Testing the Safety of Anti-Cancer Drug, CX-5461 (Pidnarulex), in Treating Lymphoma With Specific Changes in the MYC Gene

Inclusion Criteria:

• Patients must have one of the following subtypes of aggressive B-cell non-Hodgkinlymphomas: double-expressor lymphoma (DEL), high-grade B-cell lymphoma (HGBL) withMYC and BCL2 and/or BCL6 rearrangement, or Burkitt lymphoma (BL). Eligible patientsmust have received at least two prior lines of treatment for diffuse large B-celllymphoma (DLBCL) or at least one prior line of therapy for Burkitt Lymphoma and musthave disease for which no standard curative or palliative treatment options exist orremain effective (Quin et al., 2016)

• Age ≥ 18 years. Because no dosing or adverse event (AE) data are currently availableon the use of CX-5461 (Pidnarulex) in patients < 18 years of age, children areexcluded from this study

• Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2 (Karnofsky ≥ 60%).ECOG 3 is allowed if directly related to lymphoma per treating provider

• Absolute neutrophil count ≥ 1,000/mcL

• Platelets ≥ 50,000/mcL

• Total bilirubin ≤ 1.5 institutional upper limit of normal (ULN)

• Patients with documented Gilbert's syndrome may be included if total bilirubinis ≤ 3 × ULN and direct bilirubin is within normal limits

• Aspartate aminotransferase (AST)(serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase [SGPT]) ≤ 3 ×institutional upper limit of normal (ULN)

• Glomerular filtration rate (GFR) ≥ 60 mL/min/, calculated by multiplying theestimated (e)GFR (mL/min/1.73 m^2) by the individual's body surface area (BSA,calculated using an accepted formula) and dividing by 1.73 m^2

• Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviraltherapy with undetectable viral load within 6 months are eligible for this trial

• For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBVviral load must be undetectable on suppressive therapy, if indicated

• Patients with a history of hepatitis C virus (HCV) infection must have been treatedand cured. For patients with HCV infection who are currently on treatment, they areeligible if they have an undetectable HCV viral load

• Patients with a prior or concurrent malignancy whose natural history or treatmentdoes not have the potential to interfere with the safety or efficacy assessment ofthe investigational regimen are eligible for this trial

• Patients with known history or current symptoms of cardiac disease, or history oftreatment with cardiotoxic agents, should have a clinical risk assessment of cardiacfunction using the New York Heart Association Functional Classification. To beeligible for this trial, patients should be class II or better

• Patients with cytopenia related to abnormal bone marrow function in the setting ofbone marrow involvement with lymphoma or post chimeric antigen receptor (CAR) T-cellare allowed to enroll if deemed safe by treating provider

• Patients without clinical evidence of central nervous system (CNS) lymphoma

• The effects of CX-5461 (Pidnarulex) on the developing human fetus are unknown. Forthis reason, women of child-bearing potential and men must agree to use adequatecontraception (hormonal or barrier method of birth control or abstinence) 14 daysprior to study entry and for the duration of study participation and for at least 6months after the last dose of study drug. Should a woman become pregnant or suspectshe is pregnant while she or her partner is participating in this study, she shouldinform her treating physician immediately. Women should not breastfeed while takingCX-5461 (Pidnarulex) and for 6 months after cessation of treatment. Men treated orenrolled on this protocol must also agree to use adequate contraception 14 daysprior to the study, for the duration of study participation, and 6 months aftercompletion of CX-5461 (Pidnarulex) administration. Women of childbearing age shouldnot donate egg(s) and men should not donate sperm for the duration of studyparticipation and 6 months after completion of the last dose CX-5461 (Pidnarulex)

• Willingness to provide blood and biopsy samples for research purposes

• Ability to understand and the willingness to sign a written informed consentdocument

Exclusion Criteria:

• Patients must have recovered from clinically significant adverse events (AEs) oftheir most recent cancer immunotherapy to grade 1 or less (with the exception foralopecia or lymphopenia)

• Eligibility of subjects receiving any medications or substances known to affect orwith the potential to affect the activity of CX-5461 (Pidnarulex) will be determinedbased on their potential to interact with the CYP3A4 isozyme. Specifically, subjectstaking strong CYP3A4 inhibitors or strong CYP3A4 inducers will be excluded fromparticipation in the trial. For medications or substances not listed, or in cases ofuncertainty, the Principal Investigator may consult with a medical expert or apharmacologist to make an informed decision regarding eligibility

• Patients with a baseline corrected QT (QTc) interval > 480 msec

• Patients who are receiving any other investigational agents

• History of allergic reactions attributed to compounds of similar chemical orbiologic composition to CX-5461 (Pidnarulex)

• Patients with uncontrolled intercurrent illness or any other significantcondition(s) that would make participation in this protocol unreasonably hazardous

• Pregnant women are excluded from this study because CX-5461 (Pidnarulex) is an agentwith the potential for teratogenic or abortifacient effects. Because there is anunknown but potential risk for AEs in nursing infants secondary to treatment of themother with CX-5461 (Pidnarulex), breastfeeding should be discontinued if the motheris treated with CX-5461 (Pidnarulex)