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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

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
  Purpose

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.


Condition Intervention Phase
Sarcoma, Kaposi
HIV Infections
Drug: Interferon alfa-2b
Drug: Zidovudine
Drug: Sargramostim
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


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

Estimated Enrollment: 18
Study Completion Date: August 1992
Detailed Description:

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.

  Eligibility

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

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.

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00000694

Locations
United States, New York
Mem Sloan - Kettering Cancer Ctr
New York, New York, United States, 10021
Sponsors and Collaborators
Investigators
Study Chair: SE Krown
  More Information

Additional Information:
Publications:
Krown SE, Paredes J, Bundow D, Flomenberg N. Combination therapy with interferon-alpha (IFN-alpha), zidovudine (AZT), and recombinant granulocyte-macrophage colony-stimulating factor (GM-CSF): a phase I trial in patients with AIDS-associated Kaposi's sarcoma. Int Conf AIDS. 1990 Jun 20-23;6(3):214 (abstract no SB513)

Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT00000694     History of Changes
Other Study ID Numbers: ACTG 090, 11065
Study First Received: November 2, 1999
Last Updated: May 22, 2012
Health Authority: United States: Federal Government

Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):
Interferon Alfa-2b
Immune System
Drug Evaluation
Drug Therapy, Combination
Granulocyte-Macrophage Colony-Stimulating Factor
Acquired Immunodeficiency Syndrome
Zidovudine

Additional relevant MeSH terms:
AIDS-Related Opportunistic Infections
Acquired Immunodeficiency Syndrome
HIV Infections
Sarcoma
Sarcoma, Kaposi
DNA Virus Infections
Herpesviridae Infections
Immune System Diseases
Immunologic Deficiency Syndromes
Infection
Lentivirus Infections
Neoplasms
Neoplasms by Histologic Type
Neoplasms, Connective and Soft Tissue
Neoplasms, Vascular Tissue
Opportunistic Infections
Parasitic Diseases
RNA Virus Infections
Retroviridae Infections
Sexually Transmitted Diseases
Sexually Transmitted Diseases, Viral
Slow Virus Diseases
Virus Diseases
Interferon-alpha
Interferons
Molgramostim
Zidovudine
Anti-HIV Agents
Anti-Infective Agents
Anti-Retroviral Agents

ClinicalTrials.gov processed this record on November 25, 2014