Maintenance Biotherapy with Interleukin-2 (IL-2) and Granulocyte-Macrophage Colony Stimulating Factor (GM-CSF) for Patients with Metastatic Melanoma

Administering chemotherapy or biotherapy or administering both concurrently, known as biochemotherapy, in patients with metastatic melanoma has resulted in good response rates (stable disease or partial response) and some patients may have a complete response. However, the majority will fail to experience a durable response and will develop progressive disease, even with continued therapy.

In an effort to prolong the time to progression and improve the overall survival in those patients who had a response to therapy, studies have been conducted using regimens of maintenance biotherapy after completing the treatment regimen. Preliminary results were positive and the treatment was well tolerated, indicating the need for further study.

The regimen used in this study combines both low-dose IL-2 and GM-CSF with a modified decrescendo schedule of intermittent pulses of high-dose IL-2. This will be offered to patients who have shown a favorable response to prior chemo- or biologic therapy in hopes that efficacy will be optimized.

Inclusion Criteria (conditions the patient must meet)

1. SD, PR, CR following 4 or more courses of biologic therapy, chemotherapy, or biochemotherapy.
2. Patients must give written informed consent or assent if the patient is < 18 years of age
3. Histologically confirmed diagnosis of melanoma
4. Age at least 16 years
5. ECOG performance status of 0-2
6. Life expectancy > 3 months
7. Adequate major organ function to tolerate therapy, as defined by:
   • Total bilirubin < 2.0 mg/dL
   • Creatinine < 1.8 mg/dL
   • WBC > 3000/mm³
   • Platelets > 100,000/mm³
8. Patients > 50 years of age with one or more cardiac risk factors must demonstrate normal exercise stress test, stress thallium test, or comparable cardiac ischemia evaluation
9. Due to potential mutagenic effects of the treatment, women of childbearing age must agree to use barrier method birth control and demonstrate a negative pregnancy test prior to initiation of protocol therapy. Periodic negative urine pregnancy tests will also be required.

Exclusion Criteria

1. Active brain metastases
2. Concurrent use of systemic corticosteroids
3. Left ventricular ejection fraction < 40%
4. Women who are pregnant and/or lactating
5. Concurrent antineoplastic treatments including chemotherapy, biologic response modifiers, radiation, vaccine or experimental therapies

Treatment Regimen

Cycles 1-6, 8, 10 and 12 (each cycle is 28 days)
Pulse (high-dose) IL-2 is given IV in the hospital over 48 hours.
Then, low-dose IL-2 is taken 5 days/week at home via subcutaneous injection for the remainder of the 28-day cycle. GM-CSF, via subcutaneous injection, is taken daily for 14 days following discharge.

Cycles 7, 9, 11
IL-2 by subcutaneous injection 5 days/week at home for 28 days
GM-CSF by subcutaneous injection daily for the 1st 14 days of each cycle