Clinical Study of Azacitidine Combined With Homoharringtonie Based Regimens in Acute Myeloid Leukemia
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 发起方
- 入组人数
- 100
- 试验地点
- 1
- 主要终点
- CR
研究概览
简要总结
Rencent years have witnessed great progress of the treatment of acute myeloid leukemia (AML). However, most patients have poor outcomes following the currently first-line DA(daunorubicin, cytarabine)/IA(Idarubicin, cytarabine) chemotherapy, espiecially for the older patients and those not eligiable for receiving allo-HSCT. Azacitidine (AZA)，a hypomethylating agent, targets epigenetic gene silencing by inhibiting gene expression against malignant phenotypes and is currently approved to treat AML based on the NCCN guidelines. The homoharringtonie (HHT) could induce AML cell lines and primary myeloid leukemia cell apoptosis, and the effect was dose dependent. While, HHT could also induce leukemia cells to differentiate into normal state, eventually achieve the goal of treatment, and control the disease. The investigators conducted a clinical study to evaluate the efficacy and safety of the AZA plus HAG(homoharringtonie, cytarabine, G-CSF), HIA(homoharringtonie, Idarubicin, cytarabine)/HDA(homoharringtonie, daunorubicin, cytarabine). This study is aimed to demonstrate the efficacy and safety advantages of the regimens that cotain homoharringtonie and azacitidine.
详细描述
Currently, the treatment of acute myeloid leukemia (AML) still remains a therapeutic challenge. Patients received traditional chemotherapy have a low remission rate, poor prognosis and short survival for patients. New treatment strategies are needed in find out a better chemotherapy regimen.
Azacitidine (AZA), a hypomethylating agent, targets epigenetic gene silencing by inhibiting gene expression against malignant phenotypes. Azacitidine is currently approved to treat AML based on the NCCN guidelines. Novel combinations based on the azacitidine are currently undergoing, and the preliminary results brought promising hope to the treatment of AML.
The homoharringtonie (HHT) is a plant cytotoxic alkaloid derived from the trees of the genus Cephalotaxus. As a protein synthesis inhibitor, homoharringtonie plays a major role in the G1 / G2 phase in cells. In addition, it could induce AML cell lines and primary myeloid leukemia cell apoptosis, and the effect was dose dependent. Meanwhile it could also induce leukemia cells to differentiate into normal state, eventually controlled the progression of the disease.
Combination with azacitidine may become a new option.This study intends to apply azacitidine in combination with homoharringtonie for treating AML patients, aiming to improve the efficacy, reduce adverse events and improve the living qualities of patients.
Patients of de novo or relapsed AML(age≥60y or ineligibility to receive intensive chemotherapy) will receive AZA+HAG (homoharringtonie, cytarabine, G-CSF) regiment as induction therapy. After complete remission(CR), the AZA+HAG regimen was further given 4-6 cycles and followed by azacitidine maintenance or until the disease progresses.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Diagnoised with acute myeloid leukemia
- •Meet the criteria of the 2016 WHO classification system(APL were excluded), based on blood cell counting, bone marrow biopsy, and cytogeneic diagnosis
- •Volunteered to sign the informed consent.
排除标准
- •Mental disorders or other conditions that cannot meet the requirements of research, treatment and monitoring
- •Uncontrolled cardiovascular disease
- •Allergic to azacytarine, homoharringtonie, or other drugs of this study
- •Any other conditions considered by the study investgators that are not suitable for participating in this clinical trial.
研究组 & 干预措施
Azacitidine plus HAG
Patients of de novo or relapsed AML(age≥60y or ineligibility to receive intensive chemotherapy) will receive AZA+HAG (homoharringtonie, cytarabine, G-CSF) regiment as induction therapy. After complete remission(CR), the AZA+HAG regimen was further given 4-6 cycles and followed by azacitidine maintenance or until the disease progresses.
AZA -Azacitidine HAG -Homoharringtonie, Cytarabine, G-CSF
干预措施: Homoharringtonine (Drug)
Azacitidine plus HAG
Patients of de novo or relapsed AML(age≥60y or ineligibility to receive intensive chemotherapy) will receive AZA+HAG (homoharringtonie, cytarabine, G-CSF) regiment as induction therapy. After complete remission(CR), the AZA+HAG regimen was further given 4-6 cycles and followed by azacitidine maintenance or until the disease progresses.
AZA -Azacitidine HAG -Homoharringtonie, Cytarabine, G-CSF
干预措施: Azacitidine (Drug)
Azacitidine plus HIA
Patients of de novo or relapsed AML(age<60y or eligible for intensive chemotherapy) will receive AZA +HIA(homoharringtonie, Idarubicin, cytarabine) regiments as introduction therapy. After CR, post-remission therapy will follow with NCCN guidelines.
AZA -Azacitidine HIA -Homoharringtonie, Cytarabine, Idarubicin
干预措施: Homoharringtonine (Drug)
Azacitidine plus HIA
Patients of de novo or relapsed AML(age<60y or eligible for intensive chemotherapy) will receive AZA +HIA(homoharringtonie, Idarubicin, cytarabine) regiments as introduction therapy. After CR, post-remission therapy will follow with NCCN guidelines.
AZA -Azacitidine HIA -Homoharringtonie, Cytarabine, Idarubicin
干预措施: Azacitidine (Drug)
Azacitidine plus HDA
Patients of de novo or relapsed AML(age<60y or eligible for intensive chemotherapy) will receive AZA +HDA(homoharringtonie, daunorubicin, cytarabine) regiments as introduction therapy., After CR, post-remission therapy will follow with NCCN guidelines.
AZA -Azacitidine HDA -Homoharringtonie, Cytarabine, Daunorubicin
干预措施: Homoharringtonine (Drug)
Azacitidine plus HDA
Patients of de novo or relapsed AML(age<60y or eligible for intensive chemotherapy) will receive AZA +HDA(homoharringtonie, daunorubicin, cytarabine) regiments as introduction therapy., After CR, post-remission therapy will follow with NCCN guidelines.
AZA -Azacitidine HDA -Homoharringtonie, Cytarabine, Daunorubicin
干预措施: Azacitidine (Drug)
结局指标
主要结局
CR
时间窗: From date of randomization or initial treatment until the date of first documented disease relapse from any cause，assessed up to 100 weeks.
CR in months, in present of complete remission rate of all participants.
次要结局
- RFS(From date of randomization or complete remission until the date of first documented disease relapse from any cause，assessed up to 100weeks.)
- OS(From date of randomization until the date of first documented death from any cause or end of this study, whichever come first，assessed up to 100weeks.)
- Adverse events rates(From date of randomization or initial treatment until the end date of the study, assessed up to 100 weeks.)
研究者
Ge Zheng
Director of Department of Hematology
Zhongda Hospital