Busulfan Plus Clofarabine Followed by Allogeneic Hematopoietic Stem Cell Transplantation for Patients With Acute Lymphoblastic Leukemia or Lymphoma, or Biphenotypic Leukemia
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 120
- 试验地点
- 1
- 主要终点
- Treatment-Related Mortality (TRM) Defined as Non Relapse Mortality (NRM)
研究概览
简要总结
The goal of this clinical research study is to test the safety of giving clofarabine in combination with busulfan, followed by an allogeneic (from a donor) stem cell transplant, in patients with advanced leukemia or lymphoma.
详细描述
Study Treatment:
Busulfan is designed to bind to DNA (the genetic material of cells), which may cause cancer cells to die. It is commonly used in stem cell transplants.
Clofarabine is designed to interfere with the growth and development of cancer cells.
A stem cell transplant is designed to help your body attack the cancer cells that may remain in your body after chemotherapy.
Central Venous Catheter Placement:
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
- — 至 65 Years（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients with biopsy-proven acute lymphoblastic leukemia, acute lymphoblastic lymphoma, or acute biphenotypic leukemia in remission or relapse.
- •Adequate renal function, as defined by estimated serum creatinine clearance >60 ml/min.
- •Bilirubin equal or less than 1.5 (unless Gilbert's Syndrome), serum glutamate pyruvate transaminase (SGPT) <3 X upper limit of normal and alkaline phosphatase <2 X upper limit of normal.
- •Adequate pulmonary function with forced expiratory volume at one second (FEV1), forced vital capacity (FVC) and diffusion capacity of lung for carbon monoxide (DLCO) at least 45% of expected corrected for hemoglobin. Children unable to perform pulmonary functions must have an oxygen saturation greater than 92% at room air.
- •Adequate cardiac function with left ventricular ejection fraction at least 45% on appropriate medical therapy. No uncontrolled arrhythmias or symptomatic cardiac disease.
- •Zubrod performance status <2 or Lansky/Karnofsky PS equal or greater to 70%.
- •Patients must have a related, genotypically HLA identical donor, or they must have a unrelated donor who is 8/8 HLA match by high resolution typing.
- •Patient or patient's legal representative, parent(s) or guardian should provide written informed consent. Assent of a minor if participant's age is at least seven and less than eighteen years.
- •Negative Beta Human Chorionic Gonadotropin (HCG) test in a woman with child bearing potential defined as not post-menopausal for 12 months and no previous surgical sterilization.
排除标准
- •Patients with unresolved grade >2 non-hematologic toxicity from previous therapy. Patients with grade 2 toxicity will be eligible at the discretion of the PI.
- •Patients with active central nervous system (CNS) disease.
- •Evidence of acute or chronic active hepatitis or cirrhosis.
- •Uncontrolled infection, including HIV, HTLV-1, hepatitis B or hepatitis C viremia.
- •Patients greater than 65 years-old.
- •Prior autologous or allogeneic hematopoietic stem cell transplant.
研究组 & 干预措施
Busulfan + Clofarabine + Stem Cell Transplant
Busulfan test dose 32 mg/m^2 by vein over 45 minutes on Day -8; following doses on Days -6 to -3 derived from pharmacokinetic (PK) testing done up to 11 times over 11 hours after test dose.
Clofarabine 40 mg/m^2 by vein over 1 hour daily Day -6 through Day -3. Thymoglobulin 0.5 mg/kg on Day -3, 1.5 mg/kg on Day -2 and 2.0 mg/kg on Day -1; only patients with HLA nonidentical or unrelated donors.
Stem cell infusion on Day 0.
干预措施: Busulfan (Drug)
Busulfan + Clofarabine + Stem Cell Transplant
Busulfan test dose 32 mg/m^2 by vein over 45 minutes on Day -8; following doses on Days -6 to -3 derived from pharmacokinetic (PK) testing done up to 11 times over 11 hours after test dose.
Clofarabine 40 mg/m^2 by vein over 1 hour daily Day -6 through Day -3. Thymoglobulin 0.5 mg/kg on Day -3, 1.5 mg/kg on Day -2 and 2.0 mg/kg on Day -1; only patients with HLA nonidentical or unrelated donors.
Stem cell infusion on Day 0.
干预措施: Clofarabine (Drug)
Busulfan + Clofarabine + Stem Cell Transplant
Busulfan test dose 32 mg/m^2 by vein over 45 minutes on Day -8; following doses on Days -6 to -3 derived from pharmacokinetic (PK) testing done up to 11 times over 11 hours after test dose.
Clofarabine 40 mg/m^2 by vein over 1 hour daily Day -6 through Day -3. Thymoglobulin 0.5 mg/kg on Day -3, 1.5 mg/kg on Day -2 and 2.0 mg/kg on Day -1; only patients with HLA nonidentical or unrelated donors.
Stem cell infusion on Day 0.
干预措施: Thymoglobulin (Drug)
Busulfan + Clofarabine + Stem Cell Transplant
Busulfan test dose 32 mg/m^2 by vein over 45 minutes on Day -8; following doses on Days -6 to -3 derived from pharmacokinetic (PK) testing done up to 11 times over 11 hours after test dose.
Clofarabine 40 mg/m^2 by vein over 1 hour daily Day -6 through Day -3. Thymoglobulin 0.5 mg/kg on Day -3, 1.5 mg/kg on Day -2 and 2.0 mg/kg on Day -1; only patients with HLA nonidentical or unrelated donors.
Stem cell infusion on Day 0.
干预措施: Stem Cell Transplant (Procedure)
结局指标
主要结局
Treatment-Related Mortality (TRM) Defined as Non Relapse Mortality (NRM)
时间窗: 100 Days
NRM was defined as death from any cause other than disease progression or relapse and reported as percentage of participant deaths. Treatment related deaths after transplant are defined either by deaths which could not be attributed to disease relapse or progression or by deaths without previous relapse or progression. For TRM at day 100, Bayesian method of Thall, Simon, and Estey used to perform interim monitoring.
次要结局
未报告次要终点