Nonmyeloablative BMT With Post-transplant Cyclophosphamide, Rituximab and Optimized Donor Selection for B-cell Lymphomas
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 135
- 试验地点
- 1
- 主要终点
- Progression-free Survival
研究概览
简要总结
This phase II trial is studying how well giving fludarabine and cyclophosphamide together with total-body irradiation and rituximab works in treating patients with B-cell lymphoma or chronic lymphocytic leukemia who are undergoing an allogeneic (donor) bone marrow transplant. The type of bone marrow transplant is a less intensive or "mini" transplant using a relative as the bone marrow donor. The donated bone marrow stem cells may replace the patient's immune system cells and help destroy any remaining cancer (graft-versus-tumor effect). Patients undergoing this type of transplant often have more than one relative who could be a donor. The trial is also studying a new way of choosing amongst possible donors which might improve how the rituximab works.
详细描述
This phase II for relapsed or refractory B-cell malignancies builds on the platform of nonmyeloablative, related-donor, HLA (human leukocyte antigen)-matched or HLA-haploidentical BMT with post-transplantation high-dose cyclosphosphamide administered for prophylaxis of graft-versus-host disease and graft rejection. Rituximab is added to the transplant regimen with the goal of augmenting anti-tumor activity. In patients with B-cell lymphomas, specific polymorphisms in the immunoglobulin Fc receptor have been associated with greater sensitivity to rituximab or rituximab-based therapies, translating in some series into higher response rates and improved progression-free survival. This raises the possibility of selecting donors who carry this permissive polymorphism. This trial identifies and selects donors who have the favorable polymorphism at FcgammaR3A-158, thereby potentially conferring greater sensitivity to rituximab in the host after BMT.
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
- 1 Year 至 75 Years（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Poor-risk CD20+, B-cell lymphoma, as follows:
- •Low grade B-cell lymphoma that has failed at least two prior therapies (excluding single agent rituximab), or undergone histologic conversion (if histologic conversion, PR or CR is required):
- •Follicular grade 1 or 2 lymphoma
- •Follicular lymphoma not otherwise specified
- •Marginal zone (or MALT) lymphoma
- •Lymphoplasmacytic lymphoma / Waldenstrom's macroglobulinemia
- •Hairy cell leukemia
- •Small lymphocytic lymphoma / chronic lymphocytic leukemia (SLL/CLL)
- •Low grade B-cell lymphoma, unspecified
- •Nodular lymphocyte-predominant Hodgkin lymphoma
- •Poor-risk small lymphocytic lymphoma or chronic lymphocytic leukemia, defined by a 17p deletion, 11q deletion, or histologic conversion (if histologic conversion, PR or CR is required)
- •Aggressive B-cell non-Hodgkin's lymphoma that has failed at least one prior regimen of multiagent chemotherapy, is in PR (partial remission) or CR (complete remission), and patient is either ineligible for autologous hematopoietic BMT or autologous BMT is not recommended:
- •Follicular grade 3 lymphoma
- •Histoconversion of low-grade B-cell lymphoma (including SLL/CLL) to aggressive B-cell non-Hodgkin's lymphoma
- •Mantle cell lymphoma
- •Diffuse large B-cell lymphoma (excluding primary CNS [central nervous system] lymphoma)
- •"Gray zone" or composite lymphomas with combined features of primary mediastinal large B-cell and Hodgkin's lymphoma
- •Burkitt's lymphoma/leukemia
- •Atypical Burkitt's lymphoma/leukemia (high grade B-cell lymphoma, unclassified, including that with features intermediate between Burkitt's and diffuse large B-cell lymphoma)
- •Must have a related donor who is at least HLA haploidentical
- •Any previous BMT must have occurred at least 3 months prior
- •Left ventricular ejection fraction at least 35%
- •Bilirubin no more than 3.0 mg/dL (unless due to Gilbert's syndrome), and ALT (alanine aminotransferase) and AST (aspartate aminotransferase) no more than 5 x upper limit of normal
- •FEV1 (forced expiratory volume in one second) and FVC (forced vital capacity) at least 40% of predicted
- •Absence of uncontrolled infection
排除标准
- •More than 20% involvement of bone marrow by chronic lymphocytic leukemia
- •Active central nervous system lymphoma
- •ECOG (Eastern Cooperative Oncology Group) performance status greater than 1 (2,3, and 4)
- •HIV positive
- •Pregnant or breastfeeding
研究组 & 干预措施
Transplant
Non-myeloablative allogeneic bone marrow transplant (BMT) with a fludarabine (Flu), cyclophosphamide (Cy), total body irradiation (TBI) preparative regimen and post-transplant Cy, mycophenolate mofetil (MMF), and tacrolimus as GVHD (graft vs host disease) prophylaxis. Rituximab will be given as post-transplant maintenance.
