NIH Clinical Center logo     America's Clinical Research Hospital File folder iconExplore the NIH
Clinical Center
Search the Studies - NIH Clinical Research Studies

Protocol Details

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

This study is currently recruiting participants.

Summary | Eligibility | Citations | Contacts




Sponsoring Institute

National Cancer Institute (NCI)

Recruitment Detail

Type: Participants currently recruited/enrolled
Gender: Male & Female
Min Age: 18
Max Age: 99

Referral Letter Required


Population Exclusion(s)


Special Instructions

Currently Not Provided


AIDS-Related-Primary Central Nervous System Lymphoma;
High Dose Methotrexate;
Highly Active Antiretroviral Therapy

Recruitment Keyword(s)

AIDS Related-Primary Central Nervous System Lymphoma;


Brain Neoplasm

Investigational Drug(s)


Investigational Device(s)



Drug: Methotrexate
Drug: Rituximab
Drug: Leucovorin

Supporting Site

National Cancer Institute

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:

-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.

--Back to Top--



Positive HIV serology (previous records acceptable)

-Diagnosis of Primary Central Nervous System Lymphoma

-Confirmed histopathologic diagnosis by NCI Laboratory of Pathology

-If tissue diagnosis is not feasible for any reason, such as undue risk to the patient to acquire tissue diagnosis, the following will be accepted as confirmed AR-PCNSL diagnosis:

-Positive brain FDG-PET and

-EBV detected in the CSF using PCR

-Age 18 years or greater

-ECOG performance less than or equal to 0-4

-Ability to understand and willing to provide informed consent

-If patient unable to understand informed consent, a previously designated durable power of attorney for healthcare or an individual with legal authority may substitute in this capacity

-Assignment of a durable power of attorney for healthcare if not already done


-Prior therapy for CNS lymphoma

-Steroids not an exclusion

-Evidence of lymphoma outside of the central nervous system

-Ocular involvement will not exclude

-Multidrug resistant HIV not amenable to long-term suppression based on either or both:

-Clinical history of poor adherence to multiple antiretroviral drugs deemed sufficient to render effective HIV control unattainable;

-HIV mutational analysis (genotyping and/or phenotyping) that reveals high-level resistance to more than 1 class of anti-HIV drugs such that a combination regimen comprised of agents from at least two drug classes can not be devised to suppress HIV long-term.

-Refusal to adhere to HAART

-Concurrent malignancy other than Kaposi sarcoma, resectable squamous cell or basal cell skin cancer, or T1 anal cancer amenable to surgical resection.

-Heart failure, Class IV by New York Heart Association criteria

-Chronic Liver Disease, Child-Pugh class B or C


-Refusal to practice contraception during chemotherapy.

-Any condition or set of circumstances that the Principal Investigator or Protocol Chair interprets as creating undue risk to the patient by participating on this study or would make the patient unlikely to comply with the study.

--Back to Top--


Levine AM. AIDS-related malignancies: the emerging epidemic.J Natl Cancer Inst. 1993 Sep 1;85(17):1382-97. Review.

Goplen AK, Dunlop O, Liestol K, Lingjaerde OC, Bruun JN, Maehlen J. The impact of primary central nervous system lymphoma in AIDS patients: a population-based autopsy study from Oslo. J Acquir Immune Defic Syndr Hum Retrovirol. 1997 Apr 1;14(4):351-4.

von Gunten CF, Von Roenn JH. Clinical aspects of human immunodeficiency virus-related lymphoma. Curr Opin Oncol. 1992 Oct;4(5):894-9. Review.

--Back to Top--


Principal Investigator

Referral Contact

For more information:

Robert Yarchoan, M.D.
National Cancer Institute (NCI)
BG 10 RM 6N106
(240) 760-6075

Karen Aleman, R.N.
National Cancer Institute (NCI)
National Institutes of Health
Building 10
Room 13C436
10 Center Drive
Bethesda, Maryland 20892
(301) 435-5621

NCI Referral Office
National Institute of Health Clinical Center (CC), 9000 Rockville Pike, Bethesda, Maryland 20892, United States: NCI Clinical Trials Referral Office

Clinical Trials Number:


--Back to Top--


Contact the Patient Recruitment and Public Liaison Office for:

  • Details on how to participate in a study
  • Details on how to refer a patient to a study

NIH Clinical Studies Information Request

Contact the Office of Communications for:

  • General information about the NIH Clinical Center

Contact the Department Clinical Research Informatics, (DCRI) for:

  • Technical questions about Adobe Acrobat and the PDF format
  • Technical questions about this web server