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
Protocol # 06-C-0051
- Why is this trial important?
- Who is eligible for this trial?
- What types of drugs or therapies are being used?
- What is the treatment plan?
- What is the frequency and duration of the visits?
- What are the costs?
- Who is the Principal Investigator?
- Where is this trial taking place?
- Who are the contacts for this trial?
- Where can additional information be found?
Why is this trial important?
AIDS-related primary brain lymphoma is a serious and life threatening complication of HIV infection. Few individuals with this cancer survive for one year. Radiation therapy to the brain is the treatment commonly administered. Radiation therapy can make the lymphoma go away. However, many patients have recurrence of the lymphoma after radiation therapy, or develop other AIDS complications that limit survival. With the availability of highly active antiretroviral therapy, many individuals with AIDS-related primary brain lymphoma may be able to control the HIV infection long-term and go on to good health if the lymphoma can be cured. Many non-HIV-infected people treated with radiation therapy for brain lymphoma survive several years, but have severe brain problems related to the radiation treatment. Therefore, in non-HIV-infected people, chemotherapy has become the standard of care for treating this cancer. Survival with a healthy brain in such people is improved with this strategy. This clinical trial will assess whether chemotherapy will lead to several years or longer survival without brain problems in people with AIDS-related primary brain lymphoma.
Who is eligible for this trial? (PDQ)
- Positive HIV serology (previous records acceptable)
- Diagnosis of Primary Central Nervous System Lymphoma (Confirmed histopathologic diagnosis by NCI Laboratory of Pathology)
- Diagnostic procedures to be done at NIH on protocol 05-CC-0246
- 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 SPECT thallium and EBV detected in the CSF using PCR
- No prior therapy for CNS lymphoma
- No prior evidence of lymphoma outside of the central nervous system
- No multidrug-resistant HIV not amenable to long-term suppression
- No evidence of other opportunistic diseases or complications of HIV infection that would make the protocol therapy infeasible to administer
What types of drugs or therapies are being used?
The treatment being studied in this experimental trial is a combination of high-dose methotrexate, leucovorin, rituximab, and highly active antiretroviral therapy. This treatment is designed to treat the lymphoma without causing additional toxicity to the CD4+ lymphocytes. CD4+ lymphocyte recovery is essential for the long-term survival prospects of people with advanced AIDS. High-dose methotrexate is the core of most treatments for this tumor in HIV-unrelated primary brain lymphoma and it is used in that setting in conjunction with other medications. When given with leucovorin, high-dose methotrexate can usually be given without causing the expected toxicity to the bone marrow and to the immune system. Rituximab is being given because it is a monoclonal antibody that targets the lymphoma cells and helps the methotrexate kill the cancer cells. Since rituximab does not attach to the CD4+ lymphocytes, it may be possible to give methotrexate, leucovorin, and rituximab along with highly active antiretroviral therapy and simultaneously treat the cancer and the HIV. It may be possible to commence immune system recovery during the lymphoma therapy.
What is the treatment plan? (PDQ)
- Induction treatment cycles with HD-MTX and rituximab (HD-MTX-R) will be administered every 2 weeks for 6 cycles
- Two additional consolidation cycles of HD-MTX without rituximab will be administered at 4 weeks and 8 weeks following completion of the combined therapy
- MRI will be repeated at the end of cycles 2, 4, 6, and 8, and additionally as clinically indicated
- At the time of first evidence for complete tumor response by MRI criteria, FDG-PET scan and EBV DNA assessments of the blood and CSF will be repeated
- If there is not a complete response by end of cycle 6, patients will be categorized as treatment failures and will not receive the 2 additional HD-MTX doses
- At end of treatment, restaging by MRI will be performed once every 2 months X 2; then once every 3 months X 4; then once every 6 months X 4
- After this period, clinical evaluations may continue and restaging performed if clinical suspicion of CNS pathology
- Additionally, FDG-PET scan will be repeated after cycle 8 and at one year
What is the frequency and duration of the visits?
The frequency and duration of the visits are dependent on the status of the individual. In general, it will take approximately 7 days to administer each chemotherapy cycle and to monitor the methotrexate levels. Therefore, it is likely that for the first 12 weeks, every other week will be spent in the hospital. Some patients may be safely discharged sooner than 7 days, and others may need more than 7 days in the hospital for each treatment. The last 2 treatments are spread out over 4 weeks, so patients should plan on 1 week in the hospital and then 3 weeks at home before returning for the final treatment. Subsequent follow-up visits will in general require 1-2 days of evaluations, depending on the extent of tests needed.
What are the costs?
There is no charge for medical care received at the National Institutes of Health (NIH) Clinical Center. Patients will be responsible for travel costs for their initial screening visits. In most cases, once patients are enrolled in a trial, the National Cancer Institute (NCI) will pay the transportation costs for all subsequent trial-related visits for patients who do not live in the local area. In addition, these patients will receive a small per diem to help offset the costs of meals and lodging if they are being treated as outpatients.
It will be important to maintain your current insurance plan to cover all medical care that is provided away from the NIH Clinical Center.
No U.S. citizen or permanent U.S. resident residing in the U.S. who otherwise meets the eligibility requirements will be denied enrollment in clinical research protocols because of their inability to pay the costs of travel and subsistence.
Who is the Principal Investigator?
Dr. Robert Yarchoan received his B.A. from Amherst College with a major in biophysics and his M.D. from the University of Pennsylvania. He trained in internal medicine at the University of Minnesota and immunology in the Metabolism Branch, NCI. He then joined the laboratory of Dr. Samuel Broder, where he played a major role in the development of the first effective therapies for HIV infection, including zidovudine (AZT), didanosine (ddI), and zalcitabine (ddC). In particular, he led the first clinical trials of these drugs, was a co-inventor of didanosine and zalcitabine as AIDS therapies, and led initial studies of combination anti-HIV therapy. He was section chief in the Medicine Branch from 1991 to 1996 and was named chief of the newly formed HIV and AIDS Malignancy Branch in 1996. Since that time, he has focused much of his research on AIDS-related malignancies. Among other honors, he has been awarded the Assistant Secretary for Health Award and the U.S. Public Health Service Outstanding Service Medal, has been inducted as a Fellow of the American Association for the Advancement of Science, and is a member of the American Society for Clinical Investigation.
Where is this trial taking place?
NIH Clinical Center
National Institutes of Health
10 Center Drive
Bethesda, Maryland 20892
Who are the contacts for this trial?
Robert Yarchoan, M.D.
Principal Investigator
Phone: 301-496-8959
ryln@nih.gov
Referrals:
Karen Aleman, R.N., B.S.N.
Research Nurse
Phone: 301-496-8959
1-800-243-2732 ext. 4 (Toll Free)
Fax: 301-402-7552
alemank@mail.nih.gov
Kathleen Wyvill, R.N.
Research Nurse
Phone: 301-496-8959
1-800-243-2732 ext. 4 (Toll Free)
Fax: 301-402-7552
wyvillk@mail.nih.gov
Where can additional information be found?
Back to Top
