Adaptive Bridging RT in R/R B-cell Lymphoma (Pre-CAR T)

Study Overview
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Brief Summary
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Participants are invited to take part in this research study because they have relapsed (cancer has come back) or refractory (cancer has not responded to treatment) B-cell Lymphoma and will be undergoing CAR T-cell Therapy. This research is being done to see if a new radiation therapy administration schedule will positively impact the logistics, time, cost, and side effects of radiation therapy. In this research study, participants will receive radiation therapy once weekly for 5 weeks. This is a novel administration schedule and we're looking to see how this schedule impacts side effects participants may experience, the time spent receiving radiation therapy, how much radiation therapy participants can receive, and how effective this new schedule is.

Detailed Description
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This is a feasibility/pilot study of 5 Gy adaptive radiation administered every 5 business days (1 week apart) for 5 weeks prior to standard of care CAR T-cell therapy infusion. Approximately 10 participants with Relapsed/Refractory B-cell Lymphoma will take part in this research study. The primary objective is to assess the feasibility of once weekly radiation therapy for 5 weeks.

Official Title
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5-5-5 Adaptive Bridging Radiation Therapy (ABRT) for Relapsed/Refractory B-cell Lymphoma Prior to CAR T-cell Therapy

Conditions
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Mantle Cell Lymphoma, Lymphoma, B-Cell, Relapsed Cancer, Refractory Lymphoma, Diffuse Large B Cell Lymphoma, Mediastinal Large B-cell Lymphoma, High-grade B-cell Lymphoma, Follicular Lymphoma

Intervention / Treatment
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* Radiation: Adaptive Bridging Radiation Therapy (ABRT)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of relapsed or refractory B-cell lymphoma (including, but not limited to diffuse large B-cell lymphoma (DLBCL) not otherwise specified, primary mediastinal large B-cell lymphoma, high grade B-cell lymphoma, DLBCL arising from follicular lymphoma, follicular, and mantle cell lymphoma) Being planned to undergo CAR T-cell therapy (patients can be enrolled prior to apheresis) At least 1 measurable lesion according to the Lugano criteria35. Lesions that have been previously irradiated will be considered measurable only if progression has been documented following completion of radiation therapy. Re-irradiation is allowed for these patients. More than 1 lesion can be targeted as per radiation oncologist discretion. If disease is palpable, physical examination alone may be sufficient measurement for disease if a recent PET/CT or CT is not available as a radiologic measurement of the disease can be obtained during CT simulation. Age ≥ 18 years Eastern Cooperative Oncology Group (ECOG) performance status of less than or equal to 3. Ability to understand and the willingness to sign a written informed consent document Exclusion Criteria: Any medical condition likely to interfere with assessment of safety or efficacy of RT. CNS-only disease as the site for bridging radiation therapy (which cannot be reliably evaluated on CT). Patients with CNS disease with extra-axial involvement that can be evaluated on CT remain eligible. Patient likely unable to lay supine for 45 minutes Women of child-bearing potential who are pregnant because of the potentially dangerous effects of the preparative chemotherapy on the fetus or infant. Females who have undergone surgical sterilization or who have been postmenopausal for at least 2 years are not considered to be of childbearing potential In the investigator's judgment, the subject is unlikely to complete all protocol-required study visits or procedures, including follow-up visits, or comply with the study requirements for participation.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 5-5-5 Adaptive Bridging Radiation Therapy (ABRT)<br>5 Gy of adaptive radiation delivered every 5 business days (1 week apart) for up to 5 weeks prior to CAR T-cell therapy infusion | Radiation: Adaptive Bridging Radiation Therapy (ABRT)<br>* Radiation Therapy<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Feasibility | Feasibility is being measured based on the percentage of patients being able to undergo ABRT | 20 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adverse Events | Adverse events will be classified and graded according to the CTCAE v.5.0. | 20 months | 
| Objective Response Rate (ORR) | ORR is being measured using the day 30 and day 90 PET scans and assessed by Lugano lymphoma response criteria | 15 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Relapsed/Refractory B-cell Lymphoma