A Feasibility Study of Bridging Radiation to All Sites of FDG-Avid Disease for Commercial CAR T-Cell Infusion in Patients With Large B-Cell Lymphoma
试验速览
- 阶段
- 早期 1 期
- 状态
- 招募中
- 发起方
- 入组人数
- 9
- 试验地点
- 1
- 主要终点
- Proportion of participants completing planned radiation therapy
研究概览
简要总结
This early phase I clinical trial evaluates bridging radiation therapy given before chimeric antigen receptor (CAR) T-cell infusion to treat large B-cell lymphoma (LBCL) that has come back (relapsed) or has not responded to previous treatment (refractory). Patients with relapsed or refractory disease have historically poor prognosis. CAR T-cell therapy is a type of treatment in which a patient's T-cells (a type of immune system cell) are changed in the laboratory so they will attack cancer cells. T-cells are taken from a patient's blood (leukapheresis). Then the gene for a special receptor that binds to a certain protein on the patient's cancer cells is added to the T-cells in the laboratory. The special receptor is called a chimeric antigen receptor (CAR). Large numbers of the CAR T-cells are grown in the laboratory and given to the patient by infusion for treatment of certain cancers. While the outcomes from CAR T-cell therapy appear favorable, in the time between leukapheresis and CAR T-cell infusion many patients have symptomatic or life-threatening disease which often requires bridging therapy. Bridging therapy aims to slow disease progression and control symptoms during this critical period prior to CAR T-cell infusion. Radiation therapy uses high energy x-rays, particles, or radioactive seeds to kill cancer cells. Giving bridging radiation therapy to patients with relapsed or refractory LBCL prior to CAR T-cell infusion may improve treatment outcomes with minimal toxicity.
详细描述
PRIMARY OBJECTIVE:
I. Evaluate if bridging radiation to all sites of F-fluorodeoxyglucose (FDG)-avid disease can be feasibly administered prior to commercial CAR T-cell infusion in patients with large B-cell lymphoma (LBCL).
SECONDARY OBJECTIVES:
I. Assess the toxicities of bridging radiation in patients with LBCL. II. Assess overall response rate, complete response rate, progression-free survival, local control, distant control, and overall survival after bridging radiation and CAR T-cell infusion in patients with LBCL.
EXPLORATORY OBJECTIVES:
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
- •Documented informed consent of the participant and/or legally authorized representative.
- •Assent, when appropriate, will be obtained per institutional guidelines.
- •Age: >= 18 years.
- •Eastern Cooperative Oncology Group (ECOG) =< 2 or Karnofsky Performance Status (KPS) >=
- •Histologically confirmed large B-cell lymphoma.
- •Relapsed/refractory disease.
- •Planned to undergo commercial CAR T-cell infusion within 3 months of enrollment.
- •6 or fewer sites (treatable with a maximum of 3 isocenters) of FDG-PET avid disease, treatable with a a maximum of 3 isocenters.
- •Measurable disease e.g., at least 1.5 cm on CT/MRI or by Response Evaluation Criteria in Solid Tumors 1.1 (RECIST 1.1).
- •Fully recovered from the acute toxic effects (except alopecia) to =< grade 1 to prior anti-cancer therapy.
- •Women of childbearing potential (WOCBP): negative urine or serum pregnancy test (performed within 30 days prior to day 1 of protocol therapy).
- •If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
排除标准
- •Prior CD19-directed therapy.
- •Radiation therapy within 21 days prior to day 1 of protocol therapy.
- •Central nervous system (CNS) disease.
- •History of allergic reactions attributed to compounds of similar chemical or biologic composition to study agent.
- •Active diarrhea.
- •Clinically significant uncontrolled illness.
- •Active infection requiring antibiotics.
- •Other active malignancy.
- •Females only: Pregnant.
- •Any other condition that would, in the investigator's judgment, contraindicate the patient's participation in the clinical study due to safety concerns with clinical study procedures.
