Phase II Trial of Clofarabine With Parenteral Busulfan (Busulfex®) Followed by Allogeneic Related or Unrelated Donor Transplantation for the Treatment of Hematologic Malignancies and Diseases
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
- Disease free survival at one and two year
研究概览
简要总结
The purpose of this study is to determine whether Clofarabine in combination with Busulfan is effective as a preparative transplant regimen for the treatment of leukemia and myelodysplastic syndromes
详细描述
The success of allogeneic hematopoietic transplantation in the treatment of myeloid malignancies is determined by two main factors: the limiting of regimen-related toxicity and the prevention of recurrent leukemia. Over the past 10 years, considerable clinical research has been devoted to the reduction of regimen-related toxicity through the use of reduced-intensity (nonmyeloablative) transplants. However, leukemic relapse has remained a difficult obstacle. Thus, the need for highly effective, yet non-toxic regimens persists, particularly for elderly patients for whom very little overall progress has been made. Clofarabine is a chemotherapeutic agent with novel myelotoxic properties and proven low toxicity in older patients. These qualities suggest clofarabine may be a useful component of conditioning regimens for stem cell transplantation.
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
- •Disease Criteria:
- •Acute myelogenous leukemia (AML)
- •Acute lymphocytic leukemia (ALL)
- •Myelodysplastic syndromes (MDS) Refractory anemia (RA) with adverse cytogenetics (SWOG criteria) or beyond (RAEB, RAEB-T, AML)
- •Other Myeloproliferative Disorders Myelofibrosis, Agnogenic Myeloid Metaplasia, Chronic Myelomonocytic Leukemia (CMML)
- •Chronic lymphocytic leukemia (CLL) High risk or advanced disease
- •Other Inclusion Criteria:
- •18 years of age or older
- •Related or unrelated donor with HLA criteria as follows:
- •Related donors: a serologic equivalent HLA Class I (A, B, and C) and Class II DRB1 or DQB1 matched donor OR a donor who is a single 1 antigen mismatched for A, B, C, DRB1, or DQB1 loci
- •Unrelated donors: sequence-based typing fully matched A, B, C, DRB1, and DQB1 allele-matched donor OR a donor who is no greater than 1 antigen mismatched for A, B, C, DRB1, or DQB1 loci
- •Able to provide valid informed consent.
- •Female patients must have a negative serum pregnancy test within 2 weeks prior to enrollment.
- •Male and female patients must use an effective contraceptive method during the study and for up to 12 months after study treatment.
排除标准
- •Organ Function Criteria:
- •Cardiac: symptomatic coronary artery disease or ejection fraction <45% or uncontrolled cardiac failure
- •Pulmonary: FEV1 or DLCO (corrected) <50% of predicted values and/or receiving continuous supplementary oxygen
- •Hepatic: Bilirubin ≥ 1.2 mg/dL or AST/ALT ≥ 3x upper limit of normal (ULN) unless the liver is involved with malignant disease
- •Renal: creatinine clearance < 60 mL/min (24-hour urine collection) or <50 mL/min (Glofil test)
- •Karnofsky score <60%
- •Active CNS disease
- •Prior hematopoietic transplantation (autologous or allogeneic) <6 months prior to study entry
- •Use of investigational agents less than or equal to 30 days before study entry.
- •Life threatening, or clinically significant infection
- •Any significant concurrent disease, illness, or psychiatric disorder that would compromise patient safety or compliance, interfere with consent, study participation, follow up, or interpretation of study results.
- •Female patients who are pregnant or breast feeding
- •HIV-positive
研究组 & 干预措施
Clofarabine with Busulfan
Clofarabine 40 mg/m2 IV QD × 5 days Busulfan (Busulfex™) 3.2 mg/kg IV QD × 2 days
干预措施: Clofarabine with Busulfan (Drug)
结局指标
主要结局
Disease free survival at one and two year
时间窗: At 1 year and 2 Year
次要结局
- Incidence and severity of acute toxicities(100 days)
- Incidence of hematopoietic engraftment(100 days)
- Pharmacokinetic profiles of high dose busulfan and standard dose clofarabine(Lesss than 8 days)
- Acute GVHD(100 Days)