Comparing Post-Transplant Cyclophosphamide with Calcineurin Inhibitors As a GVHD Prophylaxis to Standard Care of Methotrexate and Calcineurin Inhibitors for Acute Leukemia Incorporating Patient Pharmacogenomics Profiling
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 入组人数
- 264
- 试验地点
- 1
- 主要终点
- GRFS (GVHD-free/relapse-free survival)
研究概览
简要总结
This randomized clinical trial will evaluate two approaches of GvHD prophylaxis; the standard of care GVHD prophylaxis regimen (methotrexate/calcineurin inhibitors) and post-transplant cyclophosphamide with calcineurin inhibitors for their efficacy as a new GVHD prophylaxis strategy.
详细描述
An open-label randomized clinical trial will be performed. Eligible patients are females and males, between 14 and 65 years undergoing allo-HCT for treatment of Acute Leukemia (AML or ALL). Patients must have a matching related peripheral blood stem cell donor. Patients from or referred to the KFSH&RC for allogeneic transplant consideration will be offered the opportunity to participate in this trial.
Treatment Description:
Patients will be randomized on one of the arms; an intervention or a standard of care arm.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- None
入排标准
- 年龄范围
- 14 Years 至 65 Years（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients with Acute Leukemias (AML, ALL) in morphologic complete remission with or without hematologic recovery
- •Patients must have a fully matched (8/8) related donor willing to donate peripheral blood stem cells and must meet institutional criteria for donation
- •Planned Myeloablative conditioning regimen
- •Cardiac function: ejection fraction at rest ≥ 50% by MUGA or TTE
- •Estimated creatinine clearance greater than 50 mL/minute
- •Pulmonary function: DLCO ≥ 50% (adjusted for hemoglobin), and FVC and FEV1 ≥ 50%
- •Liver function: total bilirubin < 2x the upper limit of normal (unless elevated bilirubin is attributed to Gilbert's Syndrome) and ALT/AST < 2.5x the upper normal limit
- •Signed informed consent
排除标准
- •Karnofsky or Lansky Performance Score < 70%.
- •Active disease
- •Patients with uncontrolled bacterial, viral, or fungal infections
- •Presence of fluid collection (ascites, pleural or pericardial effusion) that interferes with methotrexate clearance or makes methotrexate use contraindicated
- •Patients seropositive for HIV-1 or -2
- •Patients seropositive for HTLV-I or -II
- •Patients with active Hepatitis B or C viral replication by PCR
- •Women who are pregnant (positive serum or urine βHCG) or breastfeeding
- •Females with childbearing potential (FCBP) or men who have sexual contact with FCBP unwilling to use effective forms of birth control or abstinence for one year after transplantation
- •History of uncontrolled autoimmune disease or on active treatment
- •Patients with prior malignancies, except resected non-melanoma skin cancer or treated cervical carcinoma in situ; cancer treated with curative intent ≥ 5 years previously will be allowed; cancer treated with curative intent < 5 years previously will not be allowed.
研究组 & 干预措施
Arm 1: Intervention
Peripheral blood matched related donor HCT, using myeloablative conditioning regimen (IV Busulfan/IV Fludarabine for AML, IV VP16/TBI for ALL) HCT with cyclophosphamide, and oral tacrolimus (or another calcineurin inhibitor if intolerant for tacrolimus) for GVHD prophylaxis. Cyclophosphamide will be given at a dose of 50 mg/kg/day IV on Day +3 and Day +5 post stem cell infusion (only 2 doses).
干预措施: Cyclophosphamide 50mg (Drug)
Arm 2: Standard of Care
Peripheral blood matched related donor HCT, using myeloablative conditioning regimen (IV Busulfan/IV Fludarabine for AML, IV VP16/TBI for ALL) HCT with methotrexate, and oral tacrolimus (or another calcineurin inhibitor if intolerant for tacrolimus) for GVHD prophylaxis
干预措施: Methotrexate (Drug)
结局指标
主要结局
GRFS (GVHD-free/relapse-free survival)
时间窗: One-year post-transplant
Defined as the non-occurrence of a grade 3-4 acute GVHD, or systemic therapy-requiring chronic GVHD, or relapse, or death during the first post-transplant year.
次要结局
- Acute Graft versus Host Disease (aGVHD)(100 Day post transplant)
- Chronic Graft versus Host Disease (cGVHD)(One year Post-transplant)