Sequential Myeloablative Stem Cell Transplantation and Reduced Intensity Allogeneic Stem Cell Transplantation in Patients With Refractory or Recurrent Non-Hodgkin's Lymphoma and Hodgkin's Disease
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 30
- 试验地点
- 6
- 主要终点
- Total Number of Subjects With a Disease Relapse or Progression Following MAC AutoSCT
研究概览
简要总结
The sequential combination of myeloablative therapy and autologous stem cell transplantation (APBSCT) followed by a reduced intensity allogeneic stem cell transplant (Allo SCT) and post SCT adoptive cellular immunotherapy will be well tolerated in patients with refractory or recurrent non-Hodgkin's lymphoma (NHL) and Hodgkin's disease (HD).
详细描述
Lymphomas are the third most common group of cancers in children and adolescents in the United States. While Hodgkin's Disease (HD) has been described for many years, some subtypes of the non-Hodgkin's Lymphomas (NHL) have only recently been described. Non-Hodgkin's lymphomas traditionally have been classified as low, intermediate or high grade based on their clinical aggressiveness. More recently they have been divided into two major subgroups indolent and aggressive lymphomas by the current National Cancer Institute (NCI/PDQ) reference. Among children, aggressive histologies are prevalent including small non-cleaved cell lymphoma, lymphoblastic lymphoma, and diffuse large cell lymphoma. The most common histologic classifications of childhood non-Hodgkin's lymphoma over the past 30 years has included the morphological schema developed by Rappaport, the morphologically and immunologically based schema of Lukes and Collins, the Kiel classifications, the prognostic sub-groupings of the National Cancer Institute's Working Formulation, and the most recently developed classification that utilizes morphological, immunophenotypic and genetic information in the Revised European-American Lymphoma (REAL) classification.
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 55 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patient must have adequate organ function as below
- •Adequate renal function defined as:
- •Serum creatinine less than or equal to 2.0 x normal, or
- •Creatinine clearance or radioisotope glomerular filtration rate (GFR) >= 40 ml/min/m2 or >60 ml/min/1.73 m2 or an equivalent GFR as determined by the institutional normal range
- •Adequate liver function defined as:
- •Total bilirubin <2.0 x normal; or
- •Serum glutamic-oxaloacetic transaminase (SGOT) (aspartate aminotransferase (AST)) or serum glutamic-pyruvic transaminase (SPGT) (alanine aminotransferase (ALT)) <5.0 x normal
- •Adequate cardiac function defined as:
- •Shortening fraction of >27% by echocardiogram, or
- •Ejection fraction of >47% by radionuclide angiogram or echocardiogram
- •Adequate pulmonary function defined as:
- •Diffusing capacity of the lungs for carbon monoxide (DLCO) >50% by pulmonary function test for autologous transplant
- •DLCO > 40% by pulmonary function test for reduced intensity allogeneic transplant
- •For children who are uncooperative, no evidence of dyspnea at rest, no exercise intolerance, and a pulse oximetry >94% in room air.
- •Disease Status (Eligibility)
- •Patients with Non-Hodgkin's Lymphoma with either of the following:
- •Primary induction failure (failure to achieve initial CR) who have a partial response (PR) or stable disease (SD) with reinduction chemotherapy. *All patients are required to have a biopsy regardless of positron emission tomography (PET)/Gallium results.
- •Patients with 1st PR, 2nd CR, 2nd PR, or 2nd SD following reinduction chemotherapy
- •Patients with 3rd CR, 3rd PR, 3rd SD following reinduction chemotherapy
- •Patients with Hodgkin's Disease with either of the following:
- •Primary induction failure (failure to achieve initial CR) and/or primary refractory disease.
- •First relapse
- •Early relapse (within 12 months off therapy) (excluding those who received no therapy or radiation therapy only for initial therapy)
- •Late relapse (greater than 12 months off therapy). Only patients with recurrent Stage III or IV disease and/or those with B symptoms at relapse (all other late relapses are excluded).
- •Second relapse.
- •Third relapse.
- •Patients must achieve a CR, PR or SD after reinduction chemotherapy.
排除标准
- •Patients with NHL or HD with 4th or greater CR, PR, and/or SD
- •Patients with progressive disease (PD) unresponsive to reinduction chemo, radio, or immunotherapy
- •Hodgkin's Disease in late relapse (other than those discussed above).
