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.

Condition	Treatment or Intervention	Phase
HIV Infections Leukoencephalopathy, Progressive Multifocal	Drug: Filgrastim  Drug: Cytarabine  Drug: Zidovudine  Drug: Zalcitabine  Drug: Didanosine	Phase II

Further Study Details: 

Expected Total Enrollment:  90

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.

Patients are randomized to receive antiretroviral therapy alone (AZT plus ddI or ddC), antiretroviral therapy plus intravenous Ara-C, or antiretroviral therapy plus intrathecal Ara-C. All patients receive 24 weeks of antiretroviral therapy. Beginning at week 2, patients on the intravenous Ara-C arm receive daily infusions of Ara-C over 5 days, with cycles repeating every 21 days. Patients on the intrathecal Ara-C arm receive single administrations of Ara-C at weeks 2, 3, 4, 5, 6, 8, 10, 12, 16, 20, and 24. A brain biopsy confirmation or in situ hybridization will be required within 7 days after study entry. Patients are followed every 4 weeks.

Ages Eligible for Study:  18 Years   -   65 Years,  Genders Eligible for Study:  Both

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.

California
      San Francisco AIDS Clinic / San Francisco Gen Hosp, San Francisco,  California,  941102859,  United States
Colorado
      Univ of Colorado Health Sciences Ctr, Denver,  Colorado,  80262,  United States
Connecticut
      Yale Univ / New Haven, New Haven,  Connecticut,  065102483,  United States
District of Columbia
      Georgetown Univ Med Ctr, Washington,  District of Columbia,  20007,  United States
Florida
      Univ of Miami School of Medicine, Miami,  Florida,  331361013,  United States
Illinois
      Northwestern Univ Med School, Chicago,  Illinois,  60611,  United States
Maryland
      Johns Hopkins Hosp, Baltimore,  Maryland,  21287,  United States
Massachusetts
      Harvard (Massachusetts Gen Hosp), Boston,  Massachusetts,  02114,  United States
New York
      Univ of Rochester Medical Center, Rochester,  New York,  14642,  United States
      Mount Sinai Med Ctr, New York,  New York,  10029,  United States
      Columbia Presbyterian Med Ctr, New York,  New York,  100323784,  United States
      Adirondack Med Ctr at Saranac Lake, Albany,  New York,  122083479,  United States
      Mid - Hudson Care Ctr, Albany,  New York,  122083479,  United States
      Albany Med College / Division of HIV Medicine A158, Albany,  New York,  122083479,  United States
North Carolina
      Univ of North Carolina, Chapel Hill,  North Carolina,  275997215,  United States
Ohio
      Univ of Kentucky Lexington, Cincinnati,  Ohio,  45267,  United States
South Carolina
      Julio Arroyo, West Columbia,  South Carolina,  29169,  United States
Washington
      Univ of Washington, Seattle,  Washington,  981224304,  United States

Study chairs or principal investigators

Hall C,  Study Chair
Timpone J,  Study Chair

Study ID Numbers:  ACTG 243
Record last reviewed:  July 1996
Last Updated:  April 7, 2005
Record first received:  November 2, 1999
ClinicalTrials.gov Identifier:  NCT00001048
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08