A Trial of Tandem Autologous Stem Cell Transplants +/- Post Second Autologous Transplant Maintenance Therapy vs Single Autologous Stem Cell Transplant Followed by Matched Sibling Non-myeloablative Allogeneic Stem Cell Transplant for Patients With Multiple Myeloma (BMT CTN #0102)
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 710
- 试验地点
- 36
- 主要终点
- Progression-Free Survival (PFS)
研究概览
简要总结
The study is designed as a Phase III, multi-center trial of tandem autologous transplants versus the strategy of autologous followed by Human Leukocyte Antigen (HLA)-matched sibling non-myeloablative allogeneic transplant. Study subjects will be biologically assigned to the appropriate arm depending on the availability of an HLA-matched sibling. There is a nested randomized phase III trial of observation versus maintenance therapy following the second autologous transplant for patients on the tandem autologous transplant arm.
详细描述
Multiple myeloma (MM), characterized by malignant plasma cell proliferation, bone destruction, and immunodeficiency, is a disease with a median age at diagnosis of approximately 65 years. It is responsible for about 1 percent of all cancer-related deaths in Western Countries. Conventional treatments with chemotherapy and radiation therapy are non-curative but improve quality of life and duration of survival. Attempts to cure myeloma through high-dose therapy followed by autografting or allografting have largely failed due to a combination of relapsed disease or transplant related mortality (TRM). High-dose therapy with autologous transplantation is safe and has low TRM (less than 5%), but is associated with a continuing and nearly universal risk of disease progression and relapse. Even so, autologous transplantation is superior to continued conventional chemotherapy. Recent data indicate that tandem autologous transplants are superior to a single procedure. Even with this approach, patients remain at risk of relapse and additional approaches are needed.
DESIGN NARRATIVE:
The overall study design is that of biologic assignment, based on the availability of an HLA-matched sibling, to one of two treatment strategies for MM patients. Patients without an HLA-matched sibling will undergo tandem autologous transplants. Patients with an HLA-matched sibling will undergo an autologous transplant followed by a non-myeloablative allogeneic transplant. In addition, the tandem autologous transplant recipients will be randomized to either observation or one year of maintenance therapy to begin following the second autologous transplant. The large number of MM patients without an HLA-matched sibling enables us to evaluate the role of maintenance therapy following tandem autologous transplants.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- — 至 70 Years（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Meeting the Durie and Salmon criteria for initial diagnosis of MM
- •Stage II or III MM at diagnosis or anytime thereafter
- •Symptomatic MM requiring treatment at diagnosis or anytime thereafter
- •Received at least three cycles of initial systemic therapy and are within 2-10 months of initiation of the initial therapy (this time frame excludes the time for mobilization therapy)
- •If receiving chemotherapy-based mobilization regimens, must be able to receive high-dose melphalan between 2 and 8 weeks after the initiation of mobilization therapy whether delivered at the transplant center or at a referring center
- •Adequate organ function as measured by:
- •Cardiac: Left ventricular ejection fraction at rest greater than 40%
- •Hepatic: Bilirubin less than 2 times the upper limit of normal and alanine transaminase (ALT) and aspartate transaminase (AST) less than 3 times the upper limit of normal
- •Renal: Creatinine clearance greater than 40 ml/min (measured or calculated/estimated)
- •Pulmonary: Carbon monoxide diffusion (DLCO), Volume forcibly exhaled in one second (FEV1), and Forced Vital Capacity (FVC) greater than 50% of predicted value (corrected for hemoglobin), or O2 saturation greater than 92% of room air
