Adaptive Bridging RT in R/R B-cell Lymphoma (Pre-CAR T)

5-5-5 Adaptive Bridging Radiation Therapy (ABRT) for Relapsed/Refractory B-cell Lymphoma Prior to CAR T-cell Therapy

Participants are invited to take part in this research study because they have relapsed (cancer has come back) or refractory (cancer has not responded to treatment) B-cell Lymphoma and will be undergoing CAR T-cell Therapy.

This research is being done to see if a new radiation therapy administration schedule will positively impact the logistics, time, cost, and side effects of radiation therapy.

In this research study, participants will receive radiation therapy once weekly for 5 weeks. This is a novel administration schedule and we're looking to see how this schedule impacts side effects participants may experience, the time spent receiving radiation therapy, how much radiation therapy participants can receive, and how effective this new schedule is.

Study Overview

• Status: Recruiting
• Conditions: Lymphoma, B-Cell; Follicular Lymphoma; Mantle Cell Lymphoma; Diffuse Large B Cell Lymphoma; Refractory Lymphoma; High-grade B-cell Lymphoma; Relapsed Cancer; Mediastinal Large B-cell Lymphoma
• Intervention / Treatment: Radiation: Adaptive Bridging Radiation Therapy (ABRT)

Detailed Description

This is a feasibility/pilot study of 5 Gy adaptive radiation administered every 5 business days (1 week apart) for 5 weeks prior to standard of care CAR T-cell therapy infusion. Approximately 10 participants with Relapsed/Refractory B-cell Lymphoma will take part in this research study. The primary objective is to assess the feasibility of once weekly radiation therapy for 5 weeks.

• Study Type: Interventional
• Enrollment (Estimated): 10
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Chirayu Patel, MD; Phone Number: (617) 724-2430; Email: cpatel@mgh.harvard.edu

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Recruiting
      • Massachusetts General Hospital
      • Contact: Chirayu G Patel, MD MPH
    • Boston, Massachusetts, United States, 02215
      • Recruiting
      • Dana-Farber Cancer Institute
      • Contact: Andrea Ng, MD; Phone Number: 617-394-2668; Email: andrea_ng@dfci.harvard.edu
      • Principal Investigator: Andrea Ng, MD

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Diagnosis of relapsed or refractory B-cell lymphoma (including, but not limited to diffuse large B-cell lymphoma (DLBCL) not otherwise specified, primary mediastinal large B-cell lymphoma, high grade B-cell lymphoma, DLBCL arising from follicular lymphoma, follicular, and mantle cell lymphoma)
• Being planned to undergo CAR T-cell therapy (patients can be enrolled prior to apheresis)
• At least 1 measurable lesion according to the Lugano criteria35. Lesions that have been previously irradiated will be considered measurable only if progression has been documented following completion of radiation therapy. Re-irradiation is allowed for these patients. More than 1 lesion can be targeted as per radiation oncologist discretion. If disease is palpable, physical examination alone may be sufficient measurement for disease if a recent PET/CT or CT is not available as a radiologic measurement of the disease can be obtained during CT simulation.
• Age ≥ 18 years
• Eastern Cooperative Oncology Group (ECOG) performance status of less than or equal to 3.
• Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria:

• Any medical condition likely to interfere with assessment of safety or efficacy of RT.
• CNS-only disease as the site for bridging radiation therapy (which cannot be reliably evaluated on CT). Patients with CNS disease with extra-axial involvement that can be evaluated on CT remain eligible.
• Patient likely unable to lay supine for 45 minutes
• Women of child-bearing potential who are pregnant because of the potentially dangerous effects of the preparative chemotherapy on the fetus or infant. Females who have undergone surgical sterilization or who have been postmenopausal for at least 2 years are not considered to be of childbearing potential
• In the investigator's judgment, the subject is unlikely to complete all protocol-required study visits or procedures, including follow-up visits, or comply with the study requirements for participation.

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: 5-5-5 Adaptive Bridging Radiation Therapy (ABRT); 5 Gy of adaptive radiation delivered every 5 business days (1 week apart) for up to 5 weeks prior to CAR T-cell therapy infusion	Radiation: Adaptive Bridging Radiation Therapy (ABRT); Radiation Therapy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Feasibility: Percent of patients able to undergo ABRT	Feasibility is being measured based on the percentage of patients being able to undergo ABRT	20 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adverse Events	Adverse events will be classified and graded according to the CTCAE v.5.0.	20 months
Objective Response Rate (ORR)	ORR is being measured using the day 30 and day 90 PET scans and assessed by Lugano lymphoma response criteria	15 months

Collaborators and Investigators

• Sponsor: Massachusetts General Hospital
• Collaborators: Varian Medical Systems
• Investigators: Principal Investigator: Chirayu Patel, MD, Massachusetts General Hospital

Study record dates

Study Major Dates

• Study Start (Actual): January 14, 2024
• Primary Completion (Estimated): July 1, 2024
• Study Completion (Estimated): September 1, 2024

Study Registration Dates

• First Submitted: August 16, 2023
• First Submitted That Met QC Criteria: August 16, 2023
• First Posted (Actual): August 22, 2023

Study Record Updates

• Last Update Posted (Actual): April 16, 2024
• Last Update Submitted That Met QC Criteria: April 12, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: Relapsed/Refractory B-cell Lymphoma
• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lymphoma, Non-Hodgkin; Lymphoma; Lymphoma, B-Cell; Lymphoma, Large B-Cell, Diffuse; Lymphoma, Mantle-Cell
• Other Study ID Numbers: 23-364

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: The Dana-Farber / Harvard Cancer Center encourages and supports the responsible and ethical sharing of data from clinical trials. De-identified participant data from the final research dataset used in the published manuscript may only be shared under the terms of a Data Use Agreement. Requests may be directed to: [contact information for Sponsor Investigator or designee]. The protocol and statistical analysis plan will be made available on Clinicaltrials.gov only as required by federal regulation or as a condition of awards and agreements supporting the research.
• IPD Sharing Time Frame: Data can be shared no earlier than 1 year following the date of publication
• IPD Sharing Access Criteria: Contact the Partners Innovations team at http://www.partners.org/innovation
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes