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

Sponsor

National Institute of Allergy and Infectious Diseases (NIAID) (NIH)

Overall Status

Completed

CT.gov ID

NCT00001048

Collaborator

Bristol-Myers Squibb (Industry), Upjohn (Industry)

Enrollment

Locations

Patients Per Site

Study Details

Study Description

Brief 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.

Condition or Disease	Intervention/Treatment	Phase
HIV Infections Leukoencephalopathy, Progressive Multifocal	Drug: Filgrastim Drug: Cytarabine Drug: Zidovudine Drug: Zalcitabine Drug: Didanosine	Phase 2

Detailed Description

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.

Study Design

Study Type:

Interventional

Primary Purpose:

Treatment

Official Title:

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

Actual Study Completion Date :

Apr 1, 1997

Outcome Measures

Primary Outcome Measures

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 65 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Colorado Hospital CRS	Aurora	Colorado	United States	80262
2	Univ. of Miami AIDS CRS	Miami	Florida	United States	331361013
3	Northwestern University CRS	Chicago	Illinois	United States	60611
4	Johns Hopkins Adult AIDS CRS	Baltimore	Maryland	United States	21287
5	Massachusetts General Hospital ACTG CRS	Boston	Massachusetts	United States	02114
6	Washington U CRS	Saint Louis	Missouri	United States
7	Univ. of Rochester ACTG CRS	Rochester	New York	United States	14642
8	Unc Aids Crs	Chapel Hill	North Carolina	United States	275997215
9	University of Washington AIDS CRS	Seattle	Washington	United States	981224304