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A Phase I, Placebo-Controlled, Dose-Escalation Study of the Safety, Tolerability, and Pharmacokinetics of Thalidomide in Subjects With HIV-1 Infection
This study has been completed.
Sponsors and Collaborators: National Institute of Allergy and Infectious Diseases (NIAID)
Celgene Corporation
Information provided by: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT00000812
  Purpose

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.


Condition Intervention Phase
HIV Infections
Drug: Thalidomide
Phase I

MedlinePlus related topics: AIDS
Drug Information available for: Thalidomide
U.S. FDA Resources
Study Type: Interventional
Study Design: Treatment, Double-Blind, Pharmacokinetics Study
Official Title: A Phase I, Placebo-Controlled, Dose-Escalation Study of the Safety, Tolerability, and Pharmacokinetics of Thalidomide in Subjects With HIV-1 Infection

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

Estimated Enrollment: 36
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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00000812

Locations
United States, Colorado
Univ of Colorado Health Sciences Ctr
Denver, Colorado, United States, 80262
United States, Minnesota
Univ of Minnesota
Minneapolis, Minnesota, United States, 55455
United States, New York
Mem Sloan - Kettering Cancer Ctr
New York, New York, United States, 10021
United States, North Carolina
Univ of North Carolina
Chapel Hill, North Carolina, United States, 275997215
United States, Ohio
Case Western Reserve Univ
Cleveland, Ohio, United States, 44106
United States, Pennsylvania
Univ of Pennsylvania at Philadelphia
Philadelphia, Pennsylvania, United States, 19104
Thomas Jefferson Univ Hosp
Philadelphia, Pennsylvania, United States, 191075098
Sponsors and Collaborators
Celgene Corporation
Investigators
Study Chair: Teppler H
Study Chair: Pomerantz R
  More Information

Publications:
Wohl D, Pomerantz R, Schmitz J, Aweeka F, Fox L, Weng D, Spritzler J, Robinson W, Holohan M, Teppler H. Thalidomide pharmacokinetics (PK) safety and effect on HIV viral load and immune parameters. 8th Conf Retro and Opportun Infect. 2001 Feb 4-8 (abstract no 352)
Wohl DA, Aweeka FT, Schmitz J, Pomerantz R, Cherng DW, Spritzler J, Fox L, Simpson D, Bell D, Holohan MK, Thomas S, Robinson W, Kaplan G, Teppler H. Safety, tolerability, and pharmacokinetic effects of thalidomide in patients infected with human immunodeficiency virus: AIDS Clinical Trials Group 267. J Infect Dis. 2002 May 1;185(9):1359-63.

Study ID Numbers: ACTG 267, 42,240
Study First Received: November 2, 1999
Last Updated: June 23, 2005
ClinicalTrials.gov Identifier: NCT00000812  
Health Authority: United States: Federal Government

Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):
Acquired Immunodeficiency Syndrome
AIDS-Related Complex
Thalidomide

Study placed in the following topic categories:
Virus Diseases
Sexually Transmitted Diseases, Viral
Thalidomide
HIV Infections
Sexually Transmitted Diseases
Acquired Immunodeficiency Syndrome
AIDS-Related Complex
Retroviridae Infections
Immunologic Deficiency Syndromes

Additional relevant MeSH terms:
Communicable Diseases
Anti-Infective Agents
RNA Virus Infections
Slow Virus Diseases
Immune System Diseases
Immunologic Factors
Antineoplastic Agents
Growth Substances
Physiological Effects of Drugs
Infection
Angiogenesis Inhibitors
Immunosuppressive Agents
Pharmacologic Actions
Anti-Bacterial Agents
Therapeutic Uses
Lentivirus Infections
Growth Inhibitors
Angiogenesis Modulating Agents
Leprostatic Agents

ClinicalTrials.gov processed this record on January 15, 2009