B-Cell Lymphoma Clinical Trials

⁃ Patients must meet the following criteria for study entry:

⁃ 2\. Age ≥18 years 3. Histologically diagnosed 4. Diffuse large B-cell lymphoma, not otherwise specified (NOS) or 5. High grade B-cell lymphoma (NOS or MYC and BCL2 rearrangements) 6. International Prognostic Index score ≥ 3 or 1-2 with LDH \> 1.3 x ULN and/or bulky disease (single lesion of ≥ 7cm) 7. Received first line standard of care anthracycline-based chemoimmunotherapy for 6 cycles (with or without 2 more cycles of rituximab) for previously untreated disease

• R-CHOP (cyclophosphamide, doxorubicin, vincristine sulfate, and prednisone)

• DA-EPOCH-R

• Polatuzumab-R-CHP 8. Achieved complete metabolic response by Lugano criteria4 at the end of treatment response evaluation after first line treatment

• Or PR only if suitable for observation, defined as either negative biopsy or deemed too small or not amenable to biopsy 9. Had a response assessment within 8 weeks following completion of first line standard of care treatment 10. Detectable MRD after first line treatment (regardless of the ctDNA level) by Foresight CLARITY™12 11. Performance status ≤2 on the ECOG scale (section 6.2.5) 12. Adequate organ and marrow function as defined below:

• Absolute neutrophil count (ANC) ≥1.0 × 109 /L\*

• \*Growth factor permitted during screening

• Platelet count ≥75 × 109 /L

• Hemoglobin ≥ 8 g/dL

• Total bilirubin ≤ 3 ULN, unless consistent with Gilbert's syndrome

• AST and ALT ≤ 3x upper limit of normal (ULN)

• Alkaline phosphatase \< 2.5 ULN

• Creatinine clearance \>40 ml/min calculated by modified Cockcroft-Gault formula or estimated GFR (eGFR) \> 40 ml/min/1.73m2

• Cardiac ejection fraction ≥ 40%, no evidence of clinically significant pericardial effusion as determined by an echocardiogram (ECHO), and no clinically significant electrocardiogram (ECG) findings 13. All subjects must

• Agree to refrain from donating blood while on study treatment, and for at least 12 months following the last dose of study treatment.

• 14\. The effects of liso-cel on the developing human fetus are unknown. For this reason, women of childbearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. (Refer to Pregnancy Assessment Policy MD Anderson Institutional Policy # CLN1114). This includes all female patients, between the onset of menses (as early as 8 years of age) and 55 years unless the patient presents with an applicable exclusionary factor which may be one of the following:

• Postmenopausal (non-chemically induced menopause in greater than or equal to 12 consecutive months).

• History of hysterectomy or bilateral salpingo-oophorectomy.

• Ovarian failure (Follicle Stimulating Hormone and Estradiol in menopausal range, who have received Whole Pelvic Radiation Therapy).

• History of bilateral tubal ligation or another surgical sterilization procedure.

• 15\. Females of childbearing potential (FCBP) must:

• Have 2 negative pregnancy tests as verified by the Investigator (one negative serum beta-human chorionic gonadotropin \[ß-hCG\] pregnancy test result at screening, and within 7 days prior to the first dose of LD chemotherapy). This applies even if the subject practices true abstinence2 from heterosexual contact.

• Either commit to true abstinence from heterosexual contact (which must be reviewed monthly and source documented) or agree to use, and be able to comply with, effective contraception without interruption. Contraception methods must include 1 highly effective method from screening until at least 12 months after the LD chemotherapy.

• Agree to abstain from breastfeeding during study participation and for at least 12 months following LD chemotherapy.

• Approved methods of birth control are as follows: Hormonal contraception (i.e. birth control pills, injection, implant, transdermal patch, vaginal ring), Intrauterine device (IUD), Tubal Ligation or hysterectomy, Subject/Partner post vasectomy, Implantable or injectable contraceptives, and condoms plus spermicide. Not engaging in sexual activity for the total duration of the trial and the drug washout period is an acceptable practice; however periodic abstinence, the rhythm method, and the withdrawal method are not acceptable methods of birth control. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately.

• 16\. Male subjects must:

• Male Practice true abstinence (which must be reviewed monthly basis) or agree to use a condom during sexual contact with a pregnant female or a female of childbearing potential for 12 months after LD chemotherapy even if he has undergone a successful vasectomy.

• 17\. Willing and able to comply with the protocol treatment and procedures. 18. Ability to understand and the willingness to sign a written informed consent document.