Clinical Study of Redirected Autologous T Cells With a BCMA-targeted Chimeric Antigen Receptor in Patients With Refractory or Relapsed Multiple Myeloma
试验速览
- 阶段
- 1 期
- 发起方
- 入组人数
- 11
- 试验地点
- 1
- 主要终点
- Safety and effectivity - Incidence of study related adverse events
研究概览
简要总结
A single arm, open-label pilot study is designed to determine the safety, efficacy and cytokinetics of CAR-BCMA T cells in patients with BCMA-positive refractory or relapsed multiple myeloma.
详细描述
This study is designed to determine the safety, tolerability and engraftment potential of anti-BCMA lentivirus-transduced autologous T cells in patients with refractory or relapsed multiple myeloma.
Primary objectives:
- Determine the safety and tolerability of CAR-BCMA T cells (autologous T cells transduced with chimeric antigen receptors recognizing BCMA) in patients with refractory or relapsed multiple myeloma.
- Observe the cytokinetics of CAR-BCMA T cells.
Secondary objectives:
- Observe the anti-tumor response of CAR-BCMA T cells to refractory or relapsed multiple myeloma (evaluated by diagnostic criteria International Myeloma Working Group (IMWG2014 version) as CR, sCR, ICR, MCR or VGPR).
- Make an evaluation on the distribution and in vivo survival of CAR-BCMA T cells in peripheral blood, lymph node, and bone marrow.
- Observe the immunogenicity of CAR-BCMA T cells, and determine if there is anti-BCMA scFv cellular immune response and anti-BCMA scFv humoral immune response.
- Observe the change of T cell subsets relative to CAR-BCMA T。 (Tcm, central memory T lymphocytes; Tem, effector memory T lymphocytes; Treg, regulatory T lymphocytes).
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
- 18 Years 至 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- 未提供
排除标准
- •Patients with any of the following conditions are not eligible for this study.
- •Pregnant or lactating women.
- •HIV positive, or HCV positive
- •Uncontrolled active infection, including active tuberculosis and HBV DNA copies ≥ 1×10^3 copies/mL.
- •Concurrent use of systemic steroids. Recent or current use of inhaled steroids is not exclusionary.
- •Allergic to immunotherapies and related drugs.
- •Patients with heart disease for which treatment is needed or with poorly controlled hypertension.
- •Hyponatremia: serum sodium level < 125 mmol/L.
- •Baseline serum potassium < 3.5 mmol/L (taking potassium supplements before participating in the study to raise potassium level is acceptable).
- •Previous treatment with chemoradiotherapy, local treatment ,immunotherapy and tumor-targeting drug conducted 2 weeks prior to participation in this study or blood collection.
- •Patients have undertaken immunosuppressor for graft-versus-host disease (GVHD) within 4 weeks before participation in this study or blood collection, or the patient is diagnosed with acute or chronic GVHD.
- •Other severe disease that may restrain patients from participating in this study (e.g. diabetes, severe cardiac dysfunction, myocardial infarction or unstable arrhythmias or unstable angina in recent 6 months, gastric ulcer, active autoimmune disease, etc.).
研究组 & 干预措施
CAR-BCMA T cells
In this study, autologous T cells transduced with a BCMA-targeted chimeric antigen receptor (CAR-BCMA T cells) are used to treat patients with refractory or relapsed multiple myeloma.
Route of administration: Intravenous injection.
Lymphodepletion conditioning:
Lymphodepletion will be conducted several days prior to CAR-BCMA T cells infusion.
A combination of fludarabine and cyclophosphamide will be used for lymphodepletion.
干预措施: CAR-BCMA T cells (Genetic)
CAR-BCMA T cells
In this study, autologous T cells transduced with a BCMA-targeted chimeric antigen receptor (CAR-BCMA T cells) are used to treat patients with refractory or relapsed multiple myeloma.
Route of administration: Intravenous injection.
Lymphodepletion conditioning:
Lymphodepletion will be conducted several days prior to CAR-BCMA T cells infusion.
A combination of fludarabine and cyclophosphamide will be used for lymphodepletion.
干预措施: Fludarabine (Drug)
CAR-BCMA T cells
In this study, autologous T cells transduced with a BCMA-targeted chimeric antigen receptor (CAR-BCMA T cells) are used to treat patients with refractory or relapsed multiple myeloma.
Route of administration: Intravenous injection.
Lymphodepletion conditioning:
Lymphodepletion will be conducted several days prior to CAR-BCMA T cells infusion.
A combination of fludarabine and cyclophosphamide will be used for lymphodepletion.
干预措施: Cyclophosphamide (Drug)
结局指标
主要结局
Safety and effectivity - Incidence of study related adverse events
时间窗: 24 weeks
Incidence of study related adverse events which are defined as laboratory toxicities and clinical events that are possible, likely or definitely related to study treatment at any time from the infusion until week 24, including infusion related toxicity and any toxicity possibly related to CAR-BCMA T cells.
Engraftment
时间窗: 2 years
Duration of in vivo survival of CAR-BCMA T cells is defined as "engraftment". After 24 hours of infusion, the CAR-BCMA DNA sequence was detected by PCR according to the follow-up time point, until the result of any two consecutive tests was negative and recorded as the "engraftment endpoint" of CAR-BCMA T cells.
次要结局
- Statistical parameter of efficacy assessment：DCR(2 years)
- Statistical parameter of efficacy assessment：ORR(2 years)
- Statistical parameter of efficacy assessment：OS(5 years)
- Statistical parameter of efficacy assessment：PFS(5 years)