Single-Arm Comprehensive Ablative Bridging Irradiation I Prior to CD19 CAR-T In High-Risk R/R LBCL

Trial Title: Single-Arm Comprehensive Ablative Bridging Irradiation I Prior to CD19 CAR-T In High-Risk R/R LBCL

NCT ID: NCT06104592

Condition: Large B-cell Lymphoma
Relapsed Non-Hodgkin Lymphoma

Conditions: Official terms:
Lymphoma
Lymphoma, B-Cell

Study type: Interventional

Study phase: Phase 2

Overall status: Recruiting

Study design:

Allocation: N/A

Intervention model: Single Group Assignment

Primary purpose: Treatment

Masking: None (Open Label)

Intervention:

Intervention type: Radiation
Intervention name: Comprehensive Ablative Bridging Irradiation (CABI)
Description: Participants will receive radiation therapy to all pretreatment lesions that are able to be feasibly and safely treated.
Arm group label: Radiation Therapy and CAR T-Cell Infusion

Intervention type: Biological
Intervention name: Chimeric Antigen Receptor T-Cell Therapy
Description: Yascarta is an autologous anti-CD19 CAR T cell therapy manufactured from the patient's own T cells, which have been extracted and then reprogrammed with CAR molecules to help the T cells recognize cancer cells. The reengineered T cells are infused back into the patient to attack the cancer.
Arm group label: Radiation Therapy and CAR T-Cell Infusion

Other name: Axi-Cel

Other name: Yascarta

Summary: This is a phase 2, single-arm, open-label study to evaluate the safety and efficacy of comprehensive bridging radiation therapy prior to CD19 CAR T-cell therapy for large B-cell lymphoma patients with bulky disease, defined as any lesion ≥5 cm.

Criteria for eligibility:
Criteria:
Inclusion Criteria: - Patients with a histologically confirmed diagnosis of diffuse large B-cell lymphoma (DLBCL) who plan to receive treatment at the Moffitt Cancer Center will be eligible. - Must have ability to comprehend and the willingness to sign written informed consent for study participation. - Eligible to receive CAR T-cell therapy (axicabtagene ciloleucel) for LBCL and histological variants approved by the standard of care label - ECOG performance status 0 to 2. - At least one high-risk lesion, defined as measuring ≥ 5 cm, that is targetable for radiotherapy per investigator assessment. - Ability to undergo comprehensive bridging radiation, defined as radiation to all visible sites of disease. - No evidence or suspicion of active central nervous system (CNS) involvement of lymphoma - Adequate bone marrow and organ function as defined in protocol. The effects of therapeutic agents used in this trial on developing human fetus are unknown, and because of this, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation as outlined in criteria below: - Men must agree to take appropriate precautions to avoid fathering children (with at least 99% certainty) from screening through safety follow up and must refrain from donating sperm during this period. Permitted methods that are at least 99% effective in preventing pregnancy should be communicated to the participants in their understanding confirmed. - Women of childbearing potential must have a negative serum or urine pregnancy test at screening and at time of radiation treatment planning, per standard of care and departmental standard operating procedure. Patients must agree to take appropriate precautions to avoid pregnancy (with at least 99% certainty) from screening through safety follow up. Permitted methods that are at least 99% effective in preventing pregnancy should be communicated to the participants and their understanding confirmed. - Women of non-childbearing potential (i.e., surgically sterile with a hysterectomy and/or bilateral oophorectomy OR ≥12 months of amenorrhea) are eligible. Exclusion Criteria: - Patients who are currently receiving or who have received any other investigational study agent ≤4 weeks prior to screening visit are ineligible - Prior treatment with chimeric antigen receptor (CAR) T-cell therapy - Inability to safely deliver comprehensive radiation therapy to all sites of disease per treating radiation oncologists' discretion - Participants with clinically significant or uncontrolled cardiac disease, including unstable angina, acute myocardial infarction within 6 months from screening, New York Health Association III or IV heart failure, and circulatory collapse requiring vasopressor or inotropic support. - Participants with arrhythmias that are not stable on a medical management program within 2 weeks of screening are also excluded. - Evidence of active uncontrolled/untreated infection (viral, bacterial, fungal, opportunistic) of any origin. - Known positive Human immunodeficiency virus (HIV) status. - Participants with evidence of active and/or chronic hepatitis B virus (HBV) infection, HBV viral load must be undetectable on suppressive therapy, if indicated. - Participants with a history of hepatitis C virus (HCV) infection, HCV must have a negative nucleic acid test post-treatment or spontaneous clearance. - Participants who require the concurrent use of chronic systemic steroids or immunosuppressant medications. Steroids should not be given within 5 days prior to leukapheresis. Concomitant bridging steroids (Section 6.6) are allowed after leukapheresis. - Any condition that would, in the investigator's judgement, interfere with full participation in the study and attending required study visits (if outpatient); pose a significant risk to the participant; or interfere with interpretation of study data. - 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 including ability to safely undergo radiation treatment planning and delivery. - Women of childbearing potential who are pregnant or breastfeeding. Females who have undergone surgical sterilization or who have been postmenopausal for at least 12 months are not considered to be of childbearing potential.

Gender: All

Minimum age: 18 Years

Maximum age: N/A

Healthy volunteers: No

Locations:

Facility:
Name: Moffitt Cancer Center

Address:
City: Tampa
Zip: 33612
Country: United States

Status: Recruiting

Contact:
Last name: Marissa Folsom

Phone: 813-745-4995
Email: Marissa.Folsom@moffitt.org

Investigator:
Last name: Michael Jain, MD, PhD
Email: Principal Investigator

Investigator:
Last name: Nicholas Figura, MD
Email: Principal Investigator

Start date: November 8, 2023

Completion date: July 2026

Lead sponsor:
Agency: H. Lee Moffitt Cancer Center and Research Institute
Agency class: Other

Collaborator:
Agency: Kite, A Gilead Company
Agency class: Industry

Source: H. Lee Moffitt Cancer Center and Research Institute

Record processing date: ClinicalTrials.gov processed this data on November 12, 2024

Source: ClinicalTrials.gov page: https://clinicaltrials.gov/ct2/show/NCT06104592
https://www.moffitt.org/clinical-trials-research/clinical-trials/