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SCCA Lymphoma Clinical Trials

Vorinostat and Combination Chemotherapy With Rituximab for HIV-Related Lymphoma (FH 2483)
A Sequential Phase I/Randomized Phase II Trial of Vorinostat and Risk-Adapted Chemotherapy With Rituximab in HIV-Related B-cell Non-Hodgkin's Lymphoma
Status Conditions Phase Study ID
Recruiting Lymphoma Phase I/II FH 2483
NCT01193842
Summary

RATIONALE: Vorinostat may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Monoclonal antibodies, such as rituximab, can block cancer growth in different ways. Some find cancer cells and help kill them or carry cancer-killing substances to them. Others interfere with the ability of cancer cells to grow and spread. Giving vorinostat together with combination chemotherapy and rituximab may kill more cancer cells.

PURPOSE: This randomized phase I/II trial is studying the side effects and the best dose of vorinostat when given together with combination chemotherapy and rituximab to see how well it works compared to combination chemotherapy and alone in treating patients with previously untreated HIV-related diffuse large B-cell non-Hodgkin lymphoma.


Investigator
Ann Woolfrey, MD
Location    
Seattle Cancer Care Alliance 800-804-8824  
Eligibility Criteria (must meet the following to participate in this study)

DISEASE CHARACTERISTICS:

  • Histologically or cytologically confirmed diffuse large B-cell non-Hodgkin lymphoma

    • CD20-positive (CD20+) tumor as defined by the 2008 WHO classification

      • Patients with only a subset of tumor cells that are CD20+ allowed
      • Tumors should be tested for EBV expression by IHC or in situ hybridization
  • Previously untreated disease
  • 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) subtype (if known)
    • High-risk

      • aa-IPI: 2-3 factors*
      • Ki-67 ≥ 80%
      • Activated B-cell-like (ABC, also known as post-GCB) subtype NOTE: * Adverse factors include stage III-IV disease, elevated serum LDH, or ECOG performance status of ≥ 2.
  • 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

PATIENT CHARACTERISTICS:

  • See Disease Characteristics
  • 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 fi 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
  • No second active malignancy except nonmelanoma skin cancer, carcinoma in situ of the cervix, or Kaposi sarcoma not requiring systemic therapy
  • No active hepatitis B virus (HBV) (surface-antigen or core-antigen positive)

    • HBV core-antibody positive allowed provided patient starts or is on prophylactic therapy
  • 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

PRIOR CONCURRENT THERAPY:

  • See Disease Characteristics
  • At least 24 hours since prior colony-stimulating factor therapy
  • More than 4 weeks since prior major surgery other than diagnostic surgery
  • No prior rituximab with the past 12 months

    • Prior rituximab within the past 12 months for indications other than treatment for aggressive lymphoma allowed
  • No prior cytotoxic chemotherapy or radiotherapy for this lymphoma

    • Concurrent radiotherapy with or without steroids, or steroids alone, for emergency conditions secondary to lymphoma (e.g., cord compression) allowed
  • No prior valproic acid or another histone deacetylase inhibitor within the past 2 weeks
  • 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
  • Concurrent chronic therapy with potentially myelosuppressive agents allowed provided hematologic criteria are met
Last Updated
November 07, 2012
See this trial at ClinicalTrials.gov
Access protocol and consent forms at Fred Hutchinson Cancer Research Center
Disclaimer: We update this information regularly. However, what you read today may not be completely up to date.

Please remember:
  • Talk to your health care providers first before making decisions about your health care.
  • Whether you are eligible for a research study depends on many things. There are specific requirements to be in research studies. These requirements are different for each study.