Feasibility of Low Dose Radiation as Bridging Therapy for Lisocabtagene Maraleucel in Relapsed B-Cell Non-Hodgkin Lymphoma
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 入组人数
- 33
- 试验地点
- 1
- 主要终点
- Feasibility of the intervention in the proposed study population
研究概览
简要总结
The goal of this clinical trial is to learn about treatment for people with B-cell lymphoma that did not respond to treatment or that has gotten worse after treatment. The aim of this trial is to answer the following questions:
- If it is realistic to give people radiation treatment before they receive a chimeric antigen receptor (CAR) T-cell treatment for their cancer
- If it is safe to give people radiation treatment before they receive a CAR T-cell treatment for their cancer
详细描述
This is a pilot study to evaluate the feasibility of low-dose radiation therapy in the bridging period between chimeric antigen receptor (CAR) T-cell collection, manufacturing, and infusion (vein-to-vein) in patients with relapsed and refractory aggressive B-cell lymphoma.
Emerging cellular immunotherapies including CAR T-cell therapy have produced remarkable outcomes for this population. The Food and Drug Administration (FDA) has recently approved lisocabtagene maraleucel (liso-cel) for the management of people with relapsed and refractory B-cell lymphoma. Unfortunately, many patients undergoing liso-cel infusion will suffer progression or relapse with devastating consequences. The object of this study is to identify a novel means to enhance liso-cel activity to improve overall outcomes. The investigators hypothesize that the addition of radiation therapy targeting selected sites as bridging therapy prior to lymphodepleting chemotherapy and liso-cel infusion will be effective at improving responses for patients with relapsed and refractory B-cell lymphoma.
Results from this study will provide key justification to expand this therapeutic approach into a larger phase II clinical trial powered to examine the efficacy of this approach.
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
- 19 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Biopsy-proven relapsed or progressive diffuse large B-cell lymphoma (DLBCL), high-grade B-cell lymphoma, primary mediastinal B-cell lymphoma, grade 3B follicular lymphoma, or DLBCL arising from indolent lymphoma meeting an FDA-approved (Food and Drug Administration-approved) indication for liso-cel infusion
- •Presence of disease on imaging including at least one disease site safe for radiation as determined by treating radiation oncologist
- •Willingness to participate in clinical trial and provide informed consent
- •Adequate organ function as assessed by standard institution protocols and United States (US) prescribing information label for comorbidities, heart, and lung function to undergo FDA-approved CAR T-cell therapy as determined by institution
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
- •Age 19 years or older, there is no upper limit to the age
排除标准
- •Subject is unsafe for radiation therapy as determined by investigator and/or radiation oncologist
- •Diagnosis is primary central nervous system (CNS) lymphoma (secondary CNS lymphoma with additional systemic site is allowed)
- •Requirement for concurrent high dose methotrexate
- •Secondary active malignancy that has not been in remission for at least 2 years. This excludes non-melanoma skin cancer, definitively treated stage 1 solid tumor with low risk or recurrence, and curatively treated localized prostate cancer.
- •Pregnant or nursing women
- •Uncontrolled medical, psychological, familial, sociological, or geographical conditions that do not permit compliance with the protocol, as determined by investigator
- •Unwillingness to follow procedures required in the protocol
- •Inadequate organ or hematologic conditions that prohibit the use of lymphodepleting chemotherapy
- •Use of lymphoma-directed therapy within 14 days of T-cell pheresis
研究组 & 干预措施
Single arm
Subjects will receive 4 gray (Gy) radiation in 2 fractions in the bridging period following lymphocyte pheresis, prior to lymphodepleting chemotherapy and chimeric antigen receptor (CAR) T-cell infusion. Post CAR T-cell infusion radiation therapy will be allowed as determined by study investigator but prespecified at time of radiation oncology consultation.
干预措施: Bridging radiation therapy (Radiation)
Single arm
Subjects will receive 4 gray (Gy) radiation in 2 fractions in the bridging period following lymphocyte pheresis, prior to lymphodepleting chemotherapy and chimeric antigen receptor (CAR) T-cell infusion. Post CAR T-cell infusion radiation therapy will be allowed as determined by study investigator but prespecified at time of radiation oncology consultation.
干预措施: Liso-cel (Biological)
Single arm
Subjects will receive 4 gray (Gy) radiation in 2 fractions in the bridging period following lymphocyte pheresis, prior to lymphodepleting chemotherapy and chimeric antigen receptor (CAR) T-cell infusion. Post CAR T-cell infusion radiation therapy will be allowed as determined by study investigator but prespecified at time of radiation oncology consultation.
干预措施: Post-infusion radiation (Radiation)
结局指标
主要结局
Feasibility of the intervention in the proposed study population
时间窗: Up to 90 days
The percentage of subjects who receive a chimeric antigen receptor (CAR) T-cell infusion after receiving bridging radiation therapy. A one-sided Binomial test will be conducted to assess whether acceptable percentage (\>70% vs \<70%) of patients receive CAR T-cell perfusion after undergoing the radiation therapy.
次要结局
- Evaluate the response to the study intervention of radiation and CAR T-cell therapy(Up to 190 days)
- Monitor Cytokine release syndrome (CRS) and Immune effector cell-associated neurotoxicity syndrome (ICANS) toxicity events(Up to 270 days)
- Evaluate progression-free survival (PFS) following the study intervention(Measured from first day of apheresis to death or disease progression, whichever comes first, up to two years)
- Incidence of treatment-emergent adverse events to assess the safety of the proposed intervention(Up to 120 days)
- Evaluate duration of response (DOR) following CAR T-cell therapy(Up to 2 years)
- Monitor overall safety and toxicity of the intervention(Up to 270 days)
- Evaluate overall survival (OS) following study intervention(Up to 2 years)
- Evaluate the rate of prolonged cytopenias following the intervention(Up to 190 days)