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

This study has been completed.
Sponsor:
Collaborators:
Bristol-Myers Squibb
Upjohn
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:
NCT00001048
First received: November 2, 1999
Last updated: April 2, 2012
Last verified: April 2012
  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.


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

Study Type: Interventional
Study Design: 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

Resource links provided by NLM:


Further study details as provided by National Institute of Allergy and Infectious Diseases (NIAID):

Estimated Enrollment: 90
Study Completion Date: April 1997
Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00001048

Locations
United States, Colorado
University of Colorado Hospital CRS
Aurora, Colorado, United States, 80262
United States, Florida
Univ. of Miami AIDS CRS
Miami, Florida, United States, 331361013
United States, Illinois
Northwestern University CRS
Chicago, Illinois, United States, 60611
United States, Maryland
Johns Hopkins Adult AIDS CRS
Baltimore, Maryland, United States, 21287
United States, Massachusetts
Massachusetts General Hospital ACTG CRS
Boston, Massachusetts, United States, 02114
United States, Missouri
Washington U CRS
St. Louis, Missouri, United States
United States, New York
Univ. of Rochester ACTG CRS
Rochester, New York, United States, 14642
United States, North Carolina
Unc Aids Crs
Chapel Hill, North Carolina, United States, 275997215
United States, Washington
University of Washington AIDS CRS
Seattle, Washington, United States, 981224304
Sponsors and Collaborators
Bristol-Myers Squibb
Upjohn
Investigators
Study Chair: Hall C
Study Chair: Timpone J
  More Information

Additional Information:
Publications:
Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT00001048     History of Changes
Other Study ID Numbers: ACTG 243, 11220
Study First Received: November 2, 1999
Last Updated: April 2, 2012
Health Authority: United States: Federal Government

Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):
Leukoencephalopathy, Progressive Multifocal
Infusions, Intravenous
Cytarabine
Zalcitabine
Didanosine
Drug Therapy, Combination
Granulocyte Colony-Stimulating Factor
Acquired Immunodeficiency Syndrome
Zidovudine
Injections, Spinal

Additional relevant MeSH terms:
Acquired Immunodeficiency Syndrome
HIV Infections
Leukoencephalopathies
Leukoencephalopathy, Progressive Multifocal
Brain Diseases
Central Nervous System Diseases
Central Nervous System Infections
Central Nervous System Viral Diseases
Demyelinating Diseases
DNA Virus Infections
Encephalitis
Encephalitis, Viral
Immune System Diseases
Immunologic Deficiency Syndromes
Lentivirus Infections
Nervous System Diseases
Polyomavirus Infections
Retroviridae Infections
RNA Virus Infections
Sexually Transmitted Diseases
Sexually Transmitted Diseases, Viral
Slow Virus Diseases
Virus Diseases
Cytarabine
Didanosine
Zalcitabine
Zidovudine
Anti-HIV Agents
Anti-Infective Agents
Anti-Retroviral Agents

ClinicalTrials.gov processed this record on October 21, 2014