Relapsed or Refractory Diffuse Large B Cell Lymphoma (DLBCL)Phase 1Prime REMIXNCT07725406
Low-Dose TBI Plus CAR T-Cell Therapy for Relapsed/Refractory DLBCL and Multiple Myeloma
A Phase 1 study testing Lymphodepleting chemotherapy: Cyclophosphamide, Lymphodepleting chemotherapy: Bendamustine and Lymphodepleting chemotherapy: Fludarabine in people with Relapsed or Refractory Diffuse Large B Cell Lymphoma (DLBCL) and Relapsed or Refractory Multiple Myeloma (MM), run by Weill Medical College of Cornell University at 1 site in United States.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Relapsed or Refractory Diffuse Large B Cell Lymphoma (DLBCL), Relapsed or Refractory Multiple Myeloma (MM)
- What is being tested?
- Lymphodepleting chemotherapy: Cyclophosphamide, Lymphodepleting chemotherapy: Bendamustine and Lymphodepleting chemotherapy: Fludarabine
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 32 participants
- Where
- 1 siteUnited States
- Study dates
- Nov 2026to 31 Aug 2033
- Phase
- Phase 1
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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%
Show all 11Show fewer
- 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%
Who cannot join
- 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
Show all 19Show fewer
- 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
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
Weill Cornell Medicine/NewYork-Presbyterian Hospital
New York, New York, 10065
Nicole Santos, MPH, 646-962-6827, nis7058@med.cornell.edu
Caitlin K. Gribbin, MD, ckg2001@med.cornell.edu
About this study
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
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.
Read the detailed description
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.
Each 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.
- Conditions
- Relapsed or Refractory Diffuse Large B Cell Lymphoma (DLBCL), Relapsed or Refractory Multiple Myeloma (MM)
- Being tested
- Lymphodepleting chemotherapy: Cyclophosphamide, Lymphodepleting chemotherapy: Bendamustine, Lymphodepleting chemotherapy: Fludarabine, Lisocabtagene Maraleucel, Axicabtagene Ciloleucel
- Medical subject headings
- Recurrence, Lymphoma, Large B-Cell, Diffuse, Multiple Myeloma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Lymphodepleting chemotherapy: CyclophosphamideDrug
Lymphodepleting chemotherapy given in combination with fludarabine on Days -5 to -3.
Lymphodepleting chemotherapy: BendamustineDrug
Alternative lymphodepleting chemotherapy given on Days -5 to -4, for participants receiving ciltacabtagene autoleucel.
Lymphodepleting chemotherapy: FludarabineDrug
Lymphodepleting chemotherapy given in combination with cyclophosphamide on Days -5 to -3.
Lisocabtagene MaraleucelOther
Also called Liso-cel; Breyanzi
Commercial CD19-directed CAR T-cell therapy administered intravenously on Day 0, at least 4 hours after completion of LD-TBI.
Axicabtagene CiloleucelOther
Also called Axi-cel; Yescarta
Commercial CD19-directed CAR T-cell therapy administered intravenously on Day 0, at least 4 hours after completion of LD-TBI.
Ciltacabtagene AutoleucelOther
Also called Cilta-cel; Carvykti
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 IrradiationRadiation
Also called LD-TBI; TBI
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 group | Role | What they receive |
|---|---|---|
| Part 1: LBCL: Dose Level -1 (0.5 Gy) | Experimental | 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. Receives: Drug: Lymphodepleting chemotherapy: Cyclophosphamide; Drug: Lymphodepleting chemotherapy: Fludarabine; Other: Lisocabtagene Maraleucel; Other: Axicabtagene Ciloleucel; Radiation: Low-Dose Total Body Irradiation |
| Part 1: LBCL: Dose Level 0 (1.0 Gy, Starting Dose) | Experimental | 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. Receives: Drug: Lymphodepleting chemotherapy: Cyclophosphamide; Drug: Lymphodepleting chemotherapy: Fludarabine; Other: Lisocabtagene Maraleucel; Other: Axicabtagene Ciloleucel; Radiation: Low-Dose Total Body Irradiation |
| Part 1: LBCL: Dose Level +1 (2.0 Gy) | Experimental | 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. Receives: Drug: Lymphodepleting chemotherapy: Cyclophosphamide; Drug: Lymphodepleting chemotherapy: Fludarabine; Other: Lisocabtagene Maraleucel; Other: Axicabtagene Ciloleucel; Radiation: Low-Dose Total Body Irradiation |
| Part 1: MM: Dose Level -1 (0.5 Gy) | Experimental | 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. Receives: Drug: Lymphodepleting chemotherapy: Cyclophosphamide; Drug: Lymphodepleting chemotherapy: Bendamustine; Drug: Lymphodepleting chemotherapy: Fludarabine; Other: Ciltacabtagene Autoleucel; Radiation: Low-Dose Total Body Irradiation |
| Part 1: MM: Dose Level 0 (1.0 Gy, Starting Dose) | Experimental | 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. Receives: Drug: Lymphodepleting chemotherapy: Cyclophosphamide; Drug: Lymphodepleting chemotherapy: Bendamustine; Drug: Lymphodepleting chemotherapy: Fludarabine; Other: Ciltacabtagene Autoleucel; Radiation: Low-Dose Total Body Irradiation |
| Part 1: MM: Dose Level +1 (2.0 Gy) | Experimental | 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. Receives: Drug: Lymphodepleting chemotherapy: Cyclophosphamide; Drug: Lymphodepleting chemotherapy: Bendamustine; Drug: Lymphodepleting chemotherapy: Fludarabine; Other: Ciltacabtagene Autoleucel; Radiation: Low-Dose Total Body Irradiation |
| Part 2: LBCL: Expansion Cohort at MTD | Experimental | 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. Receives: Drug: Lymphodepleting chemotherapy: Cyclophosphamide; Drug: Lymphodepleting chemotherapy: Fludarabine; Other: Lisocabtagene Maraleucel; Other: Axicabtagene Ciloleucel; Radiation: Low-Dose Total Body Irradiation |
| Part 2: LBCL: Expansion Cohort Below MTD | Experimental | 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. Receives: Drug: Lymphodepleting chemotherapy: Cyclophosphamide; Drug: Lymphodepleting chemotherapy: Fludarabine; Other: Lisocabtagene Maraleucel; Other: Axicabtagene Ciloleucel; Radiation: Low-Dose Total Body Irradiation |
| Part 2: MM: Expansion Cohort at MTD | Experimental | 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. Receives: Drug: Lymphodepleting chemotherapy: Cyclophosphamide; Drug: Lymphodepleting chemotherapy: Bendamustine; Drug: Lymphodepleting chemotherapy: Fludarabine; Other: Ciltacabtagene Autoleucel; Radiation: Low-Dose Total Body Irradiation |
| Part 2: MM: Expansion Cohort Below MTD | Experimental | 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. Receives: Drug: Lymphodepleting chemotherapy: Cyclophosphamide; Drug: Lymphodepleting chemotherapy: Bendamustine; Drug: Lymphodepleting chemotherapy: Fludarabine; Other: Ciltacabtagene Autoleucel; Radiation: Low-Dose Total Body Irradiation |
What is being measured
The primary outcome is the main question the study is designed to answer.
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).
Measured: Through Day 28 post-CAR T cell infusion
Secondary outcomes (10)
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.
Measured: 12 months post-LDTBI and CAR T cell therapy combination
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.
Measured: 12 months post-LDTBI and CAR T cell therapy combination
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.
Measured: 12 months post-LDTBI and CAR T cell therapy combination
Incidence of Delayed Immune Effector Cell-Associated Hematotoxicity (ICAHT)
This outcome measures the number of participants experiencing delayed ICAHT, per EHA/EBMT consensus criteria. This measure is used to assess the incidence of prolonged blood count abnormalities following CAR T-cell therapy.
Measured: 12 months post-LDTBI and CAR T cell therapy combination
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.
Measured: From Lymphodepletion (Day -5) through Day 360
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.
Measured: At Days +30, +90, +180, and +365 post-CAR T-cell infusion
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.
Measured: 12 months post-LDTBI and CAR T cell therapy combination
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.
Measured: 12 months post-LDTBI and CAR T cell therapy combination
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.
Measured: Assessed throughout study follow-up (up to 2 years)
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).
