gene-modified white blood cells followed by interleukin-2 and vaccine therapy in treating patients with metastatic melanoma

Conditions: Melanoma (Skin)

Summary: rationale: inserting a gene that has been created in the laboratory into a person's white blood cells may make the body build an immune response to kill tumor cells. interleukin-2 may stimulate a person's white blood cells to kill tumor cells. vaccines may make the body build an immune response to kill tumor cells. combining gene-modified white blood cell infusions with interleukin-2 and vaccine therapy may kill more tumor cells. purpose: this phase i trial is studying how well giving gene-modified white blood cells when given together with interleukin-2 and vaccine therapy works in treating patients with metastatic melanoma.

objectives: primary * determine, preliminarily, any clinical tumor regression in lymphodepleted patients with metastatic melanoma treated with fowlpox gp100 antigen immunization and antitumor antigen t-cell receptor (tcr)-engineered tumor infiltrating lymphocytes or cd8+ autologous peripheral blood lymphocytes followed by interleukin-2. secondary * determine the in vivo survival of tcr gene-engineered cells in patients treated with this regimen. outline: patients are stratified according to their ability to produce tumor-infiltrating lymphocytes (til) (yes vs no). patients receive lymphodepleting chemotherapy comprising cyclophosphamide iv over 1 hour on days -7 and -6 and fludarabine iv over 30 minutes on days -5 to -1. * stratum 1 (til): patients receive til retrovirally transduced with gp100 antigen tcr gene iv over 20-30 minutes on day 0\*. * stratum 2 (cd8+peripheral blood lymphocytes \[pbl\]): patients receive cd8+pbl retrovirally transduced with gp100 antigen tcr gene iv over 20-30 minutes on day 0\*. note: \*day 0 is 1-4 days after the last dose of fludarabine. patients in both strata also receive fowlpox-gp100 vaccine (before til/pbl infusion) iv over 1-2 minutes on days 0 and 28 and high-dose interleukin-2 (il-2) iv over 15 minutes every 8 hours on days 0-4 and days 28-32. patients also receive g-csf sc once daily beginning on day 0 and continuing until blood counts recover. treatment continues in the absence of disease progression or unacceptable toxicity. beginning 6-8 weeks after the last dose of vaccine and high-dose il-2, patients with stable or responding disease may receive 1 retreatment course. responding patients are followed at 1, 3, 6, and 12 months and then annually thereafter. projected accrual: a total of 61 patients will be accrued for this study.

Eligibility criteria:
disease characteristics: * diagnosis of melanoma * metastatic disease * measurable disease * refractory to standard therapy, including high-dose interleukin-2 therapy * hla-a\*0201 positive * progressive disease during prior immunization to melanoma antigens or prior treatment with anti-cytotoxic t-lymphocyte-associated antigen-4 monoclonal antibody (mdx-010) cellular therapy with or without myeloablation allowed provided toxicity resolved to ≤ grade 2 (except vitiligo) and patient does not require systemic steroids * no brain metastases patient characteristics: age * 18 and over performance status * ecog 0-1 life expectancy * more than 3 months hematopoietic * absolute neutrophil count \> 1,000/mm\^3 * platelet count \> 100,000/mm\^3 * hemoglobin \> 8.0 g/dl * lymphocyte count \> 500/mm\^3 * wbc \> 3,000/mm\^3 * no coagulation disorders hepatic * ast and alt \< 3 times upper limit of normal (uln) * bilirubin ≤ 2.0 mg/dl (3.0 mg/dl in patients with gilbert's syndrome) * hepatitis b surface antigen negative * hepatitis c antibody negative (unless antigen negative) renal * creatinine ≤ 1.6 mg/dl cardiovascular * lvef ≥ 45% by cardiac stress test * no lvef \< 45% in patients ≥ 50 years of age * no myocardial infarction * no cardiac arrhythmias * no symptomatic cardiac ischemia * no prior ekg abnormalities * no other major cardiovascular illness pulmonary * fev_1 ≥ 60% of predicted and no obstructive or restrictive pulmonary disease * no symptoms of respiratory dysfunction * no other major respiratory illness immunologic * hiv negative * epstein-barr virus positive * no active systemic infections (including opportunistic infections) * no form of primary (e.g., autoimmune colitis or crohn's disease) or secondary immunodeficiency (due to chemotherapy or radiotherapy) * no prior severe immediate hypersensitivity reaction to any of the study agents including eggs * no other major illness of the immune system other * not pregnant or nursing * negative pregnancy test * fertile patients must use effective contraception during and for 4 month after study participation * willing to complete a durable power of attorney (dpa) prior concurrent therapy: biologic therapy * see disease characteristics * more than 6 weeks since prior mdx-010 chemotherapy * not specified endocrine therapy * see disease characteristics * no concurrent systemic steroid therapy radiotherapy * not specified surgery * not specified other * more than 4 weeks since other prior systemic therapy and recovered

Keywords: recurrent melanoma stage iv melanoma