Phase I/II Study to Evaluate Treatment of Relapsed or Refractory Multiple Myeloma With Dual CAR-T Cells Targeting CD38 and BCMA
试验速览
- 阶段
- 1 期
- 发起方
- 入组人数
- 80
- 试验地点
- 2
- 主要终点
- MTD of dual specificity CD38 and BCMA CAR-T cells
研究概览
简要总结
CAR-T cell therapy has shown promising results for the treatment of relapsed or refractory Multiple Myeloma,however, a subset of patients relapse due to the loss of target in tumor cells.Dual Specificity CD38 and BCMA CAR-T cells can recognize and kill the malignant cells through recognition of CD38 or BCMA. This is a phase 1/2 study designed to determine the safety of dual specificity CD38 and BCMA CAR-T cells and the feasibility of making enough to treat patients with relapsed or refractory Multiple Myeloma.
详细描述
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PRIMARY OBJECTIVES:
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To evaluate the feasibility and safety of dual specificity CD38 and BCMA CAR-T cells in patients with relapsed or refractory Multiple Myeloma.
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To evaluate the duration of in vivo persistence of adoptively transferred T cells, and the phenotype of persisting T cells.Real Time polymerase chain receptor (RT-PCR) and Flow cytometry(FCM) analysis of PB,BM and lymph node will be used to detect and quantify survival of universal dual specificity CD38 and BCMA CAR-T cells over time.
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SECONDARY OBJECTIVES:
1.For patients with detectable disease, measure anti-tumor response due to dual specificity CD38 and BCMA CAR-T cell infusions.
2.The CAR-T cells will be administered by i.v. injection over 20-30 minutes as a using Day 0: 1-5x10e6/kg total dose on day 0.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 12 Years 至 70 Years（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male or female participant
- •12 Years to 70 Years (Child, Adult, Senior)
- •Patient with relapsed or refractory Multiple Myeloma,multiple myeloma cell express CD38(over 50%) and BCMA (over 50%)
- •Estimated life expectancy ≥ 12 weeks (according to investigator's judgement)
- •Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1
- •Adequate organ function
排除标准
- •Prior malignancy, except carcinoma in situ of the skin or cervix treated with curative intent and with no evidence of active disease
- •Diagnosis of Burkitt's leukemia/lymphoma according to WHO classification or chronic myelogenous leukemia lymphoid blast crisis
- •Richter's syndrome
- •Presence of Grade II-IV (Glucksberg) or B-D (IBMTR) acute or extensive chronic GVHD at the time of screening
- •Subjects with any autoimmune disease or any immune deficiency disease or other disease in need of immunosuppressive therapy
- •Severe active infection (uncomplicated urinary tract infections, bacterial pharyngitis is allowed), Prophylactic antibiotic, antiviral and antifungal treatment is permissible
- •Active hepatitis B, active hepatitis C, or any human immunodeficiency virus (HIV) infection at the time of screening
- •Patient has an investigational medicinal product within the last 30 days prior to screening
- •Previous treatment with investigational gene or cell therapy medicine products
- •Concurrent use of systemic steroids. Recent or current use of inhaled steroids is not exclusionary
- •Pregnant or nursing women
结局指标
主要结局
MTD of dual specificity CD38 and BCMA CAR-T cells
时间窗: 4 weeks
The highest dose of dual specificity CD38 and BCMA CAR-T cells that is estimated to result in defined Dose Limiting Toxicity (DLT) with the exception of allowable 'expected' AEs associated with the intravenous infusion of dual specificity CD38 and BCMA CAR-T cells
Copies numbers of CAR in peripheral blood(PB), bone marrow(BM)and lymph nodes
时间窗: 24 weeks
Number of Participants with Severe/Adverse Events as a Measure of Safety and Tolerability
时间窗: 24weeks
次要结局
- Six-month Objective response rate of complete remission and partial remission(24 weeks)
- Six-month Overall survival(24 weeks)
- Six-month Progression free survival(24 weeks)
研究者
Han weidong
Director of Molecular & Immunological Department,Biotherapeutic Department
Chinese PLA General Hospital