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.