Chemotherapy and HAART to Treat AIDS-related Primary Brain Lymphoma
Status:
Completed
Trial end date:
2019-09-19
Target enrollment:
Participant gender:
Summary
This study will investigate the use of chemotherapy plus highly active antiretroviral therapy
(HAART) in patients with Acquired Immunodeficiency Syndrome (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, magnetic resonance
imaging (MRI), computed tomography (CT) and positron emission tomography (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 (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:
- Intellectual functioning: Before starting treatment, patients are tested for their
ability to understand basic concepts and coordination in order to be able to evaluate
how the brain lymphoma affects thinking and concentration. After the lymphoma appears to
have resolved, more formal and intensive tests are done. The intensive tests are
repeated each year, and shorter, interim tests are done about every 6 months. Also, a
specialist periodically monitors patients' understanding of HAART and the importance of
this therapy.
- Blood tests: Blood is drawn every day during hospitalizations to measure methotrexate
levels and to evaluate kidney and liver function and blood counts. Blood is also drawn
before starting therapy, when the lymphoma disappears, 6 months after completing
treatment, and any time it appears that the lymphoma may have recurred to test for
Epstein-Barr virus (EBV), a virus that is almost always present in AIDS-related primary
brain lymphoma.
- Imaging tests: Patients undergo magnetic resonance imaging (MRI) and positron emission
tomography (PET) scans periodically to monitor the effects of treatment on the lymphoma.
MRI scans are done after the 2nd, 4th, 6th, and 8th treatments, then every 2 months for
three times, every 3 months for six times, every 6 months for four times, and then every
year for 5 years, or sooner if there is a concern about the brain. PET scans are done
after the first cycle, after the MRI suggests the lymphoma is gone, and then yearly.
- Lumbar puncture (spinal tap): This test is done to look for EBV in the cerebrospinal
fluid (CSF). Under local anesthetic, a needle is inserted in the space between the bones
in the lower back where the CSF circulates below the spinal cord and a small amount of
fluid is collected through the needle. This test is done at the same times as the blood
tests for EBV.
- Eye examinations: Patients' eyes are examined periodically because brain lymphoma can
sometimes spread to the eye and because some people with AIDS-related primary brain
lymphoma are at risk of certain eye infections.