NCT00744536已完成2 期
Revlimid®, and Metronomic Melphalan in the Management of Higher Risk Myelodysplastic Syndromes (MDS) and CMML: A Phase 2 Study"
适应症
干预措施
相关药物
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 20
- 试验地点
- 1
- 主要终点
- Overall Response Rate (RR) (as defined by modified international working group standardized response criteria)
研究概览
简要总结
Angiogenesis increases in higher risk MDS patients and those with proliferative CMML. Angiogenesis is associated with increased risk of leukemic transformation and poorer prognoses. Low dose chemotherapy may have anti-angiogenic properties by targetting the genetically stable endothelial cells. Lenalidomide has been recently shown to be highly effective as monotherapy in low/low-intermediate risk MDS, particularly in the subgroup harboring a 5q- deletion. Lenalidomide has not been well studied in higher risk MDS although there are some reports of lenalidomide's efficacy in RAEB-T and AML. One potential mode of action of lenalidomide is inhibition of angiogenesis. The investigators hypothesize that by combining lenalidomide with low dose melphalan in higher risk MDS the investigators will more effectively block angiogenesis and achieve responses or hematologic improvement in MDS.
详细描述
STUDY OBJECTIVES:
Primary:
- Determine the overall response rates of low dose melphalan used in combination with lenalidomide in higher risk MDS
Secondary:
- Determine the frequency of hematologic improvement of low dose melphalan used in combination with lenalidomide in higher risk MDS·
- Determine the safety and tolerability of low dose melphalan used in combination with lenalidomide in higher risk MDS·
- Determine the effects of low dose melphalan used in combination with lenalidomide on biomarkers of angiogenesis in higher risk MDS·
- Determine the frequency of cytogenetic remissions of low dose melphalan used in combination with lenalidomide in higher risk MDS
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 or older at the time of signing the informed consent form.
- •Able to adhere to the study visit schedule and other protocol requirements.
- •Must have a diagnosis of high-intermediate or high risk MDS (de novo or secondary) or CMML fitting any of the following classifications (including CMML with wbc < 12,000 x 109/L) and IPSS > 1.5 or proliferative form of CMML (wbc > 12,000 x 109/L for which the IPSS does not apply). If the patient has unsuccessful cytogenetics, patients with WHO classification of transfusion dependent RAEB-1 will be eligible (see appendix B and C for WHO MDS classification).
- •All previous cancer therapy, including radiation, hormonal therapy and surgery, must have been discontinued at least 4 weeks (6 weeks for 5-Azacitidine or bone marrow transplant) prior to treatment in this study.
- •ECOG performance status of <= 2 at study entry (see Appendix A).
- •Laboratory test results within these ranges:
- •Serum calcium <3.0 mmol/L
- •Serum creatinine < 1.5 mg/dL
- •Total bilirubin < 1.5 mg/dL
- •AST (SGOT) and ALT (SGPT) < 2 x ULN
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 taking lenalidomide).
- •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.
- •Use of any other experimental drug or therapy within 28 days of baseline.
- •Known hypersensitivity to thalidomide or melphalan.
- •The development of erythema nodosum is characterized by a desquamating rash while taking thalidomide or similar drugs.
- •Any prior use of lenalidomide.
- •Concurrent use of other anti-cancer agents or treatments.
- •Known positive for HIV or infectious hepatitis, types A, B or C.
- •Must not have a diagnosis of AML (> 20% blasts) or other progressive malignant disease
- •Must not have received treatment with, erythropoietin, or granulocyte colony-stimulating factors within seven days of study initiation (21 days for pegfilgrastim or Aranesp). Note: use of corticosteroids (topical and inhaled) is permitted and prophylactic steroids are allowed for transfusion reactions, but ongoing oral corticosteroids are not permitted.
- •Serious or non-healing wound, ulcer, or bone fracture.
- •History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 28 days of treatment.
- •Any history of cerebrovascular accident (CVA) or transient ischemic attack within 12 months prior to study entry.
- •Histories of myocardial infarction, cardiac arrhythmia, stable/unstable angina, symptomatic congestive heart failure, or coronary/peripheral artery bypass graft or stenting within 12 months prior to study entry.
- •History of pulmonary embolism within the past 12 months.
研究组 & 干预措施
Lenalidomide and Melphalan
Experimental
Lenalidomide + Melphalan both given metronomically
干预措施: Lenalidomide and melphalan (Drug)
结局指标
主要结局
Overall Response Rate (RR) (as defined by modified international working group standardized response criteria)
时间窗: 3 years
Overall Response Rate (RR) (as defined by modified international working group standardized response criteria).
次要结局
- Safety (type, frequency, severity, and relationship of adverse events to study therapy)(3 yrs)
- Percent with cytogenetic remission(3 years)
- Percent with hematologic improvement(3 years)
- Overall, progression-free and leukemia-free-survival(3 yrs)
- Percent reduction in baseline biomarkers of angiogenesis including: circulating endothelial cells (CEC) and precursors (CEP), plasma and marrow VEGF and VEGFR 1-2 levels(3 yrs)
研究者
Dr. Rena Buckstein
Head Hematology Site Group
Sunnybrook Health Sciences Centre
研究点 (1)
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