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NCT07725406

PHASE1

Low-Dose TBI Plus CAR T-Cell Therapy for Relapsed/Refractory DLBCL and Multiple Myeloma

Sponsor: Weill Medical College of Cornell University

View on ClinicalTrials.gov

Summary

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.

Official title: 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

Key Details

Gender

All

Age Range

18 Years - Any

Study Type

INTERVENTIONAL

Enrollment

Start Date

2026-08-01

Completion Date

2033-08-31

Last Updated

2026-07-24

Healthy Volunteers

Conditions

Relapsed or Refractory Diffuse Large B Cell Lymphoma (DLBCL)Relapsed or Refractory Multiple Myeloma (MM)

Interventions

DRUG

Lymphodepleting chemotherapy: Cyclophosphamide

Lymphodepleting chemotherapy given in combination with fludarabine on Days -5 to -3.

DRUG

Lymphodepleting chemotherapy: Bendamustine

Alternative lymphodepleting chemotherapy given on Days -5 to -4, for participants receiving ciltacabtagene autoleucel.

DRUG

Lymphodepleting chemotherapy: Fludarabine

Lymphodepleting chemotherapy given in combination with cyclophosphamide on Days -5 to -3.

OTHER

Lisocabtagene Maraleucel

Commercial CD19-directed CAR T-cell therapy administered intravenously on Day 0, at least 4 hours after completion of LD-TBI.

OTHER

Axicabtagene Ciloleucel

Commercial CD19-directed CAR T-cell therapy administered intravenously on Day 0, at least 4 hours after completion of LD-TBI.

OTHER

Ciltacabtagene Autoleucel

Commercial BCMA-directed CAR T-cell therapy administered intravenously on Day 0, at least 4 hours after completion of LD-TBI.

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.

Inclusion Criteria: For Diffuse Large B-Cell Lymphoma (DLBCL) Cohort: * 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/refractory 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/CT or CT per Lugano Criteria * Adequate organ function: ANC ≥1000 cells/mm³; platelet count ≥75,000 cells/mm³; creatinine clearance or eGFR ≥45 mL/min; total bilirubin ≤2.0x ULN; AST or ALT ≤3.0x ULN; left ventricular ejection fraction \>40% For Multiple Myeloma (MM) Cohort: * 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) * Age ≥18 years * ECOG performance status ≤2 * Adequate organ function: ANC ≥1000 cells/mm³; platelet count ≥75,000 cells/mm³; creatinine clearance or eGFR ≥30 mL/min; total bilirubin ≤2.0x ULN; AST or ALT ≤3.0x ULN; left ventricular ejection fraction \>40% Exclusion Criteria: For DLBCL Cohort: * History of previous total body irradiation * Prior CAR T-cell therapy * Clonal cytopenia of uncertain significance (CCUS) * Prior history of myeloid malignancies (MDS/AML or MPN), T-cell lymphoblastic lymphoma/leukemia, 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 For MM Cohort: * History of previous total body irradiation * History of myelodysplastic syndrome, CCUS, or concurrent active hematological malignancy with bone marrow involvement * Active HIV, hepatitis B, or hepatitis C infection * Active uncontrolled systemic fungal, bacterial, or viral infection * Prior CAR T-cell therapy * Active or history of CNS myeloma or leptomeningeal infiltration * Pregnancy

Locations (1)

Weill Cornell Medicine/NewYork-Presbyterian Hospital

New York, New York, United States

Clinical Research Directory

Low-Dose TBI Plus CAR T-Cell Therapy for Relapsed/Refractory DLBCL and Multiple Myeloma

Summary

Key Details

Conditions

Interventions

Eligibility Criteria

Locations (1)