Recruiting
Phase 1

CAR T-Cell & LD-TBI

Sponsor:

Weill Medical College of Cornell University

Code:

NCT07725406

Conditions

Relapsed or Refractory Diffuse Large B Cell Lymphoma (DLBCL)

Relapsed or Refractory Multiple Myeloma (MM)

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Interventions

Lymphodepleting chemotherapy: Cyclophosphamide

Lymphodepleting chemotherapy: Bendamustine

Lymphodepleting chemotherapy: Fludarabine

Lisocabtagene Maraleucel

Axicabtagene Ciloleucel

Study Details

Brief 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.

Conditions

Relapsed or Refractory Diffuse Large B Cell Lymphoma (DLBCL)

Relapsed or Refractory Multiple Myeloma (MM)

Study ID

NCT07725406

Start date

Nov, 2026

Status verified date

Oct, 2026

Completion date

Aug 31, 2033

Anticipated

Primary completion date

Aug 1, 2028

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

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

Study Design

Enrollment

32 participants

Anticipated

Allocation

Non randomized

Intervention Model

Sequential

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: Part 1: LBCL: Dose Level -1 (0.5 Gy)

Participants with relapsed/refractory LBCL receive lymphodepletion followed by LD-TBI 0.5 Gy on Day 0, ≥4 hours before infusion of commercial CD19-directed CAR T-cell therapy. Used if de-escalation from Dose Level 0 is required due to dose-limiting toxicity.

experimental: Part 1: LBCL: Dose Level 0 (1.0 Gy, Starting Dose)

Participants with relapsed/refractory LBCL receive lymphodepletion followed by LD-TBI 1.0 Gy (starting dose) on Day 0, ≥4 hours before infusion of commercial CD19-directed CAR T-cell therapy.

experimental: Part 1: LBCL: Dose Level +1 (2.0 Gy)

Participants with relapsed/refractory LBCL receive lymphodepletion followed by LD-TBI 2.0 Gy on Day 0, ≥4 hours before infusion of commercial CD19-directed CAR T-cell therapy. Used if Dose Level 0 is tolerated.

experimental: Part 1: MM: Dose Level -1 (0.5 Gy)

Participants with relapsed/refractory multiple myeloma receive lymphodepletion followed by LD-TBI 0.5 Gy on Day 0, ≥4 hours before infusion of commercial BCMA-directed CAR T-cell therapy. Used if de-escalation from Dose Level 0 is required.

experimental: Part 1: MM: Dose Level 0 (1.0 Gy, Starting Dose)

Participants with relapsed/refractory multiple myeloma receive lymphodepletion followed by LD-TBI 1.0 Gy (starting dose) on Day 0, ≥4 hours before infusion of commercial BCMA-directed CAR T-cell therapy.

experimental: Part 1: MM: Dose Level +1 (2.0 Gy)

Participants with relapsed/refractory multiple myeloma receive lymphodepletion followed by LD-TBI 2.0 Gy on Day 0, ≥4 hours before infusion of commercial BCMA-directed CAR T-cell therapy. Used if Dose Level 0 is tolerated.

experimental: Part 2: LBCL: Expansion Cohort at MTD

Expansion-cohort participants with relapsed/refractory LBCL are randomized 1:1 to LD-TBI at the MTD or one dose level below. This arm receives LD-TBI at the MTD (single dose, Day 0), preceded by lymphodepletion and followed ≥4 hours later by commercial CD19-directed CAR T-cell therapy.

experimental: Part 2: LBCL: Expansion Cohort Below MTD

Expansion-cohort participants with relapsed/refractory LBCL are randomized 1:1 to LD-TBI at the MTD or one dose level below. This arm receives LD-TBI one dose level below the MTD (single dose, Day 0), preceded by lymphodepletion and followed ≥4 hours later by commercial CD19-directed CAR T-cell therapy.

experimental: Part 2: MM: Expansion Cohort at MTD

Expansion-cohort participants with relapsed/refractory multiple myeloma are randomized 1:1 to LD-TBI at the MTD or one dose level below. This arm receives LD-TBI at the MTD (single dose, Day 0), preceded by lymphodepletion and followed ≥4 hours later by commercial BCMA-directed CAR T-cell therapy.

experimental: Part 2: MM: Expansion Cohort Below MTD

Expansion-cohort participants with relapsed/refractory multiple myeloma are randomized 1:1 to LD-TBI at the MTD or one dose level below. This arm receives LD-TBI one dose level below the MTD (single dose, Day 0), preceded by lymphodepletion and followed ≥4 hours later by commercial BCMA-directed CAR T-cell therapy.

Interventions

Lymphodepleting chemotherapy: Cyclophosphamide

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

Lymphodepleting chemotherapy: Bendamustine

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

Lymphodepleting chemotherapy: Fludarabine

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

Lisocabtagene Maraleucel

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

Axicabtagene Ciloleucel

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

Ciltacabtagene Autoleucel

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

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.

Primary outcome measure

  • Incidence of Dose-Limiting Toxicities (DLTs) [ Time Frame: Through Day 28 post-CAR T cell infusion ]

Central Contacts and Locations

Central contacts

Nicole Santos, MPH

646-962-6827nis7058@med.cornell.edu

Caitlin Gribbin, MD

646-962-7950ckg2001@med.cornell.edu

Locations

Weill Cornell Medicine/NewYork-Presbyterian Hospital

Recruiting

New York, New York, United States, 10065

Contacts

Nicole Santos, MPH

646-962-6827nis7058@med.cornell.edu

Caitlin K. Gribbin, MD

ckg2001@med.cornell.edu

More Information

Sponsor

Weill Medical College of Cornell University

Last update posted

Oct 26, 2026

Last verified

Oct, 2026

Trial information was received from ClinicalTrials.gov and was last updated on 2026-10-27. This information was provided to ClinicalTrials.gov by Weill Medical College of Cornell University on 2026-10-26. Recruitment status is synced daily from ClinicalTrials.gov and may not reflect the sponsor's current status. Confirm during your call.