A Randomized Study of Once Daily Fludarabine-Clofarabine Versus Fludarabine Alone Combined With Intervenous Busulfan Followed by Allogeneic Hemopoietic Stem Cell Transplantation for Acute Myeloid Leukemia (AML) and Myelodysplastic Syndrome (MDS)
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 256
- 试验地点
- 1
- 主要终点
- Progression-Free Survival (PFS)
研究概览
简要总结
The goal of this clinical research study is to learn if combining busulfan with clofarabine and fludarabine can help control the disease better than the previous standard method (using busulfan and fludarabine alone) in patients with AML or MDS. The safety of this combination therapy will also be studied.
详细描述
Busulfan is designed to kill cancer cells by binding to DNA (the genetic material of cells), which may cause cancer cells to die. Busulfan is commonly used in stem cell transplantation.
Clofarabine is designed to interfere with the growth and development of cancer cells.
Fludarabine is designed to interfere with the DNA of cancer cells, which may cause the cancer cells to die.
Study Groups:
You will be randomly assigned (as in the toss of a coin) to 1 of 2 study groups.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 3 Years 至 70 Years（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients must have one of the following hematologic malignancies: a) Acute myeloid leukemia (AML) any stage and cytogenetic risk-group with the only exception being that patients with AML and favorable cytogenetics (t(8;21, inv 16, or t(15;17) who achieve complete remission with one course of induction chemotherapy are not eligible . Patients with treatment related AML are eligible. b) Myelodysplastic syndromes (MDS) with intermediate or high risk International Prognostic Scoring System score (IPSS scores) or treatment related MDS. Patients with low risk MDS are eligible if they fail to respond to hypomethylating agent therapy such as azacitidine or decitabine.
- •Age 3-70 years old. Eligibility for pediatric patients will be determined in conjunction with an MDACC pediatrician.
- •Performance score of >/= 60 by Karnofsky or PS 0 to 2 (ECOG) (age > 12 years), or Lansky Play-Performance Scale >/= 60 or greater (age <12 years).
- •Negative Beta HCG test in a woman with child bearing potential, defined as not post-menopausal for 12 months or no previous surgical sterilization. Women of child bearing potential must be willing to use an effective contraceptive measure while on study.
- •Adequate major organ system function as demonstrated by: Left ventricular ejection fraction of at least 40%.
- •Pulmonary function test (PFT) demonstrating a diffusion capacity of least 50% predicted. For children </=7 years of age who are unable to perform PFT, oxygen saturation >/=92% on room air by pulse oximetry.
- •Creatinine < 1.5 mg/dL. If question about renal function discuss with study chairman and do 24 hour creatinine clearance (clearance should be >50 ml/min).
- •Bilirubin < to 2.0 x normal (except Gilbert's Syndrome). SGPT (ALT) <
- •No evidence of chronic active hepatitis or cirrhosis.
- •Histocompatible stem cell donor: Patients must have an HLA matched related or unrelated donor (HLA A, B, C and DR) willing to donate for allogeneic hematopoietic transplantation. High resolution allele level typing is required for donors other than genotypically identical siblings.
- •No uncontrolled infection. Protocol PI or designé will be final arbiter if there is uncertainty regarding whether a previous infection is controlled on appropriate (antibiotic) therapy.
- •Patient or patient's legal representative, parent(s) or guardian able to sign informed consent.
排除标准
- •Positive for HIV, HBsAg, HCV or other viral hepatitis or cirrhosis from any cause.
- •Prior allogeneic or autologous stem cell transplant using a myeloablative busulfan or total body radiation containing conditioning regimen defined as busulfan-based using a total dose of >/=12 mg/kg given by mouth or >/=10 mg/kg given IV; or a total-body irradiation (> 4 Gy).
- •Active or prior CNS leukemia, unless in complete remission for at least 3 months.
- •Previous therapeutic XRT to the liver as part of involved-field radiation.
- •History of serious chronic mental disorder or drug-abuse accompanied by documented problems of compliance with therapeutic programs.
- •Lack of care-giver for the early (100-day) post-transplant period.
研究组 & 干预措施
Flu + Bu
Fludarabine 40 mg/m2 intravenous (IV) over 1 hour. Busulfan dose calculated to achieve a systemic exposure dose of 6000 µMol-min IV over 3 hours every 24 hours. Both delivered for 4 consecutive days (days -6 to -3). Stem cell transplant Day 0.
干预措施: Thymoglobulin (Drug)
Flu + Bu
Fludarabine 40 mg/m2 intravenous (IV) over 1 hour. Busulfan dose calculated to achieve a systemic exposure dose of 6000 µMol-min IV over 3 hours every 24 hours. Both delivered for 4 consecutive days (days -6 to -3). Stem cell transplant Day 0.
干预措施: Fludarabine (Drug)
Flu + Bu
Fludarabine 40 mg/m2 intravenous (IV) over 1 hour. Busulfan dose calculated to achieve a systemic exposure dose of 6000 µMol-min IV over 3 hours every 24 hours. Both delivered for 4 consecutive days (days -6 to -3). Stem cell transplant Day 0.
