A Phase II Multicenter Study Comparing Antiretroviral Therapy Alone to Antiretroviral Therapy Plus Cytosine Arabinoside (Cytarabine; Ara-C) for the Treatment of Progressive Multifocal Leukoencephalopathy (PML) in Human Immunodeficiency Virus (HIV)-Infected Subjects
Filgrastim
+ Cytarabine
+ Zidovudine
Infectious Encephalitis+27
+ Blood-Borne Infections
+ Neuroinflammatory Diseases
Treatment Study
Summary
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.
Protocol
This section provides details of the study plan, including how the study is designed and what the study is measuring.90 patients to be enrolled
Total number of participants that the clinical trial aims to recruit.Treatment Study
Eligibility
Researchers look for people who fit a certain description, called eligibility criteria: person's general health condition or prior treatments.Any sex
Biological sex of participants that are eligible to enroll.From 18 to 65 Years
Range of ages for which participants are eligible to join.Healthy volunteers not allowed
If individuals who are healthy and do not have the condition being studied can participate.Conditions
Pathology
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.
Study Centers
These are the hospitals, clinics, or research facilities where the trial is being conducted. You can find the location closest to you and its status.This study has 9 locations
University of Colorado Hospital CRS
Aurora, United StatesOpen University of Colorado Hospital CRS in Google MapsUniv. of Miami AIDS CRS
Miami, United StatesNorthwestern University CRS
Chicago, United StatesJohns Hopkins Adult AIDS CRS
Baltimore, United States