Nonmyeloablative PBSC Allografting From HLA Matched Related Donors Using Fludarabine and/or Low Dose TBI With Disease-Risk Based Immunosuppression
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 160
- 试验地点
- 11
- 主要终点
- Probability of severe (grade III/IV) GVHD in each arm
研究概览
简要总结
This clinical trial studies fludarabine phosphate and total-body radiation followed by donor peripheral blood stem cell transplant and immunosuppression 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 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. Sometimes the transplanted cells from a donor can make an immune response against the body's normal cells. Giving total-body irradiation together with fludarabine phosphate, cyclosporine, and mycophenolate mofetil before transplant may stop this from happening.
详细描述
PRIMARY OBJECTIVES:
I. To estimate the rate of grade III/IV graft-versus-host disease (GVHD) in patients treated with low-dose total body irradiation (TBI), fludarabine (fludarabine phosphate), PBSC infusion and immunosuppression with mycophenolate mofetil and a disease risk-based cyclosporine taper.
II. To estimate the risk of graft rejection, GVHD, disease response, non-relapse mortality and the incidence and severity of infectious complications using this treatment strategy.
OUTLINE: Patients are assigned to 1 of 2 treatment groups.
ARM I (indolent disease):
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- — 至 74 Years（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients with non-Hodgkin lymphoma (NHL), chronic lymphocytic leukemia (CLL) or multiple myeloma who are not eligible for a curative autologous transplantation or who have received a prior autologous transplantation; patients with NHL or CLL must have failed prior therapy with an alkylating agent and/or fludarabine, or be at high risk of relapse; patients with multiple myeloma must have stage II or III disease and received prior chemotherapy
- •Patients < 50 years of age with NHL, Hodgkin's disease (HD), CLL or multiple myeloma at high risk of regimen related toxicity through prior autologous transplant or through pre-existing medical conditions
- •Patients < 75 years of age with other malignant diseases treatable by allogeneic bone marrow transplant (BMT) whom through pre-existing chronic disease affecting kidneys, liver, lungs, and heart are considered to be at high risk for regimen related toxicity using standard high dose regimens; the following diseases are the likely candidates
- •Myelodysplastic syndromes
- •Myeloproliferative syndromes
- •Acute Leukemia with < 10% blasts
- •Amyloidosis
- •Hodgkin's disease
- •The Fred Hutchinson Cancer Research Center (FHCRC) Patient Care Conference (PCC) may approve patients with other malignancies or patients declining standard allografts for transplant following presentation and approval; centers outside the FHCRC that have a PCC or equivalent should obtain their Institutional approval; if there is not a comparable group at the Institution, please contact the FHCRC Principal Investigator for FHCRC approval through PCC
- •DONOR: Human leukocyte antigen (HLA) genotypically or phenotypically identical related donor
- •DONOR: Donor must consent to filgrastim (G-CSF) administration and leukapheresis
- •DONOR: Donor must have adequate veins for leukapheresis or agree to placement of central venous catheter (femoral, subclavian)
排除标准
- •Eligible for a high-priority curative autologous transplant
- •Patients with rapidly progressive aggressive NHL unless in minimal disease state
- •Any current central nervous system (CNS) involvement with disease
- •Fertile men or women unwilling to use contraceptive techniques during and for 12 months following treatment
- •Females who are pregnant
- •Patients who are human immunodeficiency virus (HIV) positive
- •Cardiac ejection fraction < 40%; ejection fraction is required if the patient has a history of anthracyclines or history of cardiac disease
- •Receiving supplementary continuous oxygen
- •Diffusing capacity of the lung for carbon monoxide (DLCO) < 30%
- •Total lung capacity (TLC) < 30%
- •Forced expiratory volume in one second (FEV1) < 30%
- •Total bilirubin > 2x the upper limit of normal
- •Serum glutamate pyruvate transaminase (SGPT) and serum glutamic oxaloacetic transaminase (SGOT) 4x the upper limit of normal
- •Karnofsky score < 50
- •Patients with poorly controlled hypertension who are unable to have blood pressure kept below 150/90 on standard medication
- •Patients with renal failure are eligible, however patients with renal compromise (serum creatinine greater than 2.0) will likely have further compromise in renal function and may require hemodialysis (which may be permanent) due to the need to maintain adequate serum cyclosporine levels
- •The addition of cytotoxic agents for "cytoreduction" with the exception of hydroxyurea and imatinib mesylate will not be allowed within two weeks of the initiation of conditioning
- •DONOR: Identical twin
- •DONOR: Age less than 12 years
- •DONOR: Pregnancy
- •DONOR: Infection with HIV
- •DONOR: Inability to achieve adequate venous access
- •DONOR: Known allergy to G-CSF
- •DONOR: Current serious systemic illness
研究组 & 干预措施
Arm I (indolent disease)
CONDITIONING REGIMEN: Patients receive fludarabine phosphate IV on days -4 to -2 and undergo TBI on day 0.
