A Two Step Approach to Reduced Intensity Allogeneic Hematopoietic Stem Cell Transplantation for Patients With Hematologic Malignancies
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 40
- 试验地点
- 1
- 主要终点
- Overall Survival (OS) in patients with haploidentical family donors with hematological malignancies in morphological or radiographic remission or with chemosensitive, indolent diseases
研究概览
简要总结
This phase II trial studies how well reduced intensity donor stem cell transplant works in treating patients with hematologic malignancies. Giving chemotherapy and total-body irradiation before a donor peripheral blood stem cell transplant helps stop the growth of cells in the bone marrow, including normal blood-forming cells (stem cells) and cancer cells. It may also stop the patient's immune system from rejecting the donor's stem cells. When the healthy 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. The donated stem cells may also replace the patient's immune cells and help destroy any remaining cancer cells. Sometimes the transplanted cells from a donor can make an immune response against the body's normal cells (called graft-versus-host disease). Giving tacrolimus and mycophenolate mofetil after the transplant may stop this from happening. Once the donated stem cells begin working, the patient's immune system may see the remaining cancer cells as not belonging in the patient's body and destroy them. Giving an infusion of the donor's white blood cells (donor lymphocyte infusion) may boost this effect.
详细描述
PRIMARY OBJECTIVES:
I. To compare the overall survival (OS) rate at 2 years post treatment using the Jefferson 2 step reduced intensity conditioning (RIC) approach in patients with haploidentical family donors with hematological malignancies in morphological or radiographic remission or with chemosensitive, indolent diseases to historical OS rates in similar populations after RIC matched donor HSCT as reported in the literature.
SECONDARY OBJECTIVES:
I. To compare the treatment-related mortality (TRM) rate at 2 years for patients treated on this study to the historical TRM rates of patients undergoing RIC matched-sibling HSCT as reported in the literature.
II. To compare the 2 year relapse rates and relapse related mortality of patients with myeloid diseases to that of patients with lymphoid diseases who are treated on this Thomas Jefferson University (TJU) RIC 2 step approach.
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 hematologic or oncologic diagnosis in which allogeneic HSCT is thought to be beneficial, and in whom front-line therapy has already been applied. Patients treated on this protocol will be without morphological evidence of disease (complete remission or "CR"), or if the patient has evidence of disease, the patient must have had at least a good partial response (PR) to the most recent therapy and the disease must be chemoresponsive.
- •Patients treated on this study will have:
- •Acute leukemia in 1st or 2nd CR
- •MDS (myelodysplastic syndrome), specific subtypes of RA (refractory anemia) or RARS (refractory anemia with ringed sideroblasts) subtypes.
- •Hodgkin or Indolent Non-Hodgkin's lymphoma with chemosensitive disease
- •Myeloma without morphological evidence of disease, or a deep PR to the most recent therapy
- •Myeloproliferative disorders with at least a PR to current therapy
- •Aplastic Anemia
- •A hematological or oncological disease (not listed) that meets the criteria reviewed above (in CR or with a good PR).
- •Patients must have a related donor who is HLA mismatched at 2, 3, or 4 antigens at the HLA-A; B; C; DR loci in the GVHD direction. (Patients with related donors who are HLA identical or are a 1-antigen mismatch may be treated on this therapeutic approach, but will have their outcomes will not be part of the statistical aims of the study (see Summary section).
- •Patients must adequate organ function:
- •LVEF (Left ventricular end diastolic function) of >50%
- •DLCO (Diffusing Capacity of the Lung for Carbon Monoxide ) ≥50% of predicted corrected for hemoglobin
- •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
- •Performance status ≥ 80% (TJU Karnofsky) for patients ≥ 60 years old or ≥70% for patients < 60 years old.
- •HCT-CI Score ≤ 4 points for patients ≥ 60 years old or ≤ 5 points for patients < 60 years old.
