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

Conditions

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

Eligibility Criteria

Sex

ALL

Age

18 Years - N/A

Healthy Volunteers

Not accepted

Interventions

• Lymphodepleting chemotherapy: Cyclophosphamide — DRUG
  Lymphodepleting chemotherapy given in combination with fludarabine on Days -5 to -3.
• Lymphodepleting chemotherapy: Bendamustine — DRUG
  Alternative lymphodepleting chemotherapy given on Days -5 to -4, for participants receiving ciltacabtagene autoleucel.
• Lymphodepleting chemotherapy: Fludarabine — DRUG
  Lymphodepleting chemotherapy given in combination with cyclophosphamide on Days -5 to -3.
• Lisocabtagene Maraleucel — OTHER
  Commercial CD19-directed CAR T-cell therapy administered intravenously on Day 0, at least 4 hours after completion of LD-TBI.
• Axicabtagene Ciloleucel — OTHER
  Commercial CD19-directed CAR T-cell therapy administered intravenously on Day 0, at least 4 hours after completion of LD-TBI.
• Ciltacabtagene Autoleucel — OTHER
  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 — RADIATION
  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.

Study Details

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.

Key Dates

First listed

Jul 24, 2026

Start date

Aug 1, 2026

Status verified

Jul 2026

Primary completion

Aug 1, 2028

Completion

Aug 31, 2033

Study Design

Enrollment

32 participants (estimated)

Allocation

NON_RANDOMIZED

Intervention model

SEQUENTIAL

Primary purpose

TREATMENT

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.

Primary Outcome Measure

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

Central Contacts

• Nicole Santos, MPH
  646-962-6827
  [email protected]
• Caitlin Gribbin, MD
  646-962-7950
  [email protected]

Locations (1)

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