Measured: From CAR T-cell infusion (Day 0) through Day 360
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Jul 2026
- Study startNov 2026 (estimated)
- Primary completion1 Aug 2028 (estimated)
- Study completion31 Aug 2033 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Relapsed or Refractory Diffuse Large B Cell Lymphoma (DLBCL)Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 32 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Weill Medical College of Cornell University
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Caitlin Gribbin, MD, Principal investigator, Weill Medical College of Cornell University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07725406
- Sponsor's protocol ID
- 23-10026672
- Acronym
- Prime REMIX
- Status last verified
- Oct 2026
- First submitted
- 21 Jul 2026
- Last updated
- 26 Oct 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 26 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT07725406
- Acronym / sponsor ID
- Prime REMIX / 23-10026672
- Conditions
- Relapsed or Refractory Diffuse Large B Cell Lymphoma (DLBCL), Relapsed or Refractory Multiple Myeloma (MM)
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 32 participants (estimated)
- Lead sponsor
- Weill Medical College of Cornell UniversityUniversity, hospital or other
- Study start
- Nov 2026 (estimated)
- Primary completion
- 1 Aug 2028 (estimated)
- Study completion
- 31 Aug 2033 (estimated)
- First posted
- 24 Jul 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
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.
Each 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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 10
| Arm | Type | Receives |
|---|---|---|
| Part 1: LBCL: Dose Level -1 (0.5 Gy) | Experimental | Drug: Lymphodepleting chemotherapy: Cyclophosphamide, Drug: Lymphodepleting chemotherapy: Fludarabine, Other: Lisocabtagene Maraleucel, Other: Axicabtagene Ciloleucel, Radiation: Low-Dose Total Body IrradiationParticipants 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. |
| Part 1: LBCL: Dose Level 0 (1.0 Gy, Starting Dose) | Experimental | Drug: Lymphodepleting chemotherapy: Cyclophosphamide, Drug: Lymphodepleting chemotherapy: Fludarabine, Other: Lisocabtagene Maraleucel, Other: Axicabtagene Ciloleucel, Radiation: Low-Dose Total Body IrradiationParticipants 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. |
| Part 1: LBCL: Dose Level +1 (2.0 Gy) | Experimental | Drug: Lymphodepleting chemotherapy: Cyclophosphamide, Drug: Lymphodepleting chemotherapy: Fludarabine, Other: Lisocabtagene Maraleucel, Other: Axicabtagene Ciloleucel, Radiation: Low-Dose Total Body IrradiationParticipants 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. |
| Part 1: MM: Dose Level -1 (0.5 Gy) | Experimental | Drug: Lymphodepleting chemotherapy: Cyclophosphamide, Drug: Lymphodepleting chemotherapy: Bendamustine, Drug: Lymphodepleting chemotherapy: Fludarabine, Other: Ciltacabtagene Autoleucel, Radiation: Low-Dose Total Body IrradiationParticipants 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. |
| Part 1: MM: Dose Level 0 (1.0 Gy, Starting Dose) | Experimental | Drug: Lymphodepleting chemotherapy: Cyclophosphamide, Drug: Lymphodepleting chemotherapy: Bendamustine, Drug: Lymphodepleting chemotherapy: Fludarabine, Other: Ciltacabtagene Autoleucel, Radiation: Low-Dose Total Body IrradiationParticipants 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. |
| Part 1: MM: Dose Level +1 (2.0 Gy) | Experimental | Drug: Lymphodepleting chemotherapy: Cyclophosphamide, Drug: Lymphodepleting chemotherapy: Bendamustine, Drug: Lymphodepleting chemotherapy: Fludarabine, Other: Ciltacabtagene Autoleucel, Radiation: Low-Dose Total Body IrradiationParticipants 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. |
| Part 2: LBCL: Expansion Cohort at MTD | Experimental | Drug: Lymphodepleting chemotherapy: Cyclophosphamide, Drug: Lymphodepleting chemotherapy: Fludarabine, Other: Lisocabtagene Maraleucel, Other: Axicabtagene Ciloleucel, Radiation: Low-Dose Total Body IrradiationExpansion-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. |
| Part 2: LBCL: Expansion Cohort Below MTD | Experimental | Drug: Lymphodepleting chemotherapy: Cyclophosphamide, Drug: Lymphodepleting chemotherapy: Fludarabine, Other: Lisocabtagene Maraleucel, Other: Axicabtagene Ciloleucel, Radiation: Low-Dose Total Body IrradiationExpansion-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. |
| Part 2: MM: Expansion Cohort at MTD | Experimental | Drug: Lymphodepleting chemotherapy: Cyclophosphamide, Drug: Lymphodepleting chemotherapy: Bendamustine, Drug: Lymphodepleting chemotherapy: Fludarabine, Other: Ciltacabtagene Autoleucel, Radiation: Low-Dose Total Body IrradiationExpansion-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. |