- •An adequate autologous graft defined as a cryopreserved PBSC graft containing at least 4.0 x 106 CD34+ cells/kg patient weight; if prior to enrollment it is known that a patient will be on the auto-allo arm (i.e., a consenting, eligible HLA-matched sibling donor is available), the required autograft must contain at least 2.0 x 10^6 CD34+ cells/kg patient weight; the graft may not be CD34+ selected or otherwise manipulated to remove tumor or other cells; the graft can be collected at the transplanting institution or by a referring center; for patients without an HLA-matched sibling donor, the autograft must be stored so that there are two products each containing at least 2 x 10^6 CD34+ cells/kg patient weight
排除标准
- •Never advanced beyond Stage I MM since diagnosis
- •Non-secretory MM (absence of a monoclonal protein [M protein] in serum as measured by electrophoresis and immunofixation and the absence of Bence Jones protein in the urine defined by use of conventional electrophoresis and immunofixation techniques)
- •Plasma cell leukemia
- •Karnofsky performance score less than 70%, unless approved by the Medical Monitor or one of the Protocol Chairs
- •Uncontrolled hypertension
- •Uncontrolled bacterial, viral, or fungal infections (currently taking medication and progression of clinical symptoms)
- •Prior malignancies except resected basal cell carcinoma or treated cervical carcinoma in situ; cancer treated with curative intent less than 5 years previously will not be allowed unless approved by the Medical Monitor or one of the Protocol Chairs; cancer treated with curative intent more than 5 years previously will be allowed
- •Pregnant or breastfeeding
- •Seropositive for the human immunodeficiency virus (HIV)
- •Unwilling to use contraceptive techniques during and for 12 months following treatment
- •Prior allograft or prior autograft
- •Received mid-intensity melphalan (more than 50 mg IV) as part of prior therapy
- •Prior organ transplant requiring immunosuppressive therapy
研究组 & 干预措施
Auto transplants plus Therapy
One autologous transplant along with a second autologous transplant will be preformed followed by one year of Dexamethasone and Thalidomide maintenance therapy.
干预措施: One Autologous Transplant (Procedure)
Auto transplants plus Therapy
One autologous transplant along with a second autologous transplant will be preformed followed by one year of Dexamethasone and Thalidomide maintenance therapy.
干预措施: Second Autologous Transplant (Procedure)
Auto transplants plus Therapy
One autologous transplant along with a second autologous transplant will be preformed followed by one year of Dexamethasone and Thalidomide maintenance therapy.
干预措施: Thalidomide (Drug)
Auto transplants plus Therapy
One autologous transplant along with a second autologous transplant will be preformed followed by one year of Dexamethasone and Thalidomide maintenance therapy.
干预措施: Dexamethasone (Drug)
Auto transplants
One autologous transplant along with a second autologous transplant will be preformed followed by one year of observation.
干预措施: One Autologous Transplant (Procedure)
Auto transplants
One autologous transplant along with a second autologous transplant will be preformed followed by one year of observation.
干预措施: Second Autologous Transplant (Procedure)
Auto transplants
One autologous transplant along with a second autologous transplant will be preformed followed by one year of observation.
干预措施: Observation (Behavioral)
Auto and Allo transplants
One autologous transplant and one non-myeloablative allogeneic transplant will be preformed and followed by one year of observation.
干预措施: One Autologous Transplant (Procedure)
Auto and Allo transplants
One autologous transplant and one non-myeloablative allogeneic transplant will be preformed and followed by one year of observation.
干预措施: Non-Myeloablative Allogeneic Transplant (Procedure)
Auto and Allo transplants
One autologous transplant and one non-myeloablative allogeneic transplant will be preformed and followed by one year of observation.
干预措施: Observation (Behavioral)
结局指标
主要结局
Progression-Free Survival (PFS)
时间窗: Year 3
Patients are considered a failure for this endpoint if they die or if they progress or relapse.
次要结局
- Overall Survival (OS) for High Risk(Year 3)
- Overall Survival (OS) for Standard Risk(Years 1, 2, and 3)
- Cumulative Incidence of Progression/Relapse(Year 3)
- Cumulative Incidence of Treatment Related Mortality (TRM)(Year 3)
- Interval From First to Second Transplantation(Year 1)
- Incidences of Graft Versus Host Disease (GVHD)(Day 100)
- Incidences of Chronic GVHD(Years 1 and 2)