Melanoma (Skin)
Conditions
Keywords
recurrent melanoma, stage IV melanoma
Brief 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.
Detailed description
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.
Interventions
BIOLOGICALaldesleukin
BIOLOGICALfilgrastim
BIOLOGICALgp100-fowlpox vaccine
BIOLOGICALtherapeutic autologous lymphocytes
DRUGcyclophosphamide
DRUGfludarabine phosphate
Sponsors
National Cancer Institute (NCI)
National Institutes of Health Clinical Center (CC)
Study design
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion 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
Countries
United States
Outcome results
None listed