Non-Myeloablative HLA-Matched Ex-Vivo T-cell Depleted Stem Cell Transplantation for Hematologic Malignancies
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 5
- 试验地点
- 2
- 主要终点
- To evaluate the risks of severe (grade III/IV) GVHD or transplant related mortality at < 100 days following HLA-matched non-myeloablative stem cell transplantation (or following "prophylactic" DLI given for chimerism conversion).
研究概览
简要总结
The purpose of this trial is to determine if patients with hematologic diseases who have a HLA 6/6 matched related donor and are not eligible for a standard myeloablative stem cell transplant will have less severe graft versus host disease (GVHD), transplant related mortality, and less graft failure when treated with a non-myeloablative T-cell depleted stem cell transplant.
详细描述
Our prior experience in the lab and in clinical trials with non-myeloablative HLA-matched and mismatched transplant strategies have been remarkable for a low transplant related mortality rate, but a still formidable risk of GVHD and graft rejection. In this trial, we have incorporated a combination ex-vivo T-cell depletion strategy to prevent GVHD with vigorous in vivo depletion of host (and to a lesser extent donor) T-cells to prevent graft rejection.
Patients will receive non-myeloablative conditioning with cyclophosphamide, thymoglobulin, fludarabine, and thymic irradiation, followed by a T-cell depleted PBSC infusion. Cyclosporine will be given for GVHD prophylaxis, and tapered beginning on day 35. Data from our mouse model and previous clinical trials have demonstrated that this approach can induce mixed chimerism without GVHD, with the potential for conversion of mixed chimerism to full donor hematopoiesis following donor leukocyte infusions.
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
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Disease statue: NHL, HD, or MM that are chemorefractory or relapsed; CLL that is Rai Stage III/IV, or lymphocyte doubling time of 6 months, or stage I/II that is resistant to > 2 chemotherapy regimens; AML or ALL in 1st or subsequent remission with poor prognostic features; CML in accelerated or blast phae; MDS with life-threatening cytopenias; patients who have had a previous autologous or allogeneic bone marrow or stem cell transplant; other hematologic disorders which allogeneic stem cell transplantation is appropriate where the risk of conventional transplantation is considered to be unacceptably high.
- •Estimated disease-free survival of less than one year
- •ECOG performance status of 0, 1, or 2
- •HLA-genotypically or phenotypically matched (at A, B, DR loci) related donor
排除标准
- •Patients who life expectancy is limited by diseases other than their hematologic malignancy.
- •Cardiac Disease: symptomatic congestive hearth failure, or RVG, or ejection fraction of < 45%, active angina pectoris, or uncontrolled hypertension.
- •Pulmonary Disease: severe chronic obstructive lung disease, or symptomatic restrictive lung disease, or DLCO of < 50%.
- •Renal Disease: serum creatinine > 2.0 mg/dl or creatinine clearance < 50 ml/min.
- •Hepatic Disease: serum bilirubin > 2.0 mg/dl or alkaline phosphatase, SGOT or SGPT > 3 times normal.
- •Neurologic Disease: symptomatic leukoencephalopathy, active CNS malignancy or other neuropsychiatric abnormalities believed to preclude transplantation
- •HIV or HTLV I antibody or Hepatitis B surface antigen positivity
- •Uncontrolled infection
研究组 & 干预措施
Transplantation
T-cell depleted HLA-matched peripheral blood stem cell transplantation
干预措施: Non-myeloablative Ex-Vivo T-cell Depleted PBSC Transplant (Procedure)
Transplantation
T-cell depleted HLA-matched peripheral blood stem cell transplantation
干预措施: T-cell depleted peripheral blood stem cell transplant (Procedure)
结局指标
主要结局
To evaluate the risks of severe (grade III/IV) GVHD or transplant related mortality at < 100 days following HLA-matched non-myeloablative stem cell transplantation (or following "prophylactic" DLI given for chimerism conversion).
时间窗: 100 days
次要结局
- To evaluate progression free and overall survival.(indefinite)
- To evaluate the incidence of graft loss.(100 days)
- To evaluate the incidence of acute and chronic GVHD.(indefinite)
研究者
Thomas Spitzer
Director, Bone Marrow Transplant Program
Massachusetts General Hospital