- •Prospective participants who, in the opinion of the investigator, may not be able to comply with all study procedures (including compliance issues related to feasibility/logistics).
研究组 & 干预措施
Treatment (leukapheresis, external beam radiation, CAR-T)
Patients undergo leukapheresis per standard of care, undergo external beam radiation therapy, and undergo CAR T-cell infusion per standard of care on study. Patients undergo PET/CT throughout the study and may undergo MRI during screening. Patients also undergo blood sample collection throughout the study.
干预措施: Biospecimen Collection (Procedure)
Treatment (leukapheresis, external beam radiation, CAR-T)
Patients undergo leukapheresis per standard of care, undergo external beam radiation therapy, and undergo CAR T-cell infusion per standard of care on study. Patients undergo PET/CT throughout the study and may undergo MRI during screening. Patients also undergo blood sample collection throughout the study.
干预措施: Chimeric Antigen Receptor T-Cell Therapy (Biological)
Treatment (leukapheresis, external beam radiation, CAR-T)
Patients undergo leukapheresis per standard of care, undergo external beam radiation therapy, and undergo CAR T-cell infusion per standard of care on study. Patients undergo PET/CT throughout the study and may undergo MRI during screening. Patients also undergo blood sample collection throughout the study.
干预措施: Computed Tomography (Procedure)
Treatment (leukapheresis, external beam radiation, CAR-T)
Patients undergo leukapheresis per standard of care, undergo external beam radiation therapy, and undergo CAR T-cell infusion per standard of care on study. Patients undergo PET/CT throughout the study and may undergo MRI during screening. Patients also undergo blood sample collection throughout the study.
干预措施: External Beam Radiation Therapy (Radiation)
Treatment (leukapheresis, external beam radiation, CAR-T)
Patients undergo leukapheresis per standard of care, undergo external beam radiation therapy, and undergo CAR T-cell infusion per standard of care on study. Patients undergo PET/CT throughout the study and may undergo MRI during screening. Patients also undergo blood sample collection throughout the study.
干预措施: Leukapheresis (Procedure)
Treatment (leukapheresis, external beam radiation, CAR-T)
Patients undergo leukapheresis per standard of care, undergo external beam radiation therapy, and undergo CAR T-cell infusion per standard of care on study. Patients undergo PET/CT throughout the study and may undergo MRI during screening. Patients also undergo blood sample collection throughout the study.
干预措施: Magnetic Resonance Imaging (Procedure)
Treatment (leukapheresis, external beam radiation, CAR-T)
Patients undergo leukapheresis per standard of care, undergo external beam radiation therapy, and undergo CAR T-cell infusion per standard of care on study. Patients undergo PET/CT throughout the study and may undergo MRI during screening. Patients also undergo blood sample collection throughout the study.
干预措施: Positron Emission Tomography (Procedure)
结局指标
主要结局
Proportion of participants completing planned radiation therapy
时间窗: From the first fraction of radiation until approximately 1 month after infusion of chimeric antigen receptor (CAR) T-cell therapy
Will be assessed by the proportion of participants completing planned radiation therapy without any grade 3 or higher radiation-attributable (possibly, probably, or definitely) adverse events (AEs), along with its associated 95% Clopper Pearson exact binomial confidence interval (CI). All participants who start protocol radiation therapy are evaluable.
次要结局
- Complete response rate(Up to 1 year)
- Local control(Time from CAR T-cell infusion to time of disease relapse/progression within the radiation field, assessed up to 1 year)
- Distant control(Time from CAR T-cell infusion to time of disease relapse/progression outside the radiation field, assessed up to 1 year)
- Incidence of AEs(Up to 1 year)
- Objective response rate(Up to 1 year)
- Progression free survival(Time from CAR T-cell infusion to time of disease relapse/progression or death due to any cause, whichever occurs first, assessed up to 1 year)
- Overall survival(Time from CAR T-cell infusion to time of death due to any cause, assessed up to 1 year)