Pilot Study T Cell Depletion in the Setting of Autologous Stem Cell Transplantation for Patients With Multiple Myeloma
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 30
- 试验地点
- 1
- 主要终点
- Purity of ex vivo depleted regulatory T cells prior to autologous stem cell transplant (arm 3 only)
研究概览
简要总结
The purpose of this study is to test whether regulatory T-cell reduction is possible and safe in myeloma subjects undergoing autologous stem cell transplantation (ASCT).
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
- 21 Years 至 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Symptomatic multiple myeloma of any subtype in any disease stage, providing that patient does not have smoldering myeloma.
- •Patient must otherwise be a candidate for ASCT as determined by treating physician.
- •No current CNS Myeloma at time of enrollment.
- •Life expectancy greater than 12 weeks.
- •Age greater than or equal to 21 and less than or equal to 70 years old.
- •EGOG performance status less than or equal to
- •No cardiac, pulmonary, hepatic, or renal contraindications for high dose chemotherapy.
- •HIV Negative.
- •No active Hepatitis B or C.
- •Patients must be able to provide written informed, consent.
排除标准
- •Pregnant or nursing women. Women of child-bearing age must be tested for pregnancy.
- •Use of systemic immunosuppressive medications, including corticosteroids, tacrolimus, mycophenolate mofetil, sirolimus or cyclosporine A.
- •Psychiatric illness which may make compliance to the clinical protocol unmanageable or which may compromise the ability of the patient to give informed consent.
- •Active autoimmune disease including but not limited to: rheumatoid arthritis inflammatory bowel disease, celiac disease, systemic lupus erythematosis, scleroderma or multiple sclerosis.
研究组 & 干预措施
Standard ASCT (Grp 1)
Standard autologous stem cell transplantation (ASCT)
干预措施: Stem cell re-infusion (Procedure)
Standard ASCT (Grp 1)
Standard autologous stem cell transplantation (ASCT)
干预措施: G-CSF (Drug)
Standard ASCT (Grp 1)
Standard autologous stem cell transplantation (ASCT)
干预措施: Plerixafor (Drug)
Standard ASCT (Grp 1)
Standard autologous stem cell transplantation (ASCT)
干预措施: Apheresis (Procedure)
Standard ASCT (Grp 1)
Standard autologous stem cell transplantation (ASCT)
干预措施: Melphalan (Drug)
Depletion of T-cells after ASCT (Grp 2)
Standard ASCT followed by treatment with basiliximab to remove certain immune cells (called regulatory T-cells or Tregs) from the blood
干预措施: G-CSF (Drug)
Depletion of T-cells after ASCT (Grp 2)
Standard ASCT followed by treatment with basiliximab to remove certain immune cells (called regulatory T-cells or Tregs) from the blood
干预措施: Plerixafor (Drug)
Depletion of T-cells after ASCT (Grp 2)
Standard ASCT followed by treatment with basiliximab to remove certain immune cells (called regulatory T-cells or Tregs) from the blood
干预措施: Apheresis (Procedure)
Depletion of T-cells after ASCT (Grp 2)
Standard ASCT followed by treatment with basiliximab to remove certain immune cells (called regulatory T-cells or Tregs) from the blood
干预措施: Melphalan (Drug)
Depletion of T-cells after ASCT (Grp 2)
Standard ASCT followed by treatment with basiliximab to remove certain immune cells (called regulatory T-cells or Tregs) from the blood
干预措施: Stem cell re-infusion (Procedure)
Depletion of T-cells after ASCT (Grp 2)
Standard ASCT followed by treatment with basiliximab to remove certain immune cells (called regulatory T-cells or Tregs) from the blood
干预措施: Basiliximab (Drug)
Depletion of T-cells before ASCT(Grp 3)
Blood collected for an ASCT will be processed using a special cell sorting machine (CliniMACS device) to remove Treg cells before the stem cells are infused back into the body during stem cell transplant.
干预措施: G-CSF (Drug)
Depletion of T-cells before ASCT(Grp 3)
Blood collected for an ASCT will be processed using a special cell sorting machine (CliniMACS device) to remove Treg cells before the stem cells are infused back into the body during stem cell transplant.
干预措施: Plerixafor (Drug)
Depletion of T-cells before ASCT(Grp 3)
Blood collected for an ASCT will be processed using a special cell sorting machine (CliniMACS device) to remove Treg cells before the stem cells are infused back into the body during stem cell transplant.
干预措施: Apheresis (Procedure)
Depletion of T-cells before ASCT(Grp 3)
Blood collected for an ASCT will be processed using a special cell sorting machine (CliniMACS device) to remove Treg cells before the stem cells are infused back into the body during stem cell transplant.
干预措施: Melphalan (Drug)
Depletion of T-cells before ASCT(Grp 3)
Blood collected for an ASCT will be processed using a special cell sorting machine (CliniMACS device) to remove Treg cells before the stem cells are infused back into the body during stem cell transplant.
干预措施: Stem cell re-infusion (Procedure)
Depletion of T-cells before ASCT(Grp 3)
Blood collected for an ASCT will be processed using a special cell sorting machine (CliniMACS device) to remove Treg cells before the stem cells are infused back into the body during stem cell transplant.
干预措施: CliniMACS CD25 microbeads and cell sorter (Device)
结局指标
主要结局
Purity of ex vivo depleted regulatory T cells prior to autologous stem cell transplant (arm 3 only)
时间窗: 1-3 days
Percentage of CD4+CD25+ regulatory T cells following ex vivo depletion in arm 3 will be analyzed by flow cytometry and compared to a pre-CD25-depletion sample. The depletion of CD25+ cells among the entire CD4+ population is expected to reach 80% efficiency.
Timing and duration of regulatory T cell depletion and recovery following autologous stem cell transplant
时间窗: 180 days
Timing and duration of regulatory T cell depletion and recovery following in vivo or ex vivo (arms 2 and 3) CD25+ T cell depletion will be performed at pre-defined timepoints prior to and following autologous stem cell transplant by flow cytometry on peripheral blood samples and directly compared to the percentages of regulatory T cells (CD4+CD25+FoxP3+ or CD4+CD25+CD127-) present at the same timepoints in patients enrolled onto arm 1 in which no regulatory T cell depletion is performed.
Incidence of autologous graft-versus-host disease following in vivo or ex vivo regulatory T cell depletion
时间窗: 180 days
The indicence of autologous graft-versus-host disease, as assessed by the development of skin rash, diarrhea and/or liver function test abnormalities consistent with autologous graft-versus-host disease following CD25+ T cell depletion and autologous stem cell transplant compared with the incidence of autologous graft-versus-host disease in patients enrolled onto arm 1 in which no regulatory T cell depletion is performed.
次要结局
- Kinetics of recovery of peripheral blood cellular elements(180 days)
- Number of patients that experience a complete response following autologous stem cell transplant based upon the assigned study arm using International Myeloma Working Group definitions(100 days)