Lymphodepletion With Low Dose Total Body Irradiation Before Standard of Care Tisagenlecleucel for the Treatment of Relapsed and Recurrent Large B-cell Lymphoma

NCT07676877 | Not Yet Recruiting Phase 1 DMC FDA Drug

• 2 other identifiers: OSU-25255NCI-2026-04299
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

Brief Summary

This phase I trial tests the safety, side effects, and best dose of total body irradiation (TBI) in combination with standard of care lymphodepletion with cyclophosphamide and fludarabine before tisagenlecleucel (Tisa-cel) and how well the combination works in patients with large B-cell lymphoma (LBCL) that has come back after a period of improvement (relapsed) or that has not responded to previous treatment (refractory). TBI is a common treatment that sends radiation (for example, through x-rays) to the entire body. Lymphodepleting chemotherapy, such as cyclophosphamide and fludarabine, along with TBI helps kill cancer cells in the body and helps prepare the body for the Tisa-cel infusion. Tisagenlecleucel is made using a patient's T cells (a type of immune system cell). A gene for a special receptor called chimeric antigen receptor (CAR) is added to the T cells in the laboratory. These changed T cells called CAR T cells are grown in large numbers in the laboratory and given to the patient by infusion. Tisa-cel binds to a protein called CD19, which is found on some leukemia and lymphoma cells. This helps the body's immune system kill cancer cells. Tisa-cel is a type of CAR T-cell therapy. Giving low dose TBI in combination with standard of care lymphodepletion therapy and Tisa-cel may be safe, tolerable, and/or effective in treating patients with relapsed or refractory (R/R) LBCL.

Conditions

Recurrent Diffuse Large B-Cell Lymphoma; Refractory Diffuse Large B-Cell Lymphoma

Outcome Measures

Primary Outcomes (2)

• Dose-limiting toxicities

  Adverse events will be graded according to National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) version (v) 5.0. Cytokine release syndrome and immune effector cell associated neurotoxicity syndrome are graded using American Society for Transplantation and Cellular Therapy (ASTCT) Consensus grading.

  Up to 30 days after infusion

• Maximum tolerated dose or recommended phase 2 dose (RP2D)

  Will define the dose as the RP2D for which the isotonic estimate of the toxicity rate is closest to the targeted toxicity rate (i.e., 25%). If there is a tie, the higher dose level when the isotonic estimate is lower than the targeted toxicity rate; and will choose the lower dose level when the isotonic estimate is greater than the targeted toxicity rate.

  Up to 30 days after infusion

Secondary Outcomes (9)

• Incidence of adverse events

  Up to 1 year

• Complete remission rate

  At days 30 and 90 from tisagenlecleucel (Tisa-cel) infusion

• Objective response rate

  At 30 and 90 days and 6 months

• Median duration of response

  Up to 1 year

• Progression-free survival

  From Tisa-cel infusion to clinical progression or death as a result of any cause, assessed at 6 months and 1 year

Study Arms (1)

Treatment (TBI, lymphodepletion, Tisa-cel)

EXPERIMENTAL

Patients undergo leukapheresis and receive lymphodepleting chemotherapy with cyclophosphamide IV and fludarabine IV on days -5 to -3 per standard of care. Patients also undergo low dose TBI on day -2 and receive standard of care Tisa-cel IV over 5-30 minutes on day 0. Additionally, patients undergo blood sample collection, PET/CT or CT throughout the study.

Procedure: Biospecimen Collection; Procedure: Computed Tomography; Drug: Cyclophosphamide; Drug: Fludarabine; Procedure: Leukapheresis; Procedure: Positron Emission Tomography; Biological: Tisagenlecleucel; Radiation: Total-Body Irradiation

Interventions

Computed Tomography PROCEDURE

Undergo PET/CT or CT

Also known as: CAT, CAT Scan, Computed Axial Tomography, Computerized Axial Tomography, Computerized axial tomography (procedure), Computerized Tomography, Computerized Tomography (CT) scan, CT, CT Scan, Diagnostic CAT Scan, Diagnostic CAT Scan Service Type, tomography

Treatment (TBI, lymphodepletion, Tisa-cel)

Cyclophosphamide DRUG

Given IV

Also known as: (-)-Cyclophosphamide, 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate, Asta B 518, B 518, B-518, B518, Carloxan, Ciclofosfamida, Ciclofosfamide, Cicloxal, Clafen, Claphene, CP monohydrate, CTX, CYCLO-cell, Cycloblastin, Cycloblastine, Cyclophospham, Cyclophosphamid monohydrate, Cyclophosphamide Monohydrate, Cyclophosphamidum, Cyclophosphan, Cyclophosphane, Cyclophosphanum, Cyclostin, Cyclostine, Cytophosphan, Cytophosphane, Cytoxan, Fosfaseron, Genoxal, Genuxal, Ledoxina, Mitoxan, Neosar, Revimmune, Syklofosfamid, WR 138719, WR- 138719, WR-138719, WR138719

Treatment (TBI, lymphodepletion, Tisa-cel)

Leukapheresis PROCEDURE

Undergo leukapheresis

Also known as: Leukocyte Adsorptive Apheresis, Leukocytopheresis, Therapeutic Leukopheresis, White Blood Cell Reduction Apheresis

Treatment (TBI, lymphodepletion, Tisa-cel)

Tisagenlecleucel BIOLOGICAL

Given IV

Also known as: CART-19, CART19, CTL 019, CTL-019, CTL019, CTL019 T-cells, Kymriah, Tisa-cel, Tisagenlecleucel-T

