The Use of Decitabine as Induction Therapy for Acute Myeloid Leukemia With Complex and/or Monosomal Karyotype
试验速览
- 阶段
- 2 期
- 入组人数
- 20
- 试验地点
- 1
- 主要终点
- Complete remission (CR):
研究概览
简要总结
Acute myeloid leukemia (AML) is a heterogeneous group of diseases with distinct clinicopathologic features sharing in common an abnormal increase in myeloblasts in blood and bone marrow (BM). In about 5-10% patients, the myeloblasts exhibit chromosomal abnormalities (complex and/or monosomal karyotype, CK/MK*) that are associated with refractoriness to conventional chemotherapy and an extremely bad prognosis.
Standard induction chemotherapy for AML comprises daunorubicin and cytarabine, the "7+3" regimen. However, treatment is largely ineffective for CK/MK AML with a temporary clearance of blasts achieved in only 30-40% cases and the cumulative toxicities resulting from repeated courses of chemotherapy have significantly increased the morbidity and mortality risks in subsequent allogeneic BMT. Therefore, standard treatment is unsatisfactory and there is an unmet clinical need for more effective and less toxic induction regimen.
Both previous and recent studies showed that 10 day course of decitabine (20 mg/m2/day) induced remission in 70-100% patients with CK/MK AML, particularly those with TP53 mutations. In this study, patients with CK/MK AML will be treated with decitabine to induce remission. Bone marrow examination will be performed after each course until complete clearance of blasts or disease progression. Patients achieving CR/CRi (see below) will continue to receive 4 more courses, after which patients eligible for BMT and for whom donors are available will receive curative BMT. We reckon that the time it takes for 4 courses of decitabine will suffice for transplantation workup in HK. . Patients ineligible for BMT will continue to receive decitabine until leukemia progression. The response rate, leukemia free survival (LFS), overall survival (OS) and percentage of patients who can be bridged to BMT will be compared with historical 7+3 regimen control.
详细描述
This is an open-label interventional study to study the use of decitabine as induction therapy for acute myeloid leukemia with complex and/or monosomal karyotype.
Subjects will receive decitabine for every 28 days, until disease progression or a bone marrow transplantation is carried out, in the schedule as below:
Cycle 1:
Receive decitabine for 10 days
Cycle 2 and Cycle 3:
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 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Adult patients (age 18-65 years old) with CK/MK AML at diagnosis
- •De novo or secondary AML is allowed
- •ECOG performance ≤ 2
- •Subjects with adequate liver, pancreatic and renal function at screening as demonstrated by :Direct bilirubin < 2 x upper limit of laboratory normal (ULN) Alanine aminotransferase (ALT) < 2.5 x ULN MDRD-eGRF > 30ml/min/1.73m2
- •Negative serum / urine pregnancy test within 7 days before starting study treatment in women with childbearing potential.
- •Subjects with ability to understand the protocol and signed a written informed consent document prior to the participation of the study.
排除标准
- •Patients with CK/MK AML who have received standard induction chemotherapy before
- •Patients with active and uncontrolled infection.
- •Patients with concurrent severe and uncontrolled concomitant medical conditions that could cause unacceptable safety risk or compromise compliance with the protocol.
研究组 & 干预措施
decitabine
Decitabine is a white to almost white powder for concentrate for solution for infusion. It is supplied as a lyophilized preparation in a clear colorless 20ml glass vial containing 50 mg decitabine.
The concentrate should be aseptically reconstituted with 10 ml of water for injections. After reconstitution, the concentrate must be diluted within 15 minutes using cooled infusion fluids and completely administered to patients within 5 hours.
The drug will then be administrated intravenously.
Dosage 20 mg/m2
28-day course, for each course, receive decitabine for 10 days
干预措施: Decitabine (Drug)
结局指标
主要结局
Complete remission (CR):
时间窗: up to 16 weeks
No increase in blasts in BM or PB (\<5% of total nucleated cells), with absolute neutrophil count ≥ 1x109/L and platelet count ≥ 100 x109/L.
次要结局
未报告次要终点
研究者
Dr. Anskar Y.H. Leung
Clinical Professor
The University of Hong Kong