Radiation, Oral Vancomycin, and CAR-T for B-Cell Lymphomas

A Pilot Trial of Bridging Radiation Therapy With Oral Vancomycin for Patients With B-cell Lymphomas Undergoing CAR-T Therapy

This clinical trial assesses whether it is feasible to use radiation therapy with vancomycin prior to CAR T-cell therapy for patients with large B-cell lymphomas

Study Overview

• Status: Recruiting
• Conditions: Diffuse Large B Cell Lymphoma Refractory; Large B Cell Lymphoma; Diffuse Large B Cell Lymphoma Relapsed; Non Hodgkin Lymphoma (NHL); Diffuse Large B Cell Lymphoma (DLBCL)
• Intervention / Treatment: Radiation: Radiation Therapy; Drug: Vancomycin 125mg; Biological: CAR-T

• Study Type: Interventional
• Enrollment (Estimated): 14
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Rachel Lundberg, PA-C; Phone Number: 215-615-5858; Email: rachel.lundberg@pennmedicine.upenn.edu
• Study Contact Backup: Name: Megan Jones, MPH; Email: megan.jones1@pennmedicine.upenn.edu

Study Locations

• United States
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Recruiting
      • Abramson Cancer Center, University of Pennsylvania
      • Contact: Brittany Koch; Phone Number: 215-615-5858; Email: brittany.koch@pennmedicine.upenn.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Male or female subject aged ≥ 18 years.
• Pathologically confirmed B-cell lymphoma patients intended for standard of care CAR-T
• ECOG Performance Status ≤ 2.
• Subjects must be clinically eligible to receive standard of care anti-CD19 CAR-T
• Subjects must have at least one site of disease amenable to radiation, with the ability to deliver radiation to at least 50% of involved sites
• Subjects must have at least one site of measurable disease based on CT or FDG PET
• Subjects must not be anticipated to require additional therapy beyond bridging radiation listed in this protocol for control of their lymphoma
• For female subjects: Negative pregnancy test or evidence of post-menopausal status. The post-menopausal status will be defined as having been amenorrheic for 12 months without an alternative medical cause.

The following age-specific requirements apply:

Women < 50 years of age: amenorrheic for ≥ 12 months following cessation of exogenous hormonal treatments; and luteinizing hormone and follicle-stimulating hormone levels in the post-menopausal range for the institution; or Underwent surgical sterilization (bilateral oophorectomy or hysterectomy).

Women ≥ 50 years of age: amenorrheic for 12 months or more following cessation of all exogenous hormonal treatments; or had radiation-induced menopause with last menses >1 year ago; or had chemotherapy-induced menopause with last menses >1 year ago; or underwent surgical sterilization (bilateral oophorectomy, bilateral salpingectomy, or hysterectomy).

• Able to provide informed consent and willing to sign an approved consent form that conforms to federal and institutional guidelines.
• Stated willingness to comply with all study procedures and availability for the duration of the study

Exclusion Criteria:

• Unable to take oral vancomycin for any reason, including: Allergy or Inability to swallow drug
• Known history of vancomycin resistant enterococcus (VRE)
• Contraindications to radiation therapy, including scleroderma, systemic lupus erythematosus, Crohn disease, ulcerative colitis, or idiopathic pulmonary fibrosis
• History of radiation pneumonitis or other grade 4 radiation-related adverse event
• Prior or concurrent malignancy whose natural history or treatment which has the potential to interfere with the safety or efficacy assessment of the radiation therapy are eligible for this trial.
• Severe, uncontrolled, significant intercurrent or recent illness that would exclude them from being a candidate for standard-of-care CART therapy.
• Known uncontrolled HIV infection with a detectable viral load at the time of screening. Note: Patients on effective antiretroviral therapy or who will plan on going on antiretroviral therapy at the time of screening are eligible for this trial. HIV testing is not required for eligibility.
• Active infection that required the use of antibiotics within 4 weeks prior to registration
• Any other condition that would, in the investigator's judgment, contraindicate the subject's participation in the clinical study due to safety concerns or compliance with clinical study procedures

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: vancomycin, radiation therapy, and CAR-T; vancomycin 125 mg orally four times per day, followed by standard of care radiation and standard of care CD19 CAR T-cells	Radiation: Radiation Therapy; Radiation Therapy; Drug: Vancomycin 125mg; oral; Biological: CAR-T; standard of care anti-CD19 CAR-T

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cytokine release syndrome	rate of CART-related cytokine release syndrome	date of CAR-T infusion to 28 days after infusion
Severe adverse events	rate of grade ≥ 3 adverse events attributed to vancomycin or radiation	CAR-T infusion to 28 days after infusion
VRE	rate of vancomycin-related enterococcus	start of vancomycin to day 28 after CAR-T infusion
Adverse Events	rate of adverse events (AEs) and serious adverse events (SAEs)	start of vancomycin until day 28 after CAR-T infusion

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Best overall response rate	percentage of all patients who receive CAR-T and have complete response and partial response after CAR-T	CAR-T infusion to 12 months after CAR-T infusion
Complete response rate	percentage of patients treated with CAR-T who have a complete response	CAR-T infusion to 12 months after CAR-T infusion

Collaborators and Investigators

• Sponsor: Abramson Cancer Center at Penn Medicine
• Collaborators: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Elise Chong, MD, Abramson Cancer Center, University of Pennsylvania

Study record dates

Study Major Dates

• Study Start (Actual): May 29, 2026
• Primary Completion (Estimated): January 1, 2029
• Study Completion (Estimated): January 1, 2029

Study Registration Dates

• First Submitted: March 3, 2026
• First Submitted That Met QC Criteria: March 13, 2026
• First Posted (Actual): March 18, 2026

Study Record Updates

• Last Update Posted (Actual): July 1, 2026
• Last Update Submitted That Met QC Criteria: June 29, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Keywords: DLBCL; NHL; large B cell lymphoma; non-hodgkin lymphoma; diffuse large B cell lymphoma
• Additional Relevant MeSH Terms: Neoplasms; Immune System Diseases; Neoplasms by Histologic Type; Lymphatic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Lymphoma, B-Cell; Lymphoma; Hemic and Lymphatic Diseases; Lymphoma, Large B-Cell, Diffuse; Lymphoma, Non-Hodgkin; Peptides; Amino Acids, Peptides, and Proteins; Therapeutics; Carbohydrates; Glycoconjugates; Glycopeptides; Vancomycin; Radiotherapy
• Other Study ID Numbers: UPCC 69425; 858761 (Other Identifier: University of Pennsylvania Institutional Review Board)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes