A Phase I Study of a Combination of 5-azacitidine Followed by Lenalidomide in High-risk MDS or Relapsed/Refractory AML Patients With Cytogenetic Abnormalities Including -5 or Del(5q)
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 试验地点
- 4
- 主要终点
- Maximum tolerated dose (MTD) of Revlimid® (lenalidomide)in combination with Vidaza®(5-azacitidine)
研究概览
简要总结
The hypothesis of this study is that 5-aza and lenalidomide act synergistically in MDS and AML patients with chromosomal abnormalities involving monosomy 5 or del5q. Therefore, this phase I study will investigate the maximum tolerated dose (MTD) of lenalidomide in combination with a fixed dose of 5-aza in this patient population.
详细描述
Cytogenetics are the main predictors of outcome in patients with AML. In fact, a monosomy 5 or del (5q) as single aberration are poor prognostic markers. Overall, the complete response rate for conventionally treated patients with newly-diagnosed AML with chromosome 5 abnormalities is about 31% to 37 % and all patients rapidly relapse if not rescued by allogeneic HSCT. The situation is almost similar in patients with high-risk MDS.Vidaza® has been shown in clinical trials to achieve remission rates in about 29% (CR+PR) of the patients while a total of 49% achieve improvement of blood counts.Revlimid® is also able to achieve complete remissions in advanced MDS and even overt leukemia with or without chromosome 5 abnormalities. Nevertheless, response rates are lower compared to low-risk MDS (IPSS Low/INT-1). Therefore, Revlimid® seems to be too weak as a single agent, but a promising compound for a combination therapy.
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
- •Understand and voluntarily sign an informed consent form.
- •Age >=18 years at the time of signing the informed consent form.
- •Able to adhere to the study visit schedule and other protocol requirements.
- •Relapsed or refractory AML (>30% blasts, FAB classification)with karyotype abnormalities involving monosomy 5 or del(5q) or MDS and t-MDS INT-2 or HIGH according to IPSS classification with karyotype abnormalities involving monosomy 5 or del(5q) either previously treated or untreated
- •Not eligible for an immediate allogeneic HSCT (due to donor unavailability)
- •All previous MDS or AML specific therapy with exception of corticosteroids not exceeding doses of 10mg/day prednisone must have been discontinued at least 1 week prior to study enrollment.
- •Non-hematological toxicity (except alopecia) resulting from previous treatment must be resolved to WHO CTC Grade ≤
- •ECOG performance status of < 3 at study entry.
- •Laboratory test results within these ranges:Serum creatinine <= 2.0 mg/dL, Total bilirubin <= 3 x ULN, AST (SGOT) and ALT (SGPT) <= 3 x ULN
- •Females of childbearing potential must agree to use a reliable form of contraception or to practice complete abstinence from heterosexual intercourse during the following time periods related to this study: 1) for at least 28 days before starting study drug; 2) while participating in the study; and 3) for at least 28 days after discontinuation from the study.
排除标准
- •Any serious medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from signing the informed consent form.
- •Pregnant or breast feeding females. (Lactating females must agree not to breast feed while on study).
- •Any condition, including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study or confounds the ability to interpret data from the study.
- •Known hypersensitivity to thalidomide, lenalidomide, 5-azacitidine or mannitol.
- •Myocardial infarction within 6 months before study entry, New York Heart Association Class III or IV heart failure, uncontrolled angina or severe uncontrolled ventricular arrhythmias.
- •The development of erythema nodosum if characterized by a desquamating rash while taking thalidomide or similar drugs.
- •Uncontrolled lung disease.
- •Known positive for HIV or acute infectious hepatitis, type A, B or C.
- •Participation in another clinical study in the 4 weeks prior to enrollment or during this study.
研究组 & 干预措施
Azacitidine and Lenalidomide
Azacitidine 75 mg/m² SC days 1-5 every 28 days for a maximum of 8 cycles and Lenalidomide 10 - 25 mg PO days 6-19 every 28 days for a maximum of 8 cycles
干预措施: Azacitidine (Drug)
Azacitidine and Lenalidomide
Azacitidine 75 mg/m² SC days 1-5 every 28 days for a maximum of 8 cycles and Lenalidomide 10 - 25 mg PO days 6-19 every 28 days for a maximum of 8 cycles
干预措施: Lenalidomide (Drug)
结局指标
主要结局
Maximum tolerated dose (MTD) of Revlimid® (lenalidomide)in combination with Vidaza®(5-azacitidine)
时间窗: during first cycle of therapy
次要结局
- Clinical and cytogenetic response(during therapy)
- Safety (type, frequency, severity, and relationship of adverse events to study treatment)(during therapy)