Radiation Post-CAR T in Refractory Lymphoma

Radiation Therapy To Enhance CAR T Efficacy Early in Post-CAR T Cell Therapy Refractory Lymphoma: A Pilot Study

This study is evaluating the safety and efficacy of using radiotherapy in participants who have refractory lymphoma shortly after receiving CAR T cell therapy (axicel or tisacel).

Study Overview

• Status: Terminated
• Conditions: Refractory Lymphoma; Hematologic Malignancy
• Intervention / Treatment: Radiation: Radiotherapy

Detailed Description

This research study is a Pilot Study, which is the first time investigators are examining this intervention after administration of CAR T cell therapy. This research study looks to systematically investigate the safety and efficacy of radiotherapy following CAR T cell therapy (axicel or tisacel) in refractory lymphoma. CAR T cell therapy involves genetically modifying T cells to target tumor cells for death. Radiotherapy is a standard treatment offered with refractory lymphoma and uses high-energy x rays, or particles, to destroy or damage cancer cells. Few have received CAR T cell therapy prior to radiation therapy and this study aims to gather more information on radiotherapy following CAR T cell therapy as a treatment option and its potential to improve participants immune system's response to cancer cells as well as its interaction with CAR T cell therapy to better treat refractory lymphoma.

The research study procedures include screening for eligibility, enrollment, biopsy following radiation, post-treatment period, and long-term follow-up.

• Participants will receive radiotherapy at a dose and schedule determined by the study doctor.
• Participants will be followed for up to 24 months after completion of study treatment.

It is expected that about 20 people will take part in this research study.

• Study Type: Interventional
• Enrollment (Actual): 3
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Chirayu G Patel, MD, MPH; Phone Number: 617-724-2340; Email: cpatel@mgh.harvard.edu

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital Cancer Center
      • Principal Investigator: Matthew J Frigault, MD
      • Contact: Chirayu G Patel, MD, MPH; Phone Number: 617-724-2340; Email: cpatel@mgh.harvard.edu
      • Principal Investigator: Chirayu G Patel, MD, MPH

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Patients must be able to undergo biopsy. Biopsy will be obtained for patients to exclude possibility of false negative residual FDG avidity on PET/CT that is not substantially increased relative to pre-CAR-T PET/CT. Exceptions are allowed for patients who have clearly progressive disease for whom delaying radiation therapy to obtain a biopsy may worsen outcome (such as cases of cord compression), and for patients for whom the risks of biopsy are high (such as patients with evidence for CNS involvement).
• Biopsy-confirmed refractory disease within 30-90 days following commercial axicabtagene ciloleucel or tisagenlecleucel therapy for a hematologic malignancy (these include relapsed or refractory large B-cell lymphoma after two or more lines of systemic therapy, including diffuse large B-cell lymphoma (DLBCL) not otherwise specified, primary mediastinal large B-cell lymphoma, high grade B-cell lymphoma, and DLBCL arising from follicular lymphoma). Of note, 'refractory' refers to patients who had early refractory disease after CAR-T cell therapy and not to patients who have received CAR-T for refractory disease, but had complete response to CAR-T cell therapy.
• At least 1 measurable lesion according to the Lugano criteria1. Lesions that have been previously irradiated will be considered measurable only if progression has been documented following completion of radiation therapy

• The following criteria pertain to pattern of progression:

  • Patients may have one refractory lesion without other residual or progressive disease as per PET/CT
  • Patients may have more than one refractory lesion, but with evidence for at least partial response of at least one other lesion as per PET/CT

  • Patients with more than one site of refractory disease without evidence for at least partial response of at least one other lesion are eligible if they are:

    • A. Symptomatic from a refractory lesion (such as cord compression or focal pain) or
    • B. Have disease that can locally affect the spinal canal or brain if left untreated.
• Toxicities due to prior therapy must be stable and recovered to ≤ Grade 1 (except for clinically non-significant toxicities such as alopecia and prolonged cytopenias that are not expected to worsen during RT) if there is concern for overlap of anticipated radiation-related toxicity and toxicity from prior therapy due to where the RT field is located.
• Age 18 or older
• Eastern Cooperative Oncology Group (ECOG) performance status of less than or equal to 2.
• 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
• Patients with more than one site of disease without any evidence for response to CAR T cell therapy who are not focally symptomatic due to progressive disease or do not have disease that can locally affect the spinal canal or brain if left untreated
• 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 investigators 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: Radiotherapy; Participants must have received CAR-T infusion within the last 90 days prior to completing a study screening and enrollment process.; Participants will be enrolled within 28 days after screening is complete and radiotherapy will occur within 14 days after study enrollment.; Radiotherapy will be administered based on a dose and schedule pre-determined by the study doctor.

Radiation: Radiotherapy; Radiotherapy at pre-determined dose and schedule

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Treatment-Related Adverse Events as Assessed by CTCAE Version 5.0	Rate and severity of radiotherapy-related toxicity as per CTCAE v5.0 criteria during radiotherapy (RT) or within the first 30 days of completing RT. The number of participants who experienced radiotherapy-related toxicity are listed below. Only one radiotherapy-related toxicity was observed - Grade 2 Dermatitis.	30 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Duration of Response (DOR)	DOR is defined as the length of time between a subject's first objective response per Lugano criteria (complete response or partial response) and local disease progression per Lugano criteria, or death regardless of cause.	Up to 2 years
Objective Response Rate (ORR)	ORR is defined as the incidence of either a complete response or a partial response by Lugano criteria. All subjects that do not meet the criteria for an objective response by the analysis data cutoff date will be considered non-responders.	Up to 2 years
Progression-free Survival (PFS)	PFS is defined as the time from radiotherapy completion date to the date of disease progression per Lugano criteria or death from any cause. Subjects not meeting the criteria for progression by the analysis data cutoff date will be censored at their last evaluable disease assessment date.	Up to 2 years
Overall Survival	Overall survival is defined as the time from radiotherapy completion to the date of death. Subjects who have not died by the analysis cutoff date will be censored at their last contact date.	Up to 2 years

Collaborators and Investigators

• Sponsor: Massachusetts General Hospital
• Investigators: Principal Investigator: Chirayu G Patel, MD, MPH, Massachusetts General Hospital

Study record dates

Study Major Dates

• Study Start (Actual): January 5, 2021
• Primary Completion (Actual): October 9, 2021
• Study Completion (Actual): July 3, 2023

Study Registration Dates

• First Submitted: July 13, 2020
• First Submitted That Met QC Criteria: July 13, 2020
• First Posted (Actual): July 16, 2020

Study Record Updates

• Last Update Posted (Actual): April 10, 2024
• Last Update Submitted That Met QC Criteria: March 12, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: Radiotherapy; Hematologic Malignancy; Refractory Lymphoma; CAR T cell therapy
• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Neoplasms by Site; Hematologic Diseases; Neoplasms; Lymphoma; Hematologic Neoplasms
• Other Study ID Numbers: 19-861

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