干预措施: Busulfan (Drug)
Flu + Bu
Fludarabine 40 mg/m2 intravenous (IV) over 1 hour. Busulfan dose calculated to achieve a systemic exposure dose of 6000 µMol-min IV over 3 hours every 24 hours. Both delivered for 4 consecutive days (days -6 to -3). Stem cell transplant Day 0.
干预措施: Stem Cell Infusion (Procedure)
Flu + Bu
Fludarabine 40 mg/m2 intravenous (IV) over 1 hour. Busulfan dose calculated to achieve a systemic exposure dose of 6000 µMol-min IV over 3 hours every 24 hours. Both delivered for 4 consecutive days (days -6 to -3). Stem cell transplant Day 0.
干预措施: Tacrolimus (Drug)
Flu + Bu
Fludarabine 40 mg/m2 intravenous (IV) over 1 hour. Busulfan dose calculated to achieve a systemic exposure dose of 6000 µMol-min IV over 3 hours every 24 hours. Both delivered for 4 consecutive days (days -6 to -3). Stem cell transplant Day 0.
干预措施: Methotrexate (Drug)
Flu +Clo + Bu
Fludarabine 10 mg/m2 over 1 hour. Clofarabine 40 mg/m2 diluted in normal saline to produce a final concentration of 0.4 mg/mL, infused over 1 hour. Busulfan dose calculated to achieve a systemic exposure dose of 6000 µMol-min IV over 3 hours every 24 hours, immediately after Clofarabine. All delivered on 4 consecutive days (days -6 through -3). Stem cell transplant Day 0.
干预措施: Fludarabine (Drug)
Flu +Clo + Bu
Fludarabine 10 mg/m2 over 1 hour. Clofarabine 40 mg/m2 diluted in normal saline to produce a final concentration of 0.4 mg/mL, infused over 1 hour. Busulfan dose calculated to achieve a systemic exposure dose of 6000 µMol-min IV over 3 hours every 24 hours, immediately after Clofarabine. All delivered on 4 consecutive days (days -6 through -3). Stem cell transplant Day 0.
干预措施: Clofarabine (Drug)
Flu +Clo + Bu
Fludarabine 10 mg/m2 over 1 hour. Clofarabine 40 mg/m2 diluted in normal saline to produce a final concentration of 0.4 mg/mL, infused over 1 hour. Busulfan dose calculated to achieve a systemic exposure dose of 6000 µMol-min IV over 3 hours every 24 hours, immediately after Clofarabine. All delivered on 4 consecutive days (days -6 through -3). Stem cell transplant Day 0.
干预措施: Busulfan (Drug)
Flu +Clo + Bu
Fludarabine 10 mg/m2 over 1 hour. Clofarabine 40 mg/m2 diluted in normal saline to produce a final concentration of 0.4 mg/mL, infused over 1 hour. Busulfan dose calculated to achieve a systemic exposure dose of 6000 µMol-min IV over 3 hours every 24 hours, immediately after Clofarabine. All delivered on 4 consecutive days (days -6 through -3). Stem cell transplant Day 0.
干预措施: Thymoglobulin (Drug)
Flu +Clo + Bu
Fludarabine 10 mg/m2 over 1 hour. Clofarabine 40 mg/m2 diluted in normal saline to produce a final concentration of 0.4 mg/mL, infused over 1 hour. Busulfan dose calculated to achieve a systemic exposure dose of 6000 µMol-min IV over 3 hours every 24 hours, immediately after Clofarabine. All delivered on 4 consecutive days (days -6 through -3). Stem cell transplant Day 0.
干预措施: Stem Cell Infusion (Procedure)
Flu +Clo + Bu
Fludarabine 10 mg/m2 over 1 hour. Clofarabine 40 mg/m2 diluted in normal saline to produce a final concentration of 0.4 mg/mL, infused over 1 hour. Busulfan dose calculated to achieve a systemic exposure dose of 6000 µMol-min IV over 3 hours every 24 hours, immediately after Clofarabine. All delivered on 4 consecutive days (days -6 through -3). Stem cell transplant Day 0.
干预措施: Tacrolimus (Drug)
Flu +Clo + Bu
Fludarabine 10 mg/m2 over 1 hour. Clofarabine 40 mg/m2 diluted in normal saline to produce a final concentration of 0.4 mg/mL, infused over 1 hour. Busulfan dose calculated to achieve a systemic exposure dose of 6000 µMol-min IV over 3 hours every 24 hours, immediately after Clofarabine. All delivered on 4 consecutive days (days -6 through -3). Stem cell transplant Day 0.
干预措施: Methotrexate (Drug)
结局指标
主要结局
Progression-Free Survival (PFS)
时间窗: From day of transplant to disease of progression or death of any cause, whichever came first, assessed up to 5 years
Number of events with progression free survival. (Progression is defined as more than 5% blast in the peripheral blood or bone marrow biopsy.) or expired from treatment related mortality post transplant.
次要结局
- Overall Survival (OS) Post Transplant at 1, 3 and 5 Years(Post transplant after 1, 3 and 5 years)
- Number of Participants in the Study Who Are With no Grade 3 or 4 Acute Graft-versus-host Disease at Any Time During the First 100 Days Post Transplant.(100 days post transplant)
- Number of Participants With Non Relapse Mortality at 100 Day Post Transplant(100 day Post Transplant)