interleukin-7 and vaccine therapy in treating patients with metastatic melanoma

Conditions: Melanoma (Skin)

Summary: rationale: interleukin-7 may stimulate a person's white blood cells to kill tumor cells. vaccines made from peptides may make the body build an immune response to kill tumor cells. combining interleukin-7 with vaccine therapy may kill more tumor cells. purpose: this phase i trial is studying the side effects and best dose of interleukin-7 when given with vaccine therapy in treating patients with metastatic melanoma.

objectives: primary * determine the maximum tolerated dose of interleukin-7 (il-7) when administered with melanoma peptide vaccine emulsified in montanide isa-51 in patients with metastatic melanoma. * determine the safety of this regimen in these patients. secondary * determine the biological effects of this regimen on t-cell function and phenotype at various doses and at the optimal biological dose in these patients. * determine the pharmacokinetic and pharmacodynamic characteristics of il-7 in patients treated with this regimen. * determine the antitumor effects of il-7, in terms of a dose-escalation strategy, in these patients. outline: this is a dose-escalation study of interleukin-7 (il-7). patients receive il-7 subcutaneously (sc) on days 0, 3, 6, 9, 12, 15, 18, and 21. patients also receive melanoma peptide vaccine comprising gp100 antigen and mart-1 antigen emulsified in montanide isa-51 sc on days 0, 7, 14, and 21 in the absence of disease progression or unacceptable toxicity. cohorts of 3-6 patients receive escalating doses of il-7 until the maximum tolerated dose (mtd) is determined. the mtd is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. after the mtd is determined, an additional 13 patients are treated at that dose level. patients are followed at 1, 2, and 5 weeks, at 3 and 6 months, and then at 1 year. projected accrual: a total of 3-37 patients will be accrued for this study within 1-12.3 months.

Eligibility criteria:
disease characteristics: * histologically confirmed melanoma * metastatic disease * measurable or evaluable disease * disease progression during or after prior interleukin-2 (il-2) or ineligible to receive high-dose il-2\* or has disease burden for which il-2 is not indicated\* note: \*if patient did not receive prior il-2, must have progressed after prior standard first-line therapy (e.g., metastasectomy for single lesions or dacarbazine) * hla-a\*0201-positive disease patient characteristics: age * 18 and over performance status * ecog 0-2 life expectancy * at least 3 months hematopoietic * absolute neutrophil count \> 1,000/mm\^3\* * absolute lymphocyte count ≥ 200/mm\^3\* * platelet count \> 100,000/mm\^3 * no proliferative hematologic disease note: \*for 2 consecutive readings performed on 2 different days hepatic * ast and alt \< 3 times upper limit of normal (uln) * pt/ptt ≤ 1.5 times uln * hepatitis b negative * positive hepatitis b serology indicative of prior immunization (i.e., positive for antibody against hepatitis b surface antigen and negative for antibody against hepatitis b core antigen) allowed * hepatitis c negative renal * creatinine ≤ 1.4 mg/dl cardiovascular * ejection fraction \> 45% by muga for patients ≥ 50 years of age or with a history of cardiac disease * no resting blood pressure \> 140/90 mm hg with standard antihypertensive therapy pulmonary * dlco/va and fev_1 \> 50% of predicted on pulmonary function test for smokers or for patients with clinical evidence of compromised pulmonary function * no history of severe asthma immunologic * hiv negative * no history of autoimmune disease * no splenomegaly other * not pregnant or nursing * negative pregnancy test * fertile patients must use effective contraception * no other medical or psychiatric disease that would preclude study participation prior concurrent therapy: biologic therapy * see disease characteristics * more than 4 weeks since prior cytokines * no prior allogeneic hematopoietic stem cell transplantation * no concurrent growth factors * no concurrent monoclonal antibodies * no other concurrent immunotherapy * no other concurrent cytokines * no other concurrent biologic agents chemotherapy * see disease characteristics * no prior intensive myeloablative chemotherapy * no concurrent chemotherapy endocrine therapy * more than 2 weeks since prior systemic corticosteroids for more than 72 hours in duration * no concurrent systemic steroids radiotherapy * not specified surgery * see disease characteristics * no prior splenectomy * no prior solid organ transplantation other * more than 4 weeks since prior cytotoxic therapy * no other concurrent cytotoxic therapy * no concurrent chronic anticoagulation therapy (e.g., high-dose warfarin, heparin, or aspirin) * concurrent low-dose warfarin (1-2 mg) allowed * no concurrent chronic medication for asthma * no concurrent immunosuppressive therapy

Keywords: recurrent melanoma stage iv melanoma