A Two Step Approach to Allogeneic Hematopoietic Stem Cell Transplantation for High-Risk Hematologic Malignancies Using Two Related Donors
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 4
- 试验地点
- 1
- 主要终点
- One Year Relapse-Free Survival
研究概览
简要总结
This phase II clinical trial studies how well two donors stem cell transplant work in treating patients with high-risk hematologic malignancies. After receiving radiation to help further treat the disease, patients receive a dose of donors' T cells. T cells can fight infection and react against cancer cells. Two days after donors' T cells are given, patients receive cyclophosphamide (CY) to help destroy the most active T cells that may cause tissue damage (called graft versus host disease or GVHD). Some of the less reactive T cells are not destroyed by CY and they remain in the patient to help fight infection. A few days after the CY is given, patients receive donors' stem cells to help their blood counts recover. Using two donors' stem cell transplant instead of one donor may be more effective in treating patients with high-risk disease and may prevent the disease from coming back.
详细描述
PRIMARY OBJECTIVES:
I. To assess 1 year relapse free survival in patients undergoing hematopoietic stem cell transplant (HSCT) using the Thomas Jefferson University (TJU) 2 step approach using 2 donors.
SECONDARY OBJECTIVES:
I. To assess the consistency and pace of engraftment. II. To assess the pace of T cell and B cell immune recovery in patients in each arm.
III. To assess regimen related toxicity, graft-versus-host disease (GVHD) incidence and severity, and overall survival.
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
- •Any patient with a hematologic malignancy with residual disease (morphological, cytogenetic, molecular, or radiographic) after treatment with 1 or more chemotherapy regimens in whom achievement of remission with additional chemoradiotherapy is felt to be unlikely or who is in 3rd or greater CR. Patients with marrow based diseases in which the marrow biopsy does not meet criteria for active disease (i.e. <5% blasts in acute leukemia) but who does not have full count recovery will be eligible for treatment on this high risk trial.
- •Patients must have two related donors that meet an acceptable scenario as described above.
- •Patients must adequate organ function:
- •LVEF of >= 50%
- •DLCO (adjusted for hemoglobin) >= 50% of predicted
- •Adequate liver function as defined by a serum bilirubin =< 1.8, AST or ALT < 2.5X upper limit of normal
- •Creatinine clearance of >= 60 ml/min
- •Karnofsky Performance Status of > 80 % on the modified KPS tool (see Appendix A).
- •Patients must be willing to use contraception if they have childbearing potential.
- •Able to give informed consent
排除标准
- •Modified KPS of < 80%
- •>= 5 Comorbidity Points on the HCT-CI Index (See Appendix B)
- •Class I or II antibodies against donor HLA antigens
- •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.
- •ATG level of >= 2 ugm/ml
- •Patients with active inflammatory processes (such as flair of an autoimmune disease) 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
Allogeneic HSCT Using Two Related Donors
CONDITIONING: Patients undergo TBI BID on days -9 to -6, undergo DLI on day -6, and receive cyclophosphamide IV over 2 hours on days -3 and -2.
TRANSPLANTATION: Patients undergo CD34+ selected allogeneic HSCT on day 0.
GVHD PROPHYLAXIS: Patients receive tacrolimus IV or PO beginning on day -1 with taper beginning on day 42 and mycophenolate mofetil IV or PO BID on days -1 to 28.
干预措施: Cyclophosphamide (CY) (Drug)
Allogeneic HSCT Using Two Related Donors
CONDITIONING: Patients undergo TBI BID on days -9 to -6, undergo DLI on day -6, and receive cyclophosphamide IV over 2 hours on days -3 and -2.
TRANSPLANTATION: Patients undergo CD34+ selected allogeneic HSCT on day 0.
GVHD PROPHYLAXIS: Patients receive tacrolimus IV or PO beginning on day -1 with taper beginning on day 42 and mycophenolate mofetil IV or PO BID on days -1 to 28.
干预措施: Total Body Irradiation (TBI) (Radiation)
Allogeneic HSCT Using Two Related Donors
CONDITIONING: Patients undergo TBI BID on days -9 to -6, undergo DLI on day -6, and receive cyclophosphamide IV over 2 hours on days -3 and -2.
TRANSPLANTATION: Patients undergo CD34+ selected allogeneic HSCT on day 0.
GVHD PROPHYLAXIS: Patients receive tacrolimus IV or PO beginning on day -1 with taper beginning on day 42 and mycophenolate mofetil IV or PO BID on days -1 to 28.
干预措施: Donor Lymphocyte Infusion (DLI) (Biological)
Allogeneic HSCT Using Two Related Donors
CONDITIONING: Patients undergo TBI BID on days -9 to -6, undergo DLI on day -6, and receive cyclophosphamide IV over 2 hours on days -3 and -2.
TRANSPLANTATION: Patients undergo CD34+ selected allogeneic HSCT on day 0.
GVHD PROPHYLAXIS: Patients receive tacrolimus IV or PO beginning on day -1 with taper beginning on day 42 and mycophenolate mofetil IV or PO BID on days -1 to 28.
干预措施: Tacrolimus (Drug)
Allogeneic HSCT Using Two Related Donors
CONDITIONING: Patients undergo TBI BID on days -9 to -6, undergo DLI on day -6, and receive cyclophosphamide IV over 2 hours on days -3 and -2.
TRANSPLANTATION: Patients undergo CD34+ selected allogeneic HSCT on day 0.
GVHD PROPHYLAXIS: Patients receive tacrolimus IV or PO beginning on day -1 with taper beginning on day 42 and mycophenolate mofetil IV or PO BID on days -1 to 28.
干预措施: Mycophenolate Mofetil (MMF) (Drug)
Allogeneic HSCT Using Two Related Donors
CONDITIONING: Patients undergo TBI BID on days -9 to -6, undergo DLI on day -6, and receive cyclophosphamide IV over 2 hours on days -3 and -2.
TRANSPLANTATION: Patients undergo CD34+ selected allogeneic HSCT on day 0.
GVHD PROPHYLAXIS: Patients receive tacrolimus IV or PO beginning on day -1 with taper beginning on day 42 and mycophenolate mofetil IV or PO BID on days -1 to 28.
干预措施: Hematopoietic Stem Cell Transplant (HSCT) (Biological)
结局指标
主要结局
One Year Relapse-Free Survival
时间窗: 1 year
To assess one year relapse-free survival (RFS) in patients undergoing HSCT (hematopoietic stem cell transplantation) using the TJU 2 step-approach with two donors. Survival will be estimated by the Kaplan-Meier method. All estimates of rates will be presented with corresponding confidence intervals. For 1 year RFS rates, the method of Atkinson and Brown will be used to allow for the two-stage design; otherwise the method of Conover.
次要结局
- Tolerance of DLI(2-6 days prior to transplant)
- Chimerism Assessment(1 year)
- Engraftment(1 year)
- Non-relapse Morbidity and Mortality(1 year)
- Assessment of Dominance(1 year)
- Relapse Rates(1 year)
- Immune Reconstitution(1 year)
- Assessment for Tumor Escape Mechanisms(1 year post transplant)