干预措施: Fludarabine (Drug)
Transplant
Non-myeloablative allogeneic bone marrow transplant (BMT) with a fludarabine (Flu), cyclophosphamide (Cy), total body irradiation (TBI) preparative regimen and post-transplant Cy, mycophenolate mofetil (MMF), and tacrolimus as GVHD (graft vs host disease) prophylaxis. Rituximab will be given as post-transplant maintenance.
干预措施: Cyclophosphamide (Drug)
Transplant
Non-myeloablative allogeneic bone marrow transplant (BMT) with a fludarabine (Flu), cyclophosphamide (Cy), total body irradiation (TBI) preparative regimen and post-transplant Cy, mycophenolate mofetil (MMF), and tacrolimus as GVHD (graft vs host disease) prophylaxis. Rituximab will be given as post-transplant maintenance.
干预措施: Total body irradiation (Radiation)
Transplant
Non-myeloablative allogeneic bone marrow transplant (BMT) with a fludarabine (Flu), cyclophosphamide (Cy), total body irradiation (TBI) preparative regimen and post-transplant Cy, mycophenolate mofetil (MMF), and tacrolimus as GVHD (graft vs host disease) prophylaxis. Rituximab will be given as post-transplant maintenance.
干预措施: Tacrolimus (Drug)
Transplant
Non-myeloablative allogeneic bone marrow transplant (BMT) with a fludarabine (Flu), cyclophosphamide (Cy), total body irradiation (TBI) preparative regimen and post-transplant Cy, mycophenolate mofetil (MMF), and tacrolimus as GVHD (graft vs host disease) prophylaxis. Rituximab will be given as post-transplant maintenance.
干预措施: Mycophenolate Mofetil (Drug)
Transplant
Non-myeloablative allogeneic bone marrow transplant (BMT) with a fludarabine (Flu), cyclophosphamide (Cy), total body irradiation (TBI) preparative regimen and post-transplant Cy, mycophenolate mofetil (MMF), and tacrolimus as GVHD (graft vs host disease) prophylaxis. Rituximab will be given as post-transplant maintenance.
干预措施: Rituximab (Drug)
Transplant
Non-myeloablative allogeneic bone marrow transplant (BMT) with a fludarabine (Flu), cyclophosphamide (Cy), total body irradiation (TBI) preparative regimen and post-transplant Cy, mycophenolate mofetil (MMF), and tacrolimus as GVHD (graft vs host disease) prophylaxis. Rituximab will be given as post-transplant maintenance.
干预措施: Allogeneic Bone Marrow Transplant (BMT) (Biological)
结局指标
主要结局
Progression-free Survival
时间窗: 1 year post-intervention
Percentage of participants alive and without relapse or disease progression.
次要结局
- Progression-free Survival(2 years post-intervention)
- Non-relapse Mortality(1 year post intervention)
- Incidence of Grades II-IV Acute Graft-versus-Host-Disease (GVHD)(1 year post intervention)
- Graft Failure(Day 60)
- Overall Survival(2 years post intervention)
- Relapse(2 years post intervention)
- Engraftment(Day 60)
- Incidence of Grades III-IV Acute GVHD(1 year post intervention)
- Incidence of Chronic GVHD(1 year post intervention)