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

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

What this study is about