Tegavivint for Treating Patients With Relapsed or Refractory Large B-Cell Lymphoma

Inclusion Criteria:

One of the following three conditions:

* Relapsed/refractory histologically confirmed germinal center B-cell-like (GCB) and non-GCB diffuse large B cell lymphoma (DLBCL) with the following features:

  * Increased expression of MYC (\>= 40%) and BCL2 (\>= 50%) by immunohistochemistry (IHC) or
  * Presence of isolated MYC translocation Or
* Relapsed/refractory histologically confirmed high-grade B-cell lymphoma (HGBCL) (double hit \[DH\] and triple hit \[TH\]) with translocations of MYC and BCL2 and/or BCL6 Or
* Histologic transformation of indolent non-Hodgkin's lymphoma (NHL) to DLBCL

  * Presence of BCL2 translocation with increased expression of MYC (≥40%) with or without MYC translocation
* Patients must have had at least two prior systemic therapies
* Patients must be ineligible for or refused autologous or allogenic hematopoietic stem cell transplantation or chimeric antigen receptor (CAR) T-cell therapy. Prior autologous stem cell transplant and/or CAR-T are allowed, if received \>= 3 months prior to enrollment
* Age \>= 18 years
* Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
* Patients must have radiographically measurable disease by standard positron emission tomography (PET) uptake with at least one site of measured disease by standardized uptake value (SUV)
* Absolute neutrophil count (ANC) ≥ 500/mcL
* Platelet count ≥ 25,000/mcL
* Total bilirubin =\< 1.5 x the upper limit of the normal range (ULN)
* Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) \< 3 x institutional ULN
* Creatinine clearance \>= 60 ml/min by Cockcroft-Gault (actual body weight will be used to estimate creatinine clearance)
* Patients must be willing and able to understand and give written informed consent and comply with all study related procedures
* Women of child-bearing potential (WOCBP) and men who are sexually active with WOCBP must agree to use one hormonal contraceptive (e.g. combined oral contraceptives, patch, vaginal ring, injectables, and implants); intrauterine device (IUD) or intrauterine system (IUS); vasectomy or tubal ligation; and one effective method of contraception, including male condom, female condom, cervical cap, diaphragm or contraceptive sponge or abstain from sex for the duration of study participation and for 4 months following completion of tegavivint administration. 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.

Contraception includes:

* Total abstinence (when this is in line with the preferred and usual lifestyle of the patient. Periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception
* Female sterilization (have had surgical bilateral oophorectomy with or without hysterectomy), total hysterectomy or tubal ligation at least 6 weeks before taking study treatment. In case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment
* Male sterilization (at least 6 months prior to screening). For female patients on the study the vasectomized male partner should be the sole partner for that patient
* Use of oral (estrogen and progesterone), injected or implanted combined hormonal methods of contraception or placement of an intrauterine device (IUD) or intrauterine system (IUS) or other forms of hormonal contraception that have comparable efficacy (failure rate \<1%), for example hormone vaginal ring or transdermal hormone contraception
* Sexually active males must use a condom during intercourse while taking drug and for 4 months after stopping study treatment and should not father a child in this period. A condom is required to be used also by vasectomized men in order to prevent delivery of the drug via seminal fluid In case of use of oral contraception women should have been stable on the same pill for a minimum of 3 months before taking study treatment. Women are considered post-menopausal and not of child bearing potential if they have had 12 months of natural (spontaneous) amenorrhea with an appropriate clinical profile (e.g. age appropriate, history of vasomotor symptoms) or have had surgical bilateral oophorectomy (with or without hysterectomy) or tubal ligation at least 6 weeks ago. In the case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment is she considered not of child bearing potential

Exclusion Criteria:

* History of allergic reactions attributed to compounds of similar chemical or biologic composition to tegavivint or other agents used in study
* Known active central nervous system (CNS) lymphoma, history of CNS involvement allowed if in remission for \>= 3 months
* Evidence of chronic active Hepatitis B, chronic active Hepatitis C infection
* Human immunodeficiency virus (HIV)-positive patients on combination antiretroviral therapy (e.g., strong CYP3A inhibitors and/or concomitant medications that are excluded) are ineligible because of the potential for pharmacokinetic interactions with tegavivint
* Known history of active TB (Bacillus Tuberculosis)
* Major surgery within 3 weeks prior to start of study treatment
* Clinically significant, uncontrolled heart disease and/or cardiac repolarization abnormality or corrected QT interval (QTc) \> 480 msec
* Uncontrolled concurrent illness including, but not limited to: ongoing or active infection (Viral, bacterial, fungal or other)
* Psychiatric illness/social situations that would limit compliance with study requirements
* Pregnant and breastfeeding women are excluded from this study. The effects of tegavivint on the developing human fetus have the potential for teratogenic or abortifacient effects. There is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with tegavivint
* Patients with abnormal serum chemistry values other than the specific limits detailed above, that in the opinion of the investigator is considered to be clinically significant, should be discussed with the Study PI before being enrolled in the study
* Personal history of malignancy except:

  * Cervical intraepithelial neoplasia;
  * Skin basal cell carcinoma;
  * Treated localized prostate carcinoma with prostate specific antigen (PSA) \<1 ng/mL or untreated indolent prostate cancer
  * Neoplasia treated with curative intent, in remission for at least three years and considered at low risk of relapse