Allogeneic Stem Cell Transplantation For Multiple Myeloma: A Two Step Approach To Reduce Toxicity Involving High Dose Melphalan and Autologous Stem Cell Transplant Followed By PBSC Allografting After Low Dose TBI
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 40
- 试验地点
- 4
- 主要终点
- PFS
研究概览
简要总结
In this study donor bone marrow transplantation is divided into a two step process to try to significantly reduce the side effects of the procedure yet still provide patients with multiple myeloma the benefits of this procedure
详细描述
PRIMARY OBJECTIVES:
I. To evaluate engraftment of human leukocyte antigen (HLA) identical peripheral blood stem cell (PBSC) allografts given after conditioning with total-body irradiation (TBI) (200 cGy) and post-grafting immunosuppression with cyclosporine (CSP)/mycophenolate mofetil (MMF) in myeloma patients initially cytoreduced with high-dose melphalan.
II. To evaluate non-relapse mortality at day 100 post allografting. III. To evaluate the efficacy of this allografting strategy in terms of long-term progression free survival (PFS).
OUTLINE:
CONDITIONING REGIMEN: Patients receive high-dose melphalan intravenously (IV) over 15-20 minutes on day -2.
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 65 Years（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Meet Salmon and Durie criteria for initial diagnosis of multiple myeloma; transplant will be offered to patients with stage II or III multiple myeloma (MM) at diagnosis or have received chemotherapy and/or radiation therapy for progressive MM after initial diagnosis of stage I disease
- •The patient must have the capacity to give informed consent
- •Have received at least 4 cycles of conventional dose chemotherapy for MM
- •DONOR: HLA genotypically identical sibling
- •DONOR: Donor must consent to filgrastim (G-CSF) administration and leukapheresis for both peripheral blood stem cell (PBSC) allograft and subsequent DLI
- •DONOR: Donor must have adequate veins for leukapheresis or agree to placement of central venous catheter (femoral, subclavian)
- •DONOR: Age < 75, older donors may be considered after consultation by Psychological Consultation Center (PCC)
排除标准
- •Karnofsky score less than 60, unless due solely to myeloma
- •Left ventricular ejection fraction less than 40%
- •Bilirubin greater than 2 X the upper limit of normal
- •Serum glutamic pyruvic transaminase (SGPT) and serum glutamic oxaloacetic transaminase (SGOT) > 2 X the upper limit of normal
- •Diffusion lung capacity of carbon monoxide (DLCO) < 50% (corrected) or receiving continuous supplemental oxygen
- •Patients with poorly controlled hypertension
- •Pregnancy
- •Seropositive for the human immunodeficiency virus
- •Fertile men or women unwilling to use contraceptive techniques during and for 12 months following treatment
- •Creatinine clearance < 40 cc/min at the time of initial autografting evaluation
- •Prior autograft (can be treated on alternative protocol)
- •DONOR: Identical twin
- •DONOR: Age less than 12 years
- •DONOR: Pregnancy
- •DONOR: Infection with human immunodeficiency virus (HIV)
- •DONOR: Inability to achieve adequate venous access
- •DONOR: Known allergy to G-CSF
- •DONOR: Current serious systemic illness
- •DONOR: Failure to meet Fred Hutchinson Cancer Research Center (FHCRC) criteria for stem cell donation as described in the standard practice guidelines of the institution
研究组 & 干预措施
Treatment (Melphalan and PBSCT before TBI and Donor PBSCT)
CONDITIONING REGIMEN: Patients receive high-dose melphalan IV over 15-20 minutes on day -2.
TRANSPLANTATION: Patients undergo autologous bone marrow or PBSCT on day 0.
NON-MYELOABLATIVE CONDITIONING REGIMEN: Beginning 40-120 days after autologous transplant, patients undergo TBI on day 0.
TRANSPLANTATION: Patients undergo donor PBSCT on day 0.
IMMUNOSUPPRESSION: Patients receive cyclosporine IV BID on days -1 and 0 and PO BID on days 1-80 with taper based on evaluation of disease response and GVHD. Patients also receive mycophenolate mofetil PO BID on days 0-27.
POST TRANSPLANT DLI: Beginning 4 weeks after immunosuppression, patients achieving persistent or progressive disease may undergo DLI over 30 minutes every 4 weeks for up to 3 treatments.
干预措施: melphalan (Drug)
Treatment (Melphalan and PBSCT before TBI and Donor PBSCT)
CONDITIONING REGIMEN: Patients receive high-dose melphalan IV over 15-20 minutes on day -2.
TRANSPLANTATION: Patients undergo autologous bone marrow or PBSCT on day 0.
NON-MYELOABLATIVE CONDITIONING REGIMEN: Beginning 40-120 days after autologous transplant, patients undergo TBI on day 0.
TRANSPLANTATION: Patients undergo donor PBSCT on day 0.
IMMUNOSUPPRESSION: Patients receive cyclosporine IV BID on days -1 and 0 and PO BID on days 1-80 with taper based on evaluation of disease response and GVHD. Patients also receive mycophenolate mofetil PO BID on days 0-27.
POST TRANSPLANT DLI: Beginning 4 weeks after immunosuppression, patients achieving persistent or progressive disease may undergo DLI over 30 minutes every 4 weeks for up to 3 treatments.
干预措施: autologous hematopoietic stem cell transplantation (Procedure)
Treatment (Melphalan and PBSCT before TBI and Donor PBSCT)
CONDITIONING REGIMEN: Patients receive high-dose melphalan IV over 15-20 minutes on day -2.
TRANSPLANTATION: Patients undergo autologous bone marrow or PBSCT on day 0.
NON-MYELOABLATIVE CONDITIONING REGIMEN: Beginning 40-120 days after autologous transplant, patients undergo TBI on day 0.
TRANSPLANTATION: Patients undergo donor PBSCT on day 0.
IMMUNOSUPPRESSION: Patients receive cyclosporine IV BID on days -1 and 0 and PO BID on days 1-80 with taper based on evaluation of disease response and GVHD. Patients also receive mycophenolate mofetil PO BID on days 0-27.
POST TRANSPLANT DLI: Beginning 4 weeks after immunosuppression, patients achieving persistent or progressive disease may undergo DLI over 30 minutes every 4 weeks for up to 3 treatments.
干预措施: autologous bone marrow transplantation (Procedure)
Treatment (Melphalan and PBSCT before TBI and Donor PBSCT)
CONDITIONING REGIMEN: Patients receive high-dose melphalan IV over 15-20 minutes on day -2.
TRANSPLANTATION: Patients undergo autologous bone marrow or PBSCT on day 0.
NON-MYELOABLATIVE CONDITIONING REGIMEN: Beginning 40-120 days after autologous transplant, patients undergo TBI on day 0.
TRANSPLANTATION: Patients undergo donor PBSCT on day 0.
IMMUNOSUPPRESSION: Patients receive cyclosporine IV BID on days -1 and 0 and PO BID on days 1-80 with taper based on evaluation of disease response and GVHD. Patients also receive mycophenolate mofetil PO BID on days 0-27.
POST TRANSPLANT DLI: Beginning 4 weeks after immunosuppression, patients achieving persistent or progressive disease may undergo DLI over 30 minutes every 4 weeks for up to 3 treatments.
干预措施: peripheral blood stem cell transplantation (Procedure)
Treatment (Melphalan and PBSCT before TBI and Donor PBSCT)
CONDITIONING REGIMEN: Patients receive high-dose melphalan IV over 15-20 minutes on day -2.
TRANSPLANTATION: Patients undergo autologous bone marrow or PBSCT on day 0.
NON-MYELOABLATIVE CONDITIONING REGIMEN: Beginning 40-120 days after autologous transplant, patients undergo TBI on day 0.
TRANSPLANTATION: Patients undergo donor PBSCT on day 0.
IMMUNOSUPPRESSION: Patients receive cyclosporine IV BID on days -1 and 0 and PO BID on days 1-80 with taper based on evaluation of disease response and GVHD. Patients also receive mycophenolate mofetil PO BID on days 0-27.
