[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"trial:NCT07725406":3,"trial-entities:NCT07725406":176,"trial-summary:NCT07725406":181},{"id":4,"nct_id":4,"org_study_id":5,"brief_title":6,"official_title":7,"overall_status":8,"completion_date":9,"status_verified_date":10,"last_update_date":11,"start_date":12,"sponsor_name":13,"lead_sponsor_class":14,"has_dmc":15,"brief_summary":16,"detailed_description":17,"conditions":18,"keywords":21,"study_type":22,"primary_purpose":23,"phases":24,"enrollment_info":26,"interventions":29,"primary_outcomes":77,"secondary_outcomes":82,"sex":118,"minimum_age":119,"maximum_age":120,"healthy_volunteers":121,"eligibility_criteria":122,"std_ages":145,"locations":148,"central_contacts":166,"overall_officials":171,"references":174,"see_also_links":175},"NCT07725406","23-10026672","Low-Dose TBI Plus CAR T-Cell Therapy for Relapsed\u002FRefractory DLBCL and Multiple Myeloma","A Phase Ib, Dose-Escalation Study of Augmented Lymphodepletion and CAR T-cell Priming With Low-dose Total Body Irradiation in Patients With Relapsed or Refractory Diffuse Large B-cell Lymphomas and Multiple Myeloma Receiving Treatment With Commercial CD19 or BCMA-directed CAR T-cell Therapies","NOT_YET_RECRUITING","2033-08-31","2026-07","2026-07-24","2026-08-01","Weill Medical College of Cornell University","OTHER",true,"This is a clinical trial to evaluate the safety of combining CAR T-cell therapy with low-dose total body irradiation (LD-TBI) in patients with previously treated large B-cell lymphoma (LBCL) or multiple myeloma (MM). The investigators' hypothesis is that the combination will make the immune system more active in fighting cancer by increasing the display of antigens and activating pathways that lead to cell death, including death receptors like FAS and TRAIL2. This approach is expected to help the CAR T cells grow and last longer, leading to stronger anti-tumor effects and more cancer cell deaths. Participants will receive LDTBI treatment before their CAR T cell therapy and will be followed up for 2 years.","This is a single-center, open-label, non-randomized, Phase Ib trial evaluating dose escalation of low-dose total body irradiation (LD-TBI) combined with standard-of-care CAR T-cell therapy in patients with relapsed or refractory large B-cell lymphoma (LBCL) or multiple myeloma (MM). The study includes two disease-specific cohorts: Cohort 1 (LBCL) receives commercial CD19-directed CAR T-cell therapy (axicabtagene ciloleucel or lisocabtagene maraleucel), and Cohort 2 (MM) receives commercial BCMA-directed CAR T-cell therapy (ciltacabtagene autoleucel). In CAR T-cell therapy, T-cells are removed via apheresis, modified to target the tumor, and infused back into the patient after lymphodepleting chemotherapy. On the same day as CAR T-cell infusion, prior to infusion, patients receive a single dose of LD-TBI.\n\nEach cohort follows a standard 3+3 dose-escalation design (Part 1) to identify the maximum tolerated dose (MTD) across three planned dose levels (0.5 Gy, 1.0 Gy starting dose, and 2.0 Gy), based on dose-limiting toxicities occurring within 28 days of treatment. Once the MTD is identified, an expansion cohort (Part 2) of up to 10 additional participants per cohort will be randomized 1:1 to the MTD or a dose level below it to further evaluate safety and activity. Approximately 16-22 participants are anticipated per disease cohort. Participants will be followed for up to 2 years after treatment.",[19,20],"Relapsed or Refractory Diffuse Large B Cell Lymphoma (DLBCL)","Relapsed or Refractory Multiple Myeloma (MM)",[],"INTERVENTIONAL","TREATMENT",[25],"PHASE1",{"count":27,"type":28},32,"ESTIMATED",[30,45,49,53,59,64,70],{"type":31,"name":32,"description":33,"armGroupLabels":34},"DRUG","Lymphodepleting chemotherapy: Cyclophosphamide","Lymphodepleting chemotherapy given in combination with fludarabine on Days -5 to -3.",[35,36,37,38,39,40,41,42,43,44],"Part 1: LBCL: Dose Level +1 (2.0 Gy)","Part 1: LBCL: Dose Level -1 (0.5 Gy)","Part 1: LBCL: Dose Level 0 (1.0 Gy, Starting Dose)","Part 1: MM: Dose Level +1 (2.0 Gy)","Part 1: MM: Dose Level -1 (0.5 Gy)","Part 1: MM: Dose Level 0 (1.0 Gy, Starting Dose)","Part 2: LBCL: Expansion Cohort Below MTD","Part 2: LBCL: Expansion Cohort at MTD","Part 2: MM: Expansion Cohort Below MTD","Part 2: MM: Expansion Cohort at MTD",{"type":31,"name":46,"description":47,"armGroupLabels":48},"Lymphodepleting chemotherapy: Bendamustine","Alternative lymphodepleting chemotherapy given on Days -5 to -4, for participants receiving ciltacabtagene autoleucel.",[38,39,40,43,44],{"type":31,"name":50,"description":51,"armGroupLabels":52},"Lymphodepleting chemotherapy: Fludarabine","Lymphodepleting chemotherapy given in combination with cyclophosphamide on Days -5 to -3.",[35,36,37,38,39,40,41,42,43,44],{"type":14,"name":54,"description":55,"armGroupLabels":56,"otherNames":57},"Lisocabtagene Maraleucel","Commercial CD19-directed CAR T-cell therapy administered intravenously on Day 0, at least 4 hours after completion of LD-TBI.",[35,36,37,41,42],[58],"Liso-cel; Breyanzi",{"type":14,"name":60,"description":55,"armGroupLabels":61,"otherNames":62},"Axicabtagene Ciloleucel",[35,36,37,41,42],[63],"Axi-cel; Yescarta",{"type":14,"name":65,"description":66,"armGroupLabels":67,"otherNames":68},"Ciltacabtagene Autoleucel","Commercial BCMA-directed CAR T-cell therapy administered intravenously on Day 0, at least 4 hours after completion of LD-TBI.",[38,39,40,43,44],[69],"Cilta-cel; Carvykti",{"type":71,"name":72,"description":73,"armGroupLabels":74,"otherNames":75},"RADIATION","Low-Dose Total Body Irradiation","A single dose of total body irradiation administered on Day 0, at least 4 hours before the start of CAR T-cell infusion. Dose level (0.5 Gy, 1.0 Gy, or 2.0 Gy) is determined by the assigned dose cohort.",[35,36,37,38,39,40,41,42,43,44],[76],"LD-TBI; TBI",[78],{"measure":79,"description":80,"timeFrame":81},"Incidence of Dose-Limiting Toxicities (DLTs)","This outcome measures the number of participants experiencing a dose-limiting toxicity (DLT) at each LD-TBI dose level, within 28 days following CAR T-cell infusion. This measure is used to assess the safety and tolerability of the treatment regimen across escalating radiation dose levels and to determine the maximum tolerated dose (MTD).","Through Day 28 post-CAR T cell infusion",[83,87,90,93,96,100,104,107,110,114],{"measure":84,"description":85,"timeFrame":86},"Incidence and Severity of Cytokine Release Syndrome (CRS)","This outcome measures the number of participants experiencing CRS of any grade, and the maximum CRS grade (1-4) observed per participant, per ASTCT Consensus Criteria. This measure is used to assess the incidence and severity of this expected immune-related toxicity following combined LD-TBI and CAR T-cell therapy.","12 months post-LDTBI and CAR T cell therapy combination",{"measure":88,"description":89,"timeFrame":86},"Incidence and Severity of Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS)","This outcome measures the number of participants experiencing ICANS of any grade, and the maximum ICANS grade (1-4) observed per participant, per ASTCT Consensus Criteria. This measure is used to assess the incidence and severity of neurologic