A Phase I, Placebo-Controlled, Dose-Escalation Study of the Safety, Tolerability, and Pharmacokinetics of Thalidomide in Subjects With HIV-1 Infection

PRIMARY: To evaluate the safety, tolerability, and pharmacokinetics of daily oral thalidomide.

SECONDARY: To examine the effect of thalidomide on antiviral activity and tumor necrosis factor-alpha (TNF-alpha) production, and the correlation between TNF-alpha inhibition and viral burden.

A protein in the blood called tumor necrosis factor (TNF-alpha) is abnormally elevated in patients with HIV infection and may cause the body to produce more virus. In vitro studies have demonstrated that thalidomide reduces TNF-alpha levels and inhibits production of HIV. However, more information on the pharmacological and immunological aspects of thalidomide is needed.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

A protein in the blood called tumor necrosis factor (TNF-alpha) is abnormally elevated in patients with HIV infection and may cause the body to produce more virus. In vitro studies have demonstrated that thalidomide reduces TNF-alpha levels and inhibits production of HIV. However, more information on the pharmacological and immunological aspects of thalidomide is needed.

Patients are randomized to receive oral thalidomide or matching placebo (3:1) at one of three dose levels daily for 8 weeks. All 12 patients at a dose level must receive treatment for at least 2 weeks before dose escalation in subsequent patients occurs. The MTD is defined as the dose level immediately below that at which 3 or more of 9 patients receiving thalidomide experience dose-limiting toxicity. Patients are followed for a total of 16 weeks.

PER 6/20/95 AMENDMENT: Patients in cohort 1 should discontinue the previous 50 mg formulation of thalidomide once the new formulation is available. Those patients may either wash out for 4 weeks and recommence the study or discontinue the study.

Study Type

Interventional

Enrollment

36

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

    • Colorado
      • Aurora, Colorado, United States, 80262
        • University of Colorado Hospital CRS
    • Minnesota
      • Minneapolis, Minnesota, United States, 55455
        • University of Minnesota, ACTU
    • New York
      • New York, New York, United States, 10021
        • Memorial Sloan-Kettering Cancer Ctr.
    • North Carolina
      • Chapel Hill, North Carolina, United States, 275997215
        • Unc Aids Crs
    • Ohio
      • Cleveland, Ohio, United States, 44106
        • Case CRS
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19104
        • Hosp. of the Univ. of Pennsylvania CRS

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria

Concurrent Medication:

Allowed for occasional use (chronic use is permitted only if clinician deems that medication can be discontinued in the event of overlapping toxicity):

  • CNS active agents, such as alcohol, narcotics (i.e., morphine, codeine, meperidine), barbiturates, benzodiazepines, tricyclic antidepressants, phenothiazines, sedating antihistamines, or over-the-counter sleeping aids.

Patients must have:

  • HIV infection.
  • CD4 count 200 - 500 cells/mm3.
  • No active opportunistic infection requiring systemic therapy within the past 14 days.
  • NOTE: Women must be post-menopausal or provide written documentation of surgical sterilization, and sexually active men must use a barrier method of contraception, beginning 4 weeks prior to study entry and continuing until 4 weeks following end of treatment.

PER AMENDMENT 8/2/96:

  • Been on stable licensed antiretroviral treatment for 60 days prior to study entry or must not have received any antiretroviral medications for 60 days prior to study entry.

Prior Medication:

Required:

  • Patients must have been on stable licensed antiretroviral treatment for 60 days prior to study entry or must not have received any antiretroviral medications for 60 days prior to study entry.

Exclusion Criteria

Co-existing Condition:

Patients with the following symptoms or conditions are excluded:

  • Malignancy requiring chemotherapy.
  • Grade 2 or worse peripheral neuropathy.
  • Medical condition that would interfere with evaluation of patient.

Concurrent Medication:

Excluded in all patients:

  • Didanosine ( ddI ).
  • Zalcitabine ( ddC ).
  • Stavudine ( d4T ).
  • Other immunologically active agents.
  • Systemic cytotoxic chemotherapy.

Excluded in all patients unless taken only occasionally or unless medication could be stopped in the event of overlapping toxicity:

  • CNS active agents, such as alcohol, narcotics (i.e., morphine, codeine, meperidine), barbiturates, benzodiazepines, tricyclic antidepressants, phenothiazines, sedating antihistamines, or over-the-counter sleeping aids.

Patients with the following prior conditions are excluded:

  • History of active tuberculosis within 3 months prior to study entry.
  • History of intolerance to thalidomide such as fever, rash, or neuropathy.

Prior Medication:

Excluded within 14 days prior to study entry:

  • Systemic chemotherapy.

Excluded within 30 days prior to study entry:

  • Topical, oral, and systemic corticosteroids.
  • Pentoxifylline.
  • Interferons.
  • Interleukins.
  • Cimetidines.
  • Acetylcysteine or other glutathione depleting agents.
  • Other putative immunomodulatory agents such as thymosin alpha 1, thymopentin, isoprinosine, ditiocarb sodium, ampligen, and immune globulin.

PER AMENDMENT 8/2/96:

Excluded within 60 days prior to study entry:

  • Therapy with investigational antiretroviral medications.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Masking: Double

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Collaborators

Investigators

  • Study Chair: Pomerantz R
  • Study Chair: Teppler H

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Completion (Actual)

July 1, 2000

Study Registration Dates

First Submitted

November 2, 1999

First Submitted That Met QC Criteria

August 30, 2001

First Posted (Estimate)

August 31, 2001

Study Record Updates

Last Update Posted (Actual)

October 28, 2021

Last Update Submitted That Met QC Criteria

October 27, 2021

Last Verified

October 1, 2021

More Information

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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