Randomized Trial of Activated Marrow Infiltrating Lymphocytes Alone or in Conjunction With an Allogeneic GM-CSF-based Myeloma Cellular Vaccine in the Autologous Transplant Setting in Multiple Myeloma
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 36
- 试验地点
- 1
- 主要终点
- Response Rates by Blade Criteria
研究概览
简要总结
Patient Population: Patients with active myeloma (Stage II/III) that have completed induction therapy and are eligible for an autologous stem cell transplant.
Number of Patients: Will treat a total of 32 evaluable patients in a 1:1 randomization of aMILs vs aMILs plus vaccine. An evaluable patient is defined as one which has received the activated MILs and is at least 6 months post-transplant.
Study Objectives:
Disease response as determined by the Blade' criteria will be the primary endpoint of the trial at one year.
Additional study endpoints include progression free survival, parameters of T cell reconstitution, anti-tumor immune responses as well as the effect on osteoclastogenesis and clonogenic myeloma precursor cells.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Durie-Salmon Stage II or III multiple myeloma
- •Newly diagnosed either prior to receiving treatment or having completed induction therapy
- •Relapsed myeloma not previously transplanted within the past 5 years
- •Measurable serum and/or urine M-protein from prior to induction therapy documented and available. A positive serum free lite assay is acceptable
- •Age greater than 18 years old
- •ECOG performance status of 0 - 2
- •Meet all institutional requirements for autologous stem cell transplantation
- •The patient must be able to comprehend and have signed the informed consent
排除标准
- •Diagnosis of any of the following plasma cell disorders: POEMS syndrome (plasma cell dyscrasia with polyneuropathy, organomegaly, endocrinopathy, monoclonal protein [M-protein] and skin changes) Non-secretory myeloma (no measurable protein on Serum Free Lite Assay)
- •Plasma cell leukemia
- •Amyloidosis
- •Use of corticosteroids (glucocorticoids) within 21 days of pre-transplant vaccine or bone marrow collection
- •Use of any myeloma-specific therapy other than lenalidomide within 21 days of pre-transplant vaccine
- •In a complete remission at the time of bone marrow collection
- •Infection requiring treatment with antibiotics, antifungal, or antiviral agents within seven days of vaccination or bone marrow collection
- •Participation in any clinical trial, within four weeks prior to vaccination or bone marrow collection on this trial, which involved an investigational drug or device
- •History of malignancy other than multiple myeloma within five years of vaccination or bone marrow collection, except adequately treated basal or squamous cell skin cancer
- •Active autoimmune disease (e.g., rheumatoid arthritis, multiple sclerosis, systemic lupus erythematosis) requiring systemic treatment. Hypothyroidism without evidence of Grave's Disease or Hashimoto's thyroiditis is permitted
- •Evidence of spinal cord compression at time of transplant
研究组 & 干预措施
ASCT + MILs
Cyclophosphamide and filgrastim will be given to mobilize peripheral blood stem cells. Leukapheresis will be performed to collect peripheral blood from which activated marrow infiltrating lymphocytes will be produced. A melphalan conditioning regimen will be used prior to autologous stem cell transplant, and the MILs product will be administered on Days 3 and 4.
干预措施: Activated marrow infiltrating lymphocytes (Biological)
ASCT + MILs
Cyclophosphamide and filgrastim will be given to mobilize peripheral blood stem cells. Leukapheresis will be performed to collect peripheral blood from which activated marrow infiltrating lymphocytes will be produced. A melphalan conditioning regimen will be used prior to autologous stem cell transplant, and the MILs product will be administered on Days 3 and 4.
干预措施: Cyclophosphamide (Drug)
ASCT + MILs
Cyclophosphamide and filgrastim will be given to mobilize peripheral blood stem cells. Leukapheresis will be performed to collect peripheral blood from which activated marrow infiltrating lymphocytes will be produced. A melphalan conditioning regimen will be used prior to autologous stem cell transplant, and the MILs product will be administered on Days 3 and 4.
干预措施: Filgrastim (Biological)
ASCT + MILs
Cyclophosphamide and filgrastim will be given to mobilize peripheral blood stem cells. Leukapheresis will be performed to collect peripheral blood from which activated marrow infiltrating lymphocytes will be produced. A melphalan conditioning regimen will be used prior to autologous stem cell transplant, and the MILs product will be administered on Days 3 and 4.
干预措施: Leukapheresis (Procedure)
ASCT + MILs
Cyclophosphamide and filgrastim will be given to mobilize peripheral blood stem cells. Leukapheresis will be performed to collect peripheral blood from which activated marrow infiltrating lymphocytes will be produced. A melphalan conditioning regimen will be used prior to autologous stem cell transplant, and the MILs product will be administered on Days 3 and 4.
干预措施: Melphalan (Drug)
ASCT + MILs
Cyclophosphamide and filgrastim will be given to mobilize peripheral blood stem cells. Leukapheresis will be performed to collect peripheral blood from which activated marrow infiltrating lymphocytes will be produced. A melphalan conditioning regimen will be used prior to autologous stem cell transplant, and the MILs product will be administered on Days 3 and 4.
