Single-Arm Comprehensive Ablative Bridging Irradiation I Prior to CD19 CAR-T In High-Risk R/R LBCL
- Conditions
- Large B-cell LymphomaRelapsed Non-Hodgkin Lymphoma
Recruitment & Eligibility
- Status
- Recruiting
- Sex
- All
- Target Recruitment
- 27
Inclusion Criteria:<br><br> - Patients with a histologically confirmed diagnosis of diffuse large B-cell lymphoma<br> (DLBCL) who plan to receive treatment at the Moffitt Cancer Center will be eligible.<br><br> - Must have ability to comprehend and the willingness to sign written informed consent<br> for study participation.<br><br> - Eligible to receive CAR T-cell therapy (axicabtagene ciloleucel) for LBCL and<br> histological variants approved by the standard of care label<br><br> - ECOG performance status 0 to 2.<br><br> - At least one high-risk lesion, defined as measuring = 5 cm, that is targetable for<br> radiotherapy per investigator assessment.<br><br> - Ability to undergo comprehensive bridging radiation, defined as radiation to all<br> visible sites of disease.<br><br> - No evidence or suspicion of active central nervous system (CNS) involvement of<br> lymphoma<br><br> - Adequate bone marrow and organ function as defined in protocol.<br><br>The effects of therapeutic agents used in this trial on developing human fetus are<br>unknown, and because of this, women of child-bearing potential and men must agree to use<br>adequate contraception (hormonal or barrier method of birth control; abstinence) prior to<br>study entry and for the duration of study participation as outlined in criteria below:<br><br> - Men must agree to take appropriate precautions to avoid fathering children (with at<br> least 99% certainty) from screening through safety follow up and must refrain from<br> donating sperm during this period. Permitted methods that are at least 99% effective<br> in preventing pregnancy should be communicated to the participants in their<br> understanding confirmed.<br><br> - Women of childbearing potential must have a negative serum or urine pregnancy test<br> at screening and at time of radiation treatment planning, per standard of care and<br> departmental standard operating procedure. Patients must agree to take appropriate<br> precautions to avoid pregnancy (with at least 99% certainty) from screening through<br> safety follow up. Permitted methods that are at least 99% effective in preventing<br> pregnancy should be communicated to the participants and their understanding<br> confirmed.<br><br> - Women of non-childbearing potential (i.e., surgically sterile with a hysterectomy<br> and/or bilateral oophorectomy OR =12 months of amenorrhea) are eligible.<br><br>Exclusion Criteria:<br><br> - Patients who are currently receiving or who have received any other investigational<br> study agent =4 weeks prior to screening visit are ineligible<br><br> - Prior treatment with chimeric antigen receptor (CAR) T-cell therapy<br><br> - Inability to safely deliver comprehensive radiation therapy to all sites of disease<br> per treating radiation oncologists' discretion<br><br> - Participants with clinically significant or uncontrolled cardiac disease, including<br> unstable angina, acute myocardial infarction within 6 months from screening, New<br> York Health Association III or IV heart failure, and circulatory collapse requiring<br> vasopressor or inotropic support.<br><br> - Participants with arrhythmias that are not stable on a medical management program<br> within 2 weeks of screening are also excluded.<br><br> - Evidence of active uncontrolled/untreated infection (viral, bacterial, fungal,<br> opportunistic) of any origin.<br><br> - Known positive Human immunodeficiency virus (HIV) status.<br><br> - Participants with evidence of active and/or chronic hepatitis B virus (HBV)<br> infection, HBV viral load must be undetectable on suppressive therapy, if indicated.<br><br> - Participants with a history of hepatitis C virus (HCV) infection, HCV must have a<br> negative nucleic acid test post-treatment or spontaneous clearance.<br><br> - Participants who require the concurrent use of chronic systemic steroids or<br> immunosuppressant medications. Steroids should not be given within 5 days prior to<br> leukapheresis. Concomitant bridging steroids (Section 6.6) are allowed after<br> leukapheresis.<br><br> - Any condition that would, in the investigator's judgement, interfere with full<br> participation in the study and attending required study visits (if outpatient); pose<br> a significant risk to the participant; or interfere with interpretation of study<br> data.<br><br> - In the investigator's judgment, the subject is unlikely to complete all<br> protocol-required study visits or procedures, including follow-up visits, or comply<br> with the study requirements for participation including ability to safely undergo<br> radiation treatment planning and delivery.<br><br> - Women of childbearing potential who are pregnant or breastfeeding. Females who have<br> undergone surgical sterilization or who have been postmenopausal for at least 12<br> months are not considered to be of childbearing potential.
Not provided
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Progression Free Survival (PFS)
- Secondary Outcome Measures
Name Time Method Rate of local relapse (i.e., relapse of lymphoma at a body site that received bridging radiation therapy);Rate of distant relapse (i.e., relapse of lymphoma at a body site that did not receive bridging radiation therapy);Number of serious adverse events attributed to bridging radiotherapy;Number of serious adverse events attributed to CAR T-cell infusion;Number of participants experiencing severe cytokine release syndrome (CRS);Number of participants experiencing severe immune cell associated neurotoxicity syndrome (ICANS)