A Feasibility Trial of Tazemetostat Plus CAR T Cell Therapy in B-cell Lymphomas
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 入组人数
- 15
- 试验地点
- 2
- 主要终点
- Number of participants who experience adverse events classified per CTCAEv5
研究概览
简要总结
This is a clinical trial to evaluate the feasibility and safety of giving tazemetostat followed by standard of care CAR T cell infusion in previously treated diffuse large b-cell lymphoma (DLBCL), follicular lymphoma (FL), and mantle cell lymphoma (MCL). The investigators hypothesis is that this combination has the potential to significantly improve the ability of CART cells to recognize and kill lymphoma cells without a significant impact on safety. Participants will receive the tazemetostat pills before and after receiving their CAR T cell therapy, for up to 12 months after CAR T cell administration. Patients will be followed for up to 5 years.
详细描述
This is a single arm, open label, clinical trial to evaluate the feasibility and safety of oral tazemetostat followed by standard of care CAR T cell infusion in previously treated DLBCL, FL, and MCL. The investigators hypothesis is that this combination has the potential to significantly improve the ability of CART cells to recognize and kill lymphoma cells without a significant impact on safety.
Tazemetostat 800 mg will be given twice daily by mouth for at least 1 week prior to apheresis, during the period between apheresis and CAR T infusion, and following lymphodepletion chemotherapy until Day 7 post-CAR T therapy. Once patients' platelets and neutrophil counts recover, tazemetostat will be resumed. Tazemetostat treatment will continue for up to 6 months in patients with complete responses and up to 12 months in patients with partial responses.
A 3+3 trial design will be implemented for the first six patients enrolled. The regimen will be considered feasible if at least 12 out of 15 subjects are able to receive at least 2 weeks of tazemetostat, generate the CAR T cell product and receive CAR T cell therapy.
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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Confirmed diagnosis of DLBCL, FL, or MCL
- •Eligible to receive standard of care CAR T cells
- •Have received at least 1 prior therapies
排除标准
- •Active viral infection with HIV or hepatitis type B or C
- •Active, uncontrolled systemic fungal, bacterial or viral infection
- •Active treatment for another cancer
- •Pregnant or breastfeeding
- •Unable to take oral medication
- •Certain significant past medical history, such recent stroke, pulmonary embolism, myocardial infarction, congestive heart failure, uncontrolled hypertension, or certain arrhythmias
研究组 & 干预措施
Tazemetostat and CAR T-Cell Therapy
Tazemetostat is being administered prior to, and following, standard of care CAR T cell therapy. The use of tazemetostat in this way is investigational.
干预措施: Tazemetostat Pill (Drug)
结局指标
主要结局
Number of participants who experience adverse events classified per CTCAEv5
时间窗: From start of treatment until 30 days after the last dose of tazemetostat, for a maximum of approximately 13 months
Adverse reactions will be graded as per National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.
次要结局
- Overall response rate (ORR) reported as per Lugano response criteria(From start of treatment until disease progression or death, for a maximum of approximately 6 years)
- Mean Progression-Free Survival (PFS)(From start of treatment until disease progression or death, for a maximum of approximately 6 years)
- Number of patients who experience cytokine release syndrome (CRS) by ASTCT Consensus Grading system during therapy(From start of treatment until Day 21 days following CAR T cell infusion)
- Number of patients who experience immune effector cell neurotoxicity syndrome (ICANS) by ASTCT Consensus Grading system during therapy(From start of treatment until Day 21 days following CAR T cell infusion)
- Mean Overall Survival (OS)(From start of treatment until death, for a maximum of approximately 6 years)