Phase Ib Study of Eltanexor and Venetoclax in Relapsed or Refractory Myelodysplastic Syndrome and Acute Myeloid Leukemia
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 60
- 试验地点
- 3
- 主要终点
- Incidence of adverse events
研究概览
简要总结
This phase I trial tests the safety, side effects, and best dose of eltanexor in combination with venetoclax for the treatment of patients with myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML) that has come back after a period of improvement (relapsed) or that has not responded to previous treatment (refractory). Eltanexor works by trapping "tumor suppressing proteins" within the cell, thus causing the cancer cells to die or stop growing. 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 eltanexor together with venetoclax may be safe, tolerable and/or effective in treating patients with relapsed or refractory MDS or AML.
详细描述
Primary objective:
• To establish the safe and biologically effective dose (BED) of eltanexor in combination with venetoclax in patients with R/R MDS and/or AML
Secondary objectives:
- To estimate the complete remission (CR) rate with eltanexor and venetoclax in patients with R/R MDS and/or AML
- To assess the overall response rate (ORR) following treatment with eltanexor/venetoclax
- To assess the overall survival of patients
- To assess the progression free survival (PFS) and duration of response (DOR) in patients treated with eltanexor/venetoclax
Exploratory objectives:
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 must be able to meet all study requirements.
- •For Myelodysplastic Syndrome (MDS):
- •Morphologically confirmed diagnosis of MDS with increased blasts (\>/= 5%), with a prior DNA methyltransferase inhibitor (DNMTi) treatment and progression after 2 cycles or stable disease after 4 cycles
- •For Acute Myeloid Leukemia (AML):
- •Morphologically confirmed diagnosis of AML in accordance with WHO diagnostic criteria that is relapsed or refractory following \>/= 1 line(s) of therapy.
- •* WBC must be less than 25,000/ul prior to study start (hydroxyurea allowed).
- •* A bone marrow aspirate must be performed, and tissue collected for entrance to the trial unless circulating blasts \>/= 5% in which case, peripheral blood can be used.
- •* Eastern Cooperative Oncology Group Performance Status of 0 - 2.
- •* Must have adequate hepatic and renal function as demonstrated by the following:
- •ALT(SGPT) and/or AST (SGOT) \ 50 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
- •* Anticancer therapy, including investigational agents \/= 10mg/day or patients within 4 weeks of stopping calcineurin inhibitors for GVHD.
- •* Radiation therapy or major surgery within 3 weeks.
- •* Active, uncontrolled infection. Patients with infection under active treatment and controlled with antibiotics are eligible. Prophylaxis, even if parenteral, is acceptable.
- •* Inability to swallow oral medications.
- •* Active documented central nervous system leukemia.
- •* Second active malignancy within past 2 years except for basal or squamous cell carcinoma of the skin, ductal carcinoma of breast in situ or cervical carcinoma in situ.
- •* Women of childbearing age or potential must have negative pregnancy test and must not be actively breastfeeding to enroll on the study
- •* 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.
- •* QT interval corrected by Fridericia's formula (QTcF)\>470msec for both males and females on screening ECG. Patients with a bundle branch block or in-situ pacemaker must have appropriate QT interval corrections for these conditions.
- •* Any condition not listed but 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
Eltanexor + Venetoclax
Participants receive eltanexor PO QD for 5 days per week for 14, 21, or 28 days every cycle, and venetoclax PO QD on days 1-14 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Participants undergo bone marrow aspiration and biopsy and blood sample collection throughout the study.
干预措施: Bone Marrow Aspiration and Biopsy (Procedure)
Eltanexor + Venetoclax
Participants receive eltanexor PO QD for 5 days per week for 14, 21, or 28 days every cycle, and venetoclax PO QD on days 1-14 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Participants undergo bone marrow aspiration and biopsy and blood sample collection throughout the study.
干预措施: Eltanexor (Drug)
Eltanexor + Venetoclax
Participants receive eltanexor PO QD for 5 days per week for 14, 21, or 28 days every cycle, and venetoclax PO QD on days 1-14 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Participants undergo bone marrow aspiration and biopsy and blood sample collection throughout the study.
干预措施: Venetoclax (Drug)
Eltanexor + Venetoclax
Participants receive eltanexor PO QD for 5 days per week for 14, 21, or 28 days every cycle, and venetoclax PO QD on days 1-14 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Participants undergo bone marrow aspiration and biopsy and blood sample collection throughout the study.
干预措施: Biospecimen Collection (Procedure)
结局指标
主要结局
Incidence of adverse events
时间窗: Up to 2 years
Adverse medical events will be tabulated and graded according to the Common Terminology Criteria for Adverse Events (CTCAE) version 5.
Biologically effective dose (BED) of eltanexor in combination with venetoclax
时间窗: Up to 2 years
Measured by complete remission
次要结局
- Complete remission(Up to 2 years)
- Overall response rate(Up to 2 years)
- Progression free survival(Up to 2 years)
- Overall survival(From date on study to death for any reason, up to 2 years)
- Duration of response(From the date of first objective response until disease progression or death for any reason up to 2 years)
研究者
Somedeb Ball
Assistant Professor of Medicine
Vanderbilt-Ingram Cancer Center