A Two Step Approach to Allogeneic Hematopoietic Stem Cell Transplantation for High-Risk Hematologic Malignancies Using One Haploidentical Donor
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 41
- 试验地点
- 1
- 主要终点
- Count of Participants That Experience 1 Year Relapse Free Survival After Undergoing Hematopoietic Stem Cell Transplantation (HSCT) Using the Thomas Jefferson University 2 Step Approach
研究概览
简要总结
This phase II trial studies how well total-body irradiation, donor lymphocyte infusion, and cyclophosphamide before donor stem cell transplant works in treating patients with high-risk hematologic malignancies. Giving total-body irradiation, donor lymphocyte infusion, and chemotherapy before a donor 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 certain 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 and giving tacrolimus and mycophenolate mofetil may stop this from happening.
详细描述
PRIMARY OBJECTIVES:
- To assess 1 year relapse free survival in high risk patients undergoing hematopoietic stem cell transplant (HSCT) using the Thomas Jefferson University (TJU) 2 step approach with 2 days inserted between the last fraction of total-body irradiation (TBI) and the infusion of donor T cells (donor lymphocyte infusion [DLI]).
SECONDARY OBJECTIVES:
- To assess regimen related toxicity in this updated conditioning regimen, graft-versus-host disease (GVHD) incidence and severity, and overall survival in patients undergoing treatment on this protocol.
- To assess the consistency and pace of engraftment.
- To assess the pace of T cell and B cell immune recovery.
OUTLINE:
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
- •This treatment is for patients with high risk hematologic malignancies. High risk is defined as:
- •Any patient with a hematologic malignancy with residual disease after treatment with 1 or more chemotherapy regimens in whom achievement of remission with additional chemoradiotherapy is felt to be unlikely
- •Patients without morphologic evidence of disease but with high risk features which would predict for relapse despite remission at HSCT such as adverse cytogenetics, 3rd or greater CR (complete response), or failure to recover peripheral blood counts to normal ranges. While these patients do not have detectable disease by current methods, like all patients they have non-detectable disease which in their case is highly aggressive.
- •Patients must have one related donor who is HLA (human leukocyte antigen) mismatched in the GVHD direction at two or more HLA loci
- •Patients must adequate organ function:
- •LVEF (left ventricular ejection fraction) of >50 %
- •Diffusing capacity of the lungs for carbon monoxide (DLCO) (adjusted for hemoglobin) >50 % of predicted and forced expiration to the full FEV-1 >50 %
- •Adequate liver function as defined by a serum bilirubin <1.8, AST (aspartate aminotransferase) or ALT (alanine aminotransferase) < 2.5X upper limit of normal
- •Creatinine clearance of > 60 ml/min
- •Karnofsky Performance Status (KPS) of > 80% on the modified (KPS) tool
- •Patients must be willing to use contraception if they have childbearing potential
- •Able to give informed consent
排除标准
- •Modified (KPS) Karnofsky Performance status of <80%
- •> 5 Comorbidity Points on the Hematopoietic cell transplantation - specific comorbidity (HCT-CI) Index (See Appendix B)
- •Class I or II antibodies against donor human leukocyte antigens (HLA)
- •HIV positive
- •Active involvement of the central nervous system with malignancy
- •Psychiatric disorder that would preclude patients from signing an informed consent
- •Pregnancy, or unwillingness to use contraception if they have child bearing potential
- •Patients with life expectancy of < 6 months for reasons other than their underlying hematologic/oncologic disorder
- •Alemtuzumab treatment within 8 weeks of HSCT admission
- •Anti-thymocyte globulin (ATG) level of > 2 ugm/ml
- •Patients with active inflammatory processes including T max >101 or active tissue inflammation are excluded
- •Inability to tolerate cyclophosphamide or undergo total body irradiation at the doses specified in the treatment plan
研究组 & 干预措施
Treatment (TBI, DLI, cyclophosphamide, CD34+ donor HSCT)
CONDITIONING REGIMEN: Patients undergo TBI BID on days -10 to -8, undergo DLI on day -6, and receive cyclophosphamide IV over 2 hours on days -3 and -2.
