Clinical trial NCT05621096: Low Dose Radiation as Bridging Therapy in Relapsed B-Cell Non-Hodgkin Lymphoma
Official title: Feasibility of Low Dose Radiation as Bridging Therapy for Lisocabtagene Maraleucel in Relapsed B-Cell Non-Hodgkin Lymphoma
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
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
Lead sponsor: University of Nebraska
Sponsor class: OTHER
Collaborators: name: Bristol-Myers Squibb
First posted: 2022-11-17
Enrollment: 33
Sex: ALL
Minimum age (years): 19
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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

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.

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

Primary outcomes:
measure: Feasibility of the intervention in the proposed study population
timeFrame: Up to 90 days
Secondary outcomes:
measure: Incidence of treatment-emergent adverse events to assess the safety of the proposed intervention
timeFrame: Up to 120 days
measure: Evaluate the response to the study intervention of radiation and CAR T-cell therapy
timeFrame: Up to 190 days
measure: Evaluate progression-free survival (PFS) following the study intervention
timeFrame: Measured from first day of apheresis to death or disease progression, whichever comes first, up to two years
measure: Evaluate duration of response (DOR) following CAR T-cell therapy
timeFrame: Up to 2 years
measure: Evaluate overall survival (OS) following study intervention
timeFrame: Up to 2 years
measure: Evaluate the rate of prolonged cytopenias following the intervention
timeFrame: Up to 190 days
measure: Monitor overall safety and toxicity of the intervention
timeFrame: Up to 270 days
measure: Monitor Cytokine release syndrome (CRS) and Immune effector cell-associated neurotoxicity syndrome (ICANS) toxicity events
timeFrame: Up to 270 days
Other outcomes:
measure: Prospectively bank serum and peripheral blood mononuclear cells (PBMCs)
timeFrame: Up to 270 days
measure: Prospectively bank stool samples for future gut microbiome exploratory analyses
timeFrame: Up to 270 days
measure: Evaluate in-field versus out-of-field disease progression following radiation therapy
timeFrame: Up to 270 days
Locations:
city: Omaha
country: United States
facility: University of Nebraska Medical Center
state: Nebraska
Study officials:
affiliation: University of Nebraska
name: Christopher R D'Angelo, MD
role: PRINCIPAL_INVESTIGATOR
References: