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

Primary Purpose

HIV Infections, Leukoencephalopathy, Progressive Multifocal

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Filgrastim
Cytarabine
Zidovudine
Zalcitabine
Didanosine
Sponsored by
National Institute of Allergy and Infectious Diseases (NIAID)
About
Eligibility
Locations
Outcomes
Full info

About this trial

This is an interventional treatment trial for HIV Infections focused on measuring Leukoencephalopathy, Progressive Multifocal, Infusions, Intravenous, Cytarabine, Zalcitabine, Didanosine, Drug Therapy, Combination, Granulocyte Colony-Stimulating Factor, Acquired Immunodeficiency Syndrome, Zidovudine, Injections, Spinal

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept 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.

Sites / Locations

  • University of Colorado Hospital CRS
  • Univ. of Miami AIDS CRS
  • Northwestern University CRS
  • Johns Hopkins Adult AIDS CRS
  • Massachusetts General Hospital ACTG CRS
  • Washington U CRS
  • Univ. of Rochester ACTG CRS
  • Unc Aids Crs
  • University of Washington AIDS CRS

Outcomes

Primary Outcome Measures

Secondary Outcome Measures

Full Information

First Posted
November 2, 1999
Last Updated
October 28, 2021
Sponsor
National Institute of Allergy and Infectious Diseases (NIAID)
Collaborators
Bristol-Myers Squibb, Upjohn
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1. Study Identification

Unique Protocol Identification Number
NCT00001048
Brief Title
Comparison of Anti HIV Drugs Used Alone or in Combination With Cytosine Arabinoside to Treat Progressive Multifocal Leukoencephalopathy (PML) in HIV-Infected Patients
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
Study Type
Interventional

2. Study Status

Record Verification Date
October 2021
Overall Recruitment Status
Completed
Study Start Date
undefined (undefined)
Primary Completion Date
undefined (undefined)
Study Completion Date
April 1997 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
National Institute of Allergy and Infectious Diseases (NIAID)
Collaborators
Bristol-Myers Squibb, Upjohn

4. Oversight

5. 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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
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

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Enrollment
90 (false)

8. Arms, Groups, and Interventions

Intervention Type
Drug
Intervention Name(s)
Filgrastim
Intervention Type
Drug
Intervention Name(s)
Cytarabine
Intervention Type
Drug
Intervention Name(s)
Zidovudine
Intervention Type
Drug
Intervention Name(s)
Zalcitabine
Intervention Type
Drug
Intervention Name(s)
Didanosine

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility 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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Hall C
Official's Role
Study Chair
First Name & Middle Initial & Last Name & Degree
Timpone J
Official's Role
Study Chair
Facility Information:
Facility Name
University of Colorado Hospital CRS
City
Aurora
State/Province
Colorado
ZIP/Postal Code
80262
Country
United States
Facility Name
Univ. of Miami AIDS CRS
City
Miami
State/Province
Florida
ZIP/Postal Code
331361013
Country
United States
Facility Name
Northwestern University CRS
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60611
Country
United States
Facility Name
Johns Hopkins Adult AIDS CRS
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21287
Country
United States
Facility Name
Massachusetts General Hospital ACTG CRS
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02114
Country
United States
Facility Name
Washington U CRS
City
Saint Louis
State/Province
Missouri
Country
United States
Facility Name
Univ. of Rochester ACTG CRS
City
Rochester
State/Province
New York
ZIP/Postal Code
14642
Country
United States
Facility Name
Unc Aids Crs
City
Chapel Hill
State/Province
North Carolina
ZIP/Postal Code
275997215
Country
United States
Facility Name
University of Washington AIDS CRS
City
Seattle
State/Province
Washington
ZIP/Postal Code
981224304
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
11364014
Citation
Cytarabine nixed for PML. GMHC Treat Issues. 1996 Nov;10(11):9.
Results Reference
background
PubMed Identifier
10588116
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.
Results Reference
background
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
Results Reference
background
PubMed Identifier
10360779
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. doi: 10.1002/1531-8249(199906)45:63.0.co;2-w.
Results Reference
background
PubMed Identifier
9571254
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. doi: 10.1056/NEJM199805073381903.
Results Reference
background
Citation
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. .
Results Reference
background

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

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