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

Sponsor

Memorial Sloan Kettering Cancer Center (Other)

Overall Status

Recruiting

CT.gov ID

NCT05574114

Collaborator

(none)

Enrollment

Locations

Arm

35.9

Anticipated Duration (Months)

3.7

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Non-Hodgkin Lymphoma Non-Hodgkin's Lymphoma, Relapsed Non-Hodgkin's Lymphoma Refractory	Radiation: Bridging radiotherapy (BRT) Drug: Conditioning chemotherapy Biological: CAR T-cell product	Phase 1

Study Design

Study Type:

Interventional

Anticipated Enrollment :

26 participants

Allocation:

N/A

Intervention Model:

Sequential Assignment

Intervention Model Description:

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.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.

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Phase I Study Of Split-Course Bridging Radiotherapy (SC-BRT) Prior To Commercial CD19 CAR T-Cell Therapies For Patients With Relapsed or Refractory B-Cell Lymphomas

Actual Study Start Date :

Oct 5, 2022

Anticipated Primary Completion Date :

Oct 1, 2025

Anticipated Study Completion Date :

Oct 1, 2025

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Radiation Therapy Before CAR T Cell Therapy For the purposes of this protocol, day 0 will be considered the date of planned CAR T infusion. Day -25 to -10: BRT Part I (intervention is 9 fractions of 3 Gy to a total dose of 27 Gy). Day -9 to -6: Patients will have a period for recovery, and undergo protocol-mandated reassessments. Day -5 to -3: 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 a final 3 Gy fraction to 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) Day -25 to -10: BRT Part I (intervention is 9 fractions of 3 Gy to a total dose of 27 Gy). Day -2: BRT Part II (intervention is a final 3 Gy fraction to a total dose of 3 Gy). Drug: Conditioning chemotherapy Day -5 to -3: Patients will receive standard of care lymphodepleting chemotherapy Biological: CAR T-cell product Day 0: Subject will receive standard of care infusion of a manufactured commercial CAR T-cell product.

Arm

Intervention/Treatment

Experimental: Radiation Therapy Before CAR T Cell Therapy

For the purposes of this protocol, day 0 will be considered the date of planned CAR T infusion. Day -25 to -10: BRT Part I (intervention is 9 fractions of 3 Gy to a total dose of 27 Gy). Day -9 to -6: Patients will have a period for recovery, and undergo protocol-mandated reassessments. Day -5 to -3: 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 a final 3 Gy fraction to 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)

Day -25 to -10: BRT Part I (intervention is 9 fractions of 3 Gy to a total dose of 27 Gy). Day -2: BRT Part II (intervention is a final 3 Gy fraction to a total dose of 3 Gy).

Drug: Conditioning chemotherapy

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

Biological: CAR T-cell product

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

Outcome Measures

Primary Outcome Measures

number of patients who develop unanticipated severe toxicity events [1 year]
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.

Secondary Outcome Measures

number of patients who are able to receive comprehensive BRT prior to infusion of CAR T cells [2 years]
Comprehensive is defined as delivery of high- or low-dose RT to all sites of PET-avid disease.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

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 (Deauville 4+) 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
Adequate bone marrow function without a requirement for blood product transfusion or growth factor support in the previous 7 days, unless the cytopenias are felt to be due to the underlying lymphoma in the best judgement of the study investigator:
Active secondary central nervous system (CNS) lymphoma is allowed
Age 18 or older
ECOG status ≤2
Adequate bone marrow function without a requirement for blood product transfusion or growth factor support in the previous 7 days, unless the cytopenias are felt to be due to the underlying lymphoma in the best judgement of the study investigator:
Absolute neutrophil count ≥ 1.0 k/µL
Platelets ≥ 50k /µL
Hemoglobin ≥ 7g/dL.
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

Exclusion Criteria:

Subject is planned to receive any form of systemic therapy after apheresis and before re-infusion of CAR T cells including conventional chemotherapy, immunotherapy, targeted agents or high dose steroids [Note: Planned lymphodepletion chemotherapy in preparation for CAR T cell administration is not an exclusion criterion]
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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Memorial Sloan Kettering Basking Ridge (Limited Protocol Activities)	Basking Ridge	New Jersey	United States	07920
2	Memorial Sloan Kettering Monmouth (Limited Protocol Activities)	Middletown	New Jersey	United States	07748
3	Memorial Sloan Kettering Bergen (Limited Protocol Activities)	Montvale	New Jersey	United States	07645
4	Memorial Sloan Kettering Suffolk - Commack (Limited Protocol Activities)	Commack	New York	United States	11725
5	Memorial Sloan Kettering Westchester (Limited Protocol Activities)	Harrison	New York	United States	10604
6	Memorial Sloan Kettering Cancer Center	New York	New York	United States	10065
7	Memorial Sloan Kettering Nassau (Limited Protocol Activities)	Uniondale	New York	United States	11553

Sponsors and Collaborators

Memorial Sloan Kettering Cancer Center

Investigators

Principal Investigator: Lia Palomba, MD, Memorial Sloan Kettering Cancer Center

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

Memorial Sloan Kettering Cancer Center

Publications

None provided.

Responsible Party:

Memorial Sloan Kettering Cancer Center

ClinicalTrials.gov Identifier:

NCT05574114

Other Study ID Numbers:

22-217

First Posted:

Oct 10, 2022

Last Update Posted:

Jan 26, 2023

Last Verified:

Jan 1, 2023

Individual Participant Data (IPD) Sharing Statement:

Yes

Plan to Share IPD:

Yes

Studies a U.S. FDA-regulated Drug Product:

Yes

Studies a U.S. FDA-regulated Device Product:

Product Manufactured in and Exported from the U.S.:

Keywords provided by Memorial Sloan Kettering Cancer Center

Split-Course Bridging Radiotherapy

CD19 CAR T-Cell Therapies

22-217

Additional relevant MeSH terms:

Lymphoma

Lymphoma, Non-Hodgkin

Study Results

No Results Posted as of Jan 26, 2023