toxicity following combined LD-TBI and CAR T-cell therapy.",{"measure":91,"description":92,"timeFrame":86},"Incidence and Severity of Immune Effector Cell-Associated Hemophagocytic Syndrome (IEC-HS)","This outcome measures the number of participants experiencing IEC-HS of any grade, and the maximum IEC-HS grade (1-5) observed per participant, per ASTCT criteria. This measure is used to assess the incidence and severity of this rare but serious immune-related toxicity.",{"measure":94,"description":95,"timeFrame":86},"Incidence of Delayed Immune Effector Cell-Associated Hematotoxicity (ICAHT)","This outcome measures the number of participants experiencing delayed ICAHT, per EHA\u002FEBMT consensus criteria. This measure is used to assess the incidence of prolonged blood count abnormalities following CAR T-cell therapy.",{"measure":97,"description":98,"timeFrame":99},"Incidence and Severity of Treatment-Related Adverse Events","This outcome measures the number of participants experiencing at least one treatment-related adverse event, summarized by event term and maximum CTCAE v5.0 grade (1-5) per participant. This measure is used to characterize the overall safety profile of combined LD-TBI and CAR T-cell therapy.","From Lymphodepletion (Day -5) through Day 360",{"measure":101,"description":102,"timeFrame":103},"Overall Response Rate (ORR)","This outcome measures the counts and proportion of response to treatment for participants achieving a partial response (PR), VGPR (for MM only) and complete response (CR), per Lugano Criteria (LBCL) or IMWG criteria (MM). This measure is used to estimate the preliminary anti-tumor activity of combined LD-TBI and CAR T-cell therapy.","At Days +30, +90, +180, and +365 post-CAR T-cell infusion",{"measure":105,"description":106,"timeFrame":86},"Overall Survival (OS)","This outcome measures the probability of survival over time, estimated by the Kaplan-Meier method, from start of treatment to death from any cause. This measure is used to estimate the overall survival associated with combined LD-TBI and CAR T-cell therapy.",{"measure":108,"description":109,"timeFrame":86},"Progression-Free Survival (PFS)","This outcome measures the probability of remaining free of disease progression over time, estimated by the Kaplan-Meier method, from start of treatment to disease progression or death from any cause, whichever occurs first. This measure is used to estimate the durability of disease control with combined LD-TBI and CAR T-cell therapy.",{"measure":111,"description":112,"timeFrame":113},"Duration of Response (DoR)","This outcome measures the median duration of response, estimated by the Kaplan-Meier method, from first documentation of complete or partial response until disease progression or relapse. This measure is used to estimate how durable a response to combined LD-TBI and CAR T-cell therapy is among participants who respond.","Assessed throughout study follow-up (up to 2 years)",{"measure":115,"description":116,"timeFrame":117},"Adverse Event of Interest","This outcome measures the incidence of pre-specified adverse events of interest following combined LD-TBI and CAR T-cell therapy. Adverse events of interest include parkinsonism (in participants receiving ciltacabtagene autoleucel), prolonged cytopenias, infections after Day +28, and immune effector cell-associated hemophagocytic syndrome (IEC-HS).","From CAR T-cell infusion (Day 0) through Day 360","ALL","18 Years",null,false,{"inclusion":123,"exclusion":131,"raw_text":144},[124,125,126,127,128,129,125,126,130],"Diagnosis of DLBCL that is refractory to first-line chemoimmunotherapy, relapses