TRANSPLANT: Patients undergo CD34+ (cluster of differentiation 34+) selected allogeneic HSCT on day 0.
GVHD PROPHYLAXIS: Patients receive tacrolimus IV or PO beginning on day -1 with taper beginning by day 42, and mycophenolate mofetil IV BID on days -1 to 28.
干预措施: Total-Body Irradiation (TBI) (Radiation)
Treatment (TBI, DLI, cyclophosphamide, CD34+ donor HSCT)
CONDITIONING REGIMEN: Patients undergo TBI BID on days -10 to -8, undergo DLI on day -6, and receive cyclophosphamide IV over 2 hours on days -3 and -2.
TRANSPLANT: Patients undergo CD34+ (cluster of differentiation 34+) selected allogeneic HSCT on day 0.
GVHD PROPHYLAXIS: Patients receive tacrolimus IV or PO beginning on day -1 with taper beginning by day 42, and mycophenolate mofetil IV BID on days -1 to 28.
干预措施: Donor Lymphocyte Infusion (DLI) (Biological)
Treatment (TBI, DLI, cyclophosphamide, CD34+ donor HSCT)
CONDITIONING REGIMEN: Patients undergo TBI BID on days -10 to -8, undergo DLI on day -6, and receive cyclophosphamide IV over 2 hours on days -3 and -2.
TRANSPLANT: Patients undergo CD34+ (cluster of differentiation 34+) selected allogeneic HSCT on day 0.
GVHD PROPHYLAXIS: Patients receive tacrolimus IV or PO beginning on day -1 with taper beginning by day 42, and mycophenolate mofetil IV BID on days -1 to 28.
干预措施: Cyclophosphamide (Drug)
Treatment (TBI, DLI, cyclophosphamide, CD34+ donor HSCT)
CONDITIONING REGIMEN: Patients undergo TBI BID on days -10 to -8, undergo DLI on day -6, and receive cyclophosphamide IV over 2 hours on days -3 and -2.
TRANSPLANT: Patients undergo CD34+ (cluster of differentiation 34+) selected allogeneic HSCT on day 0.
GVHD PROPHYLAXIS: Patients receive tacrolimus IV or PO beginning on day -1 with taper beginning by day 42, and mycophenolate mofetil IV BID on days -1 to 28.
干预措施: Allogeneic hematopoietic stem cell transplantation (HSCT) (Procedure)
Treatment (TBI, DLI, cyclophosphamide, CD34+ donor HSCT)
CONDITIONING REGIMEN: Patients undergo TBI BID on days -10 to -8, undergo DLI on day -6, and receive cyclophosphamide IV over 2 hours on days -3 and -2.
TRANSPLANT: Patients undergo CD34+ (cluster of differentiation 34+) selected allogeneic HSCT on day 0.
GVHD PROPHYLAXIS: Patients receive tacrolimus IV or PO beginning on day -1 with taper beginning by day 42, and mycophenolate mofetil IV BID on days -1 to 28.
干预措施: Mycophenolate mofetil (Drug)
结局指标
主要结局
Count of Participants That Experience 1 Year Relapse Free Survival After Undergoing Hematopoietic Stem Cell Transplantation (HSCT) Using the Thomas Jefferson University 2 Step Approach
时间窗: Up to 1 year after HSCT
次要结局
- Median Pace of T Cell Immune Recovery at 28 Days Post Hematopoietic Stem Cell Transplantation (HSCT)(At 28 days post HSCT)
- Median Pace of T Cell Immune Recovery at 90 Days Post Hematopoietic Stem Cell Transplantation (HSCT)(90 days post HSCT)
- Count of Participants That Experienced Death as a Result of Graft-versus-host Disease (GVHD)(Up to 1 year after HSCT)
- Number of Participants With Successful Engraftment(Up to 1 year after HSCT)