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

NCT00001048 | Completed Phase 2

• 2 other identifiers: ACTG 24311220
• Study Type: interventional
• Target: 90
• Locations: 1 country
• Sites: 9

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.

Conditions

HIV Infections; Leukoencephalopathy, Progressive Multifocal

Keywords

Leukoencephalopathy, Progressive Multifocal; Infusions, Intravenous; Cytarabine; Zalcitabine; Didanosine; Drug Therapy, Combination; Granulocyte Colony-Stimulating Factor; Acquired Immunodeficiency Syndrome; Zidovudine; Injections, Spinal

Interventions

Filgrastim DRUG

Cytarabine DRUG

Zidovudine DRUG

Zalcitabine DRUG

Didanosine DRUG

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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:

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead
• Bristol-Myers Squibb: collaborator
• Upjohn: collaborator

Study Sites (9)

University of Colorado Hospital CRS

Aurora, Colorado, 80262, United States

Location

Univ. of Miami AIDS CRS

Miami, Florida, 331361013, United States

Location

Northwestern University CRS

Chicago, Illinois, 60611, United States

Location

Johns Hopkins Adult AIDS CRS

Baltimore, Maryland, 21287, United States

Location

Massachusetts General Hospital ACTG CRS

Boston, Massachusetts, 02114, United States

Location

Washington U CRS

St Louis, Missouri, United States

Location

Univ. of Rochester ACTG CRS

Rochester, New York, 14642, United States

Location

Unc Aids Crs

Chapel Hill, North Carolina, 275997215, United States

Location

University of Washington AIDS CRS

Seattle, Washington, 981224304, United States

Location

Related Publications (6)

• Cytarabine nixed for PML. GMHC Treat Issues. 1996 Nov;10(11):9.

  PMID: 11364014 BACKGROUND

• 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 BACKGROUND

• 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

  BACKGROUND

• 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. doi: 10.1002/1531-8249(199906)45:63.0.co;2-w.

  PMID: 10360779 BACKGROUND

• 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. doi: 10.1056/NEJM199805073381903.

  PMID: 9571254 BACKGROUND

• Crit Path AIDS Proj 1994-95 Winer; (No 30): 28-29. A phase II Multicenter Study Comparing Antiretroviral Therapy Alone to Antiretroviral Therapy Plku Cytosine Arabinosine (Cytarabine; Ara-C) for the Treatment of Progressive Multifocal Leukoencephalopathy (PML) in Human Immunodeficiency Virus (HIV)-Infected Subjects. .

  BACKGROUND

MeSH Terms

Conditions

HIV Infections; Leukoencephalopathy, Progressive Multifocal; Acquired Immunodeficiency Syndrome

Interventions

Filgrastim; Cytarabine; Zidovudine; Zalcitabine; Didanosine

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases; Encephalitis, Viral; Central Nervous System Viral Diseases; Central Nervous System Infections; Infectious Encephalitis; Polyomavirus Infections; DNA Virus Infections; Slow Virus Diseases; Encephalitis; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Leukoencephalopathies; Demyelinating Diseases; Neuroinflammatory Diseases

Intervention Hierarchy (Ancestors)

Granulocyte Colony-Stimulating Factor; Colony-Stimulating Factors; Glycoproteins; Glycoconjugates; Carbohydrates; Hematopoietic Cell Growth Factors; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Arabinonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Thymidine; Dideoxynucleosides; Deoxyribonucleosides; Deoxycytidine; Inosine; Purine Nucleosides; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Ribonucleosides

Study Officials

• Hall C

  STUDY CHAIR

• Timpone J

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 2
• Purpose: TREATMENT
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 2, 1999
• First Posted: August 31, 2001
• Study Completion: April 1, 1997
• Last Updated: November 1, 2021

Record last verified: 2021-10

Locations

US (9)