Allogeneic Hematopoietic Stem Cell Transplantation for Induction of Mixed Hematopoietic Chimerism in Patients Infected With Human Immunodeficiency Virus-1 Using a Non-Marrow Ablative Conditioning Regimen Containing Total Body Irradiation in Combination With Post-Transplant Immunosuppression With Cyclosporine and Mycophenolate Mofetil
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 5
- 试验地点
- 1
- 主要终点
- Death From GVHD
研究概览
简要总结
This clinical trial studies the side effects and best dose of giving fludarabine and total-body irradiation (TBI) together followed by a donor stem cell transplant and cyclosporine and mycophenolate mofetil in treating human immunodeficiency virus (HIV)-positive patients with or without cancer. Giving low doses of chemotherapy, such as fludarabine, and TBI before a donor bone marrow or peripheral blood stem cell transplant helps stop the growth of cancer or abnormal cells and helps stop the patient's immune system from rejecting the donor's stem cells. The donated stem cells may replace the patient's immune cells and help destroy any remaining cancer cells (graft-versus-tumor effect). Sometimes the transplanted cells from a donor can also make an immune response against the body's normal cells. Giving cyclosporine (CSP) and mycophenolate mofetil (MMF) after the transplant may stop this from happening.
详细描述
PRIMARY OBJECTIVES:
I. To determine the safety of treating high-risk HIV1-infected patients with 200 centigray (cGy) TBI plus post-transplant MMF/CSP.
II. To determine whether 200 cGy TBI plus post-transplant MMF/CSP results in stable mixed donor lymphocyte chimerism (5-95% donor cluster of differentiation [CD]3) in high-risk human immunodeficiency virus (HIV)-1 infected patients.
SECONDARY OBJECTIVES:
I. To define the kinetics of immune reconstitution following a non-lethal conditioning regimen in HIV1-infected patients.
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
- — 至 75 Years（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients with hematologic malignancy, lymphoma or other HIV-associated malignancy are eligible provided these criteria are met:
- •The malignancy is in complete remission or very good partial remission, defined as a significant reduction of disease with therapy and no evidence for continued tumor growth in the case of lymphoma or solid tumors
- •Highly active antiretroviral therapy (HAART) is initiated within one month of hematopoietic cell transplant
- •Viral load has decreased by >= 1.5 logs or viral load < 5000 copies/ml plasma on HAART therapy
- •CD4 count is allowed to be > 100 cells/ul
- •HIV infected patients without malignancy who have failed HAART are eligible provided that these criteria are met:
- •They have been treated with more than one regimen of HAART for a total of at least 6 months duration
- •The viral load is < 50 copies/ml plasma
- •The CD4 count < 100 cells/ul
- •DONOR: Human leukocyte antigen (HLA) genotypically/phenotypically identical donor; if more than one HLA-identical sibling is available, priority will be given to donors matched for cytomegalovirus (CMV) status, ABO titer, and sex
- •Peripheral blood stem cells will be collected from donors greater than 12 years of age
- •Bone marrow will be collected from donors less than 12 years of age
- •DONOR: HLA phenotypically identical unrelated donor; match grades allowed:
- •Match grade 1: Matched at allele level for HLA-A, B, C, DRB1, and DQB1
- •Match grade 2.1: Single allele disparity for HLA-A, B, C, DRB1, and DQB1
排除标准
- •Positive serology for toxoplasma gondii on treatment or with evidence of active infection
- •Patients with other disease or organ dysfunction that would limit survival to less than 30 days
- •Patients with medical history of noncompliance with HAART or medical therapy
- •DONOR: Donors for whom medical or psychologic reasons would make donor procedure intolerable
- •DONOR: Marrow donors who have increased anesthetic risk
- •DONOR: Donors who are HIV positive
- •DONOR: Age > 75 years
研究组 & 干预措施
Treatment (allogeneic hematopoietic stem cell transplantation)
CONDITIONING REGIMEN: Patients receive fludarabine IV over 2 hours on days -4, -3, and -2. Patients undergo TBI on day 0.
TRANSPLANTATION: After completion of TBI, patients undergo allogeneic bone marrow or peripheral blood stem cell transplantation on day 0.
IMMUNOSUPPRESSION: Patients receive cyclosporine IV or PO 2 to 3 times daily on days -3 to 99 with taper beginning on day 100 and continuing until day 177 in the absence of GVHD. Beginning within 6 hours after transplantation, patients also receive mycophenolate mofetil IV or PO 3 times daily on days 0 to 40 followed by a taper in the absence of GVHD.
