Vorinostat and Combination Chemotherapy With Rituximab in Treating Patients With HIV-Related Diffuse Large B-Cell Non-Hodgkin Lymphoma or Other Aggressive B-Cell Lymphomas

Inclusion Criteria:

• Histologically, or cytologically documented diffuse large B-cell lymphoma, and other aggressive CD20+ non-Burkitt non-Hodgkin B-cell lymphoma variants as defined by the 2008 WHO classification; rare aggressive CD20 negative B-cell lymphomas are also eligible
• Subjects who are untreated or who received a maximum of one (1) cycle of chemotherapy prior are eligible; previous treatment must occur at least 4 weeks prior to enrollment
• All stages of disease allowed
• CD4 count ≥ 50 cells/mm³

• Must meet 1 of the following risk sets of criteria:

  • Low-risk

    • Age-adjusted (aa)-international prognostic index (IPI) scores: 0-1 factors*
    • Ki-67 < 80%
    • Germinal center B-cell-like (GCB) DLBCL or non-Burkitt subtype (if known)

  • High-risk

    • aa-IPI: 2-3 factors*
    • Ki-67 ≥ 80%
    • Activated B-cell-like (ABC, also known as post-GCB) subtype DLBCL if known, or any other aggressive non-Burkitt B-cell lymphomas

• Serologically confirmed HIV infection by ELISA or western blot, or by another federally approved licensed HIV test

  • Prior documentation of HIV seropositivity allowed

• Measurable or non-measurable tumor

  • Non-measurable tumor parameters are defined as not having bidimensional measurements (e.g., gastric or marrow involvement), but that can be followed for response by other diagnostic tests such as gallium, PET imaging, and/or bone marrow biopsy
• No CNS involvement including parenchymal brain or spinal cord lymphoma, or known leptomeningeal disease
• Concurrent chronic therapy with potentially myelosuppressive agents allowed provided hematologic criteria are met
• ECOG performance status (PS) 0-2 (Karnofsky PS 50-100%)
• Life expectancy ≥ 2 months
• ANC ≥ 1,000/mm³
• Platelet count ≥ 75,000/mm³ (unless abnormal due to lymphomatous involvement of bone marrow)
• Creatinine < 2.0 mg/dL OR creatinine clearance ≥ 60 mL/min (< 50 mL/min if due to kidney involvement by tumor)
• Total bilirubin ≤ 1.5 times upper limit of normal (ULN) (unless due to hepatic involvement or HIV medication such as indinavir, tenofovir, or atazanavir [drug adjustment may be needed if direct bilirubin > 1.2 times ULN due to hepatic involvement])
• AST and ALT ≤ 2.5 times ULN (unless elevated due to secondary lymphomatous involvement of the liver)
• LVEF normal by MUGA scan or ECHO within the past 6 weeks
• Negative pregnancy test
• Not pregnant or nursing
• Fertile patients must use effective contraception during and for 6 months after completion of study treatment
• Able to swallow oral medications
• Presence of second active tumor, other than non-melanoma skin cancer, carcinoma in situ of the cervix, or Kaposi's sarcoma (KS) that requires systemic therapy
• Subjects who are Hepatitis B core antibody positive are eligible only if they start or are on prophylactic therapy; subjects with known active Hepatitis B (surface antigen, core antigen, or viral load positive) are ineligible; a hepatitis B viral load should be confirmed negative on all patients who are hepatitis B core antibody positive, but hepatitis B antigen negative
• No known chronic hepatitis C virus infection
• Must be able to comply with protocol requirements and provide adequate informed consent, in the opinion of the principal investigator
• No serious, ongoing, non-malignant disease or infection, including opportunistic infections that, in the opinion of the investigator and/or the sponsor, would compromise other protocol objectives
• No history of cutaneous or mucocutaneous reactions, or other disease due to any cause, severe enough to cause hospitalization or inability to eat or drink for > 2 days

• No acute, inter-current infection that may interfere with planned protocol treatment

  • Patients with mycobacterium avium infection allowed

• None of the following:

  • Myocardial infarction within the past 6 months
  • NYHA class II-IV heart failure
  • Uncontrolled angina
  • Severe uncontrolled ventricular arrhythmias
  • Clinically significant pericardial disease
  • Electrocardiographic evidence of acute ischemic or active conduction system abnormalities

• Concurrent highly active antiretroviral (HAART) regimen that is in accordance with the current International AIDS Society guidelines allowed

  • Changes to HAART therapy allowed if medically necessary (e.g., toxicity, failure of regimen)
  • HAART-naive patients must start therapy after completion of course 1 of chemotherapy
  • Concurrent agents currently available on expanded access program allowed
  • No experimental antiretroviral agents

  • No concurrent agents containing zidovudine, including Combivir® and Trizivir®

    • Zidovudine or a zidovudine-containing regimen (including Combivir® and Trizivir®) is prohibited until 2 months after completion of study chemotherapy
• At least 24 hours since prior colony-stimulating factor therapy
• More than 4 weeks since prior major surgery other than diagnostic surgery
• Rituximab therapy within the 12 months prior to study entry except as outlined above; patients treated with rituximab within 12 months prior to study registration are eligible only if it was given for indications other than the treatment of aggressive lymphoma except as outlined above
• No prior cytotoxic chemotherapy or radiotherapy for this lymphoma, except as outlined above
• No prior valproic acid or another histone deacetylase inhibitor within the past 2 weeks
• Patients who received more than one (1) prior cycle of chemotherapy are not allowed; patients may have received one prior cycle of chemotherapy similar to CHOP or EPOCH with or without rituximab