- •Patients with post-transplant lymphoproliferative disease following a solid organ transplantation or AIDS associated NHL
- •Patients who don't have an eligible donor
- •Women who are pregnant
研究组 & 干预措施
Arm A - Family Donor
Fludarabine and Busulfan: Patients who have a matched family (allogeneic) donor will go on to receive non-ablative therapy, followed by an infusion of donor stem cells; this is called an allogeneic peripheral blood stem cell transplant. The non-ablative therapy will be busulfan and fludarabine, Usually large (myeloablative) doses of these drugs are used for an allogeneic transplant. However, in this study lower doses (non-ablative) of chemotherapy will be given. In patients who still have evidence of disease after allogeneic transplant, additional donor immune cells (donor lymphocyte infusion) (DLI) will be given twice to further treat the lymphoma.
干预措施: Fludarabine (Drug)
Arm A - Family Donor
Fludarabine and Busulfan: Patients who have a matched family (allogeneic) donor will go on to receive non-ablative therapy, followed by an infusion of donor stem cells; this is called an allogeneic peripheral blood stem cell transplant. The non-ablative therapy will be busulfan and fludarabine, Usually large (myeloablative) doses of these drugs are used for an allogeneic transplant. However, in this study lower doses (non-ablative) of chemotherapy will be given. In patients who still have evidence of disease after allogeneic transplant, additional donor immune cells (donor lymphocyte infusion) (DLI) will be given twice to further treat the lymphoma.
干预措施: Busulfan (Drug)
Arm B - Unrelated Cord Blood or Adult
Fludarabine, Busulfan and ATG: For patients who don't have a matched family donor, a cord blood search and unrelated adult search will be done at all of the cord blood banks and adult donor registries in the world. If a closely matched cord blood donor or unrelated adult donor is found, non-ablative chemotherapy with busulfan, fludarabine and antithymocyte globulin (ATG) followed by the infusion of matched unrelated cord blood cells or adult donor stem cells or bone marrow to restore the bone marrow will be given.
干预措施: Fludarabine (Drug)
Arm B - Unrelated Cord Blood or Adult
Fludarabine, Busulfan and ATG: For patients who don't have a matched family donor, a cord blood search and unrelated adult search will be done at all of the cord blood banks and adult donor registries in the world. If a closely matched cord blood donor or unrelated adult donor is found, non-ablative chemotherapy with busulfan, fludarabine and antithymocyte globulin (ATG) followed by the infusion of matched unrelated cord blood cells or adult donor stem cells or bone marrow to restore the bone marrow will be given.
干预措施: Busulfan (Drug)
Arm B - Unrelated Cord Blood or Adult
Fludarabine, Busulfan and ATG: For patients who don't have a matched family donor, a cord blood search and unrelated adult search will be done at all of the cord blood banks and adult donor registries in the world. If a closely matched cord blood donor or unrelated adult donor is found, non-ablative chemotherapy with busulfan, fludarabine and antithymocyte globulin (ATG) followed by the infusion of matched unrelated cord blood cells or adult donor stem cells or bone marrow to restore the bone marrow will be given.
干预措施: Anti-Thymocyte Globulin (Drug)
结局指标
主要结局
Total Number of Subjects With a Disease Relapse or Progression Following MAC AutoSCT
时间窗: Up to 1 year post-transplantation
Includes subjects with any measurable growth of disease in a previously affected site or detection of disease in a new site confirmed by biopsy.
Total Number of Subjects With a Complete Response (CR) Following Myeloablative Conditioning (MAC) and Autologous Stem Cell Transplantation (AutoSCT)
时间窗: Up to 1 year post-transplantation
Complete Response is defined as the complete resolution of B symptoms (i.e., weight loss, night sweats and fever) and normalization of all sites of disease on the basis of physical exam, bone marrow biopsy, and imaging studies.
Total Number of Subjects With Partial Response or Stable Disease Following MAC AutoSCT
时间窗: Up to 1 year post-transplantation
Total includes subjects with partial response and patients with stable disease, defined as \<50% reduction in measurable disease or the uninterrupted persistence of B symptoms.
次要结局
- Time to Neutrophil Engraftment(Up to 1 year post-transplantation)
- Total Number of Subjects That Experienced Transplant-related Mortality (TRM)(Up to 1 year post-transplantation)
- Time to Platelet Engraftment(Up to 1 year post-transplantation)
- Total Number of Subjects With Grade II-IV Acute Graft-versus-Host-Disease (GVHD)(Up to 1 year post-transplantation)
研究者
Prakash Satwani
Assistant Professor of Clinical Pediatrics
Columbia University