Comparison of Anti HIV Drugs Used Alone or in Combination With Cytosine Arabinoside to Treat Progressive Multifocal Leukoencephalopathy (PML) in HIV-Infected Patients

• Status: Completed
• Trial end date: 1997-04-01
• Target enrollment: 0
• Participant gender: All

Summary

To compare the safety and efficacy of antiretroviral therapy (zidovudine plus either didanosine or dideoxycytidine) versus antiretroviral therapy plus intravenous cytarabine (Ara-C) versus antiretroviral therapy plus intrathecal Ara-C in the maintenance or improvement of neurological function over 6 months in HIV-infected individuals who have developed progressive multifocal leukoencephalopathy (PML). To compare the effect of these three treatment regimens on Karnofsky score and MRI studies.

The effectiveness of Ara-C in the treatment of PML, caused by a human DNA papovavirus (designated JC virus) infection, has not been determined, although the most encouraging results have occurred with intrathecal administration of the drug.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
• Collaborators: Bristol-Myers Squibb; Upjohn
• Treatments: Cytarabine; Didanosine; Zalcitabine; Zidovudine

Criteria

Inclusion Criteria

Concurrent Medication:

Allowed:

• Local intralesional chemotherapy for mucocutaneous Kaposi's sarcoma.

• Topical antifungals, clotrimazole, ketoconazole, fluconazole, and amphotericin B for treatment of mucosal and esophageal candidiasis.

• Foscarnet for newly developed CMV infection, only after discussion with the protocol chair.

• Prophylactic and maintenance therapy for other opportunistic infections, provided patients are considered clinically stable.

• No more than 1000 mg/day acyclovir for herpes simplex.

• Antibiotics for bacterial infections as clinically indicated.

• Antipyretics, analgesics, and antiemetics.

Concurrent Treatment:

Allowed:

• Local radiation therapy for mucocutaneous Kaposi's sarcoma.

Patients must have:

• HIV infection.

• Confirmed PML.

• No other current active opportunistic infections requiring systemic therapy.

• Life expectancy of at least 3 months.

NOTE:

• A durable power of attorney is recommended where severe neurologic or psychiatric impairment can be foreseen while the patient is on study.

Exclusion Criteria

Co-existing Condition:

Patients with the following symptoms or conditions are excluded:

• Current active cryptococcal meningitis, cytomegaloviral encephalitis, toxoplasmosis encephalitis, CNS lymphoma, or neurosyphilis.

NOTE:

• Patients on maintenance therapy for cryptococcal meningitis or toxoplasmosis encephalitis that has been stable for 4 months are permitted.

• Conditions that seriously increase risk of a surgical procedure (e.g., coagulopathy, severe thrombocytopenia).

• Any other disease that would interfere with evaluation of the patient.

• Other life-threatening complications likely to cause death in < 3 months.

Concurrent Medication:

Excluded:

• Ganciclovir.

• Interferon.

• Systemic chemotherapy other than Ara-C (unless specifically allowed).

• Antiretroviral medications other than AZT, ddI, or ddC.

Patients with the following prior conditions are excluded:

History of allergy or intolerance to G-CSF.

Prior Medication:

Excluded:

• Any prior Ara-C.

Excluded within 14 days prior to study:

• Ganciclovir or foscarnet.

• Interferon.

• Antiretroviral medications other than AZT, ddI, or ddC.

• Experimental medications for treatment of PML.