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

Non-Hodgkin Lymphoma Clinical Trial

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05574114
• Other study ID #: 22-217
• Status: Recruiting
• Phase: Phase 1
• Start date: October 5, 2022
• Est. completion date: October 2025

Study information

• Verified date: December 2023
• Source: Memorial Sloan Kettering Cancer Center
• Contact: M. Lia Palomba, MD
• Phone: 646-608-3711
• Email: palombam[@]mskcc.org
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 20
• Est. completion date: October 2025
• Est. primary completion date: October 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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 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 systemic therapy after initiation of BRT and before re-infusion of CAR T cells including conventional chemotherapy, immunotherapy or targeted agents [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

Related Conditions & MeSH terms

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

Intervention

Radiation:
• Bridging radiotherapy (BRT)
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).

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.

Locations

Country	Name	City	State
United States	Memorial Sloan Kettering Basking Ridge (Limited Protocol Activities)	Basking Ridge	New Jersey
United States	Memorial Sloan Kettering Suffolk - Commack (Limited Protocol Activities)	Commack	New York
United States	Memorial Sloan Kettering Westchester (Limited Protocol Activities)	Harrison	New York
United States	Memorial Sloan Kettering Monmouth (Limited Protocol Activities)	Middletown	New Jersey
United States	Memorial Sloan Kettering Bergen (Limited Protocol Activities)	Montvale	New Jersey
United States	Memorial Sloan Kettering Cancer Center	New York	New York
United States	Memorial Sloan Kettering Nassau (Limited Protocol Activities)	Uniondale	New York

Sponsors (1)

Lead Sponsor	Collaborator
Memorial Sloan Kettering Cancer Center

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	number of patients who are able to receive comprehensive BRT prior to infusion of CAR T cells	Comprehensive is defined as delivery of high- or low-dose RT to all sites of PET-avid disease.	2 years

External Links

•   Memorial Sloan Kettering Cancer Center