- •Patients must have adequate Karnofsky performance status (KPS) and hematopoietic cell transplantation comorbidity index (HCT-CI) scores:
- •Patients < age 60 years must have a KPS of >= 80% and an HCT-CI score of 5 or less
- •Patients aged 60 to 65 years must have a KPS of >= 80% and an HCT-CI score of 4 or less
- •Patients aged 66 to 69 years must have a KPS of 90% and an HCT-CI score of 3 or less
- •Patients aged 70 years or more must have a KPS of 90% and an HCT-CI score of 2 or less
- •Patients with greater than the allowable HCT-CI points for age can be enrolled for trial with approval of the principal investigator (PI) and at least 1 co-investigator (Co-I) not on the primary care team of the patient; this is an adjustment to account for healthy patients who meet the spirit of this protocol but have histories that result in higher than guideline HCT-CI points; an example is a patient with a solid tumor malignancy in their remote history (adds 3 points to HCT-CI total) where the treatment for the malignancy occurred years to decades before and there has been complete recovery of toxicities
- •Patients must be willing to use contraception if they have childbearing potential
- •Able to give informed consent
排除标准
- •Human immunodeficiency virus (HIV) positive
- •Active involvement of the central nervous system with malignancy
- •Inability to obtain informed consent
- •Pregnancy
- •Patients with life expectancy of =< 6 months for reasons other than their underlying hematologic/oncologic disorder
- •Patients who have received alemtuzumab or anti-thymocyte globulin (ATG) within 8 weeks of the transplant admission; (documented by the absence of these agents in the medical record)
- •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 (Allogeneic PBSCT)
REDUCED INTENSITY CONDITIONING: Patients receive fludarabine phosphate IV over 60 minutes on days -11 to -8 and busulfan IV over 3 hours on days -10 to -9. Patients undergo TBI on day -6. Patients also receive cyclophosphamide IV over 2 hours on days -3 and -2.
TRANSPLANTATION: Patients undergo DLI on day -6 and CD-34+ allogeneic PBSCT on day 0.
GVHD PROPHYLAXIS: Beginning on day -1, patients receive tacrolimus IV or PO with taper beginning on day 42. Patients also receive mycophenolate mofetil IV BID on days -1 to 28.
干预措施: Fludarabine (Drug)
Treatment (Allogeneic PBSCT)
REDUCED INTENSITY CONDITIONING: Patients receive fludarabine phosphate IV over 60 minutes on days -11 to -8 and busulfan IV over 3 hours on days -10 to -9. Patients undergo TBI on day -6. Patients also receive cyclophosphamide IV over 2 hours on days -3 and -2.
TRANSPLANTATION: Patients undergo DLI on day -6 and CD-34+ allogeneic PBSCT on day 0.
GVHD PROPHYLAXIS: Beginning on day -1, patients receive tacrolimus IV or PO with taper beginning on day 42. Patients also receive mycophenolate mofetil IV BID on days -1 to 28.
干预措施: Cyclophosphamide (CY) (Drug)
Treatment (Allogeneic PBSCT)
REDUCED INTENSITY CONDITIONING: Patients receive fludarabine phosphate IV over 60 minutes on days -11 to -8 and busulfan IV over 3 hours on days -10 to -9. Patients undergo TBI on day -6. Patients also receive cyclophosphamide IV over 2 hours on days -3 and -2.
TRANSPLANTATION: Patients undergo DLI on day -6 and CD-34+ allogeneic PBSCT on day 0.
GVHD PROPHYLAXIS: Beginning on day -1, patients receive tacrolimus IV or PO with taper beginning on day 42. Patients also receive mycophenolate mofetil IV BID on days -1 to 28.
干预措施: Tacrolimus (Drug)
Treatment (Allogeneic PBSCT)
REDUCED INTENSITY CONDITIONING: Patients receive fludarabine phosphate IV over 60 minutes on days -11 to -8 and busulfan IV over 3 hours on days -10 to -9. Patients undergo TBI on day -6. Patients also receive cyclophosphamide IV over 2 hours on days -3 and -2.
TRANSPLANTATION: Patients undergo DLI on day -6 and CD-34+ allogeneic PBSCT on day 0.
GVHD PROPHYLAXIS: Beginning on day -1, patients receive tacrolimus IV or PO with taper beginning on day 42. Patients also receive mycophenolate mofetil IV BID on days -1 to 28.
干预措施: Mycophenolate mofetil (Drug)
Treatment (Allogeneic PBSCT)
REDUCED INTENSITY CONDITIONING: Patients receive fludarabine phosphate IV over 60 minutes on days -11 to -8 and busulfan IV over 3 hours on days -10 to -9. Patients undergo TBI on day -6. Patients also receive cyclophosphamide IV over 2 hours on days -3 and -2.
TRANSPLANTATION: Patients undergo DLI on day -6 and CD-34+ allogeneic PBSCT on day 0.
GVHD PROPHYLAXIS: Beginning on day -1, patients receive tacrolimus IV or PO with taper beginning on day 42. Patients also receive mycophenolate mofetil IV BID on days -1 to 28.