Treatment (TBI, lymphodepletion, Tisa-cel)

Total-Body Irradiation RADIATION

Undergo low dose TBI

Also known as: SCT_TBI, TBI, Total Body Irradiation, Whole Body, Whole Body Irradiation, Whole-Body Irradiation

Treatment (TBI, lymphodepletion, Tisa-cel)

Biospecimen Collection PROCEDURE

Undergo blood sample collection

Also known as: Biological Sample Collection, Biospecimen Collected, Sample Collection, Specimen Collection

Treatment (TBI, lymphodepletion, Tisa-cel)

Fludarabine DRUG

Given IV

Also known as: Fluradosa

Treatment (TBI, lymphodepletion, Tisa-cel)

Positron Emission Tomography PROCEDURE

Undergo PET/CT

Also known as: Medical Imaging, Positron Emission Tomography, PET, PET Scan, Positron emission tomography (procedure), Positron Emission Tomography Scan, Positron-Emission Tomography, PT

Treatment (TBI, lymphodepletion, Tisa-cel)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Eligible for standard of care anti-CD19 CAR-T treatment with Tisa-cel
• Age ≥ 18 years
• Biopsy-confirmed relapsed or refractory large B-cell lymphoma after 2 lines of prior therapy
• Qualitative CD19 expression by either immunohistochemistry (IHC) or flow cytometry
• Measurable disease prior to lymphodepletion as determined by Lugano criteria
• Non-RT bridging therapy allowed, but requires re-staging prior to lymphodepletion (LD) to confirm measurable disease
• Adequate performance status Eastern Cooperative Oncology Group (ECOG) ≤ 2
• Platelets above 75K
• Hemoglobin above 8.0 g/dL without transfusion within 1 week
• Absolute neutrophil count (ANC) above 1,000 without granulocyte colony-stimulating factor (G-CSF) within 1 week
• Total bilirubin \< 1.5 x upper limit of normal (ULN)
• Alanine aminotransferase (ALT) =\< 3 x ULN
• Glomerular filtration rate (GFR) \> 60 ml/min calculated by the Cockcroft - Gault formula
• Oxygen saturation (SpO2) \> 92% without supplemental oxygen
• Ejection fraction more than 45%

You may not qualify if:

• Active central nervous system (CNS) disease at screening or prior to lymphodepletion
• Prior therapy with autologous or allogenic CAR-T or CAR-natural killer (NK) cell therapy
• Prior anti-CD19 therapies (such as, but not limited to tafasitamab or loncastuximab)
• Prior allogeneic stem cell transplant
• Bridging therapy with radiation not allowed
• Any contra-indications to receive low-dose TBI, standard of care lymphodepleting chemotherapy or Tisa-cel per treating physician
• A minimum of 28 days must have elapsed between prior treatment with investigational agent(s) and start of lymphodepletion
• Uncontrolled major medical problem as infections
• Active malignancy, other than non-melanoma skin cancer or carcinoma in situ (e.g. cervix, bladder, breast). Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial (e.g. low Gleason score prostate cancer)
• Patients with uncontrolled intercurrent illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, pulmonary abnormalities or psychiatric illness/social situations that would limit compliance with study requirements
• Pregnant or breastfeeding women are excluded from this study because CAR-T cell therapy may be associated with the potential for teratogenic or abortifacient effects. Women of childbearing potential must have a negative serum pregnancy test. Because there is an unknown, but potential risk for adverse events in nursing infants secondary to treatment of the mother with CAR-T cells, breastfeeding should be discontinued. These potential risks may also apply to other agents used in this study
• Evidence of myelodysplasia or cytogenetic abnormality indicative of myelodysplasia on any bone marrow biopsy prior to initiation of therapy
• Active hepatitis B or C as indicated by serology (for details please refer to Novartis Leukapheresis Reference Manual version \[v\] 4)
• Patients with history of clinically relevant CNS pathology such as epilepsy, seizure disorders, paresis, aphasia, uncontrolled cerebrovascular disease, severe brain injuries, dementia and Parkinson's disease
• History of autoimmune disease (e.g., rheumatoid arthritis, systemic lupus erythematosus) with requirement of systemic immunosuppressive medication within 6 months

Sponsors & Collaborators

• Nathan Denlinger: lead
• Novartis: collaborator

Study Sites (1)

Ohio State University Comprehensive Cancer Center

Columbus, Ohio, 43210, United States

Location

Related Links

• The Jamesline

MeSH Terms

Conditions

Lymphoma, Large B-Cell, Diffuse

Interventions

Specimen Handling; Cyclophosphamide; fludarabine; Leukapheresis; Magnetic Resonance Spectroscopy; tisagenlecleucel; CTL019 chimeric antigen receptor; Whole-Body Irradiation

Condition Hierarchy (Ancestors)

Lymphoma, B-Cell; Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Investigative Techniques; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Cytapheresis; Biological Therapy; Therapeutics; Blood Component Removal; Leukocyte Reduction Procedures; Cell Separation; Cytological Techniques; Spectrum Analysis; Chemistry Techniques, Analytical; Radiotherapy

Study Officials

• Nathan Denlinger, DO

  Ohio State University Comprehensive Cancer Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Ohio State University Comprehensive Cancer Center

CONTACT

800-293-5066; OSUCCCClinicaltrials@osumc.edu

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: June 23, 2026
• First Posted: June 30, 2026
• Study Start (Estimated): September 1, 2026
• Primary Completion (Estimated): December 31, 2027
• Study Completion (Estimated): December 31, 2027
• Last Updated: June 30, 2026

Record last verified: 2026-06

Locations

US (1)