Study of VIP152, Venetoclax, and Prednisone (VVIP) in Relapsed/Refractory Lymphoid Malignancies

* INCLUSION CRITERIA:
* Participants must have a histologically or cytologically confirmed lymphoid malignancy as listed below, confirmed by the Laboratory of Pathology, National Cancer Institute (NCI), as follows:

  * Refractory/relapsed (R/R) MYC-rearranged diffuse large B-cell lymphoma (DLBCL)/High-grade B-cell lymphoma (HGBCL) (MYC aberration must be confirmed by NCI Laboratory of Pathology to enroll)
  * R/R non-germinal center B-cell (non-GCB) DLBCL without MYC-rearrangement (Cell of origin (COO) and non-MYC aberration must be confirmed by NCI Laboratory of Pathology to enroll. COO determination at enrollment will utilize immunohistochemistry and Han's algorithm)
  * R/R Peripheral T-cell lymphoma (PTCL-not otherwise specified (NOS), PTCL-T follicular helper (TFH), follicular T-cell lymphoma (TCL), angioimmunoblastic T-cell lymphoma (AITL), adult T-cell leukemia/lymphoma (ATLL), anaplastic lymphoma kinase (ALK)+ anaplastic large-cell lymphoma (ALCL) and ALK- ALCL per 2016 World Health Organization (WHO) classification)
* Relapsed and/or refractory disease, as defined below:

  * Aggressive B-cell lymphoma: relapsed after and/or refractory to at least 2 prior systemic therapies, 1 or more which includes an anthracycline and anti-cluster of differentiation 20 (CD20) targeting agent
  * PTCL: relapsed after and/or refractory to at least 2 prior systemic therapies, 1 or more which includes an anthracycline (and a brentuximab vedotin-containing regimen for participants with ALK+ or ALK- ALCL)
* Must have evaluable disease by clinical exam (i.e., palpable lymphadenopathy, measurable skin lesions, etc.), laboratory assessment (i.e., disease involvement of bone marrow or peripheral blood by morphology, cytology or flow cytometry), and/or imaging (measurable lymph nodes, masses, or bony lesions on computed tomography (CT) or magnetic resonance imaging (MRI) and/or evaluable FD-Gavid lesions on positron emission tomography (PET).

NOTE: Lesions that have been irradiated cannot be included in the tumor assessment unless unequivocal tumor progression has been documented in these lesions after radiation therapy.

* Age \>= 18 years
* Eastern Cooperative Oncology Group (ECOG) performance status \<= 2
* Adequate organ and marrow function as defined below unless dysfunction is secondary to disease:

  * Absolute neutrophil count\* \>=1,000/mcL
  * Hemoglobin\* \>=8 g/dL
  * Platelets \>=75,000/mcL
  * International normalized ratio (INR) \<=1.5 X institutional upper limit of normal (ULN) for participants not receiving therapeutic anticoagulation
  * Partial thromboplastin time (PTT)/activated partial thromboplastin time (aPTT) \<= 1.5 X institutional ULN normal except if the aPTT is elevated because of a positive Lupus Anticoagulant
  * Total bilirubin\*\* \<=1.5 X institutional ULN (or \<=3 X institutional ULN for participants with documented Gilbert's syndrome)
  * Aspartate aminotransferase (AST) serum glutamic-oxaloacetic transaminase (SGOT)(SGOT)/Alanine aminotransferase (ALT) serum glutamic-pyruvic transaminase (SGPT)\*\*\* \<= 2.5 X institutional ULN
  * Serum creatinine \<= 2.0 mg/dL

OR

--Creatinine clearance\*\*\*\* \>= 40 mL/min/1.73 m\^2 for participants with creatinine levels above 2 mg/dL

Creatinine clearance (Cr Cl) will be calculated with the use of the 24-hour creatinine clearance or modified

Cockcroft-Gault equation (eCCR; with the use of ideal body mass \[IBM\] instead of mass): (140 - Age) x IBM (kg) x \[0.85 if female\] / 72 x serum creatinine (mg/dL)

\*Red blood cell (RBC) transfusions and use of granulocyte colony-stimulating factor (G-CSF) will be allowed in order to meet eligibility parameters.

* Total bilirubin must be \<= 3 X institutional ULN for eligibility even if secondary to disease.

  * AST(SGOT)/ALT(SGPT) must be \<= 5 X institutional ULN for eligibility even if secondary to disease.

    * Creatinine clearance must be \>= 30 mL/min for eligibility even if secondary to disease.

      * Negative serum or urine pregnancy test must be obtained within 7 days before the first dose of study drug in individuals of childbearing potential. Postmenopausal individuals, as defined below, are allowed to enroll without a pregnancy test:

        --Age \>50 years with amenorrhea for at least 12 months or

        --Age \<=50 years with 6 months of spontaneous amenorrhea and follicle stimulating hormone (FSH) level within postmenopausal range (\>40 mIU/mL) OR
        * Permanently sterilized (e.g., tubal occlusion, hysterectomy, bilateral salpingectomy, uterine ablation)
      * Individuals of reproductive potential must agree to use highly effective contraception when sexually active. This applies for the period between signing of the informed consent and 90 days after the last administration of study drug.

