A Phase 2 Study to Evaluate CD19-Specific Chimeric Antigen Receptor (CAR)-T Cells Combined With Acalabrutinib for Patients With Relapsed or Refractory Mantle Cell Lymphoma (MCL)
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 发起方
- 入组人数
- 36
- 试验地点
- 1
- 主要终点
- Occurrence of dose-limiting toxicities (DLTs) (Safety Lead-in)
研究概览
简要总结
This phase II trial investigates the side effects of CD19 chimeric antigen receptor (CAR) T cells and acalabrutinib, and to see how well they work in treating patients with mantle cell lymphoma that has come back (relapsed) or does not respond to treatment (refractory). T cells are infection fighting blood cells that can kill cancer cells. The T cells given in this study will come from the patient and will have a new gene put in them that makes them able to recognize CD19, a protein on the surface of the cancer cells. These CD19-specific T cells may help the body's immune system identify and kill CD19 positive cancer cells. Acalabrutinib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Giving CD19 CAR T cells together with acalabrutinib may kill more cancer cells.
详细描述
PRIMARY OBJECTIVES:
I. Evaluate the safety of adding CD19CAR-CD28-CD3zeta-EGFRt-expressing Tn/mem-enriched T-lymphocytes (CD19 CAR T cells) to acalabrutinib treatment. (Safety Lead-in) II. Estimate the complete response (CR) rate within 6 months after adding CD19 CAR T cells to acalabrutinib treatment. (Phase 2)
SECONDARY OBJECTIVES:
I. Assess best response, time to and duration of CR. II. Estimate the 1-year progression free survival (PFS) rate and overall survival (OS).
III. Describe the full toxicity profile.
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 75 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
- 未提供
研究组 & 干预措施
Treatment (CD19 CAR T cells, acalabrutinib)
Patients receive acalabrutinib PO BID on days -5 to 28 of cycle 1 and on days 1-28 of subsequent cycles. Patients also receive CD19 CAR T cells IV on day 0. Treatment with acalabrutinib repeats every 28 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity. Patients who have not attained CR after the first disease assessment and tolerated the initial CAR T cell infusion may receive a second CAR T cell infusion in cycle 2.
干预措施: Acalabrutinib (Drug)
Treatment (CD19 CAR T cells, acalabrutinib)
Patients receive acalabrutinib PO BID on days -5 to 28 of cycle 1 and on days 1-28 of subsequent cycles. Patients also receive CD19 CAR T cells IV on day 0. Treatment with acalabrutinib repeats every 28 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity. Patients who have not attained CR after the first disease assessment and tolerated the initial CAR T cell infusion may receive a second CAR T cell infusion in cycle 2.
干预措施: CD19CAR-CD28-CD3zeta-EGFRt-expressing Tn/mem-enriched T-lymphocytes (Biological)
结局指标
主要结局
Occurrence of dose-limiting toxicities (DLTs) (Safety Lead-in)
时间窗: Day 0 up to 28 days after the first chimeric antigen receptor (CAR) T cell infusion
Rates and associated 95% Clopper and Pearson exact confidence interval (CI) will be estimated for DLTs at the safe dose.
Complete response (CR) (Phase II)
时间窗: Within 6 months of CAR T-cell infusion and concurrent acalabrutinib therapy
Response will be assessed based on Lugano classification. CR rate is defined as the proportion of response-evaluable participants who achieve a best response of CR within 6 months of CAR T-cell infusion and concurrent acalabrutinib therapy. Rates and associated 95% Clopper and Pearson exact CI will be estimated for CR within 6 months.
次要结局
- Overall survival (OS)(From start of protocol treatment (start of lymphodepletion) to death due to any cause, assessed at 1 year)
- Duration of CR(From the first achievement of CR after CAR T cell infusion through disease relapse or progression or death, assessed up to 15 years)
- Time to CR(From the first achievement of CR after CAR T cell infusion through disease relapse or progression or death, assessed up to 15 years)
- Best response(Up to 1 year post CAR T cell infusion)
- Progression-free survival (PFS)(From start of protocol treatment (start of lymphodepletion) to the first observation of disease relapse/progression or death due to any cause, whichever occurs first, assessed at 1 year)
- Incidence of adverse events(Up to 15 year post CAR T cell infusion)