Hyperfractionated Dual Equivalent Fractionated (HyDEF) Bridging Radiation Therapy in Patients With Relapsed or Refractory Diffuse Large B-Cell Lymphoma Undergoing T-Cell Redirection Therapy
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 10
- 试验地点
- 2
- 主要终点
- Feasibility Assessment of Dual Fractionated Radiation Therapy Enrollment and Treatment
研究概览
简要总结
This study evaluates the feasibility and safety of bridging radiation therapy, including a novel method for comparing the effectiveness of hypofractionated versus hyperfractionated radiation therapy in participants with relapsed/refractory diffuse large B-cell lymphoma (R/R DLBCL) undergoing T-cell redirection therapies (CAR T-cell therapy or bispecific antibodies).
详细描述
The purpose of this study is to assess the feasibility and safety of bridging radiation, including a novel method to study the relative effectiveness of hypo- vs. hyperfractionated therapy (i.e., once daily vs. twice daily treatment) in patients with R/R DLBCL undergoing T-cell redirection therapies. This trial will serve as proof-of-concept, feasibility, and safety for a novel dual fractionation trial design, treating the same tumor with two fractionation schedules, paving the way for future radiotherapy trial designs and direct comparison of the efficacy of once vs. twice daily treatment. Correlative studies of immune exhaustion will evaluate the mechanistic underpinnings between radiotherapy and the immune environment. Finally, with the use of RefleXion BGRT, we will collect PET imaging data to provide the basis for this emerging method for administering bridging radiation in 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
- 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
- •Provision of signed and dated informed consent form.
- •Stated willingness to comply with all study procedures and availability for the duration of the study.
- •Adult aged 18 years or older.
- •Histologically confirmed diagnosis of R/R DLBCL with plan for CAR T or BsAb therapy at Yale New Haven Hospital.
- •ECOG performance status 0 to
- •Ability to present for once or twice daily (M-F) fractionated radiation therapy, without contraindications for radiotherapy as determined by the treating radiation oncologist.
- •Women of childbearing potential must have a negative serum or urine pregnancy test at screening and at time of radiation treatment planning, per standard of care and departmental standard operating procedure. Participants must agree to take appropriate precautions to avoid pregnancy (with at least 99% certainty) from screening through safety follow-up. Permitted methods that are at least 99% effective in preventing pregnancy should be communicated to the participants and their understanding confirmed.
排除标准
- •Participants who meet any of the following criteria will be disqualified from entering the study:
- •Participants who are pregnant or currently breastfeeding.
- •a. Females who have undergone surgical sterilization or who have been postmenopausal for at least 12 months are not considered to be of childbearing potential.
- •Participants with history of prior radiation exposure for research purposes within the past year, such that participation in this study would place them over the FDA limits for annual radiation exposure.
- •Participants who are unable to safely receive FDG PET tracer.
- •Any condition that would, in the investigator's judgment, interfere with full participation in the study and attending required study visits (if outpatient); pose a significant risk to the participant; or interfere with interpretation of study data.
- •Participants who would not be anticipated to derive any clinical benefit from bridging radiotherapy, are unable to participate in twice daily radiotherapy, or have clinical contraindications to radiation therapy per treating investigator.
研究组 & 干预措施
Dual Hyperfractionated Radiation Therapy
All patients enrolled will receive radiation as a bridge to subsequent planned T Cell Directed therapy. The same tumor will be treated daily, with one area receiving once daily and the other receiving twice daily radiation therapy.
干预措施: Bridging Radiation Therapy (Other)
结局指标
主要结局
Feasibility Assessment of Dual Fractionated Radiation Therapy Enrollment and Treatment
时间窗: Approximately one year
The feasibility of the clinical trial's intervention will be assessed based on the ability to enroll and treat at least 5 participants with the proposed dual fractionated radiation therapy, where one half of the tumor receives once daily radiation and the other half receives twice daily radiation. This number is estimated to be sufficient to determine the feasibility of treating a single tumor with different radiation schedules.
Safety analysis of the proposed dual fractionated radiation therapy schema
时间窗: Throughout the study, approximately two years
Safety will be assessed by analyzing the incidence of severe (grade ≥ 3) acute toxicities. The therapy will be considered safe if fewer than 30% of study participants receiving dual fractionated radiation therapy experience these toxicities.
Feasibility Assessment of Bridging Radiation Therapy
时间窗: Approximately one year
Feasibility will be assessed by the proportion of enrolled participants who are successfully treated according to the proposed bridging radiation therapy schema.
Safety analysis of Bridging Radiation Therapy
时间窗: Throughout the study, approximately two years
Safety will be assessed by analyzing the incidence of severe (grade ≥ 3) acute toxicities. The therapy will be considered safe if fewer than 30% of study participants receiving dual fractionated radiation therapy experience these toxicities.
Dynamics of Circulating Tumor DNA (ctDNA) as a Marker of Minimal Residual Disease
时间窗: Baseline (0-7 days prior to radiation therapy) to post-radiation therapy (prior to initiation of lymphodepleting chemotherapy)
Changes in serum ctDNA levels will be measured at baseline and after radiation therapy (RT) to characterize ctDNA dynamics and assess minimal residual disease. Comparisons will focus on quantitative shifts in ctDNA burden in relation to treatment response.
Biomarkers of Hypoxia and Immune Exhaustion in Relation to Treatment Response
时间窗: Baseline (0-7 days prior to radiation therapy) to post-radiation therapy (prior to initiation of lymphodepleting chemotherapy).
Serum biomarkers associated with tumor hypoxia and immune exhaustion will be evaluated at baseline and after radiation therapy (RT). Changes in these biomarkers will be compared to characterize biological responses to treatment and their relationship to clinical outcomes.
次要结局
未报告次要终点