干预措施: Total Body Irradiation (TBI) (Radiation)
Treatment (Allogeneic PBSCT)
REDUCED INTENSITY CONDITIONING: Patients receive fludarabine phosphate IV over 60 minutes on days -11 to -8 and busulfan IV over 3 hours on days -10 to -9. Patients undergo TBI on day -6. Patients also receive cyclophosphamide IV over 2 hours on days -3 and -2.
TRANSPLANTATION: Patients undergo DLI on day -6 and CD-34+ allogeneic PBSCT on day 0.
GVHD PROPHYLAXIS: Beginning on day -1, patients receive tacrolimus IV or PO with taper beginning on day 42. Patients also receive mycophenolate mofetil IV BID on days -1 to 28.
干预措施: Donor Lymphocyte Infusion (DLI) (Biological)
Treatment (Allogeneic PBSCT)
REDUCED INTENSITY CONDITIONING: Patients receive fludarabine phosphate IV over 60 minutes on days -11 to -8 and busulfan IV over 3 hours on days -10 to -9. Patients undergo TBI on day -6. Patients also receive cyclophosphamide IV over 2 hours on days -3 and -2.
TRANSPLANTATION: Patients undergo DLI on day -6 and CD-34+ allogeneic PBSCT on day 0.
GVHD PROPHYLAXIS: Beginning on day -1, patients receive tacrolimus IV or PO with taper beginning on day 42. Patients also receive mycophenolate mofetil IV BID on days -1 to 28.
干预措施: Allogeneic hematopoietic stem cell transplantation (Device)
Treatment (Allogeneic PBSCT)
REDUCED INTENSITY CONDITIONING: Patients receive fludarabine phosphate IV over 60 minutes on days -11 to -8 and busulfan IV over 3 hours on days -10 to -9. Patients undergo TBI on day -6. Patients also receive cyclophosphamide IV over 2 hours on days -3 and -2.
TRANSPLANTATION: Patients undergo DLI on day -6 and CD-34+ allogeneic PBSCT on day 0.
GVHD PROPHYLAXIS: Beginning on day -1, patients receive tacrolimus IV or PO with taper beginning on day 42. Patients also receive mycophenolate mofetil IV BID on days -1 to 28.
干预措施: Peripheral blood stem cell transplantation (PBSCT) (Procedure)
Treatment (Allogeneic PBSCT)
REDUCED INTENSITY CONDITIONING: Patients receive fludarabine phosphate IV over 60 minutes on days -11 to -8 and busulfan IV over 3 hours on days -10 to -9. Patients undergo TBI on day -6. Patients also receive cyclophosphamide IV over 2 hours on days -3 and -2.
TRANSPLANTATION: Patients undergo DLI on day -6 and CD-34+ allogeneic PBSCT on day 0.
GVHD PROPHYLAXIS: Beginning on day -1, patients receive tacrolimus IV or PO with taper beginning on day 42. Patients also receive mycophenolate mofetil IV BID on days -1 to 28.
干预措施: Busulfan (Drug)
结局指标
主要结局
Overall Survival (OS) in patients with haploidentical family donors with hematological malignancies in morphological or radiographic remission or with chemosensitive, indolent diseases
时间窗: At 2 years
The primary null hypothesis is that 2 year OS rate is at most 35%. This hypothesis will be rejected if the 95% confidence interval for year OS rate computed from the estimated Kaplan-Meier survival curves will be entirely above 0.35.
Overall Survival (OS) in Patients With Haploidentical Family Donors With Hematological Malignancies in Morphological or Radiographic Remission or With Chemosensitive, Indolent Diseases
时间窗: At 2 years
The primary null hypothesis is that 2 year OS rate is at most 35%. This hypothesis will be rejected if the 95% confidence interval for year OS rate computed from the estimated Kaplan-Meier survival curves will be entirely above 0.35.
次要结局
- Relapse Related Mortality(At 2 years)
- Lymphoid Reconstitution(100 days post-transplant)
- Treatment Related Mortality (TRM)(At 2 years)
- Engraftment Rates(Assessed up to 2 years)
- Incidence of Treatment Related Mortality (TRM)(At 100 days)
- Incidence and severity of GVHD, graded according to standard criteria(Assessed up to 2 years)
- Relapse Rate(At 2 years)
- Number of Participants With Acute G2-4 and/or Chronic Moderate or Severe GVHD(Assessed up to 2 years)
- Engraftment Rates(44 weeks)