Highly effective contraception includes:

* Established use of oral, injected or implanted hormonal methods of contraception
* Placement of certain intrauterine devices (IUD) or intrauterine systems (IUS)
* Hysterectomy, oophorectomy, salpingectomy or vasectomy of the partner (provided that partner is the sole sexual partner of the individual of childbearing potential trial participant and that the vasectomized partner has received medical assessment of the surgical success)

In addition, participants must agree to use condoms.

* Participants that are positive for hepatitis B core antibody (HBcAb), hepatitis B surface antigen (HBsAg), or hepatitis C antibody (HCVAb) must have a negative hepatitis B and/or C viral load by polymerase chain reaction (PCR), and agree to additional monitoring.
* Ability of participant to understand and the willingness to sign a written informed consent document.
* Nursing participants must be willing to discontinue nursing from study treatment initiation through 90 days after the last administration of study drug.

EXCLUSION CRITERIA:

-The following restrictions apply to current or prior anti-cancer treatment, prior to the first dose of study drug:

* Participants who are actively receiving any other anti-cancer investigational agents.
* Any chemotherapy, targeted therapy, or anti-cancer antibodies within 2 weeks prior to the first dose of study drug
* Radio- or toxin-immunoconjugates within 10 weeks prior to the first dose of study drug
* Prior allogeneic stem cell (or other organ) transplant within 6 months or any evidence of active graft-versus-host disease or requirement for immunosuppressants within 28 days prior to first dose of study drug
* Not recovered (i.e., \<= Grade 1 or baseline) from adverse events due to previously administered anti-cancer treatment, surgery, or procedure.

NOTE: Exceptions to this include events not considered to place the participant at unacceptable risk of participation in the opinion of the principal investigator (PI) (e.g., alopecia).

-Participants requiring the following agents within 14 days or 5 half-lives of the drug (whichever is shorter) prior to the first dose of venetoclax and VIP152 are excluded:

* Strong cytochrome P450, family 3, subfamily A (CYP3A) inhibitors
* Strong CYP3A inducers
* Moderate CYP3A inhibitors (dose-escalation cohort only)
* Moderate CYP3A inducers (dose-escalation cohort only)

NOTE: Moderate CYP3A inhibitors and inducers should be used with caution for participants in the dose-expansion cohorts and an alternative medication used, whenever possible.

* Known allergy to both xanthine oxidase inhibitors and rasburicase; or known hypersensitivity to any of the study drugs
* Known active bacterial, viral, fungal, mycobacterial, parasitic, or other infection (excluding fungal infections of nail beds) at study enrollment, or any major episode of infection requiring treatment with IV antibiotics or hospitalization (relating to the completion of the course of antibiotics) within 2 weeks prior to first dose of study drug
* HIV-positive participants
* Active cytomegalovirus (CMV) infection as determined by a positive CMV polymerase chain reaction (PCR)
* Active severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection based on PCR assay; prior SARs-CoV-2 infection allowed if completely recovered from infection and negative PCR testing
* Clinically significant history of liver disease, including viral or other hepatitis, current alcohol abuse, or cirrhosis; as well as active infection with hepatitis B Virus (HBV) or Hepatitis C Virus (HCV) except as noted above in inclusion criteria

  * Participants with occult or prior HBV infection (defined as positive hepatitis B surface antigen (HBsAg) or positive hepatitis B core antibody (HBcAb)) may be included if HBV deoxyribonucleic acid (DNA) is undetectable (i.e., none detected in copies/mL or IU/mL). These individuals must be willing to undergo HBV DNA testing during treatment and in surveillance for at least 12 months after completion of study therapy.
  * Participants who are positive for HCV antibody must be negative for HCV by polymerase chain reaction (PCR) to be eligible for study participation
* Malabsorption syndrome or other condition that precludes enteral route of administration
* History of other active malignancy requiring therapy that could affect compliance with the protocol or interpretation of results
* Symptomatic congestive heart failure, unstable angina pectoris, or cardiac arrhythmia
* Left ventricular ejection fraction (LVEF) \< 45%
* Clinically relevant findings on electrocardiogram (ECG) such as a second- or third-degree AV block or prolongation of the heart-rate corrected QT interval (Qtc) (Fridericia) over 470 msec (participants with atrioventricular (AV) block and pacemaker in place for \>1 year and checked by a cardiologist within \<6 months before the first dose of study drug, will not be excluded).
* Uncontrolled intercurrent illness (including psychiatric) or social situations that may limit interpretation of results or that could increase risk to the participant