干预措施: Autologous stem cell transplant (Biological)
ASCT + MILs + vaccine
Cyclophosphamide and filgrastim will be given to mobilize peripheral blood stem cells. Leukapheresis will be performed to collect peripheral blood from which activated marrow infiltrating lymphocytes will be produced. A melphalan conditioning regimen will be used prior to autologous stem cell transplant, and the MILs product will be administered on Days 3 and 4. The allogeneic myeloma vaccine will be administered on Days 21, 60, 180, and 300.
干预措施: Activated marrow infiltrating lymphocytes (Biological)
ASCT + MILs + vaccine
Cyclophosphamide and filgrastim will be given to mobilize peripheral blood stem cells. Leukapheresis will be performed to collect peripheral blood from which activated marrow infiltrating lymphocytes will be produced. A melphalan conditioning regimen will be used prior to autologous stem cell transplant, and the MILs product will be administered on Days 3 and 4. The allogeneic myeloma vaccine will be administered on Days 21, 60, 180, and 300.
干预措施: Allogeneic Myeloma Vaccine (Biological)
ASCT + MILs + vaccine
Cyclophosphamide and filgrastim will be given to mobilize peripheral blood stem cells. Leukapheresis will be performed to collect peripheral blood from which activated marrow infiltrating lymphocytes will be produced. A melphalan conditioning regimen will be used prior to autologous stem cell transplant, and the MILs product will be administered on Days 3 and 4. The allogeneic myeloma vaccine will be administered on Days 21, 60, 180, and 300.
干预措施: Cyclophosphamide (Drug)
ASCT + MILs + vaccine
Cyclophosphamide and filgrastim will be given to mobilize peripheral blood stem cells. Leukapheresis will be performed to collect peripheral blood from which activated marrow infiltrating lymphocytes will be produced. A melphalan conditioning regimen will be used prior to autologous stem cell transplant, and the MILs product will be administered on Days 3 and 4. The allogeneic myeloma vaccine will be administered on Days 21, 60, 180, and 300.
干预措施: Filgrastim (Biological)
ASCT + MILs + vaccine
Cyclophosphamide and filgrastim will be given to mobilize peripheral blood stem cells. Leukapheresis will be performed to collect peripheral blood from which activated marrow infiltrating lymphocytes will be produced. A melphalan conditioning regimen will be used prior to autologous stem cell transplant, and the MILs product will be administered on Days 3 and 4. The allogeneic myeloma vaccine will be administered on Days 21, 60, 180, and 300.
干预措施: Leukapheresis (Procedure)
ASCT + MILs + vaccine
Cyclophosphamide and filgrastim will be given to mobilize peripheral blood stem cells. Leukapheresis will be performed to collect peripheral blood from which activated marrow infiltrating lymphocytes will be produced. A melphalan conditioning regimen will be used prior to autologous stem cell transplant, and the MILs product will be administered on Days 3 and 4. The allogeneic myeloma vaccine will be administered on Days 21, 60, 180, and 300.
干预措施: Melphalan (Drug)
ASCT + MILs + vaccine
Cyclophosphamide and filgrastim will be given to mobilize peripheral blood stem cells. Leukapheresis will be performed to collect peripheral blood from which activated marrow infiltrating lymphocytes will be produced. A melphalan conditioning regimen will be used prior to autologous stem cell transplant, and the MILs product will be administered on Days 3 and 4. The allogeneic myeloma vaccine will be administered on Days 21, 60, 180, and 300.
干预措施: Autologous stem cell transplant (Biological)
结局指标
主要结局
Response Rates by Blade Criteria
时间窗: Up to 1 year
Number of participants with each disease response category utilizing the Blade criteria: * Complete Response (CR): Defined as negative serum and urine immunofixation and a bone marrow aspirate with \< 5% plasma cells. * Near Complete Response (nCR): Defined as negative serum and urine paraprotein, positive serum and/or urine immunofixation, and a bone marrow aspirate with \< 5% plasma cells. * Very Good Partial Response (VGPR): Defined as negative serum and urine paraprotein with positive serum and/or urine immunofixation; or a 90% decrease in serum paraprotein with urine paraprotein \< 100 mg/24 hours. * Partial Response (PR): Defined as a 50-89% decrease in serum paraprotein. * Minimal Response (MR): Defined as a 25-49% decrease in serum paraprotein. * Stable Disease (SD): Defined as not falling into any other response category. * Overall response rate (ORR): Total of CR, nCR, VGPR, and PR.
次要结局
- Overall Survival(Up to 5 years)
- Feasibility as Measured by Participant Withdrawal or Removal(Up to 1 year)
- Safety as Measured by Grade 3-5 Adverse Events(Up to 1 year)
- Progression-free Survival(Up to 5 years)
- Anti-tumor Immune Response(Days 60, 180, and 360)
- The Effect of aMILs on Osteoclastogenesis as Measured by Bone Turnover (RANKL/OPG Ratio)(Days 60, 180, and 360)
- The Effect of aMILs on Osteoclastogenesis as Measured by Bone Turnover (Serum C Telopeptide Levels)(Days 60, 180, 360)
- The Effect of aMILs on Osteoclastogenesis as Measured by Bone Turnover (bAlkaline Phosphatase Levels)(Days 60, 180, 360)
- The Effect of aMILs on Osteoclastogenesis as Measured by Bone Turnover (Osteocalcin Levels)(Days 60, 180, 360)
- Effect of aMILs on Clonogenic Myeloma Precursors(Days 60, 180, and 360)