Phase 2 Study of Decitabine and Cedazuridine in Combination With Venetoclax for AML Relapse After Allogeneic Hematopoietic Cell Transplantation
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 发起方
- 入组人数
- 1
- 试验地点
- 1
- 主要终点
- Number of Participants That Achieved a Complete Response to Therapy
研究概览
简要总结
This phase II trial tests how well decitabine and cedazuridine (DEC-C) works in combination with venetoclax in treating acute myeloid leukemia (AML) in patients whose AML has come back after a period of improvement (relapse) after a donor stem cell transplant. Cedazuridine is in a class of medications called cytidine deaminase inhibitors. It prevents the breakdown of decitabine, making it more available in the body so that decitabine will have a greater effect. Decitabine is in a class of medications called hypomethylation agents. It works by helping the bone marrow produce normal blood cells and by killing abnormal cells in the bone marrow. Venetoclax is in a class of medications called B-cell lymphoma-2 (BCL-2) inhibitors. It may stop the growth of cancer cells by blocking Bcl-2, a protein needed for cancer cell survival. Giving DEC-C in combination with venetoclax may kill more cancer cells in patients with relapsed AML.
详细描述
PRIMARY OBJECTIVE:
I. To assess the effect of DEC-C/venetoclax on the investigator-assessed composite complete remission (CR) rate (CR/complete remission with partial hematologic recovery [CRh]/complete remission with incomplete hematologic recovery [CRi]).
SECONDARY OBJECTIVES:
I. To assess the rate of partial response (PR) and morphologic leukemia free state (MLFS) following treatment with DEC-C/venetoclax. II. To assess the relapse free survival of patients treated with DEC-C/venetoclax.
III. To assess overall survival of patients treated with DEC-C/venetoclax. IV. To assess the safety and tolerability of DEC-C/venetoclax in the post-hematopoietic cell transplant (HCT) setting.
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
- •Age >= 18 years at the time of signing the Informed Consent Form (ICF); must voluntarily sign an ICF and meet all study requirements
- •History of morphologically confirmed AML (per World Health Organization [WHO] diagnostic criteria) with evidence of disease recurrence (>= 5% blasts consistent with prior disease) that occurs after allogeneic hematopoietic cell transplantation (HCT). Patients transplanted for another indication (e.g., myelodysplastic syndrome/chronic myelomonocytic leukemia [MDS/CMML]) who relapse with AML are eligible to enroll
- •White blood cells (WBC) must be less than 25,000/ul for at least three days prior to cycle 1, day 1 (C1D1) (hydroxyurea allowed)
- •A bone marrow biopsy must be performed and tissue collected for entrance to the trial
- •Eastern Cooperative Oncology Group Performance Status of 0 - 2
- •Alanine transaminase (ALT) serum glutamic pyruvic transaminase (SGPT) and/or aspartate aminotransferase (AST) serum glutamic-oxaloacetic transaminase (SGOT) less than or equal to 3x upper limit of normal (ULN)
- •Total bilirubin < 1.5 x ULN
- •* Patients with Gilbert's syndrome (hereditary indirect hyperbilirubinemia) must have a total bilirubin of < 3 x ULN
- •Calculated creatinine clearance >= 30 ml/min (per the Cockroft-Gault formula)
- •Willingness to abide by all study requirements, including contraception, maintenance of a pill diary, and acceptance of recommended supportive care medications
排除标准
- •Prior relapse or progression while receiving venetoclax or other commercially available or investigational BCL-2 inhibitor
- •Anticancer therapy, including investigational agents =< 2 weeks or =< 5 half-lives of the drug, whichever is shorter, prior to C1D
- •(Use of hydroxyurea is permitted)
- •Inadequate recovery from toxicity attributed to prior anti-cancer therapy to =< Grade 1 (National Cancer Institute Common Terminology Criteria for Adverse Events [NCI CTCAE] version [v]5.0), excluding alopecia or fatigue
- •History of allogeneic HCT, or other cellular therapy product, within 3 months of signing consent
- •Clinically active acute or chronic graft versus host disease (GVHD). Patients must be off calcineurin inhibitors for at least 4 weeks to be eligible
- •Radiation therapy or major surgery within 3 weeks of signing consent
- •Active, uncontrolled infection. Patients with infection under active treatment and controlled with antibiotics are eligible. Prophylaxis is acceptable
- •Inability to tolerate oral medication, presence of poorly controlled gastrointestinal disease, or dysfunction that could affect study drug absorption
- •Active documented central nervous system leukemia
- •Concurrent treatment with a non-permitted concomitant medication
- •Other malignancy IF currently being treated or likely to be treated in next 6 months except for basal or squamous cell carcinoma of the skin or cervical carcinoma in situ
- •Pregnancy or breastfeeding females
- •Known chronic alcohol or drug abuse
- •Clinically significant cardiovascular disease with major event or cardiac intervention within the past 6 months (e.g. percutaneous intervention, coronary artery bypass graft, documented cardiac heart failure) as determined by the investigator
- •Any other condition deemed by the investigator to make the patient a poor candidate for clinical trial and/or treatment with investigational agents
研究组 & 干预措施
Treatment (Venetoclax, DEC-C)
Patients receive venetoclax PO daily for 28 days in a 28-day cycle. Patients receive DEC-C PO daily on days 1-5 of a 28-day cycle. Patients undergo bone marrow biopsy and aspiration and blood sample collection throughout the study.
干预措施: Venetoclax (Drug)
Treatment (Venetoclax, DEC-C)
Patients receive venetoclax PO daily for 28 days in a 28-day cycle. Patients receive DEC-C PO daily on days 1-5 of a 28-day cycle. Patients undergo bone marrow biopsy and aspiration and blood sample collection throughout the study.
干预措施: Decitabine (Drug)
Treatment (Venetoclax, DEC-C)
Patients receive venetoclax PO daily for 28 days in a 28-day cycle. Patients receive DEC-C PO daily on days 1-5 of a 28-day cycle. Patients undergo bone marrow biopsy and aspiration and blood sample collection throughout the study.
干预措施: Cedazuridine (Drug)
Treatment (Venetoclax, DEC-C)
Patients receive venetoclax PO daily for 28 days in a 28-day cycle. Patients receive DEC-C PO daily on days 1-5 of a 28-day cycle. Patients undergo bone marrow biopsy and aspiration and blood sample collection throughout the study.
干预措施: Bone Marrow Aspiration and Biopsy (Procedure)
Treatment (Venetoclax, DEC-C)
Patients receive venetoclax PO daily for 28 days in a 28-day cycle. Patients receive DEC-C PO daily on days 1-5 of a 28-day cycle. Patients undergo bone marrow biopsy and aspiration and blood sample collection throughout the study.
干预措施: Biospecimen Collection (Procedure)
结局指标
主要结局
Number of Participants That Achieved a Complete Response to Therapy
时间窗: 9 months
次要结局
- Number of Participants That Achieved a Partial Response to Therapy(9 months)
- Rate of Morphologic Leukemia Free State (MLFS) Following Treatment With DEC-C/Venetoclax(Up to 24 months post-treatment.)
- Rate of Relapse Free Survival(Up to 24 months post-treatment.)
- Rate of Overall Survival(Up to 24 months post-treatment.)
- Number of Treatment-related Adverse Events(The one patient that was enrolled on the study was on treatment for 3 months and adverse event data were followed during treatment and 35 days after completing treatment.)
- Rate of Measurable Residual Disease Negativity in Patients Achieving a CR(Up to 24 months post-treatment.)
研究者
Sanjay Mohan
Assistant Professor of Medicine
Vanderbilt-Ingram Cancer Center