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


Phase 1
18 Years
N/A
Not Enrolling
Both
Sarcoma, Kaposi, HIV Infections

Thank you

Trial Information

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


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.

Inclusion 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.

Type of Study:

Interventional

Study Design:

Endpoint Classification: Safety Study, Primary Purpose: Treatment

Principal Investigator

SE Krown

Investigator Role:

Study Chair

Authority:

United States: Federal Government

Study ID:

ACTG 090

NCT ID:

NCT00000694

Start Date:

Completion Date:

August 1992

Related Keywords:

  • Sarcoma, Kaposi
  • HIV Infections
  • Interferon Alfa-2b
  • Immune System
  • Drug Evaluation
  • Drug Therapy, Combination
  • Granulocyte-Macrophage Colony-Stimulating Factor
  • Acquired Immunodeficiency Syndrome
  • Zidovudine
  • HIV Infections
  • Acquired Immunodeficiency Syndrome
  • Sarcoma, Kaposi
  • AIDS-Related Opportunistic Infections
  • Sarcoma

Name

Location
Mem Sloan - Kettering Cancer Ctr New York, New York  10021