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

University of Nebraska

Status and phase: Active, not recruiting; Phase 1

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

Treatments: Radiation: Post-infusion radiation; Biological: Liso-cel; Radiation: Bridging radiation therapy

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT05621096

0770-22-FB

Details and patient eligibility

About

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

Full 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.

Enrollment: 33 estimated patients

Sex: All

Ages: 19+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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33 participants in 1 patient group

Single arm

Experimental group

Description:

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.

Treatment:

Radiation: Bridging radiation therapy

Biological: Liso-cel

Radiation: Post-infusion radiation