A Study of Radiation Therapy Before CAR T Cell Therapy for People With B Cell Lymphoma

NCT05574114 | Active Not Recruiting Phase 1 FDA Drug

• 1 other identifier: 22-217
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 7

Brief Summary

The purpose of this study is to test whether radiation therapy given before standard CAR T cell therapy is a safe and effective treatment for people with relapsed and refractory B cell lymphoma. The researchers will also study whether radiation therapy used in this study is a practical treatment option before standard CAR T cell therapy.

Conditions

Non-Hodgkin Lymphoma; Non-Hodgkin's Lymphoma, Relapsed; Non-Hodgkin's Lymphoma Refractory

Keywords

Split-Course Bridging Radiotherapy; CD19 CAR T-Cell Therapies; 22-217

Outcome Measures

Primary Outcomes (1)

• number of patients who develop unanticipated severe toxicity events

  Reporting of toxicities will be based on Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 except for CRS and ICANS which will be evaluated using ASTCT Consensus grading.

  1 year

Secondary Outcomes (1)

• number of patients who are able to receive comprehensive BRT prior to infusion of CAR T cells

  2 years

Study Arms (1)

Radiation Therapy Before CAR T Cell Therapy

EXPERIMENTAL

For the purposes of this protocol, day 0 will be considered the date of planned CAR T infusion. BRT Part I (intervention is 9 fractions of 3 Gy to a total dose of 27 Gy). Post-BRT Phase I re- evaluation period: Following delivery of the first 9- fractions of BRT, patients will have a period for recovery, and undergo protocol-mandated reassessment (e.g., PET scan and biopsy). Patients will receive standard of care lymphodepleting chemotherapy. Substitutions to the lymphodepleting regimen will be permitted at the discretion of the treating investigator. Day -2: BRT Part II (intervention is one fraction 3 Gy to receive a total dose of 3 Gy). Day -1: No protocol scheduled treatment interventions. Day 0: Subject will receive standard of care infusion of a manufactured commercial CAR T-cell product, as an inpatient or outpatient, at the discretion of the treating investigator.

Radiation: Bridging radiotherapy (BRT); Drug: Conditioning chemotherapy; Biological: CAR T-cell product

Interventions

Bridging radiotherapy (BRT) RADIATION

RT Part I. The target will be to complete the 9th fraction of radiotherapy (i.e., total of 27Gy) between days -12 and -8 Day -2: BRT Part II (intervention is one fraction 3 Gy to receive a total dose of 3 Gy).

Radiation Therapy Before CAR T Cell Therapy

Conditioning chemotherapy DRUG

Day -5 to -3: Patients will receive standard of care lymphodepleting chemotherapy

Radiation Therapy Before CAR T Cell Therapy

CAR T-cell product BIOLOGICAL

Day 0: Subject will receive standard of care infusion of a manufactured commercial CAR T-cell product.

Radiation Therapy Before CAR T Cell Therapy

Eligibility Criteria

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

You may qualify if:

• Histologically confirmed, relapsed or refractory non-Hodgkin lymphoma patients eligible for a CAR T-cell therapy, such as DLBCL (including transformed follicular lymphoma), high grade B-cell lymphoma, primary mediastinal B-cell lymphoma, and follicular lymphoma of any grade
• Patient is approved for, and planned to receive, anyone of the three commercially available anti-CD19 CAR T-cell products (axicabtagene ciloleucel, maraleucel or tisagenlecleucel)
• Patient has at least one site of disease with avidity greater than liver on a screening FDG-PET scan performed within 2 months of RT simulation. Measurable disease is not required.
• Active secondary central nervous system (CNS) lymphoma is allowed
• Age 18 or older
• ECOG status ≤2
• Female subjects of childbearing potential should be willing to use 2 methods of birth control or be surgically sterile or abstain from sexual activity for the course of the study through 120 days after the last dose of radiotherapy. Subjects of childbearing potential are those who have not been surgically sterilized or have not been free from menses for \> 1 year. Note: Abstinence is acceptable if this is the established and preferred contraception for the subject
• Male subjects should agree to use an adequate method of contraception starting with the first dose of study therapy through 120 days after the last dose of study therapy. Note: Abstinence is acceptable if this is the established and preferred contraception for the subject

You may not qualify if:

• Subject has received prior RT to any site(s) planned for bridging therapy such that the composite dose considering the protocol-mandated BRT would exceed normal tissue tolerances in the determination of the investigator.
• The treating investigator deems that it would be impossible to comprehensively treat the patient with radiotherapy given concerns about feasibility or potential toxicities
• Current or planned pregnancy
• Known additional malignancy that is progressing or requires any treatment other than active surveillance or hormonal therapy. Exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or in situ cervical cancer that has undergone potentially curative therapy.
• Subject has any significant medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from participating in the study based on the investigator´s judgment

Sponsors & Collaborators

• Memorial Sloan Kettering Cancer Center: lead

Study Sites (7)

Memorial Sloan Kettering Basking Ridge (Limited Protocol Activities)

Basking Ridge, New Jersey, 07920, United States

Location

Memorial Sloan Kettering Monmouth (Limited Protocol Activities)

Middletown, New Jersey, 07748, United States

Location

Memorial Sloan Kettering Bergen (Limited Protocol Activities)

Montvale, New Jersey, 07645, United States

Location

Memorial Sloan Kettering Suffolk - Commack (Limited Protocol Activities)

Commack, New York, 11725, United States

Location

Memorial Sloan Kettering Westchester (Limited Protocol Activities)

Harrison, New York, 10604, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

Memorial Sloan Kettering Nassau (Limited Protocol Activities)

Uniondale, New York, 11553, United States

Location

Related Links

• Memorial Sloan Kettering Cancer Center

MeSH Terms

Conditions

Lymphoma, Non-Hodgkin; Recurrence

Condition Hierarchy (Ancestors)

Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Lia Palomba, MD

  Memorial Sloan Kettering Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

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

Model Details: This is a single arm, Phase I trial designed to describe the feasibility and safety of a standardized, stage-adapted, split-course BRT regimen prior to standard of care, commercial anti-CD19 CAR T-cell therapy. This design incorporates a small early safety cohort with the option for a potential patient expansion cohort.

Study Record Dates

• First Submitted: October 6, 2022
• First Posted: October 10, 2022
• Study Start: October 5, 2022
• Primary Completion (Estimated): October 1, 2026
• Study Completion (Estimated): October 1, 2026
• Last Updated: November 4, 2025

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will share

Locations

US (7)