A Study of a Reduced-Intensity Conditioning Regimen With Treosulfan and Fludarabine for Allogeneic Hematopoietic Cell Transplantation for Patients With Acute Leukemia
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 60
- 试验地点
- 6
- 主要终点
- Number of Patients Experiencing Regimen-related Toxicity Events in Study Population
研究概览
简要总结
RATIONALE: Drugs used in chemotherapy, such as treosulfan and fludarabine, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving treosulfan and fludarabine together with a donor bone marrow transplant or a peripheral stem cell transplant may be an effective treatment for acute myeloid leukemia, acute lymphoblastic leukemia, or myelodysplastic syndrome.
PURPOSE: This phase II trial is studying giving treosulfan together with fludarabine to see how well it works in treating patients who are undergoing a donor stem cell transplant for acute myeloid leukemia, acute lymphoblastic leukemia, or myelodysplastic syndrome.
详细描述
OBJECTIVES:
Primary Phase
- Determine the best dose of treosulfan when administered with fludarabine as a reduced-intensity conditioning regimen followed by allogeneic hematopoietic stem cell transplantation, in terms of incidence of severe to fatal toxicity to major organ systems and incidence of graft failure, in patients with acute myeloid leukemia, lymphoblastic leukemia, or myelodysplastic syndrome.
Secondary Phase
- Determine the safety of this regimen, in terms of incidence of grade II-IV acute and chronic graft-versus-host disease, in these patients.
- Determine, preliminarily, the efficacy of this regimen, in terms of incidence of relapse, overall and disease-free survival, donor chimerism on days 28 and 100, and incidence of 200-day and 1-year nonrelapse mortality, in these patients.
- Determine the pharmacokinetic and pharmacodynamic profile of treosulfan in patients treated with this regimen.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- — 至 60 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •DISEASE CHARACTERISTICS:
- •Diagnosis of acute myeloid leukemia, lymphoblastic leukemia, or myelodysplastic syndrome
- •Any phase allowed, including any of the following:
- •Disease in remission
- •Relapsed or primary refractory disease
- •No CNS leukemic involvement not clearing with prior intrathecal chemotherapy and/or cranial radiotherapy
- •Planning to undergo unmanipulated allogeneic bone marrow or peripheral blood stem cell transplantation
- •Filgrastim (G-CSF) mobilization of bone marrow or stem cells allowed
- •Donor available, meeting 1 of the following criteria:
- •HLA-identical related donor
- •HLA-A, -B, -C, -DRB1, and -DQB1 matched unrelated donor by high-resolution DNA typing
- •A single allele mismatch allowed
- •PATIENT CHARACTERISTICS:
- •Performance status
- •Karnofsky 70-100% OR
- •Lansky 70-100%
- •Life expectancy
- •Not specified
- •Hematopoietic
- •Not specified
- •Bilirubin ≤ 2 times upper limit of normal (ULN)
- •AST ≤ 2 times ULN
- •No evidence of synthetic dysfunction
- •No severe cirrhosis
- •No active infectious hepatitis
- •Creatinine clearance ≥ 50%
- •Creatinine ≤ 2 times ULN
- •Dialysis independent
- •Cardiovascular
- •No cardiac insufficiency requiring treatment
- •No symptomatic coronary artery disease
- •Ejection fraction ≥ 35% (for patients with history of cardiac disease or anthracycline exposure)
- •PO_2 ≥ 70 mm Hg AND DLCO ≥ 70% of predicted OR
- •PO_2 ≥ 80 mm Hg AND DLCO ≥ 60% of predicted
- •Not requiring supplementary continuous oxygen
- •Not pregnant or nursing
- •Negative pregnancy test
- •Fertile patients must use effective contraception
- •No other disease that would severely limit life expectancy
- •No HIV positivity
- •No active infection requiring deferral of conditioning
- •No known hypersensitivity to the study drugs
- •PRIOR CONCURRENT THERAPY:
- •Biologic therapy
- •See Disease Characteristics
- •No prior allogeneic bone marrow or stem cell transplantation
- •No concurrent umbilical cord blood or autologous transplantation
- •Chemotherapy
- •See Disease Characteristics
- •Radiotherapy
- 另有 3 项未显示
排除标准
- 未提供
结局指标
主要结局
Number of Patients Experiencing Regimen-related Toxicity Events in Study Population
时间窗: 34 days and 2 years
Proportion of patients experiencing regimen-related toxicity to major organ systems from day minus 6 to day 28. Major organ systems: cardiac, bladder/renal, pulmonary, hepatic, neurologic and gastrointestinal
Number of Patients Experiencing Graft Failure
时间窗: 42 days
Graft versus Host Disease (GVHD) is a frequent complication of allogeneic bone marrow transplant in which the engrafted donor cells attacks the patient's organs and tissue. Acute GVHD (aGVHD) usually occurs during the first three months following an allogeneic BMT. Chronic GVHD (cGVHD) usually develops after the third month post-transplant. Patients may experience one, both or neither.
Incidence (Percent of Participants) With Nonrelapse Mortality (NRM) by Day 200 (Secondary Phase Only)
时间窗: 200 days
NRM (Non relapse mortality) - death not attributed to the primary cancer.
次要结局
- Number of Subjects Who Are Without Disease at One Year as Indicator of Disease Free Survival.(One year)