Adjuvant, Combined Interleukin 2 (Proleukin) and DTIC (Dacarbazine) in High-risk Melanoma Patients

The prognosis of patients with malignant melanomas that are greater than 4 mm deep or involve
regional lymph nodes is poor, even after successful surgical removal. The concept of adjuvant
therapy for melanoma is derived from the hypothesis that these therapies may kill
micro-metastatic seeds of melanoma cells.

The rationale for this particular drug combination regimen is that melanoma cells may act as
a vaccine from which to generate melanoma-specific T cell expansion by way of IL2
administration. In unpublished results, forty-two stage II and III melanoma patients were
treated with this regimen at the University of Alabama with IRB approval. Analysis of relapse
free survival and overall survival in patients treated with this combination suggested a
small improvement in disease-free survival when compared to historical controls or another
study whose patients had similar but not identical staging (median follow-up time of 30
months). Importantly, no unanticipated side effects were observed as a result of the
combination of these two drugs (both of which are FDA-approved for use in melanoma patients).

Inclusion Criteria:

- Patients must fulfill one of the following criteria:

- T4 NO MO - Deep primary melanoma (> 4.0 mm) with or without lymphadenectomy.

- T1-4 N1-3 MO - Primary melanoma with regional lymph node metastases found at
lymphadenectomy or sentinel lymph node sampling, but clinically undetectable (occult).

- T1-4 N1-3 MO - Primary melanoma with clinically apparent (overt) regional lymph node
metastases confirmed by lymphadenectomy.

- T1-4 N1-3 MO - Recurrence of melanoma at the proximal regional lymph node(s).

- Patients must have undergone a wide excision of the primary and, if >1mm in depth,
have completed sentinel lymph node sampling or lymphadenectomy as is standard of
practice. Patients must have confirmation of adequate surgical margins around the
primary lesion (1 or 2 cm minimum, for primary lesions of 1-2 mm depth; 2 cm for
primary lesions equal to or greater than 2 mm depth). When entering this study with
recurrent regional lymph node disease, the patient must be enrolled no later than 90
days from the date of lymphadenectomy.

- For subungual melanomas a distal interphalangeal. amputation is required. For patients
with regional lymph node recurrence, the same evidence for adequate margins around the
primary are required as for patients at initial presentation.

- For safety reasons, patients must be of age between 18 and 85.

- Patients must have ECOG performance status 0-2.

- Patients must have WBC >3,000, platelet count >100,000, and hematocrit >33.

- Patients must have SGOT and bilirubin <2x normal; creatinine <2.3; BUN <33.

- Patients must have no active medical or psychiatric disorders requiring therapy that
would prevent completion of the protocol.

- Patients must give written informed consent.

Exclusion Criteria:

- Patients for whom histopathologic examination of the primary or metastatic melanoma is
not positive are ineligible.

- Patients who have clinical, radiological, laboratory, or pathological evidence of
incompletely resected melanoma or any distant metastatic disease are ineligible.

- Patients with an active second cancer (except in situ cervical cancer, or basal or
squamous skin cancer) are ineligible. Exceptions may be discussed with the principal
investigator.

- Patients with organic brain syndrome or significant impairment of basal cognitive
function or any psychiatric disorder that might preclude participation in the full
protocol, are ineligible.

- Patients who have had prior adjuvant chemotherapy, immunotherapy, including
preoperative infusion or perfusion therapy are ineligible.

- Patients with recurrent melanoma at regional lymph nodes must not have been previously
entered into this study.

- Patients with more than one lymph node group involved are ineligible.

- Women of child bearing age who are not on adequate birth control are ineligible.

- Women who are pregnant or breast feeding are ineligible.