monoclonal antibody therapy and interleukin-2 in treating patients with metastatic melanoma

Conditions: Intraocular Melanoma; Melanoma (Skin)

Summary: rationale: biological therapies, such as mdx-010, work in different ways to stimulate the immune system and stop tumor cells from growing. interleukin-2 may stimulate a person's white blood cells to kill tumor cells. combining monoclonal antibody therapy with interleukin-2 may kill more tumor cells. purpose: phase i/ii trial to study the effectiveness of combining monoclonal antibody therapy with interleukin-2 in treating patients who have metastatic melanoma.

objectives: * determine the maximum tolerated dose (mtd) of anti-cytotoxic t-lymphocyte-associated antigen-4 monoclonal antibody (mdx-ctla4) in combination with high-dose interleukin-2 (il-2) in patients with metastatic melanoma. (phase i is closed to accrual as of 4/13/2004). * determine the activity of mdx-ctla4 administered at the mtd with high-dose il-2 in these patients. * determine whether the administration of il-2 alters the pharmacokinetics of mdx-ctla4 in these patients. * determine the safety and adverse event profile of this regimen in these patients. outline: this is an open-label, dose-escalation study of anti-cytotoxic t-lymphocyte-associated antigen-4 monoclonal antibody (mdx-ctla4). * phase i: patients receive mdx-ctla4 iv on days 0, 21, and 42. patients also receive high-dose interleukin-2 (il-2) iv over 15 minutes every 8 hours for up to 15 doses beginning on days 22 and 43. treatment repeats every 63 days for up to 3 courses in the absence of disease progression or unacceptable toxicity. patients with an ongoing partial response and no greater than grade 1 toxicity may receive additional courses of therapy. patients who require discontinuation of mdx-ctla4 due to toxicity may continue receiving il-2 at the discretion of the investigator. cohorts of 3-6 patients receive escalating doses of mdx-ctla4 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. (phase i is closed to accrual as of 4/13/2004). * phase ii: patients receive treatment as in phase i at the mtd of mdx-ctla4. patients who achieve a partial or complete response and later develop recurrent or progressive disease may be retreated at the same dose. patients are followed at 3 weeks, every 3 months for 1 year, every 6 months for 2 years, and then annually thereafter. projected accrual: a total of 3-51 patients (3-18 for phase i and 19-33 for phase ii) will be accrued for this study within 1 year. (phase i is closed to accrual as of 4/13/2004).

Eligibility criteria:
disease characteristics: * histologically confirmed stage iv melanoma * mucosal or ocular melanoma also eligible * clinically evaluable disease * at least 1 site of measurable disease patient characteristics: age * 16 and over performance status * ecog 0-1 life expectancy * at least 3 months hematopoietic * wbc at least 2,500/mm\^3 * absolute neutrophil count at least 1,500/mm\^3 * platelet count at least 100,000/mm\^3 * hemoglobin at least 10 g/dl * hematocrit at least 30% hepatic * bilirubin no greater than upper limit of normal (uln)\* (less than 3.0 mg/dl in patients with gilbert's syndrome) * ast no greater than 3 times uln\* * hepatitis b surface antigen negative * hepatitis c antibody nonreactive * no evidence or history of significant hepatic disease that would preclude safe administration of high-dose il-2 note: \*unless attributable to disease renal * creatinine no greater than 2.0 mg/dl * no evidence or history of significant renal disease that would preclude safe administration of high-dose il-2 cardiovascular * no evidence or history of significant cardiac disease that would preclude safe administration of high-dose il-2 * thallium stress test normal (for patients over 50 years of age or with a history of cardiovascular disease) pulmonary * no evidence or history of significant pulmonary disease that would preclude safe administration of high-dose il-2 immunologic * hiv negative * no autoimmune disease (including uveitis and autoimmune inflammatory eye disease) * no active infection other * not pregnant or nursing * negative pregnancy test * fertile patients must use effective contraception * no other malignancy within the past 5 years except adequately treated basal cell or squamous cell skin cancer, superficial bladder cancer, or carcinoma in situ of the cervix * no evidence or history of significant gastrointestinal disease that would preclude safe administration of high-dose il-2 * no evidence or history of psychiatric disease that would preclude safe administration of high-dose il-2 * no other underlying medical condition that would make the administration of the study drug hazardous or obscure the interpretation of adverse events * no other concurrent medical condition that would preclude study entry prior concurrent therapy: biologic therapy * at least 3 weeks since prior immunotherapy for melanoma and recovered * no prior anti-cytotoxic t-lymphocyte-associated antigen-4 monoclonal antibody (mdx-ctla4) * no prior high-dose (at least 600,000 iu/kg every 8 hours) interleukin-2 (il-2) chemotherapy * at least 3 weeks since prior chemotherapy for melanoma and recovered * no concurrent chemotherapy endocrine therapy * at least 3 weeks since prior hormonal therapy for melanoma and recovered * at least 4 weeks since prior corticosteroids * no concurrent systemic or topical corticosteroids radiotherapy * at least 3 weeks since prior radiotherapy for melanoma and recovered surgery * not specified other * no concurrent immunosuppressive agents (e.g., cyclosporine or its analog)

Keywords: stage iv melanoma extraocular extension melanoma recurrent melanoma iris melanoma ciliary body and choroid melanoma, medium/large size ciliary body and choroid melanoma, small size recurrent intraocular melanoma