| ID | Type | Description | Link |
|---|---|---|---|
| 04-C-0181 | |||
| NCI-6470 | |||
| CDR0000370798 |
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| Name | Class |
|---|---|
| National Cancer Institute (NCI) | NIH |
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
Secondary
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.
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.
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| aldesleukin | Biological | |||
| filgrastim | Biological | |||
| gp100-fowlpox vaccine | Biological | |||
| therapeutic autologous lymphocytes | Biological | |||
| therapeutic tumor infiltrating lymphocytes | Biological | |||
| cyclophosphamide | Drug | |||
| fludarabine phosphate | Drug |
DISEASE CHARACTERISTICS:
Diagnosis of melanoma
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
Performance status
Life expectancy
Hematopoietic
Hepatic
Renal
Cardiovascular
LVEF ≥ 45% by cardiac stress test
No myocardial infarction
No cardiac arrhythmias
No symptomatic cardiac ischemia
No prior EKG abnormalities
No other major cardiovascular illness
Pulmonary
Immunologic
Other
PRIOR CONCURRENT THERAPY:
Biologic therapy
Chemotherapy
Endocrine therapy
Radiotherapy
Surgery
Other
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| Name | Affiliation | Role |
|---|---|---|
| Steven A. Rosenberg, MD, PhD | NCI - Surgery Branch | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Warren Grant Magnuson Clinical Center - NCI Clinical Trials Referral Office | Bethesda | Maryland | 20892-1182 | United States | ||
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| NCI - Surgery Branch |
| Bethesda |
| Maryland |
| 20892-1201 |
| United States |
| ID | Term |
|---|---|
| D008545 | Melanoma |
| ID | Term |
|---|---|
| D018358 | Neuroendocrine Tumors |
| D017599 | Neuroectodermal Tumors |
| D009373 | Neoplasms, Germ Cell and Embryonal |
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
| D009380 | Neoplasms, Nerve Tissue |
| D018326 | Nevi and Melanomas |
| D012878 | Skin Neoplasms |
| D009371 | Neoplasms by Site |
| D012871 | Skin Diseases |
| D017437 | Skin and Connective Tissue Diseases |
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| ID | Term |
|---|---|
| C082598 | aldesleukin |
| D000069585 | Filgrastim |
| D003520 | Cyclophosphamide |
| C042382 | fludarabine phosphate |
| ID | Term |
|---|---|
| D016179 | Granulocyte Colony-Stimulating Factor |
| D003115 | Colony-Stimulating Factors |
| D006023 | Glycoproteins |
| D006001 | Glycoconjugates |
| D002241 | Carbohydrates |
| D016298 | Hematopoietic Cell Growth Factors |
| D016207 | Cytokines |
| D036341 | Intercellular Signaling Peptides and Proteins |
| D010455 | Peptides |
| D000602 | Amino Acids, Peptides, and Proteins |
| D011506 | Proteins |
| D001685 | Biological Factors |
| D010752 | Phosphoramide Mustards |
| D009588 | Nitrogen Mustard Compounds |
| D009150 | Mustard Compounds |
| D006846 | Hydrocarbons, Halogenated |
| D006838 | Hydrocarbons |
| D009930 | Organic Chemicals |
| D063088 | Phosphoramides |
| D009943 | Organophosphorus Compounds |
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