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

Study Overview
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Brief Summary
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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
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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.

Official Title
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Treatment of Patients With Metastatic Melanoma by Lymphodepleting Conditioning Followed by Infusion of TCR-Gene Engineered Lymphocytes and Subsequent Fowlpox gp100 Vaccination

Conditions
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Melanoma (Skin)

Intervention / Treatment
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* Biological: aldesleukin
* Biological: filgrastim
* Biological: gp100-fowlpox vaccine
* Biological: therapeutic autologous lymphocytes
* Biological: therapeutic tumor infiltrating lymphocytes
* Drug: cyclophosphamide
* Drug: fludarabine phosphate


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Biological: aldesleukin|nan|
|Biological: filgrastim|nan|
|Biological: gp100-fowlpox vaccine|nan|
|Biological: therapeutic autologous lymphocytes|nan|
|Biological: therapeutic tumor infiltrating lymphocytes|nan|
|Drug: cyclophosphamide|nan|
|Drug: fludarabine phosphate|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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recurrent melanoma, stage IV melanoma