干预措施: fludarabine phosphate (Drug)
Treatment (allogeneic hematopoietic stem cell transplantation)
CONDITIONING REGIMEN: Patients receive fludarabine IV over 2 hours on days -4, -3, and -2. Patients undergo TBI on day 0.
TRANSPLANTATION: After completion of TBI, patients undergo allogeneic bone marrow or peripheral blood stem cell transplantation on day 0.
IMMUNOSUPPRESSION: Patients receive cyclosporine IV or PO 2 to 3 times daily on days -3 to 99 with taper beginning on day 100 and continuing until day 177 in the absence of GVHD. Beginning within 6 hours after transplantation, patients also receive mycophenolate mofetil IV or PO 3 times daily on days 0 to 40 followed by a taper in the absence of GVHD.
干预措施: total-body irradiation (Radiation)
Treatment (allogeneic hematopoietic stem cell transplantation)
CONDITIONING REGIMEN: Patients receive fludarabine IV over 2 hours on days -4, -3, and -2. Patients undergo TBI on day 0.
TRANSPLANTATION: After completion of TBI, patients undergo allogeneic bone marrow or peripheral blood stem cell transplantation on day 0.
IMMUNOSUPPRESSION: Patients receive cyclosporine IV or PO 2 to 3 times daily on days -3 to 99 with taper beginning on day 100 and continuing until day 177 in the absence of GVHD. Beginning within 6 hours after transplantation, patients also receive mycophenolate mofetil IV or PO 3 times daily on days 0 to 40 followed by a taper in the absence of GVHD.
干预措施: peripheral blood stem cell transplantation (Procedure)
Treatment (allogeneic hematopoietic stem cell transplantation)
CONDITIONING REGIMEN: Patients receive fludarabine IV over 2 hours on days -4, -3, and -2. Patients undergo TBI on day 0.
TRANSPLANTATION: After completion of TBI, patients undergo allogeneic bone marrow or peripheral blood stem cell transplantation on day 0.
IMMUNOSUPPRESSION: Patients receive cyclosporine IV or PO 2 to 3 times daily on days -3 to 99 with taper beginning on day 100 and continuing until day 177 in the absence of GVHD. Beginning within 6 hours after transplantation, patients also receive mycophenolate mofetil IV or PO 3 times daily on days 0 to 40 followed by a taper in the absence of GVHD.
干预措施: cyclosporine (Drug)
Treatment (allogeneic hematopoietic stem cell transplantation)
CONDITIONING REGIMEN: Patients receive fludarabine IV over 2 hours on days -4, -3, and -2. Patients undergo TBI on day 0.
TRANSPLANTATION: After completion of TBI, patients undergo allogeneic bone marrow or peripheral blood stem cell transplantation on day 0.
IMMUNOSUPPRESSION: Patients receive cyclosporine IV or PO 2 to 3 times daily on days -3 to 99 with taper beginning on day 100 and continuing until day 177 in the absence of GVHD. Beginning within 6 hours after transplantation, patients also receive mycophenolate mofetil IV or PO 3 times daily on days 0 to 40 followed by a taper in the absence of GVHD.
干预措施: mycophenolate mofetil (Drug)
Treatment (allogeneic hematopoietic stem cell transplantation)
CONDITIONING REGIMEN: Patients receive fludarabine IV over 2 hours on days -4, -3, and -2. Patients undergo TBI on day 0.
TRANSPLANTATION: After completion of TBI, patients undergo allogeneic bone marrow or peripheral blood stem cell transplantation on day 0.
IMMUNOSUPPRESSION: Patients receive cyclosporine IV or PO 2 to 3 times daily on days -3 to 99 with taper beginning on day 100 and continuing until day 177 in the absence of GVHD. Beginning within 6 hours after transplantation, patients also receive mycophenolate mofetil IV or PO 3 times daily on days 0 to 40 followed by a taper in the absence of GVHD.
干预措施: laboratory biomarker analysis (Other)
结局指标
主要结局
Death From GVHD
时间窗: Within the first 360 days
Death From Regimen Toxicity or Opportunistic Infection
时间窗: Within the first 100 days
Successful Induction of Mixed Hematopoietic Chimerism as Assessed by the Percentage of Peripheral Blood T Cells That Are of Donor Origin
时间窗: Up to day 80
Determined by a DNA-based assay that compares the profile of amplified fragment length polymorphisms (ampFLP) of the patient and donor.
次要结局
- Overall Survival(Up to 1 year)
- Progression of HIV(Within 1 year)
- Reconstitution of HIV-specific Immunity(Up to 1 year)
研究者
Ann Woolfrey
Principal Investigator
Fred Hutchinson Cancer Center