Clinical Trial: Chemotherapy and HAART to Treat AIDS-related Primary Brain Lymphoma

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Interventional

Official Title: AIDS-Related Primary Central Nervous System Lymphoma: A Phase II Pilot Study of High-Dose Intravenous Methotrexate With Rituximab Leucovorin Rescue and Highly Active Antiretroviral Therapy

Brief Summary:

This study will investigate the use of chemotherapy plus highly active antiretroviral therapy (HAART) in patients with AIDS-related primary brain lymphoma. None of the drugs used in this study are experimental, but chemotherapy plus HAART has not been established as a standard treatment in patients with AIDS. The chemotherapy regimen used in this study (see below) was chosen because it may be less toxic to immune cells called T-lymphocytes than most drug treatments for lymphoma.

People with AIDS 18 and older and have primary brain lymphoma may be eligible for this study. Candidates are screened with a medical history and physical examination, MRI, CT and PET scans, cerebrospinal fluid studies, brain biopsy at tumor sites, if possible, electrocardiogram and blood tests.

Participants undergo six 2-week "induction treatment" cycles of HAART plus chemotherapy with methotrexate, rituximab and leucovorin, followed by two 4-week "consolidation" treatment cycles using HAART, methotrexate and leucovorin, and then HAART alone. Rituximab is given by intravenous (IV, through a vein) day 1 of each cycle. Also on day 1 IV fluids are given to lower acidity in the urine to protect the kidneys from the methotrexate. On day 2, methotrexate is infused through a vein over 4 hours. Starting 24 hours after initiation of the methotrexate infusion, leucovorin is given every 3 to 6 hours (first IV and then possibly by mouth) until the drug decreases to a target level in the blood. HAART is begun as soon as possible. The specific HAART regimen for each patient is determined individually. All patients are hospitalized the first week of every 2-week treatment cycle for safety monitoring. In addition to HAART and chemotherapy, patients undergo the following tests and procedures:

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    Detailed Summary:

    Background: AIDS-related primary central nervous system lymphoma (AR-PCNSL) is an Epstein-Barr virus (EBV)-driven lymphoproliferative process that typically results in death within a few months. Essentially all of the cases are immunoblastic CD20+ tumors, and occur once the CD4+ cells have fallen to below 50 cells/mm3 . Highly active antiretroviral therapy (HAART) can result in immune reconstitution that decreases the risk of AR-PCNSL. However, a subset of HIV-infected patients still develop ARPCNSL, often because they are unaware that they are HIV infected, or they do not take HAART. Treatment options for such patients are limited. In the non-AIDS setting, chemotherapy has become the standard of care for primary central nervous system lymphoma (PCNSL) and late neurocognitive decline consequent to radiotherapy can be avoided by such approaches. In the pre-HAART era, AR-PCNSL was generally treated with whole brain radiotherapy, however death due to recurrent lymphoma or to other AIDS complications occurred prior to the potential manifestations of late occurring radiation-related neurotoxicity. Radiation-sparing approaches have not been studied in AR-PCNSL in the HAART era, where advances in antiretroviral therapy have made curative intent chemotherapy feasible for most patients with HIV infection.

    Objectives: The primary objective of this study is to estimate the fraction of patients with AR-PCNSL receiving experimental treatment consisting of HAART, combined with rituximab, high-dose methotrexate and leucovorin (R-HD-MTX) who are alive and without recurrent lymphoma or severe cognitive problems at two years. Secondary objectives include evaluation of safety and toxicities associated with R-HD-MTX plus HAART in patients with AR-PCNSL as well as estimating the complete response rate, progression-free, disease-free, overall survivals and long-term neurocognitive outcomes. Ad
    Sponsor: National Cancer Institute (NCI)

    Current Primary Outcome: The number of patients alive at 2 years without recurrent brain lymphoma or severe neurocognitive defects [ Time Frame: 2 years ]

    Original Primary Outcome:

    Current Secondary Outcome:

    Original Secondary Outcome:

    Information By: National Institutes of Health Clinical Center (CC)

    Dates:
    Date Received: December 21, 2005
    Date Started: December 15, 2005
    Date Completion: July 31, 2021
    Last Updated: May 12, 2017
    Last Verified: September 26, 2016