within 12 months of first-line chemoimmunotherapy, relapses after 12 months in a transplant-ineligible patient, or is relapsed\u002Frefractory after two or more lines of systemic therapy. Eligible histologies include DLBCL not otherwise specified, primary mediastinal large B-cell lymphoma, high-grade B-cell lymphoma, and DLBCL arising from indolent lymphoma (follicular lymphoma, marginal zone lymphoma, or chronic lymphocytic leukemia)","Age ≥18 years","ECOG performance status ≤2","Measurable disease on PET\u002FCT or CT per Lugano Criteria","Adequate organ function: ANC ≥1000 cells\u002Fmm³; platelet count ≥75,000 cells\u002Fmm³; creatinine clearance or eGFR ≥45 mL\u002Fmin; total bilirubin ≤2.0x ULN; AST or ALT ≤3.0x ULN; left ventricular ejection fraction \\>40%","Relapsed or refractory multiple myeloma after ≥1 prior line of therapy, including a proteasome inhibitor and an immunomodulatory agent, with disease refractory to lenalidomide (progression within 60 days of last lenalidomide dose)","Adequate organ function: ANC ≥1000 cells\u002Fmm³; platelet count ≥75,000 cells\u002Fmm³; creatinine clearance or eGFR ≥30 mL\u002Fmin; total bilirubin ≤2.0x ULN; AST or ALT ≤3.0x ULN; left ventricular ejection fraction \\>40%",[132,133,134,135,136,137,138,139,140,141,132,142,139,140,133,143,141],"History of previous total body irradiation","Prior CAR T-cell therapy","Clonal cytopenia of uncertain significance (CCUS)","Prior history of myeloid malignancies (MDS\u002FAML or MPN), T-cell lymphoblastic lymphoma\u002Fleukemia, or B-cell acute lymphoblastic leukemia","Current or prior CNS involvement by lymphoma","Significant cardiovascular impairment (CHF greater than NYHA Class II, uncontrolled hypertension, unstable angina, MI or stroke within 6 months, or cardiac ventricular arrhythmia)","Decompensated cirrhosis","Active HIV, hepatitis B, or hepatitis C infection","Active uncontrolled systemic fungal, bacterial, or viral infection","Pregnancy","History of myelodysplastic syndrome, CCUS, or concurrent active hematological malignancy with bone marrow involvement","Active or history of CNS myeloma or leptomeningeal infiltration","Inclusion Criteria:\n\nFor Diffuse Large B-Cell Lymphoma (DLBCL) Cohort:\n\n* Diagnosis of DLBCL that is refractory to first-line chemoimmunotherapy, relapses within 12 months of first-line chemoimmunotherapy, relapses after 12 months in a transplant-ineligible patient, or is relapsed\u002Frefractory after two or more lines of systemic therapy. Eligible histologies include DLBCL not otherwise specified, primary mediastinal large B-cell lymphoma, high-grade B-cell lymphoma, and DLBCL arising from indolent lymphoma (follicular lymphoma, marginal zone lymphoma, or chronic lymphocytic leukemia)\n* Age ≥18 years\n* ECOG performance status ≤2\n* Measurable disease on PET\u002FCT or CT per Lugano Criteria\n* Adequate organ function: ANC ≥1000 cells\u002Fmm³; platelet count ≥75,000 cells\u002Fmm³; creatinine clearance or eGFR ≥45 mL\u002Fmin; total bilirubin ≤2.0x ULN; AST or ALT ≤3.0x ULN; left ventricular ejection fraction \\>40%\n\nFor Multiple Myeloma (MM) Cohort:\n\n* Relapsed or refractory multiple myeloma after ≥1 prior line of therapy, including a proteasome inhibitor and an immunomodulatory agent, with disease refractory to lenalidomide (progression within 60 days of last lenalidomide dose)\n* Age ≥18 years\n* ECOG performance status ≤2\n* Adequate organ function: ANC ≥1000 cells\u002Fmm³; platelet count ≥75,000 cells\u002Fmm³; creatinine clearance or eGFR ≥30 mL\u002Fmin; total bilirubin ≤2.0x ULN; AST or ALT ≤3.0x ULN; left ventricular ejection