TRANSPLANTATION: Patients undergo donor PBSCT on day 0.
IMMUNOSUPPRESSION: Patients receive cyclosporine PO BID or IV every 8-12 hours on days -3 to 56 with a taper to day 180 and mycophenolate mofetil PO BID or IV every 8-12 hours on days 0 to 27.
干预措施: fludarabine phosphate (Drug)
Arm I (indolent disease)
CONDITIONING REGIMEN: Patients receive fludarabine phosphate IV on days -4 to -2 and undergo TBI on day 0.
TRANSPLANTATION: Patients undergo donor PBSCT on day 0.
IMMUNOSUPPRESSION: Patients receive cyclosporine PO BID or IV every 8-12 hours on days -3 to 56 with a taper to day 180 and mycophenolate mofetil PO BID or IV every 8-12 hours on days 0 to 27.
干预措施: total-body irradiation (Radiation)
Arm I (indolent disease)
CONDITIONING REGIMEN: Patients receive fludarabine phosphate IV on days -4 to -2 and undergo TBI on day 0.
TRANSPLANTATION: Patients undergo donor PBSCT on day 0.
IMMUNOSUPPRESSION: Patients receive cyclosporine PO BID or IV every 8-12 hours on days -3 to 56 with a taper to day 180 and mycophenolate mofetil PO BID or IV every 8-12 hours on days 0 to 27.
干预措施: peripheral blood stem cell transplantation (Procedure)
Arm I (indolent disease)
CONDITIONING REGIMEN: Patients receive fludarabine phosphate IV on days -4 to -2 and undergo TBI on day 0.
TRANSPLANTATION: Patients undergo donor PBSCT on day 0.
IMMUNOSUPPRESSION: Patients receive cyclosporine PO BID or IV every 8-12 hours on days -3 to 56 with a taper to day 180 and mycophenolate mofetil PO BID or IV every 8-12 hours on days 0 to 27.
干预措施: allogeneic hematopoietic stem cell transplantation (Procedure)
Arm I (indolent disease)
CONDITIONING REGIMEN: Patients receive fludarabine phosphate IV on days -4 to -2 and undergo TBI on day 0.
TRANSPLANTATION: Patients undergo donor PBSCT on day 0.
IMMUNOSUPPRESSION: Patients receive cyclosporine PO BID or IV every 8-12 hours on days -3 to 56 with a taper to day 180 and mycophenolate mofetil PO BID or IV every 8-12 hours on days 0 to 27.
干预措施: cyclosporine (Drug)
Arm I (indolent disease)
CONDITIONING REGIMEN: Patients receive fludarabine phosphate IV on days -4 to -2 and undergo TBI on day 0.
TRANSPLANTATION: Patients undergo donor PBSCT on day 0.
IMMUNOSUPPRESSION: Patients receive cyclosporine PO BID or IV every 8-12 hours on days -3 to 56 with a taper to day 180 and mycophenolate mofetil PO BID or IV every 8-12 hours on days 0 to 27.
干预措施: mycophenolate mofetil (Drug)
Arm I (indolent disease)
CONDITIONING REGIMEN: Patients receive fludarabine phosphate IV on days -4 to -2 and undergo TBI on day 0.
