Chapel Hill, North Carolina 27599

  • Leukoencephalopathy, Progressive Multifocal

Purpose:

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.


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.


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 is Available At:


Original ID:

ACTG 243


NCT ID:

NCT00001048


Secondary ID:

11220


Study Acronym:


Brief Title:

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


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)-Infecte


Overall Status:

Completed


Study Phase:

Phase 2


Genders:

Both


Minimum Age:

18 Years


Maximum Age:

65 Years


Quick Facts

Healthy Volunteers
Oversight Has DMC
Study Is FDA Regulated
Study Is Section 801
Has Expanded Access

Study Source:

National Institute of Allergy and Infectious Diseases (NIAID)


Oversight Authority:

United States: Federal Government


Reasons Why Stopped:


Study Type:

Interventional


Study Design:

Primary Purpose: Treatment


Number of Arms:

0


Number of Groups:

0


Total Enrollment:

90


Enrollment Type:


Overall Contact Information

Official Name:Hall C
Study Chair

Study Dates

Completion Date:April 1997
Completion Type:Actual
Verification Date:April 2012
Last Changed Date:April 2, 2012
First Received Date:November 2, 1999

Study Outcomes

There are no available Study Outcomes

Study Interventions

Intervention Type:Drug
Name:Filgrastim
Intervention Type:Drug
Name:Cytarabine
Intervention Type:Drug
Name:Zidovudine
Intervention Type:Drug
Name:Zalcitabine
Intervention Type:Drug
Name:Didanosine

Study Arms

There are no available Study Arms

Study Agencies

Agency Class:NIH
Agency Type:Lead Sponsor
Agency Name:National Institute of Allergy and Infectious Diseases (NIAID)
Agency Class:Industry
Agency Type:Collaborator
Agency Name:Bristol-Myers Squibb

Sample and Retention Information

There are no available Sample and Retention Information

Study References

Reference Type:Reference
Citation:[No authors listed] Cytarabine nixed for PML. GMHC Treat Issues. 1996 Nov;10(11):9. No abstract available.
PMID:11364014
Reference Type:Reference
Citation:Post MJ, Yiannoutsos C, Simpson D, Booss J, Clifford DB, Cohen B, McArthur JC, Hall CD. Progressive multifocal leukoencephalopathy in AIDS: are there any MR findings useful to patient management and predictive of patient survival? AIDS Clinical Trials Group, 243 Team. AJNR Am J Neuroradiol. 1999 Nov-Dec;20(10):1896-906.
PMID:10588116
Reference Type:Reference
Citation:Hall C, Timpone J, Dafni I, Antonijevic Z, Millar L, Booss J, Clifford D, Cohen B, McArthur J, Hollander H. ARA-C treatment of PML in AIDS patients. Conf Retroviruses Opportunistic Infect.1997 Jan 22-26;4th:66 (abstract no 8)PMID: 97926517
Reference Type:Reference
Citation:Yiannoutsos CT, Major EO, Curfman B, Jensen PN, Gravell M, Hou J, Clifford DB, Hall CD. Relation of JC virus DNA in the cerebrospinal fluid to survival in acquired immunodeficiency syndrome patients with biopsy-proven progressive multifocal leukoencephalopathy. Ann Neurol. 1999 Jun;45(6):816-21.
PMID:10360779
Reference Type:Reference
Citation:Hall CD, Dafni U, Simpson D, Clifford D, Wetherill PE, Cohen B, McArthur J, Hollander H, Yainnoutsos C, Major E, Millar L, Timpone J. Failure of cytarabine in progressive multifocal leukoencephalopathy associated with human immunodeficiency virus infection. AIDS Clinical Trials Group 243 Team. N Engl J Med. 1998 May 7;338(19):1345-51.
PMID:9571254

Data Source: ClinicalTrials.gov

Date Processed: April 03, 2020

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