months to closely monitor disease status. At any point of the study if molecular relapse (including MRD emergence), or morphologic relapse, therapy will be reinitiated.
If only molecular relapse, HMA (azacitidine or decitabine)/VEN (venetoclax) will be reinitiated with the same monitoring schedule as before.
If morphologic relapse, HMA (azacitidine or decitabine)/VEN (venetoclax) will be reinitiated for 2 cycles.
If no response (NR), patient will be taken off Study.
干预措施: Azacitidine (Drug)
Consolidation and Discontinuation
Consolidation: Patient will receive HMA (azacitidine or decitabine)/VEN (venetoclax) as part of standard of care treatment.
At the conclusion of consolidation, if the results of the bone marrow biopsy are a negative Measurable Residual Disease (MRD), patient will continue to Discontinuation.
Discontinuation:
Monthly clinic visits with laboratory assessment and bone marrow biopsies (BMBs) with MRD testing every 3 months to closely monitor disease status. At any point of the study if molecular relapse (including MRD emergence), or morphologic relapse, therapy will be reinitiated.
If only molecular relapse, HMA (azacitidine or decitabine)/VEN (venetoclax) will be reinitiated with the same monitoring schedule as before.
If morphologic relapse, HMA (azacitidine or decitabine)/VEN (venetoclax) will be reinitiated for 2 cycles.
If no response (NR), patient will be taken off Study.
干预措施: Decitabine (Drug)
Consolidation and Discontinuation
Consolidation: Patient will receive HMA (azacitidine or decitabine)/VEN (venetoclax) as part of standard of care treatment.
At the conclusion of consolidation, if the results of the bone marrow biopsy are a negative Measurable Residual Disease (MRD), patient will continue to Discontinuation.
Discontinuation:
Monthly clinic visits with laboratory assessment and bone marrow biopsies (BMBs) with MRD testing every 3 months to closely monitor disease status. At any point of the study if molecular relapse (including MRD emergence), or morphologic relapse, therapy will be reinitiated.
If only molecular relapse, HMA (azacitidine or decitabine)/VEN (venetoclax) will be reinitiated with the same monitoring schedule as before.
If morphologic relapse, HMA (azacitidine or decitabine)/VEN (venetoclax) will be reinitiated for 2 cycles.
If no response (NR), patient will be taken off Study.
干预措施: Venetoclax (Drug)
结局指标
主要结局
Rates of Complete Response (CR)/Complete Response with incomplete hematologic recovery (CRi)
时间窗: Up to 18 Months
Rates of CR/CRi at 18 months from the time of initial CR/CRi in patients who discontinue frontline HMA (azacitidine or decitabine)/VEN (venetoclax) after achieving Measurable Residual Disease (MRD) negativity by MFC within 12 months of starting therapy. The Null hypothesis (p0) will be tested against the alternative hypothesis (p1). Null hypothesis: p0 ≤ 50% will remain in CR/CRi at 18 months from the time of initial CR/CRi Alternative hypothesis: p1 ≥ 70% will remain in CR/CRi at 18 months from the time of initial CR/CRi
次要结局
- Rates to Re-Treatment(Up to 36 Months)
- Overall Survival (OS)(Up to 36 Months)
- Treatment Free Molecular Remission (TFMR)(Up to 36 Months)
- EuroQoL-5 Dimensions-5 Levels (EQ-5D-5L) Visual Analog Scale (VAS)(Day 1 (start of enrollment), start of Discontinuation Phase, and monthly until EOT (Up to 36 Months))
- European Organization for Research and Treatment of Cancer (EORTC-QLQ-C30)/Quality of Life (QoL)(Day 1 (start of enrollment), start of Discontinuation Phase, and monthly until EOT (Up to 36 Months))
- Patient Reported Outcome Measurement Information System (PROMIS)(Day 1 (start of enrollment), start of Discontinuation Phase, and monthly until EOT (Up to 36 Months))