Low Dose Radiation as Bridging Therapy in Relapsed B-Cell Non-Hodgkin Lymphoma

Trial Title: Low Dose Radiation as Bridging Therapy in Relapsed B-Cell Non-Hodgkin Lymphoma

NCT ID: NCT05621096

Condition: DLBCL - Diffuse Large B Cell Lymphoma
High-grade B-cell Lymphoma
Follicular Lymphoma
Mediastinal Large B-cell Lymphoma
Indolent B-Cell Non-Hodgkin Lymphoma
Relapsed Non-Hodgkin Lymphoma
Refractory Non-Hodgkin Lymphoma

Conditions: Official terms:
Lymphoma
Lymphoma, Non-Hodgkin
Lymphoma, B-Cell
Lymphoma, Large B-Cell, Diffuse

Study type: Interventional

Study phase: Phase 1

Overall status: Recruiting

Study design:

Allocation: N/A

Intervention model: Single Group Assignment

Primary purpose: Treatment

Masking: None (Open Label)

Intervention:

Intervention type: Radiation
Intervention name: Bridging radiation therapy
Description: Days -20 to -7: Patients will receive 2 fractions of 2 gray (Gy) for a total of 4 Gy received.
Arm group label: Single arm

Intervention type: Biological
Intervention name: Liso-cel
Description: Day 0: Patients will receive an infusion of liso-cel CAR T-cell product. Prior to the liso-cell infusion (Days -5 to -3), patients will receive lymphodepleting chemotherapy using fludarabine 30mg/m2 and cyclophosphamide 300mg/m2 per institutional standard procedures.
Arm group label: Single arm

Other name: Chimeric antigen receptor (CAR) T-cell product

Intervention type: Radiation
Intervention name: Post-infusion radiation
Description: Days 30 to 80: Patients eligible for post-infusion radiation will receive a total dose of up to 32 Gy.
Arm group label: Single arm

Summary: 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

Detailed description: 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.

Criteria for eligibility:
Criteria:
Inclusion Criteria: 1. 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 2. Presence of disease on imaging including at least one disease site safe for radiation as determined by treating radiation oncologist 3. Willingness to participate in clinical trial and provide informed consent 4. 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 5. Eastern Cooperative Oncology Group (ECOG) performance status of 0-2 6. Age 19 years or older, there is no upper limit to the age Exclusion Criteria: 1. Subject is unsafe for radiation therapy as determined by investigator and/or radiation oncologist 2. Diagnosis is primary central nervous system (CNS) lymphoma (secondary CNS lymphoma with additional systemic site is allowed) 3. Requirement for concurrent high dose methotrexate 4. 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. 5. Pregnant or nursing women 6. Uncontrolled medical, psychological, familial, sociological, or geographical conditions that do not permit compliance with the protocol, as determined by investigator 7. Unwillingness to follow procedures required in the protocol 8. Inadequate organ or hematologic conditions that prohibit the use of lymphodepleting chemotherapy 9. Use of lymphoma-directed therapy within 14 days of T-cell pheresis

Gender: All

Minimum age: 19 Years

Maximum age: N/A

Healthy volunteers: No

Locations:

Facility:
Name: University of Nebraska Medical Center

Address:
City: Omaha
Zip: 68198
Country: United States

Status: Recruiting

Contact:
Last name: Maribeth A Hohenstain, RN

Phone: 402-559-9053
Email: mahohens@unmc.edu

Start date: March 21, 2023

Completion date: July 2025

Lead sponsor:
Agency: University of Nebraska
Agency class: Other

Collaborator:
Agency: Bristol-Myers Squibb
Agency class: Industry

Source: University of Nebraska

Record processing date: ClinicalTrials.gov processed this data on November 12, 2024

Source: ClinicalTrials.gov page: https://clinicaltrials.gov/ct2/show/NCT05621096