Phase I Study to Evaluate Treatment of Relapsed or Refractory Leukemia With Donor-derived HSCT Following Donor-derived CD19/22 Bispecific CAR-T Cells or CD19-directed CAR-T Cells
试验速览
- 阶段
- 1 期
- 发起方
- 入组人数
- 10
- 试验地点
- 2
- 主要终点
- Number of Participants with Severe/Adverse Events as a Measure of Safety and Tolerability
研究概览
简要总结
Allogenic hematopoietic stem cell transplant (Allo-HSCT) is routinely used for treatment of aggressive hematological malignancies. The biological foundation of allo-HSCT is the graft-versus-leukemia (GVL) effect, which is primarily mediated by donor T cells present in the graft and is able to eradicate malignant B cells either CD19+ or CD19-. Relapse following an allo-HSCT remains a major challenge in the treatment of B-ALL. CD19-directed CAR-T cell therapy has shown promising results for the treatment of relapsed or refractory B-cell malignancies; however, a subset of patients relapse due to the loss of CD19 in tumor cells. Co-infusion of donor-derived CD19/22 bispecific CAR-T cells or CD19-directed CAR-T cells and donor-derived-HSCT has the potential to combine the CAR-T cell mediated targeted elimination of CD19 expressing B cells with GVL effect, which could have clear advantages in reducing the risk of relapse and the evolution of CD19- escape variants or clonally related malignancies in other lineages. Therefore, a complete and durable tumor responses induced by this immunotherapy could be expected.
详细描述
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PRIMARY OBJECTIVES:
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To evaluate the feasibility and safety of donor-derived HSCT following donor-derived CD19/22 bispecific CAR-T cells or CD19-directed CAR-T cells in patients with relapsed or refractory leukemia.
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To evaluate the duration of in vivo persistence of adoptively transferred CAR-T cells, and the phenotype of persisting T cells. Real Time polymerase chain receptor (RT-PCR) and Flow cytometry(FCM) analysis of PB,BM will be used to detect and quantify survival of infused allo-CAR-T cells over time.
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To evaluate the donor chimerism after co-infusion of donor-derived CD19/22 bispecific CAR-T cells or CD19-directed CAR-T cells and donor-derived-HSCT
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SECONDARY OBJECTIVES:
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For patients with detectable disease, measure anti-tumor response due to co-infusion of donor-derived CD19/22 bispecific CAR-T cells or CD19-directed CAR-T cells and donor-derived-HSCT.
The allo-CAR-T cells will be infused in a fractionated manner, 1/3 on day 0, 2/3 on day 1.The allo-HSCT will be infused on day 2.
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 60 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male or female participant
- •12 Years to 60 Years
- •Patient with relapsed or refractory B-cell leukemia or lymphoma
- •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
Number of Participants with Severe/Adverse Events as a Measure of Safety and Tolerability
时间窗: 24 weeks
次要结局
- Overall remission rate (ORR) = CR + CRi(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
Chinese PLA General Hospital