A Phase I Trial of Recombinant Human Granulocyte-Macrophage Colony Stimulating Factor (rHuGM-CSF), Recombinant Alpha Interferon and Azidothymidine (AZT) in AIDS-Associated Kaposi's Sarcoma

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:
NCT00000694
First received: November 2, 1999
Last updated: May 22, 2012
Last verified: May 2012

November 2, 1999
May 22, 2012
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Complete list of historical versions of study NCT00000694 on ClinicalTrials.gov Archive Site
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A Phase I Trial of Recombinant Human Granulocyte-Macrophage Colony Stimulating Factor (rHuGM-CSF), Recombinant Alpha Interferon and Azidothymidine (AZT) in AIDS-Associated Kaposi's Sarcoma
A Phase I Trial of Recombinant Human Granulocyte-Macrophage Colony Stimulating Factor (rHuGM-CSF), Recombinant Alpha Interferon and Azidothymidine (AZT) in AIDS-Associated Kaposi's Sarcoma

To define the best doses of sargramostim ( granulocyte-macrophage colony-stimulating factor; GM-CSF ), interferon alfa-2b ( IFN-A2b ), and zidovudine ( AZT ) to give together in patients with AIDS-associated Kaposi's sarcoma ( KS ), to learn about the side effects of these drugs when they are given together for 8 weeks, and to find out whether the combination of GM-CSF, IFN-A2b, and AZT has any effect on KS, HIV, or the immune system.

Studies show that IFN-A2b can cause KS tumors to shrink or disappear in about 30 percent of patients. IFN-A2b can greatly reduce the growth of the HIV virus in test tube experiments and perhaps in patients. AZT has also been shown to reduce the growth of HIV and show improvements in the immune system with fewer infections. Test tube experiments show that when IFN-A2b and AZT are used together, they reduce the growth of the HIV virus much more effectively than when either drug is used alone. In recent studies of the combination of interferon alpha and AZT in patients with KS, more than 40 percent of the patients showed shrinkage of their tumors, and some showed evidence for suppression of HIV growth in the body. However, the combination of IFN-A2b with AZT often caused a marked lowering of the white blood cell (WBC) count, especially a type of WBC called the granulocyte (or neutrophil) which is important in the body's defense against infection. Recombinant human GM-CSF is a human protein which is produced in bacteria. It has been shown to cause an increase in the WBC count.

Studies show that IFN-A2b can cause KS tumors to shrink or disappear in about 30 percent of patients. IFN-A2b can greatly reduce the growth of the HIV virus in test tube experiments and perhaps in patients. AZT has also been shown to reduce the growth of HIV and show improvements in the immune system with fewer infections. Test tube experiments show that when IFN-A2b and AZT are used together, they reduce the growth of the HIV virus much more effectively than when either drug is used alone. In recent studies of the combination of interferon alpha and AZT in patients with KS, more than 40 percent of the patients showed shrinkage of their tumors, and some showed evidence for suppression of HIV growth in the body. However, the combination of IFN-A2b with AZT often caused a marked lowering of the white blood cell (WBC) count, especially a type of WBC called the granulocyte (or neutrophil) which is important in the body's defense against infection. Recombinant human GM-CSF is a human protein which is produced in bacteria. It has been shown to cause an increase in the WBC count.

AMENDED: 900910 to allow one patient to be treated beyond one year. Original design: GM-CSF, IFN-A2b, and AZT are given every day for 8 weeks. There are 6 patients per dose level. IFN-A2b and GM-CSF are given in two separate injections under the skin (subcutaneous injection) once a day. AZT is given orally every 4 hours (6 times/day). The first patients are given doses of the drugs that are quite well tolerated when given alone. If these dosages are tolerated without serious side effects, the dosage of IFN-A2b is increased in subsequent groups of patients. Maintenance treatment consisting of the same dose received at the conclusion of the initial 8 week course of treatment will be resumed with eligible patients for up to 1 year.

Interventional
Phase 1
Endpoint Classification: Safety Study
Primary Purpose: Treatment
  • Sarcoma, Kaposi
  • HIV Infections
  • Drug: Interferon alfa-2b
  • Drug: Zidovudine
  • Drug: Sargramostim
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
18
August 1992
Not Provided

Inclusion Criteria

Concurrent Medication:

Allowed:

  • Prophylaxis for Pneumocystis carinii pneumonia (PCP) with aerosolized pentamidine. Ibuprofen, not to exceed 1600 mg/day, for fever or analgesia.

Biopsy-proven Kaposi's sarcoma confined to the skin, lymph nodes, or non-nodular lesions of the hard palate. Positive antibody to HIV confirmed by any federally licensed ELISA test kit. Patients must be able to give informed consent.

  • Allowed: Basal cell carcinoma.

Exclusion Criteria

Co-existing Condition:

Patients with the following are excluded:

  • Prior or concurrent opportunistic infection or B symptoms (unexplained fever, night sweats, > 10 percent involuntary weight loss or diarrhea persisting > 2 weeks).
  • Visceral (non-nodal) Kaposi's sarcoma including extensive oral lesions.
  • Severe (> 2+) tumor-associated edema.
  • Concurrent neoplasia (excluding basal cell carcinoma).
  • Significant cardiac disease (New York Heart Association class III or IV) or history of myocardial infarction o significant cardiac arrhythmias.
  • Dementia (= or > stage 2).

Concurrent Medication:

Excluded:

  • Any systemic chemoprophylaxis not specifically allowed.
  • Aspirin and acetaminophen.
  • Nonsteroidal anti-inflammatory agents not specifically allowed.
  • Corticosteroids.
  • Barbiturates.
  • Other antiviral agents, immunotherapy, hormonal therapy, chemotherapy directed at treatment of viral infection or malignancy.
  • Other investigational agents.

Concurrent Treatment:

Excluded:

  • Radiation therapy directed at treatment of viral infection or malignancy.

Patients with the following are excluded:

  • Prior or concurrent opportunistic infection or B symptoms (unexplained fever, night sweats, > 10 percent involuntary weight loss or diarrhea persisting > 2 weeks).
  • Visceral (non-nodal) Kaposi's sarcoma including extensive oral lesions.
  • Severe (> 2+) tumor-associated edema.
  • Concurrent neoplasia (excluding basal cell carcinoma).
  • Significant cardiac disease (New York Heart Association class III or IV) or history of myocardial infarction or significant cardiac arrhythmias.
  • Dementia (= or > stage 2).

Prior Medication:

Excluded:

  • Interferon alpha-2b.
  • Granulocyte-macrophage colony-stimulating factor (GM-CSF).
  • Prior grade 3 or grade 4 toxicity during AZT therapy.
  • Excluded within 30 days of study entry:
  • Zidovudine (AZT).
  • Corticosteroids.
  • Biologic response modifiers.
  • Cytotoxic chemotherapy.
  • Antiretroviral agents.
  • Toxicity grades according to NIAID Recommendations for Grading Acute and Subacute Toxic Effects (Adults).

Prior Treatment:

Excluded within 30 days of study entry:

  • Requirement for red blood cell transfusions within 30 days of study entry.
  • Radiation therapy.

Active drug or alcohol abuse.

Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00000694
ACTG 090, 11065
Not Provided
National Institute of Allergy and Infectious Diseases (NIAID)
National Institute of Allergy and Infectious Diseases (NIAID)
Not Provided
Study Chair: SE Krown
National Institute of Allergy and Infectious Diseases (NIAID)
May 2012

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