Chemotherapy and HAART to Treat AIDS-related Primary Brain Lymphoma

Conditions

• AIDS-Related-Primary Central Nervous System Lymphoma

Eligibility Criteria

Sex

ALL

Age

18 Years - 99 Years

Healthy Volunteers

Not accepted

Interventions

• Methotrexate — DRUG
  6000 mg/m\^2 will be administered by intravenous infusion over 4 hours after confirming that the recipient patients urine pH is within the range greater than or equal to 7 to less than or equal to 8, and urine output is greater than or equal to 100 mL/hour.
• Rituximab — DRUG
  375 mg/m\^2 intravenous (IV) day 1 of each cycle prior to administration of high-dose methotrexate
• Leucovorin — DRUG
  Leucovorin calcium doses will be administered orally or by short intravenous (IV) infusion over 15 minutes

Study Details

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.

Key Dates

Start date

Sep 14, 2006

Status verified

May 2020

Primary completion

Sep 18, 2019

Completion

Sep 19, 2019

Study Design

Enrollment

12 participants (actual)

Allocation

NA

Intervention model

SINGLE_GROUP

Primary purpose

TREATMENT

Arms

• Experimental: Rituximab, High-Dose Methotrexate & Leucovorin Treatment
  Induction treatment cycles with rituximab, high-dose methotrexate and leucovorin will be administered every 2 weeks for 6 cycles. Two additional consolidation cycles of high-dose methotrexate without rituximab will be administered at 4 weeks and 8 weeks following completion of the combined therapy.

Primary Outcome Measure

Number of Patients Alive at 2 Years Without Recurrent Brain Lymphoma or Severe Neurocognitive Defects [ Time Frame: 2 years ]

Locations (1)

Find similar trials in Bethesda, MD