IL-1 Receptor Antagonist to Prevent Severe Chimeric Antigen Receptor T-Cell Related Encephalopathy Syndrome
试验速览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 入组人数
- 23
- 试验地点
- 2
- 主要终点
- Number of patients who met the eligibility criteria to receive and did receive anakinra
研究概览
简要总结
This phase II trial studies how well anakinra works in preventing severe chimeric antigen receptor T-cell-related encephalopathy syndrome after chimeric antigen receptor T-cell therapy in patients with large B-cell lymphoma that has come back or has not responded to treatment. Immunosuppressive therapy, such as anakinra, is used to decrease the body?s immune response, which may prevent severe chimeric antigen receptor T-cell-related encephalopathy syndrome.
详细描述
PRIMARY OBJECTIVES:
I. To determine if it is feasible to accrue a sufficient number of study participants at one site, in order to justify expanding the trial to three additional sites (pilot study).
II. To estimate the efficacy of anakinra in prevention of severe immune effector cell-associated neurotoxicity syndrome. syndrome (ICANS) (full study).
SECONDARY OBJECTIVES:
I. To estimate the impact that anakinra has on the efficacy of chimeric antigen receptor (CAR) T-cell therapy for relapsed/refractory lymphoma.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Prevention
- 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
- •Patients with relapsed or refractory large B-cell lymphoma that has progressed on two prior lines of therapy, who meet the indication for the Food and Drug Administration (FDA)-approved therapy axicabtagene ciloleucel
- •Large B-cell lymphoma includes diffuse large B-cell lymphoma (DLBCL) not otherwise specified, primary mediastinal large B-cell lymphoma, high grade B-cell lymphoma, and DLBCL arising from follicular lymphoma
- •The above includes patients with progressive or stable disease as the best response to the most recent treatment regimen or disease progression within 12 months after autologous hematopoietic stem cell transplantation
- •Patients with central nervous system (CNS) involvement of large B-cell lymphoma that originated outside of the CNS will be included (not primary CNS lymphoma)
- •Serum alanine aminotransferase (ALT)/aspartate aminotransferase (AST) =< 2.5 upper limit of normal
- •Total bilirubin =< 2.0 mg/dL
- •Creatinine clearance > 30 mL/min based on Cockcroft-Gault formula
- •Patients with human immunodeficiency virus (HIV) who have an undetectable viral load will be included
- •Deemed competent to make medical decisions
排除标准
- •Patients who receive CAR T-cell therapy with a product other than axicabtagene ciloleucel
- •Primary CNS lymphoma
- •Transformed DLBCL from chronic lymphocytic leukemia (CLL)
- •Burkitt?s lymphoma
- •Bridging chemotherapy completed < 7 days prior to CAR T-cell lymphodepleting chemotherapy
- •In patients who receive bridging chemotherapy, positron emission tomography (PET)-computed tomography (CT) or CT of chest, abdomen, pelvis was not done after bridging chemotherapy prior lympho-depleting therapy
- •Most recent PET-CT or CT of all known disease is sites done more than 6 weeks prior to CAR T-cell infusion
- •Any individual CNS tumor mass > 2 cm
- •History of autologous hematopoietic stem cell transplantation administered less than 100 days prior to CAR T-cell infusion
- •History of allogeneic hematopoietic stem cell transplantation
- •Treatment with alemtuzumab within 6 months prior to leukapheresis, or treatment with clofarabine or cladribine within 3 months prior to leukapheresis
- •Less than 3 half-lives elapsed since receiving immune checkpoint inhibitor (pembrolizumab, ipilimumab, nivolumab, atezolizumab, etc.)
- •Presence of uncontrolled fungal, bacterial, or viral infection that require intravenous (IV) antimicrobial treatment
- •History of autoimmune disease resulting in end-organ damage, or autoimmune disease requiring systemic immunosuppressants or disease-modifying antirheumatic drug (DMARDs) within the past 6 months
- •Hypersensitivity to E. Coli-derived proteins
- •Patients with HIV who have a detectable viral load
- •Pregnant or nursing
- •Fertile women who decline use of contraception during the study period
研究组 & 干预措施
Prevention (anakinra, CAR T-cell therapy)
Patients receive standard lymphodepleting therapy including fludarabine and cyclophosphamide on days -5 to -3, then receive axicabtagene ciloleucel CAR T-cell infusion. Patients with clinical evidence of ICANS of any grade, or CRS >= grade 3 receive anakinra SC every 6-12 hours for 12-36 doses over 9 days in the absence of unacceptable toxicity.
干预措施: Anakinra (Biological)
Prevention (anakinra, CAR T-cell therapy)
Patients receive standard lymphodepleting therapy including fludarabine and cyclophosphamide on days -5 to -3, then receive axicabtagene ciloleucel CAR T-cell infusion. Patients with clinical evidence of ICANS of any grade, or CRS >= grade 3 receive anakinra SC every 6-12 hours for 12-36 doses over 9 days in the absence of unacceptable toxicity.
干预措施: Axicabtagene Ciloleucel (Biological)
Prevention (anakinra, CAR T-cell therapy)
Patients receive standard lymphodepleting therapy including fludarabine and cyclophosphamide on days -5 to -3, then receive axicabtagene ciloleucel CAR T-cell infusion. Patients with clinical evidence of ICANS of any grade, or CRS >= grade 3 receive anakinra SC every 6-12 hours for 12-36 doses over 9 days in the absence of unacceptable toxicity.
干预措施: Cyclophosphamide (Drug)
Prevention (anakinra, CAR T-cell therapy)
Patients receive standard lymphodepleting therapy including fludarabine and cyclophosphamide on days -5 to -3, then receive axicabtagene ciloleucel CAR T-cell infusion. Patients with clinical evidence of ICANS of any grade, or CRS >= grade 3 receive anakinra SC every 6-12 hours for 12-36 doses over 9 days in the absence of unacceptable toxicity.
干预措施: Fludarabine (Drug)
Prevention (anakinra, CAR T-cell therapy)
Patients receive standard lymphodepleting therapy including fludarabine and cyclophosphamide on days -5 to -3, then receive axicabtagene ciloleucel CAR T-cell infusion. Patients with clinical evidence of ICANS of any grade, or CRS >= grade 3 receive anakinra SC every 6-12 hours for 12-36 doses over 9 days in the absence of unacceptable toxicity.
干预措施: Fludarabine Phosphate (Drug)
结局指标
主要结局
Number of patients who met the eligibility criteria to receive and did receive anakinra
时间窗: Up to 12 months
The study will be considered feasible if 8 study participants are enrolled over 12 months at University of California, Los Angeles.
Rate of severe chimeric antigen receptor T-cell-related encephalopathy syndrome (ICANS)
时间窗: Up to 30 days
Will be defined as grade \>= 3 neurotoxicity by Common Terminology Criteria for Adverse Events (CTCAE) version (v)4.03. The proportion of patients developing severe ICANS and the corresponding 90% binomial exact confidence interval (CI) will be reported.
次要结局
- Duration of neurotoxicity(From first day of ICANS of >= grade 3 to improvement of ICANS to < grade 3, assessed up to 100 days)
- Persistent hepatotoxicity(Up to 100 days)
- Objective response rate (ORR)(Up to 90 days)
- Incidence of adverse events (AEs)(Up to 100 days)
- Proportion of patients who received anakinra and develop ICAN(Up to 30 days)