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

NCT05621096 | Active Not Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: 0770-22-FB
• Study Type: interventional
• Target: 33
• Locations: 1 country
• Sites: 1

Brief 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

Conditions

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

Outcome Measures

Primary Outcomes (1)

• Feasibility of the intervention in the proposed study population

  The percentage of subjects who receive a chimeric antigen receptor (CAR) T-cell infusion after receiving bridging radiation therapy. A one-sided Binomial test will be conducted to assess whether acceptable percentage (\>70% vs \<70%) of patients receive CAR T-cell perfusion after undergoing the radiation therapy.

  Up to 90 days

Secondary Outcomes (8)

• Incidence of treatment-emergent adverse events to assess the safety of the proposed intervention

  Up to 120 days

• Evaluate the response to the study intervention of radiation and CAR T-cell therapy

  Up to 190 days

• Evaluate progression-free survival (PFS) following the study intervention

  Measured from first day of apheresis to death or disease progression, whichever comes first, up to two years

• Evaluate duration of response (DOR) following CAR T-cell therapy

  Up to 2 years

• Evaluate overall survival (OS) following study intervention

  Up to 2 years

Other Outcomes (3)

• Prospectively bank serum and peripheral blood mononuclear cells (PBMCs)

  Up to 270 days

• Prospectively bank stool samples for future gut microbiome exploratory analyses

  Up to 270 days

• Evaluate in-field versus out-of-field disease progression following radiation therapy

  Up to 270 days

Study Arms (1)

Single arm

EXPERIMENTAL

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.

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

Interventions

Bridging radiation therapy RADIATION

Days -20 to -7: Patients will receive 2 fractions of 2 gray (Gy) for a total of 4 Gy received.

Single arm

Liso-cel BIOLOGICAL

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.

Also known as: Chimeric antigen receptor (CAR) T-cell product

Single arm

Post-infusion radiation RADIATION

Days 30 to 80: Patients eligible for post-infusion radiation will receive a total dose of up to 32 Gy.

Single arm

Eligibility Criteria

• Age: 19 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• Presence of disease on imaging including at least one disease site safe for radiation as determined by treating radiation oncologist
• Willingness to participate in clinical trial and provide informed consent
• 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
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
• Age 19 years or older, there is no upper limit to the age

You may not qualify if:

• Subject is unsafe for radiation therapy as determined by investigator and/or radiation oncologist
• Diagnosis is primary central nervous system (CNS) lymphoma (secondary CNS lymphoma with additional systemic site is allowed)
• Requirement for concurrent high dose methotrexate
• 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.
• Pregnant or nursing women
• Uncontrolled medical, psychological, familial, sociological, or geographical conditions that do not permit compliance with the protocol, as determined by investigator
• Unwillingness to follow procedures required in the protocol
• Inadequate organ or hematologic conditions that prohibit the use of lymphodepleting chemotherapy
• Use of lymphoma-directed therapy within 14 days of T-cell pheresis

Sponsors & Collaborators

• University of Nebraska: lead
• Bristol-Myers Squibb: collaborator

Study Sites (1)

University of Nebraska Medical Center

Omaha, Nebraska, 68198, United States

Location

MeSH Terms

Conditions

Dendritic Cell Sarcoma, Interdigitating; Lymphoma, Follicular; Lymphoma, Non-Hodgkin

Interventions

Receptors, Chimeric Antigen; Automobiles

Condition Hierarchy (Ancestors)

Histiocytic Disorders, Malignant; Neoplasms by Histologic Type; Neoplasms; Histiocytosis; Lymphatic Diseases; Hemic and Lymphatic Diseases; Lymphoma; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Receptors, Artificial; Receptors, Cell Surface; Membrane Proteins; Proteins; Amino Acids, Peptides, and Proteins; Receptors, Antigen, T-Cell; Receptors, Antigen; Receptors, Immunologic; Receptors, Cytoplasmic and Nuclear; Motor Vehicles; Transportation; Technology, Industry, and Agriculture

Study Officials

• Christopher R D'Angelo, MD

  University of Nebraska

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 27, 2022
• First Posted: November 17, 2022
• Study Start: March 21, 2023
• Primary Completion: January 20, 2025
• Study Completion (Estimated): September 1, 2027
• Last Updated: September 25, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)