We're building a better ClinicalTrials.gov. Check it out and tell us what you think!
Try the New Site
We're building a modernized ClinicalTrials.gov! Visit Beta.ClinicalTrials.gov to try the new functionality.
Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00000812
Recruitment Status : Completed
First Posted : August 31, 2001
Last Update Posted : October 28, 2021
Sponsor:
Collaborator:
Celgene Corporation
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)

Tracking Information
First Submitted Date  ICMJE November 2, 1999
First Posted Date  ICMJE August 31, 2001
Last Update Posted Date October 28, 2021
Study Start Date  ICMJE Not Provided
Primary Completion Date Not Provided
Current Primary Outcome Measures  ICMJE Not Provided
Original Primary Outcome Measures  ICMJE Not Provided
Change History
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Phase I, Placebo-Controlled, Dose-Escalation Study of the Safety, Tolerability, and Pharmacokinetics of Thalidomide in Subjects With HIV-1 Infection
Official Title  ICMJE A Phase I, Placebo-Controlled, Dose-Escalation Study of the Safety, Tolerability, and Pharmacokinetics of Thalidomide in Subjects With HIV-1 Infection
Brief Summary

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.

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  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Masking: Double
Primary Purpose: Treatment
Condition  ICMJE HIV Infections
Intervention  ICMJE Drug: Thalidomide
Study Arms  ICMJE Not Provided
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Enrollment  ICMJE
 (submitted: June¬†23,¬†2005)
36
Original Enrollment  ICMJE Same as current
Actual Study Completion Date  ICMJE July 2000
Primary Completion Date Not Provided
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00000812
Other Study ID Numbers  ICMJE ACTG 267
42,240
11243 ( Registry Identifier: DAIDS-ES )
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Current Responsible Party National Institute of Allergy and Infectious Diseases (NIAID)
Original Responsible Party Not Provided
Current Study Sponsor  ICMJE National Institute of Allergy and Infectious Diseases (NIAID)
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE Celgene Corporation
Investigators  ICMJE
Study Chair: Teppler H
Study Chair: Pomerantz R
PRS Account National Institute of Allergy and Infectious Diseases (NIAID)
Verification Date October 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP