A Phase 2 Study of Azacitidine and Venetoclax to Treat Acute Myeloid Leukemia Patients With Measurable Residual Disease Before an Allogeneic Stem Cell Transplant

Memorial Sloan Kettering Cancer Center7 个研究点分布在 1 个国家目标入组 30 人2025年1月7日

适应症Acute Myeloid Leukemia (AML)

干预措施Azacitidine (AZC)Venetoclax

概览

阶段: 2 期
干预措施: Azacitidine (AZC)
疾病 / 适应症: Acute Myeloid Leukemia (AML)
发起方: Memorial Sloan Kettering Cancer Center
入组人数: 30
试验地点: 7
主要终点: rate of MRD conversion
状态: 招募中
最后更新: 2个月前

概览研究者入排标准研究组 & 干预措施结局指标研究点相似试验

概览

简要总结

The purpose of this study is to find out if azacitidine and venetoclax are an effective treatment approach to get rid of or lower measurable residual disease (MRD) in people with acute myeloid leukemia (AML) who have received standard chemotherapy and are planning to have an allogeneic hematopoietic stem cell transplant (HSCT). Allogeneic HSCT, sometimes called a bone marrow transplant, involves receiving healthy blood-forming cells (stem cells) from a donor in order to replace the patient's immune system and lower the chances of the disease returning (relapse).

注册库

clinicaltrials.gov

开始日期

2025年1月7日

结束日期

2027年1月1日

最后更新

2个月前

研究类型

Interventional

研究设计

Single Group

性别

All

研究者

发起方

Memorial Sloan Kettering Cancer Center

责任方

Sponsor

入排标准

入选标准

•1\. Adult patient ≥18 years of age at the time of signing the informed consent form (ICF). Legal Authorized Representatives (LAR) are permitted.
•2\. Patient is willing and able to adhere to the study visit schedule and other protocol requirements.
•3\. Patient has a confirmed diagnosis of de-novo AML (non-APL) as per World Health Organization (2022) guidelines. All (non-APL) subtypes of AML are permitted, irrespective of ELN risk category or mutational status.
•4\. Patient has received 1-3 cycles of intensive chemotherapy for remission induction.
•5\. Patient is in a morphologic remission, defined as less than 5% percent blasts seen by aspirate differential (or immunohistochemistry if no aspirate available) from bone marrow biopsy.
•6\. Patient and is either in CR, or CR with partial count recovery, either CRi/CRh\\\^
•1CR= BM with \<5% blasts, absence of circulating blasts; absence of extramedullary disease, absolute neutrophil count (ANC) ≥ 1000 cells/µL and platelet (PLT) count ≥ 100,000/µL. CRh = CR with ANC 500-1000 cells/µL and PLT 50,000-100,000 /µL. CRi = CR without meeting CRh criteria (residual neutropenia or thrombocytopenia).
•7\. Patient has positive measurable residual disease (MRD) at or above a level of 0.1%, by flow cytometry (MFC) or in molecular cases (NPM1 mutated or one of the CBF translocations) RT-qPCR at or above 0.01%, as described above (see section 3.6). If RT-qPCR is not available, MFC will be allowed for determining eligibility for molecular patients (at or above 0.1%).
•8\. Patient is eligible for intensive chemotherapy and immediate allogeneic transplant, with intention to proceed to transplant after trial intervention.
•9\. Patient has an ECOG performance status of ≤3

排除标准

•1\. Patients with acute promyelocytic leukemia (APL) or relapsed/refractory AML
•Blast crisis of chronic myeloid leukemia
•Patient with 5% blasts or more by bone marrow aspirate differential (or IHC if no aspirate available)
•Patient has received previous therapy with a venetoclax containing regimen.
•Patient has presence of any other condition that may increase the risk associated with study participation, and in the opinion of the investigator, would make the patient inappropriate for entry into the study.
•6\. Patient has active uncontrolled systemic fungal, bacterial, or viral infection.
•7\. Patient had recent, significant venous or arterial thrombotic event that would necessitate full anticoagulation or dual anti-platelet therapy, including PE within 30 days prior to start of treatment or insertion of drug eluting stent within 6 months prior to start of treatment. Chronic indications for anticoagulation such as atrial fibrillation, can be included if CHADS2 score below
•8\. Patient has mechanical heart valve.
•Patient had recent significant hemorrhagic episode, at the discretion of investigator.
•10\. Patient has significant active cardiac disease within 6 months prior to start of study treatment.

研究组 & 干预措施

Azacitidine and Venetoclax

Cycle length: 28 days Azacitidine 75 mg/m2 daily, on days 1-7, given IV or SC (generally given IV in our institution) Venetoclax 400 mg orally daily on days 1-28

干预措施: Azacitidine (AZC)

Azacitidine and Venetoclax

Cycle length: 28 days Azacitidine 75 mg/m2 daily, on days 1-7, given IV or SC (generally given IV in our institution) Venetoclax 400 mg orally daily on days 1-28

干预措施: Venetoclax

结局指标

主要结局

rate of MRD conversion

时间窗: 1 year

MRD status will be assessed from end-of-cycle bone marrow aspirate, in all patients. MRD will be assessed by flow cytometry (MFC) or by RT-qPCR in molecular patients. This is a dichotomous variable of positive versus negative MRD, with a pre-defined threshold as described above, of 0.1% for MFC or 0.01% in molecular patients .