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

NCT ID: NCT00001048

Last Updated: 2021-11-01

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

90 participants

Study Classification

INTERVENTIONAL

Study Completion Date

1997-04-30

Brief Summary

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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

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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.

Conditions

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HIV Infections Leukoencephalopathy, Progressive Multifocal

Keywords

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

Study Design

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Primary Study Purpose

TREATMENT

Interventions

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Filgrastim

Intervention Type DRUG

Cytarabine

Intervention Type DRUG

Zidovudine

Intervention Type DRUG

Zalcitabine

Intervention Type DRUG

Didanosine

Intervention Type DRUG

Eligibility Criteria

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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.
Minimum Eligible Age

18 Years

Maximum Eligible Age

65 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Bristol-Myers Squibb

INDUSTRY

Sponsor Role collaborator

Upjohn

INDUSTRY

Sponsor Role collaborator

National Institute of Allergy and Infectious Diseases (NIAID)

NIH

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Hall C

Role: STUDY_CHAIR

Timpone J

Role: STUDY_CHAIR

Locations

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University of Colorado Hospital CRS

Aurora, Colorado, United States

Site Status

Univ. of Miami AIDS CRS

Miami, Florida, United States

Site Status

Northwestern University CRS

Chicago, Illinois, United States

Site Status

Johns Hopkins Adult AIDS CRS

Baltimore, Maryland, United States

Site Status

Massachusetts General Hospital ACTG CRS

Boston, Massachusetts, United States

Site Status

Washington U CRS

St Louis, Missouri, United States

Site Status

Univ. of Rochester ACTG CRS

Rochester, New York, United States

Site Status

Unc Aids Crs

Chapel Hill, North Carolina, United States

Site Status

University of Washington AIDS CRS

Seattle, Washington, United States

Site Status

Countries

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United States

References

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

Reference Type BACKGROUND
PMID: 11364014 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 10588116 (View on PubMed)

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 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.

Reference Type BACKGROUND
PMID: 10360779 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 9571254 (View on PubMed)

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. .

Reference Type BACKGROUND

Other Identifiers

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11220

Identifier Type: REGISTRY

Identifier Source: secondary_id

ACTG 243

Identifier Type: -

Identifier Source: org_study_id