Patient case: 74-year-old female with melanoma; genetic feature: no tumor infiltrating lymphocytes

Clinical trial: Gene-Modified White Blood Cells Followed By Interleukin-2 and Vaccine Therapy in Treating Patients With Metastatic Melanoma

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.

Eligibility: 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

Relevance to patient case: not relevant