Low-Dose TBI Plus CAR-T Therapy for relapsed/refractory DLBCL or multiple myeloma

Is this trial a fit for you?

A plain-English reading of the study's rules. Only the study team can confirm whether you qualify.

What this trial studies

This is a Phase Ib, single-center, open-label study evaluating dose-escalation of low-dose total body irradiation combined with standard CAR-T therapy in adults with relapsed/refractory DLBCL or multiple myeloma. Two disease-specific cohorts receive either CD19-directed CAR-T cells (for DLBCL) or BCMA-directed CAR-T cells (for myeloma) after specified lymphodepleting chemotherapy; LD-TBI is given on the day of CAR-T infusion. The study uses a 3+3 design to identify the maximum tolerated radiation dose (0.5, 1.0, and 2.0 Gy) and then expands cohorts to assess safety and preliminary activity. Participants will be followed for up to 2 years to monitor outcomes and adverse events.

Why it matters

Who can join: the full rules

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

Where it's running

• Weill Cornell Medicine/NewYork-Presbyterian Hospital
  New York, New York, United States Recruiting

Study contacts

• Principal investigator: Caitlin Gribbin, MD — Weill Medical College of Cornell University
• Study coordinator: Nicole Santos, MPH
• Email: nis7058@med.cornell.edu
• Phone: 646-962-6827

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How to take part

1. Review the eligibility criteria above with your treating physician.
2. Check the official listing on ClinicalTrials.gov for the latest contact details and recruitment status.
3. Contact the study coordinator or principal investigator to ask for pre-screening. Pre-screening is free and never obligates you to enroll.