A Phase II Trial of CD34+ Enriched Transplants From HLA-Compatible Related or Unrelated Donors for Treatment of Patients With Leukemia or Lymphoma
试验速览
- 阶段
- 2 期
- 状态
- 尚未招募
- 发起方
- 入组人数
- 100
- 试验地点
- 1
- 主要终点
- Incidence rate of graft versus host disease (GvHD)
研究概览
简要总结
This study will evaluate whether processing blood stem cell transplants using an investigational device (the CliniMACS system) results in less complications for patients undergoing transplant for treatment of a blood malignancy (cancer) or blood disorder.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 74 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Malignant conditions or other life-threatening disorders correctable by transplant for which CD34+ selected, T-cell depleted allogeneic hematopoietic stem cell transplantation is indicated such as:
- •AML in 1st remission - for patients who is AML does not have 'good risk' cytogenetic features (i.e. t8:21, t 15: 17, inv16).
- •Secondary AML in 1st remission
- •AML in 1st relapse or 2nd remission
- •ALL/CLL in patient remission clinical or molecular features indicating a high risk for relapse; or ALL/CLL 2nd remission
- •CML failing to respond to or not tolerating imatinib or dasatinib in first chronic phase of disease; CML in accelerated phase, second chronic phase, or in CR after accelerated phase or blast crisis.
- •Non-Hodgkin's lymphoma with chemo responsive disease in any of the following categories:
- •Intermediate or high-grade lymphomas who have failed to achieve a first CR or have relapsed following a 1st remission who are not candidates for autologous transplants.
- •Any NHL in remission which is considered not curable with chemotherapy alone and not eligible/appropriate for autologous transplant.
- •Chronic myelomonocyte leukemia: CMML-1 and CMML-
- •The following inclusion criteria are also required:
- •Patient's age includes from ≥18 to ≤74 years old.
- •Patients may be of either gender or any ethnic background.
- •Patients must have a Karnofsky (adult) Performance Status of at least 70%
- •Patients must have adequate organ function measured by:
- •Cardiac: asymptomatic or if symptomatic then LVEF at rest must be 50% and must improve with exercise.
- •Hepatic: < 3x ULN AST and: s 1.5 total serum bilirubin, unless there is congenital benign hyperbilirubinemia or if the hyperbilirubinemia is directly caused by the disease in which the patient is receiving a transplant (e.g. AML Chloroma obstructing the biliary tree). Patients with higher bilirubin levels due to causes other than active liver disease is also eligible with Pl approval e.g. patients with PNH, Gilbert's disease or other hemolytic disorders.
- •Renal: serum creatinine: s; 1.2 mg/dL or if serum creatinine is outside the normal range, then CrCl > 30 ml/min (measured or calculated/estimated).
- •Pulmonary: asymptomatic or if symptomatic, DLCO 50% of predicted (corrected for hemoglobin).
- •Each patient must be willing to participate as a research subject and must sign an informed consent form.
排除标准
- •Female patients who are pregnant or breast-feeding
- •Active viral, bacterial or fungal infection
- •Patient seropositive for HIV-I /II; HTLV -I /II
- •Presence of leukemia in the CNS
研究组 & 干预措施
Regimen A: TBI/Thiotepa/Cyclophosphamide
Patients in enrolled in Regimen A will receive the following:
- Total Body Irradiation (TBI), hyper-fractionated to a dose of 1320 cGy depending on age, stage of disease and requirement of general anesthesia with lung shielding
- Thiotepa, 5 mg/kg/day x 2 days via IV infusion over 4 hours daily or 10 mg/kg on one day
- Cyclophosphamide, 60 mg/kg/day x 2 days via IV infusion over 2 hours daily (or if cyclophosphamide is contraindicated, fludarabine at 25 mg/m^2 x 5 days may be substituted)
干预措施: Total Body Irradiation (TBI) (Radiation)
Regimen A: TBI/Thiotepa/Cyclophosphamide
Patients in enrolled in Regimen A will receive the following:
- Total Body Irradiation (TBI), hyper-fractionated to a dose of 1320 cGy depending on age, stage of disease and requirement of general anesthesia with lung shielding
- Thiotepa, 5 mg/kg/day x 2 days via IV infusion over 4 hours daily or 10 mg/kg on one day
- Cyclophosphamide, 60 mg/kg/day x 2 days via IV infusion over 2 hours daily (or if cyclophosphamide is contraindicated, fludarabine at 25 mg/m^2 x 5 days may be substituted)
干预措施: Thiotepa (Drug)
Regimen A: TBI/Thiotepa/Cyclophosphamide
Patients in enrolled in Regimen A will receive the following:
- Total Body Irradiation (TBI), hyper-fractionated to a dose of 1320 cGy depending on age, stage of disease and requirement of general anesthesia with lung shielding
- Thiotepa, 5 mg/kg/day x 2 days via IV infusion over 4 hours daily or 10 mg/kg on one day
- Cyclophosphamide, 60 mg/kg/day x 2 days via IV infusion over 2 hours daily (or if cyclophosphamide is contraindicated, fludarabine at 25 mg/m^2 x 5 days may be substituted)
干预措施: Cyclophosphamide (Drug)
Regimen B: Busulfan/Melphalan/Fludarabine
Patients in enrolled in Regimen B will receive the following:
- Busulfan, IV 0.8 mg/kg q6hours x 10 or 12 doses over 3 days, depending on the disease
- Melphalan, 70 mg/m^2/day x 2 days via IV infusion over 30 minutes daily
- Fludarabine, 25 mg/m^2/day x 5 days via IV infusion over 30 minutes daily
干预措施: Busulfan (Drug)
Regimen B: Busulfan/Melphalan/Fludarabine
Patients in enrolled in Regimen B will receive the following:
- Busulfan, IV 0.8 mg/kg q6hours x 10 or 12 doses over 3 days, depending on the disease
- Melphalan, 70 mg/m^2/day x 2 days via IV infusion over 30 minutes daily
- Fludarabine, 25 mg/m^2/day x 5 days via IV infusion over 30 minutes daily
干预措施: Melphalan (Drug)
Regimen B: Busulfan/Melphalan/Fludarabine
Patients in enrolled in Regimen B will receive the following:
- Busulfan, IV 0.8 mg/kg q6hours x 10 or 12 doses over 3 days, depending on the disease
- Melphalan, 70 mg/m^2/day x 2 days via IV infusion over 30 minutes daily
- Fludarabine, 25 mg/m^2/day x 5 days via IV infusion over 30 minutes daily
干预措施: Fludarabine (Drug)
结局指标
主要结局
Incidence rate of graft versus host disease (GvHD)
时间窗: Two years
Incidence of acute and chronic GvHD
Severity of disease
时间窗: Two years
Severity of the adverse events will be reported based on the CTCAE Version 5.
Incidence of transplant-related mortality (TRM)
时间窗: Two years
TRM includes fatal complications resulting from the allogeneic transplant and/ or treatment regimens such as graft failure, GvHD, hemorrhages, and infections.
Change in overall survival (OS)
时间窗: Six months, one year, two years
OS is defined as time from transplant to death or last follow-up.
Change in disease free survival (DFS)
时间窗: Six months, one year, two years
DFS is defined as the minimum time interval of times to relapse/recurrence, to death or to the last follow- up, from the time of transplant.
次要结局
- Proportion of patients optimal and suboptimal doses(Two years)
研究者
Guenther Koehne
Deputy Director and Chief of Blood and Marrow Transplant, Hematologic Oncology and Benign Hematology
Baptist Health South Florida