| Part 2: MM: Expansion Cohort Below MTD | Experimental | Drug: Lymphodepleting chemotherapy: Cyclophosphamide, Drug: Lymphodepleting chemotherapy: Bendamustine, Drug: Lymphodepleting chemotherapy: Fludarabine, Other: Ciltacabtagene Autoleucel, Radiation: Low-Dose Total Body IrradiationExpansion-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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- 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%
Key exclusion criteria (19 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Lymphodepleting chemotherapy: CyclophosphamideLymphodepleting chemotherapy given in combination with fludarabine on Days -5 to -3. | Drug | 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 |
| Lymphodepleting chemotherapy: BendamustineAlternative lymphodepleting chemotherapy given on Days -5 to -4, for participants receiving ciltacabtagene autoleucel. | Drug | 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: MM: Expansion Cohort Below MTD, Part 2: MM: Expansion Cohort at MTD |
| Lymphodepleting chemotherapy: FludarabineLymphodepleting chemotherapy given in combination with cyclophosphamide on Days -5 to -3. | Drug | 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 |
| Lisocabtagene MaraleucelAlso: Liso-cel; BreyanziCommercial CD19-directed CAR T-cell therapy administered intravenously on Day 0, at least 4 hours after completion of LD-TBI. | Other | 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 2: LBCL: Expansion Cohort Below MTD, Part 2: LBCL: Expansion Cohort at MTD |
| Axicabtagene CiloleucelAlso: Axi-cel; YescartaCommercial CD19-directed CAR T-cell therapy administered intravenously on Day 0, at least 4 hours after completion of LD-TBI. | Other | 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 2: LBCL: Expansion Cohort Below MTD, Part 2: LBCL: Expansion Cohort at MTD |
| Ciltacabtagene AutoleucelAlso: Cilta-cel; CarvyktiCommercial BCMA-directed CAR T-cell therapy administered intravenously on Day 0, at least 4 hours after completion of LD-TBI. | Other | 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: MM: Expansion Cohort Below MTD, Part 2: MM: Expansion Cohort at MTD |
| Low-Dose Total Body IrradiationAlso: LD-TBI; TBIA 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. | Radiation | 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 |
Primary outcome
Incidence of Dose-Limiting Toxicities (DLTs)
Time frame: Through Day 28 post-CAR T cell infusion
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).
10 secondary outcomes
Incidence and Severity of Cytokine Release Syndrome (CRS)
Time frame: 12 months post-LDTBI and CAR T cell therapy combination
Incidence and Severity of Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS)
Time frame: 12 months post-LDTBI and CAR T cell therapy combination
Incidence and Severity of Immune Effector Cell-Associated Hemophagocytic Syndrome (IEC-HS)
Time frame: 12 months post-LDTBI and CAR T cell therapy combination
Incidence of Delayed Immune Effector Cell-Associated Hematotoxicity (ICAHT)
Time frame: 12 months post-LDTBI and CAR T cell therapy combination
Incidence and Severity of Treatment-Related Adverse Events
Time frame: From Lymphodepletion (Day -5) through Day 360
Overall Response Rate (ORR)
Time frame: At Days +30, +90, +180, and +365 post-CAR T-cell infusion
Overall Survival (OS)
Time frame: 12 months post-LDTBI and CAR T cell therapy combination
Progression-Free Survival (PFS)
Time frame: 12 months post-LDTBI and CAR T cell therapy combination
Duration of Response (DoR)
Time frame: Assessed throughout study follow-up (up to 2 years)
Adverse Event of Interest
Time frame: From CAR T-cell infusion (Day 0) through Day 360
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Oct 2026.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Caitlin Gribbin, MD principal investigator
Weill Medical College of Cornell University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Lymphodepleting chemotherapy: Cyclophosphamide, Lymphodepleting chemotherapy: Bendamustine and Lymphodepleting chemotherapy: Fludarabine in people with Relapsed or Refractory Diffuse Large B Cell Lymphoma (DLBCL) and Relapsed or Refractory Multiple Myeloma (MM), run by Weill Medical College of Cornell University at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 11 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 26 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Nicole Santos, MPH (646-962-6827, nis7058@med.cornell.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Incidence of Dose-Limiting Toxicities (DLTs) (time frame: Through Day 28 post-CAR T cell infusion). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Oct 2026.