A Phase I Study of Clofarabine Plus High Dose Melphalan as a Conditioning Regimen for Allogeneic Transplantation
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 20
- 试验地点
- 2
- 主要终点
- Maximum tolerated dose
研究概览
简要总结
RATIONALE: Giving chemotherapy, such as clofarabine and melphalan, before a donor stem cell transplant helps stop the growth of cancer or abnormal cells. It also helps stop the patient's immune system from rejecting the donor's stem cells. When the healthy stem cells from a donor are infused into the patient, they may help the patient's bone marrow make stem cells, red blood cells, white blood cells, and platelets. Sometimes the transplanted cells from a donor can make an immune response against the body's normal cells. Giving cyclosporine and mycophenolate mofetil after the transplant may stop this from happening.
PURPOSE: This phase I trial is studying the side effects and best dose of clofarabine when given together with high-dose melphalan followed by a donor stem cell transplant in treating patients with acute myeloid leukemia, acute lymphocytic leukemia, or myelodysplastic syndromes.
详细描述
OBJECTIVES:
- To determine the maximum tolerated dose and toxicities of clofarabine when administered with high-dose melphalan as a conditioning regimen in patients undergoing allogeneic stem cell transplantation for acute myeloid leukemia, acute lymphocytic leukemia, or myelodysplastic syndromes.
- To assess the efficacy of this regimen in facilitating engraftment in these patients.
- To perform correlative laboratory studies of engraftment, immune reconstitution, and therapeutic outcomes.
OUTLINE: This is a dose-escalation study of clofarabine. Patients are stratified according to age (< 18 years vs ≥ 18 years).
- Reduced-intensity conditioning regimen: Patients receive clofarabine IV over 30 minutes on days -9 to -5 and high-dose melphalan IV over 30 minutes on day -4.
Cohorts of 3-6 patients receive escalating doses of clofarabine until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. At least 6 patients are treated at the MTD.
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
- 1 Year 至 120 Years（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •DISEASE CHARACTERISTICS:
- •Diagnosis of one of the following:
- •Acute myeloid leukemia
- •Acute lymphocytic leukemia
- •Myelodysplastic syndromes
- •Disease meets 1 of the following criteria:
- •In first complete remission (CR)
- •In second CR
- •In relapse
- •No more than 50% blasts in bone marrow
- •Not deemed eligible for standard transplantation regimens by the attending physician, or at high risk for relapse
- •No suspected or proven CNS leukemia
- •HLA-matched (6/6) sibling donor available
- •PATIENT CHARACTERISTICS:
- •Karnofsky performance status 50-100%
- •Glomerular filtration rate (pediatric patients) or creatinine clearance ≥ 60 mL/min OR serum creatinine < 1.5 times upper limit of normal (ULN)
- •Serum bilirubin ≤ 2.0 mg/dL
- •AST and ALT ≤ 2.5 times ULN
- •LVEF ≥ 50% by ECHO or MUGA scan
- •DLCO or FEV_1 ≥ 40% predicted
- •Not pregnant
- •Negative pregnancy test
- •No concurrent uncontrolled illness including, but not limited to, any of the following:
- •Ongoing, active, or poorly controlled infection
- •Symptomatic congestive heart failure
- •Unstable angina pectoris
- •Cardiac arrhythmia
- •Poorly controlled pulmonary disease
- •Psychiatric illness/social situation that would limit compliance with study requirement
- •No active cytomegalovirus (CMV) or fungal disease
- •HIV negative
- •PRIOR CONCURRENT THERAPY:
- •Recovered from prior intensive chemotherapy (pediatric patients)
- •At least 100 days since prior autologous stem cell transplantation
- •At least 100 days since prior radiotherapy administered as part of a transplantation conditioning regimen
- •At least 4 weeks since prior chemotherapy
- •At least 24 hours since prior hydroxyurea for blast count control
排除标准
- 未提供
结局指标
主要结局
Maximum tolerated dose
时间窗: 4 weeks from the start of treatment
Dose-limiting toxicity as assessed by NCI CTCAE v3.0 and the Modified Bearman scale
时间窗: 4 weeks from the start of treatment
Graft failure or rejection
时间窗: 35 days post-transplant
次要结局
- Efficacy(One year post-transplant)
- Correlative laboratory studies of engraftment, immune reconstitution, and therapeutic outcomes(One year post-transplant)