Phase II Feasibility Study of T-Cell Depletion in Allogeneic Unrelated Bone Marrow Transplantation (MUD ALLO BMT) Followed by Delayed T-Cell Infusions
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 13
- 试验地点
- 1
- 主要终点
- Treatment-related Mortality (TRM)
研究概览
简要总结
RATIONALE: Giving chemotherapy and total-body irradiation before a donor peripheral blood stem cell transplant helps stop the growth of cancer and abnormal cells and helps stop the patient's immune system from rejecting the donor's stem cells. When stem cells from a donor are infused into the patient they may help the patient's bone marrow make stem cells, red blood cells, white blood cells, and platelets. Sometimes the transplanted cells from a donor can make an immune response against the body's normal cells. Removing the T cells from the donor cells before transplant may stop this from happening. Giving an infusion of the donor's T cells (donor lymphocyte infusion) after the transplant may help destroy any remaining cancer cells (graft-versus-tumor effect).
PURPOSE: This phase II trial is studying T-cell depletion in donor stem cell transplant followed by delayed T cell infusions in treating patients with hematologic cancer or other disease.
详细描述
OBJECTIVES:
Primary
- Determine if T-cell depletion of a peripheral blood progenitor cell (PBPC) graft followed by delayed add-backs of defined doses of donor lymphocytes decreases the rate of graft-versus-host disease and its complications in matched unrelated donor (MUD) allogeneic peripheral blood progenitor cell (PBPC) transplantation in patients with hematologic cancers or other diseases.
- Determine whether targeted T-cell dosages in the PBPC graft can be achieved in these patients by positive CD34+ selection using the Baxter Inc. Isolex 300i v. 2.5.
- Determine the effects of T-cell depletion on the rate of engraftment in these patients.
- Develop a matched unrelated donor (MUD) allogeneic transplantation regimen that will decrease overall treatment-related mortality in these patients.
OUTLINE: This is a non-randomized study.
- Myeloablative preparative regimen: Patients receive cyclophosphamide IV once daily on days -5 and -4 followed by total body irradiation twice daily on days -3, -2, and -1. Patients also receive tacrolimus on day -1 administered by continuous IV infusion over 24 hours.
- Peripheral blood progenitor cell graft transplantation: Patients receive T-cell depleted, peripheral blood progenitor cells (PBPC) by IV infusion on day 0. Beginning 1 day after completion of the PBPC infusion, patients receive filgrastim (G-CSF) subcutaneously once daily until blood counts recover.
- Post transplantation T cell add-backs: Patients receive defined doses of donor T cells by IV infusion on days 45 and 100, in the absence of active graft-versus-host disease (GVHD) requiring steroids*.
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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •DISEASE CHARACTERISTICS:
- •Diagnosis of any of the following hematologic cancers or other diseases:
- •Acute myelogenous leukemia
- •Relapsed or refractory disease with poor-risk cytogenetics
- •Acute lymphoblastic leukemia
- •Relapsed or refractory disease with poor-risk cytogenetics
- •Chronic myelogenous leukemia
- •Persistent disease after at least 6 months of treatment with imatinib mesylate (Gleevec)
- •Myelodysplasia, meeting 1 of the following criteria:
- •French-American-British Classification of refractory anemia with excess blasts (RAEB) or RAEB with transformation
- •International Prognostic Scoring System score > 2
- •Lymphoid malignancies, including non-Hodgkin lymphoma, Hodgkin disease, chronic lymphocytic leukemia, and prolymphocytic leukemia
- •Relapsed or refractory disease after at least 1 prior therapy
- •Myelofibrosis
- •Transfusion dependent (RBC's, platelets, or both)
- •Paroxysmal nocturnal hemoglobinuria (transfusion dependent)
- •Myeloproliferative disorder
- •Eosinophilic leukemia
- •Severe aplastic anemia
- •Corrected reticulocyte count < 1%
- •Platelet count < 30,000/mm³ (untransfused)
- •Bone marrow biopsy with < 15% cellularity
- •Plasma cell leukemia
- •No essential thrombocytopenia or polycythemia vera
- •No matched related donor available
- •Must have an 8/8 or 7/8 serologic HLA matched unrelated donor available
- •PATIENT CHARACTERISTICS:
- •Cardiac ejection fraction ≥ 45% (if < 45%, then cardiac consult required)
- •Not pregnant or nursing
- •Negative pregnancy test
- •FEV_1 and DLCO ≥ 45% predicted
- •Creatinine < 2.0 mg/dL
- •Bilirubin < 2.0 mg/dL
- •HIV negative
- •PRIOR CONCURRENT THERAPY:
- •See Disease Characteristics
- •No prior allogeneic bone marrow transplantation
- •No concurrent administration of steroids with T-cell add-backs
- •INCLUSION CRITERIA:
- •Patient actual weight must not be greater than 1.5x their ideal body weight
- •Cardiac ejection fraction >45%. If less than 45%, a Cardiac consult will be obtained.
