Recruiting

Phase 1

TBI, Cyclophosphamide, Fludarabine, Tisa-celLymphodepletion With Low Dose Total Body Irradiation Before Standard of Care Tisagenlecleucel for the Treatment of Relapsed and Recurrent Large B-cell Lymphoma

Sponsor:

Nathan Denlinger

Code:

NCT07676877

Conditions

Recurrent Diffuse Large B-Cell Lymphoma

Refractory Diffuse Large B-Cell Lymphoma

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Interventions

Biospecimen Collection

Computed Tomography

Cyclophosphamide

Fludarabine

Leukapheresis

Study Details

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

Study ID

NCT07676877

Start date

Dec 1, 2026

Status verified date

Oct, 2026

Completion date

Dec 31, 2027

Anticipated

Primary completion date

Dec 31, 2027

Anticipated

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Inclusion Criteria:

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%
Patients must have the ability to understand and the willingness to sign a written informed consent document
For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use a contraceptive method with a failure rate of < 1% per year during the treatment period and for at least 12 months after Tisa-cel and until CAR T-cells are no longer present by quantitative polymerase chain reaction (qPCR) on two consecutive tests
A woman is considered to be of childbearing potential if she is postmenarcheal, has not reached a postmenopausal state (< 12 continuous months of amenorrhea with no identified cause other than menopause), and has not undergone surgical sterilization (removal of ovaries and/or uterus). Examples of contraceptive methods with a failure rate of < 1% per year include bilateral tubal ligation, male sterilization, hormonal contraceptive s that inhibit ovulation, hormone-releasing intrauterine devices, and copper intrauterine devices
The reliability of sexual abstinence should be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the patient. Periodic abstinence (e.g., calendar, ovulation, symptothermal, or postovulation methods) and withdrawal are not acceptable methods of contraception
For men: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures, and agreement to refrain from donating sperm, as defined below:

With female partners of childbearing potential, men must remain abstinent or use a condom plus an additional contraceptive method that together result in a failure rate of < 1% per year during the treatment period and for at least 12 months after Tisa-cel infusion and until CAR T-cells are no longer present by qPCR on two consecutive tests. Men must refrain from donating sperm during this same period
With pregnant female partners, men must remain abstinent or use a condom during the treatment period and for at least 6 months after Tisa-cel infusion to avoid potential embryonal or fetal exposure. The reliability of sexual abstinence should be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the patient. Periodic abstinence (e.g., calendar, ovulation, symptothermal, or postovulation methods) and withdrawal are not acceptable methods of contraception
For patients with prior irradiation: the study radiation oncologist co-investigator will review the patient's prior history of radiation to confirm that the investigational low dose total body irradiation is feasible and safe to respect the maximum cumulative organ radiation exposure

Exclusion Criteria:

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
Live vaccines given in 28 days prior to lymphodepleting chemotherapy
Active substance use disorders

Study Design

Enrollment

18 participants

Anticipated

Intervention Model

Single group

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: Treatment (TBI, lymphodepletion, Tisa-cel)

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.

Interventions

Biospecimen Collection

Undergo blood sample collection

Computed Tomography

Undergo PET/CT or CT

Cyclophosphamide

Given IV

Fludarabine

Given IV

Leukapheresis

Undergo leukapheresis

Positron Emission Tomography

Undergo PET/CT

Tisagenlecleucel

Given IV

Total-Body Irradiation

Undergo low dose TBI

Primary outcome measure

Dose-limiting toxicities [ Time Frame: Up to 30 days after infusion ]
Maximum tolerated dose or recommended phase 2 dose (RP2D) [ Time Frame: Up to 30 days after infusion ]

Central Contacts and Locations

Central contacts

Ohio State University Comprehensive Cancer Center

800-293-5066 OSUCCCClinicaltrials@osumc.edu

Locations

Ohio State University Comprehensive Cancer Center

Recruiting

Columbus, Ohio, United States, 43210

Contacts

Nathan Denlinger, DO

614-293-3316 Nathan.Denlinger@osumc.edu

Principal Investigator:

Nathan Denlinger, DO

More Information

Sponsor

Nathan Denlinger

Last update posted

Oct 9, 2026

Last verified

Oct, 2026

Trial information was received from ClinicalTrials.gov and was last updated on 2026-10-10. This information was provided to ClinicalTrials.gov by Nathan Denlinger on 2026-10-09. Recruitment status is synced daily from ClinicalTrials.gov and may not reflect the sponsor's current status. Confirm during your call.