A Two Step Approach to Haploidentical Hematopoietic Stem Cell Transplantation for Patients in Remission From HLA Partially-Matched Related Donors-Effect of Maternal Donors on Outcomes
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
- Number of Participants With Disease-free Survival (DFS)
研究概览
简要总结
This phase II trial studies how well haploidentical donor hematopoietic stem cell transplant works in treating patients with hematologic malignancies. Giving chemotherapy and total-body irradiation before a donor stem cell transplant helps stop the growth of cancer cells. It may also stop the patient's immune system from rejecting the donor's stem cells. Giving an infusion of the donor's T cells (donor lymphocyte infusion) may replace the patient's immune cells and help destroy any remaining cancer cells. When the stem cells from a related donor, that closely matches the patient's blood, are infused into the patient they may help the patient's bone marrow make stem cells, red blood cells, white blood cells, and platelets.
详细描述
PRIMARY OBJECTIVES:
I. Examine the 1 year disease free survival (DFS) rate of patients with maternal donors or sibling donors who share the maternal haplotype (maternal group) and compare them to patients receiving cells from donors who have points from other characteristics such as killer immunoglobulin-like receptor (KIR) ligand mismatching, minor histocompatibility antigen (MHag) differences, or number of human leukocyte antigen (HLA) mismatches (non-maternal group).
SECONDARY OBJECTIVES:
I. Assess the incidences of relapse and graft-versus-host disease (GVHD) in maternal recipients whose only eligible donors are offspring.
II. Assess the incidence of grades III-IV GVHD in female recipients with male donors.
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 or oncologic diagnosis without morphological evidence of disease in which allogeneic HSCT is thought to be beneficial.
- •Patients must have a related donor who is a two or more allele mismatch at the HLA-A; B; C; DR loci.
- •Patients must have adequate organ function:
- •LVEF (Left ventricular ejection fraction) of >50%
- •Diffusion Capacity for Carbon Monoxide (DLCO) >50% of predicted corrected for hemoglobin
- •Adequate liver function as defined by a serum bilirubin <1.8, Aspartate Aminotransferase (AST) or alanine aminotransferase (ALT) < 2.5X upper limit of normal
- •Creatinine clearance of > 60 ml/min
- •Performance status > 80% (TJU Karnofsky)
- •Hematopoietic Comorbidity Index (HCT-CI) Score < 5 Points
- •Patients must be willing to use contraception if they have childbearing potential
- •Able to give informed consent, or if decisionally impaired, have a legal next of kin or guardian that can give informed consent
排除标准
- •Performance status < 80 % (TJU Karnofsky)
- •HCT-CI Score > 5 Points
- •Combination of Performance status of < 80% (TJU Karnofsky) and an HCT-CI of 4 points or more.
- •HIV positive
- •Active involvement of the central nervous system with malignancy
- •Psychiatric disorder that would preclude patients from signing an informed consent
- •Patients with life expectancy of < 6 months for reasons other than their underlying hematologic/oncologic disorder
- •Patients who have received alemtuzumab within 8 weeks of the transplant admission, or who have recently received horse or rabbit anti-thymocyte globulin and have an ATG level of > 2 ugm/ml
- •Patients who cannot receive cyclophosphamide
- •Patients with evidence of another malignancy, exclusive of a skin cancer that requires only local treatment, should not be enrolled on this protocol
研究组 & 干预措施
Treatment (haploidentical allogeneic HSCT)
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.
TRANSPLANT: Patients undergo haploidentical allogeneic hematopoietic stem cell transplant on day 0.
GVHD PROPHYLAXIS: Patients receive tacrolimus IV beginning on day -1 with taper beginning on day 42, and mycophenolate mofetil IV BID from day -1 to day 28.
干预措施: Total-body irradiation (Radiation)
Treatment (haploidentical allogeneic HSCT)
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.
TRANSPLANT: Patients undergo haploidentical allogeneic hematopoietic stem cell transplant on day 0.
GVHD PROPHYLAXIS: Patients receive tacrolimus IV beginning on day -1 with taper beginning on day 42, and mycophenolate mofetil IV BID from day -1 to day 28.
干预措施: Donor lymphocytes infusion (DLI) (Biological)
Treatment (haploidentical allogeneic HSCT)
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.
TRANSPLANT: Patients undergo haploidentical allogeneic hematopoietic stem cell transplant on day 0.
GVHD PROPHYLAXIS: Patients receive tacrolimus IV beginning on day -1 with taper beginning on day 42, and mycophenolate mofetil IV BID from day -1 to day 28.
干预措施: Cyclophosphamide (Drug)
Treatment (haploidentical allogeneic HSCT)
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.
TRANSPLANT: Patients undergo haploidentical allogeneic hematopoietic stem cell transplant on day 0.
GVHD PROPHYLAXIS: Patients receive tacrolimus IV beginning on day -1 with taper beginning on day 42, and mycophenolate mofetil IV BID from day -1 to day 28.
干预措施: Allogeneic hematopoietic stem cell transplantation (HSCT) (Procedure)
Treatment (haploidentical allogeneic HSCT)
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.
TRANSPLANT: Patients undergo haploidentical allogeneic hematopoietic stem cell transplant on day 0.
GVHD PROPHYLAXIS: Patients receive tacrolimus IV beginning on day -1 with taper beginning on day 42, and mycophenolate mofetil IV BID from day -1 to day 28.
干预措施: Tacrolimus (Drug)
Treatment (haploidentical allogeneic HSCT)
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.
TRANSPLANT: Patients undergo haploidentical allogeneic hematopoietic stem cell transplant on day 0.
GVHD PROPHYLAXIS: Patients receive tacrolimus IV beginning on day -1 with taper beginning on day 42, and mycophenolate mofetil IV BID from day -1 to day 28.
干预措施: Mycophenolate mofetil (Drug)
结局指标
主要结局
Number of Participants With Disease-free Survival (DFS)
时间窗: 1 year
Disease free survival (DFS), defined as the time to death, relapse or disease progression.
次要结局
- Number of Participants With Relapse of Disease(Up to 1 year)
- Rate of Grade III-IV GVHD in Female Recipients With Male Donors(Up to 1 year)
- The Rates of Grade III-IV GVHD in Female Recipients With Male Donors Will be Computed With Corresponding Exact Binomial 95% Confidence Intervals.(Up to 1 year)