Clinical Study of Efficacy and Safety of Chidamide Combined With Cladribine Regimen in Refractory/Relapsed Acute Myeloid Leukemia
试验速览
- 阶段
- 2 期
- 发起方
- 入组人数
- 31
- 试验地点
- 1
- 主要终点
- Complete Remission (CR) rate
研究概览
简要总结
Acute myeloid leukemia (AML) is highly heterogeneous, the efficacy of the individual varies greatly, and the risk of recurrence is high. A large number of newly diagnosed AML patients cannot achieve complete remission (CR) after standard induction chemotherapy. The prognosis of AML patients after relapse is extremely poor, and only a few patients can get remission through salvage treatment.
Chidamide is a histone deacetylase inhibitor (HDACi) independently developed by China. It has been marketed in recent years and the first innovative drug approved by the U.S. Food and Drug Administration for clinical research in the United States. Chidamide can increase the sensitivity of leukemia cells to conventional chemotherapy by inhibiting cell proliferation, inducing apoptosis, and increasing cell cycle arrest. Chidamide and other drugs have different effects in combination, and jointly bear the anti-tumor effect, which provides a theoretical basis for Chidamide in the treatment of acute myeloid leukemia.
Cladribine is a purine nucleoside analog, which has the ability to inhibit DNA synthesis, repair, induce apoptosis, and has anti-leukemia activity for cells in both mitotic and quiescent phases. In the past ten years, many studies have proved that Cladribine and its combination therapy are effective in patients with relapsed and refractory AML and de novo AML. The NCCN guidelines recommend the combination of cladribine as a category 1 recommendation for newly-diagnosed and refractory or relapsed adult AML. Several studies have confirmed the use of Cladribine in the treatment of refractory and relapsed AML.
The strong synergistic anti-cancer effect of HDACi combined with Cladribine has been shown in many cancers such as B-cell chronic lymphocytic leukemia, colon cancer, multiple myeloma, natural killer large granular lymphocytic leukemia, B-cell non-Hodgkin's lymphoma, and mantle cell lymphoma. Our previous study found a synergistic effect on combination of Chidamide and Cladribine in AML cell lines and primary cells. In clinical observation, refractory and relapsed AML patients also responded well to the combination of Chidamide plus Cladribine regimen. This provides a theoretical and practical basis for the use of the combination of Chidamide and Cladribine in AML patients.
详细描述
This study is aimed to observe the efficacy and safety of the Chidamide Plus Cladribine regimen in treating patients with refractory or relapsed AML. Patients must provide written informed consent and meet all the inclusion criteria and none of the exclusion criteria to be eligible. The eligible patients with refractory or relapsed AML will receive chidamide plus cladribine regimen. Response criteria will be assessed according to the guidelines of the International Working Group for Diagnosis, Standardization of Response Criteria, Treatment Outcomes, and Reporting Standards for Therapeutic Trials in AML. In case of partial remission, the second identical course will be started. In case of complete remission, allogeneic hematopoietic stem cell transplantation will be performed if available. Patients without complete remission after two courses of treatment will be withdrawn from the study.
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 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age greater than 18 years old and less than 75 years old;
- •Clinical diagnosis of Relapsed/Refractory AML (non-APL);
- •ECOG performance status score 0-3;
- •Participant has the ability to understand and willingness to sign a written consent document.
排除标准
- •Pregnancy or nursing
- •Uncontrolled significant cardiac disorder
- •Psychiatric disorder may interfere with his / her compliance with the study protocol
- •Known history of intolerance or allergy to any component of the research regimen
- •Any condition not suitable for the trial as judged by the study investigator.
研究组 & 干预措施
Chidamide plus Cladribine
Chidamide 30mg/d per os (p.o.), twice per week, begins at day 1; Cladribine 5mg/m2/d, intravenous injection (i.v.), days 1-5, once per day; A cycle is during 28 days.
干预措施: Chidamide (Drug)
Chidamide plus Cladribine
Chidamide 30mg/d per os (p.o.), twice per week, begins at day 1; Cladribine 5mg/m2/d, intravenous injection (i.v.), days 1-5, once per day; A cycle is during 28 days.
干预措施: Cladribine (Drug)
结局指标
主要结局
Complete Remission (CR) rate
时间窗: Bone marrow examination will be performed at the end of Cycle 1 (each cycle is 28 days)
Less than 5 percent of blast cells in bone marrow aspiration is defined as CR.
次要结局
- Overall Survival (OS)(OS is defined as the number of days from the date of the study enrollment to the date of death of any cause with a minimal 12 months of follow up. Subjects that have not died will be censored at the last known date to be alive.)
- Incidences of Adverse Events (AEs)(All AEs reported from the time of study drug administration until 30 days after discontinuation of study drug administration will be collected.)
研究者
Ge Zheng
Director of Department of Hematology
Zhongda Hospital