fraction \\>40%\n\nExclusion Criteria:\n\nFor DLBCL Cohort:\n\n* History of previous total body irradiation\n* Prior CAR T-cell therapy\n* Clonal cytopenia of uncertain significance (CCUS)\n* Prior history of myeloid malignancies (MDS\u002FAML or MPN), T-cell lymphoblastic lymphoma\u002Fleukemia, or B-cell acute lymphoblastic leukemia\n* Current or prior CNS involvement by lymphoma\n* Significant cardiovascular impairment (CHF greater than NYHA Class II, uncontrolled hypertension, unstable angina, MI or stroke within 6 months, or cardiac ventricular arrhythmia)\n* Decompensated cirrhosis\n* Active HIV, hepatitis B, or hepatitis C infection\n* Active uncontrolled systemic fungal, bacterial, or viral infection\n* Pregnancy\n\nFor MM Cohort:\n\n* History of previous total body irradiation\n* History of myelodysplastic syndrome, CCUS, or concurrent active hematological malignancy with bone marrow involvement\n* Active HIV, hepatitis B, or hepatitis C infection\n* Active uncontrolled systemic fungal, bacterial, or viral infection\n* Prior CAR T-cell therapy\n* Active or history of CNS myeloma or leptomeningeal infiltration\n* Pregnancy",[146,147],"ADULT","OLDER_ADULT",[149],{"facility":150,"city":151,"state":151,"zip":152,"country":153,"contacts":154,"geoPoint":163},"Weill Cornell Medicine\u002FNewYork-Presbyterian Hospital","New York","10065","United States",[155,160],{"name":156,"role":157,"phone":158,"email":159},"Nicole Santos, MPH","CONTACT","646-962-6827","nis7058@med.cornell.edu",{"name":161,"role":157,"email":162},"Caitlin K. Gribbin, MD","ckg2001@med.cornell.edu",{"lat":164,"lon":165},40.71427,-74.00597,[167,168],{"name":156,"role":157,"phone":158,"email":159},{"name":169,"role":157,"phone":170,"email":162},"Caitlin Gribbin, MD","646-962-7950",[172],{"name":169,"affiliation":13,"role":173},"PRINCIPAL_INVESTIGATOR",[],[],{"nct_id":4,"conditions":177,"biomarkers":180},[178,179],"Diffuse Large B-Cell Lymphoma","Multiple Myeloma",[],{"nct_id":4,"found":15,"summary":182,"prompt_version":192},{"design":183,"status":184,"heading":185,"summary":186,"follow_up":187,"word_count":188,"commitments":189,"compensation":190,"drugs_mentioned":191},"This is a single-center, open-label (everyone knows what treatment is given), non-randomized Phase Ib study with about 32 participants. It uses a 3+3 dose-escalation design to find the safest dose of radiation.","completed","Low-Dose Radiation with CAR T-Cell Therapy for Lymphoma and Myeloma","This study is testing a new way to combine CAR T-cell therapy with a small amount of radiation, called low-dose total body irradiation (LD-TBI), for people with diffuse large B-cell lymphoma (DLBCL) or multiple myeloma (MM) that has come back or not responded to previous treatments. The CAR T-cell therapies being used are Lisocabtagene Maraleucel or Axicabtagene Ciloleucel for DLBCL, and Ciltacabtagene Autoleucel for MM. Researchers believe this combination might help the CAR T-cells work better and last longer by making your immune system more active against cancer. The main goal is to see how safe this combination is, especially looking at any serious side effects within 28 days after CAR T-cell infusion. You may be eligible if you have DLBCL that is difficult to treat or has returned after initial therapies.","Participants will be followed for 2 years after receiving the CAR T-cell therapy.",132,"Participants will have T-cells removed, receive chemotherapy (Cyclophosphamide, Fludarabine, or Bendamustine), then LD-TBI, and finally the CAR T-cell infusion. You will be followed for 2 years after treatment.","Not stated in the trial record.",[54,60],"v2"]