TRANSPLANTATION: Patients undergo donor PBSCT on day 0.
IMMUNOSUPPRESSION: Patients receive cyclosporine PO BID or IV every 8-12 hours on days -3 to 56 with a taper to day 180 and mycophenolate mofetil PO BID or IV every 8-12 hours on days 0 to 27.
干预措施: laboratory biomarker analysis (Other)
Arm II (aggressive disease)
CONDITIONING REGIMEN: Patients receive fludarabine phosphate and undergo TBI as in Arm I.
TRANSPLANTATION: Patients undergo donor PBSCT on day 0.
IMMUNOSUPPRESSION: Patients receive cyclosporine PO BID or IV every 8-12 hours on days -3 to 56 with a taper to day 70 and mycophenolate mofetil as in Arm I.
干预措施: fludarabine phosphate (Drug)
Arm II (aggressive disease)
CONDITIONING REGIMEN: Patients receive fludarabine phosphate and undergo TBI as in Arm I.
TRANSPLANTATION: Patients undergo donor PBSCT on day 0.
IMMUNOSUPPRESSION: Patients receive cyclosporine PO BID or IV every 8-12 hours on days -3 to 56 with a taper to day 70 and mycophenolate mofetil as in Arm I.
干预措施: total-body irradiation (Radiation)
Arm II (aggressive disease)
CONDITIONING REGIMEN: Patients receive fludarabine phosphate and undergo TBI as in Arm I.
TRANSPLANTATION: Patients undergo donor PBSCT on day 0.
IMMUNOSUPPRESSION: Patients receive cyclosporine PO BID or IV every 8-12 hours on days -3 to 56 with a taper to day 70 and mycophenolate mofetil as in Arm I.
干预措施: peripheral blood stem cell transplantation (Procedure)
Arm II (aggressive disease)
CONDITIONING REGIMEN: Patients receive fludarabine phosphate and undergo TBI as in Arm I.
TRANSPLANTATION: Patients undergo donor PBSCT on day 0.
IMMUNOSUPPRESSION: Patients receive cyclosporine PO BID or IV every 8-12 hours on days -3 to 56 with a taper to day 70 and mycophenolate mofetil as in Arm I.
干预措施: allogeneic hematopoietic stem cell transplantation (Procedure)
Arm II (aggressive disease)
CONDITIONING REGIMEN: Patients receive fludarabine phosphate and undergo TBI as in Arm I.
TRANSPLANTATION: Patients undergo donor PBSCT on day 0.
IMMUNOSUPPRESSION: Patients receive cyclosporine PO BID or IV every 8-12 hours on days -3 to 56 with a taper to day 70 and mycophenolate mofetil as in Arm I.
干预措施: cyclosporine (Drug)
Arm II (aggressive disease)
CONDITIONING REGIMEN: Patients receive fludarabine phosphate and undergo TBI as in Arm I.
TRANSPLANTATION: Patients undergo donor PBSCT on day 0.
IMMUNOSUPPRESSION: Patients receive cyclosporine PO BID or IV every 8-12 hours on days -3 to 56 with a taper to day 70 and mycophenolate mofetil as in Arm I.
干预措施: mycophenolate mofetil (Drug)
Arm II (aggressive disease)
CONDITIONING REGIMEN: Patients receive fludarabine phosphate and undergo TBI as in Arm I.
TRANSPLANTATION: Patients undergo donor PBSCT on day 0.
IMMUNOSUPPRESSION: Patients receive cyclosporine PO BID or IV every 8-12 hours on days -3 to 56 with a taper to day 70 and mycophenolate mofetil as in Arm I.
干预措施: laboratory biomarker analysis (Other)
结局指标
主要结局
Probability of severe (grade III/IV) GVHD in each arm
时间窗: Up to 5 years
95% confidence intervals will be calculated.
次要结局
- Incidence of graft rejection(Day 365)
- Incidence of non-relapse mortality(Up to 5 years)
- Incidence of infectious complications(Up to 5 years)
- Severity of infectious complications(Up to 5 years)