Efficacy and Safety of Cladribine in Combination With G-CSF,Low-dose Cytarabine and Aclarubicin in Newly Diagnosed Unfit Patients With Acute Myeloid Leukemia
试验速览
- 阶段
- 2 期
- 发起方
- 入组人数
- 34
- 试验地点
- 1
- 主要终点
- Cumulative Complete Remission (CR) / CR with incomplete blood count (CRi) rate
研究概览
简要总结
In this study, the investigators conducted a phase II trial that evaluated the efficacy and safety of cladribine in combination with modified CAG regimen (low-dose cytarabine and aclarubicin) in elderly patients with AML.
详细描述
The low-intensity chemotherapy were developed to reduce the early mortality and improve the benefit-risk ratio for longterm survival in elderly or unfit AML patients.Previous studies revealed that the standard dose of CAG regimen consisting of low-dose cytarabine and aclarubicin in combination with granulocyte colonystimulating factor (G-CSF) priming as an induction therapy was well-tolerated by patients and led to a complete remission (CR) rate of 50.0% in patients aged≥ 70 years. Cladribine (2-chlorodeoxyadenosine ) is a nucleoside analogue of anti-adenosine deaminase that has extensive antitumor activity in hematological tumor.The purine analog 2-CdA increases the uptake of Ara-C and the accumulation of its active cytotoxic metabolite 5α-triphosphate Ara-C (Ara-CTP) in leukemia cells. This finding suggests that synergy occurs between cladribine and cytarabine. In this study, the investigators conducted a phase II trial that evaluated the efficacy and safety of cladribine in combination with modified CAG regimen (low-dose cytarabine and aclarubicin) in unfit patients with AML.Patients will receive C-CAG regimen as follows: cladribine 5 mg/m2, d1-5; G-CSF 300 µg, d0-9; aclarubicin 10 mg, d3-6; cytarabine 10mg/ m2 q12h, SC, d3-9; 4 weeks per cycle. The participants are permitted to quit the study if complete remission (CR) was not achieved after two courses of chemotherapy.The participants will be treated for a total of six cycles unless disease progression or unacceptable side effects are observed or participants withdrew their consent.
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 90 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients with:
- •a diagnosis of AML according to WHO 2016 classification (excluding acute promyelocytic leukemia) including secondary AML (after an antecedent hematological disease (e.g. MDS) and therapy-related AML
- •Patients 60 years and older.
- •Patients NOT eligible for standard chemotherapy, defined as hematopoietic cell transplantation comorbidity index (HCT-CI) ≥ 3 or Patients NOT eligible for standard chemotherapy for other reasons (wish of patient).
- •White blood cell (WBC) ≤ 10 x109/L (prior hydroxyurea allowed for a maximum of 5 days, stop 2 days before start cladribine treatment)
- •Adequate renal and hepatic functions unless clearly disease related as indicated by the following laboratory values:
- •Serum creatinine ≤ 221.7 µmol/L (≤ 2.5 mg/dL ), unless considered AML-related -Serum bilirubin ≤ 2.5 x upper limit of normal (ULN), unless considered AML-
- •related or due to Gilbert's syndrome
- •Alanine transaminase (ALT) ≤ 2.5 x ULN, unless considered AML-related
- •WHO performance status 0, 1 or
- •Patient is willing and able to use adequate contraception during and until 5 months after the last protocol treatment.
- •Written informed consent.
- •Patient is capable of giving informed consent.
排除标准
- •Acute promyelocytic leukemia.
- •Acute leukemia's of ambiguous lineage according to WHO 2016
- •Patient has symptomatic central nervous system (CNS) leukemia (NO routinely lumbar puncture required to investigate CNS involvement)
- •Blast crisis of chronic myeloid leukemia.
- •Diagnosis of any previous or concomitant malignancy is an exclusion criterion:
- •except when the patient completed successfully treatment (chemotherapy and/or surgery and/or radiotherapy) with curative intent for this malignancy at least 6 months prior to randomization. OR
- •except for basal and squamous cell carcinoma of the skin or in situ carcinoma of the cervix
- •Patients previously treated for AML (any antileukemic therapy including investigational agents), a short treatment period ( ≤ 5 days) with Hydroxyurea is allowed
- •Current concomitant chemotherapy, radiation therapy, or immunotherapy; other than hydroxyurea
- •Concurrent severe and/or uncontrolled medical condition (e.g. uncontrolled diabetes, infection, hypertension, pulmonary disease etc.)
- •Cardiac dysfunction as defined by:
- •Myocardial infarction within the last 3 months of study entry, or
- •Reduced left ventricular function with an ejection fraction < 40% as measured by MUGA scan or echocardiogram or
- •Unstable angina or
- •New York Heart Association grade IV congestive heart failure or
- •Unstable cardiac arrhythmias.
- •History of stroke or intracranial hemorrhage within 6 months prior to randomization.
- •Patient has a history of human immunodeficiency virus or active infection with Hepatitis C or B.
- •Patients known to be pregnant
- •Patients with a history of non-compliance to medical regimens or who are considered unreliable with respect to compliance.
- •Patients with any serious concomitant medical condition which could, in the opinion of the investigator, compromise participation in the study.
- •Patients who have senile dementia, mental impairment or any other psychiatric disorder that prohibits the patient from understanding and giving informed consent.
- •Any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule
研究组 & 干预措施
C-CAG
cladribine 5 mg/m2, d1-5; G-CSF 300 µg, d0-9; aclarubicin 10 mg, d3-6; cytarabine 10mg/ m2 q12h, SC, d3-9; 4 weeks per cycle.
干预措施: Cladribine Injection (Drug)
C-CAG
cladribine 5 mg/m2, d1-5; G-CSF 300 µg, d0-9; aclarubicin 10 mg, d3-6; cytarabine 10mg/ m2 q12h, SC, d3-9; 4 weeks per cycle.
干预措施: Aclarubicin (Drug)
C-CAG
cladribine 5 mg/m2, d1-5; G-CSF 300 µg, d0-9; aclarubicin 10 mg, d3-6; cytarabine 10mg/ m2 q12h, SC, d3-9; 4 weeks per cycle.
干预措施: G-CSF (Drug)
C-CAG
cladribine 5 mg/m2, d1-5; G-CSF 300 µg, d0-9; aclarubicin 10 mg, d3-6; cytarabine 10mg/ m2 q12h, SC, d3-9; 4 weeks per cycle.
干预措施: cytarabine (Drug)
结局指标
主要结局
Cumulative Complete Remission (CR) / CR with incomplete blood count (CRi) rate
时间窗: At the end of Cycle 2 (each cycle is 28 days)
Cumulative CR/CRi rate during 2 cycles
次要结局
- Overall survival (OS)(5 years)
- Prognostic value of MRD(9 months and at relapse)
- Safety and tolerability of Cladribine in Combination With CAG determined by the type, frequency, severity and relationship of adverse events to study treatment(1 years)
- Event free survival (EFS)(5 years)
研究者
wanghua
Director, Head of hematology, Principal Investigator, Clinical Professor
Sun Yat-sen University