POST TRANSPLANT DLI: Beginning 4 weeks after immunosuppression, patients achieving persistent or progressive disease may undergo DLI over 30 minutes every 4 weeks for up to 3 treatments.
干预措施: total-body irradiation (Radiation)
Treatment (Melphalan and PBSCT before TBI and Donor PBSCT)
CONDITIONING REGIMEN: Patients receive high-dose melphalan IV over 15-20 minutes on day -2.
TRANSPLANTATION: Patients undergo autologous bone marrow or PBSCT on day 0.
NON-MYELOABLATIVE CONDITIONING REGIMEN: Beginning 40-120 days after autologous transplant, patients undergo TBI on day 0.
TRANSPLANTATION: Patients undergo donor PBSCT on day 0.
IMMUNOSUPPRESSION: Patients receive cyclosporine IV BID on days -1 and 0 and PO BID on days 1-80 with taper based on evaluation of disease response and GVHD. Patients also receive mycophenolate mofetil PO BID on days 0-27.
POST TRANSPLANT DLI: Beginning 4 weeks after immunosuppression, patients achieving persistent or progressive disease may undergo DLI over 30 minutes every 4 weeks for up to 3 treatments.
干预措施: cyclosporine (Drug)
Treatment (Melphalan and PBSCT before TBI and Donor PBSCT)
CONDITIONING REGIMEN: Patients receive high-dose melphalan IV over 15-20 minutes on day -2.
TRANSPLANTATION: Patients undergo autologous bone marrow or PBSCT on day 0.
NON-MYELOABLATIVE CONDITIONING REGIMEN: Beginning 40-120 days after autologous transplant, patients undergo TBI on day 0.
TRANSPLANTATION: Patients undergo donor PBSCT on day 0.
IMMUNOSUPPRESSION: Patients receive cyclosporine IV BID on days -1 and 0 and PO BID on days 1-80 with taper based on evaluation of disease response and GVHD. Patients also receive mycophenolate mofetil PO BID on days 0-27.
POST TRANSPLANT DLI: Beginning 4 weeks after immunosuppression, patients achieving persistent or progressive disease may undergo DLI over 30 minutes every 4 weeks for up to 3 treatments.
干预措施: mycophenolate mofetil (Drug)
Treatment (Melphalan and PBSCT before TBI and Donor PBSCT)
CONDITIONING REGIMEN: Patients receive high-dose melphalan IV over 15-20 minutes on day -2.
TRANSPLANTATION: Patients undergo autologous bone marrow or PBSCT on day 0.
NON-MYELOABLATIVE CONDITIONING REGIMEN: Beginning 40-120 days after autologous transplant, patients undergo TBI on day 0.
TRANSPLANTATION: Patients undergo donor PBSCT on day 0.
IMMUNOSUPPRESSION: Patients receive cyclosporine IV BID on days -1 and 0 and PO BID on days 1-80 with taper based on evaluation of disease response and GVHD. Patients also receive mycophenolate mofetil PO BID on days 0-27.
POST TRANSPLANT DLI: Beginning 4 weeks after immunosuppression, patients achieving persistent or progressive disease may undergo DLI over 30 minutes every 4 weeks for up to 3 treatments.
干预措施: therapeutic allogeneic lymphocytes (Biological)
结局指标
主要结局
PFS
时间窗: From the date of transplant until the time of progression, relapse, death, or the date the patient was last known to be in remission, up to 3 years
The current study will be regarded as potentially efficacious if the observed 3-year PFS rate among all patients treated exceeds 30%. The Kaplan-Meier (KM) estimate of PFS will be used.
Decrease in the short-term transplant-related mortality
时间窗: Day 100 after allograft
Establish stable allogeneic engraftment (mixed or full donor chimerism)
时间窗: At day 56 after allografting
次要结局
- Overall survival(Up to 3 years)
- Response rate(Up to 3 years)
- Relapse rate(Up to 3 years)
- Ability to convert mixed to full donor chimerism with DLI(Up to 3 years)