- •A suitably matched unrelated donor that is at least a 7 out of 8 HLA serologic match.
- •Patient is not pregnant.
- •FEV 1 and DLCO > 45% predicted on pulmonary function testing.
- •Serum creatinine <2.0 mg/dl, serum bilirubin <2.0 mg/dl.
- •Patient and donor are HIV negative.
- •Diagnosis of one of the following diseases
- •Acute myelogenous leukemia
- •Relapsed disease,
- •Refractory disease, or
- 另有 22 项未显示
排除标准
- •Inability to give informed consent
- •Absence of any of the above mentioned medical conditions
- •Availability of matched-related donor
- •History of prior allogeneic BMT
研究组 & 干预措施
T-Cell Depletion Transplant
Our protocol is designed to attempt to improve the current results of matched unrelated donor (MUD) allo bone marrow transplant (BMT) and will be a major step towards the introduction and refinement of graft engineering. Our approach will address in a rational fashion all major technical and clinical aspects of MUD allo BMT.
Peripheral blood lymphocyte therapy; cyclophosphamide, tacrolimus, peripheral blood stem cell transplantation; total-body irradiation; 'allogeneic hematopoietic stem cell transplantation'
干预措施: peripheral blood lymphocyte therapy (Procedure)
T-Cell Depletion Transplant
Our protocol is designed to attempt to improve the current results of matched unrelated donor (MUD) allo bone marrow transplant (BMT) and will be a major step towards the introduction and refinement of graft engineering. Our approach will address in a rational fashion all major technical and clinical aspects of MUD allo BMT.
Peripheral blood lymphocyte therapy; cyclophosphamide, tacrolimus, peripheral blood stem cell transplantation; total-body irradiation; 'allogeneic hematopoietic stem cell transplantation'
干预措施: allogeneic hematopoietic stem cell transplantation (Procedure)
T-Cell Depletion Transplant
Our protocol is designed to attempt to improve the current results of matched unrelated donor (MUD) allo bone marrow transplant (BMT) and will be a major step towards the introduction and refinement of graft engineering. Our approach will address in a rational fashion all major technical and clinical aspects of MUD allo BMT.
Peripheral blood lymphocyte therapy; cyclophosphamide, tacrolimus, peripheral blood stem cell transplantation; total-body irradiation; 'allogeneic hematopoietic stem cell transplantation'
干预措施: peripheral blood stem cell transplantation (Procedure)
T-Cell Depletion Transplant
Our protocol is designed to attempt to improve the current results of matched unrelated donor (MUD) allo bone marrow transplant (BMT) and will be a major step towards the introduction and refinement of graft engineering. Our approach will address in a rational fashion all major technical and clinical aspects of MUD allo BMT.
Peripheral blood lymphocyte therapy; cyclophosphamide, tacrolimus, peripheral blood stem cell transplantation; total-body irradiation; 'allogeneic hematopoietic stem cell transplantation'
干预措施: total-body irradiation (TBI) (Radiation)
结局指标
主要结局
Treatment-related Mortality (TRM)
时间窗: 180 days after transplant
The complication rate in matched unrelated donor (MUD) allogeneic bone marrow transplant (allo BMT) is known to be high. Graft failure and severe graft versus host disease (GvHD) are the most significant contributors to treatment related mortality (TRM). This treatment regimen will be considered unacceptable if the number of patients that experience TRM is 55% or greater, and effective if TRM is 33% or less.
次要结局
- The Rate of Acute Graft Versus Host Disease (GVHD)(D+100 from transplant)
- Number of Participants With Relapse-free Survival(after 7 years of follow up)
- Number of Participants With Duration of Absolute Neutropenia(D+100 from transplant)
- Number of Participants Able to Receive T-cell Add Backs(through D+100)
研究者
Jaroslaw Maciejewski
Department Chair of Translational Hematology and Oncology Research
The Cleveland Clinic