RATIONALE: Biological therapies use different ways to stimulate the immune system and stop cancer cells from growing. PURPOSE: Phase I/II trial to study the effectiveness of biological therapy in treating patients who have metastatic melanoma.

Condition	Treatment or Intervention	Phase
Stage IV Melanoma Recurrent Melanoma	Procedure: biological response modifier therapy  Procedure: tumor infiltrating lymphocyte therapy  Procedure: gene therapy  Procedure: cytokine therapy  Procedure: interleukin therapy  Procedure: leukocyte therapy  Drug: interleukin-2	Phase I Phase II

Further Study Details: 

OBJECTIVES: I. Assess the safety and toxicity of cellular adoptive immunotherapy using autologous CD8+ antigen specific T-cell clones in patients with metastatic melanoma. II. Estimate the duration of in vivo persistence of adoptively transferred CD8+ antigen specific cytotoxic T-cell clones. III. Evaluate the antitumor effects of CD8+ antigen specific T-cell clones in patients with metastatic melanoma. IV. Evaluate the development of host anti-HyTK T-cell responses in melanoma patients receiving HyTK transduced T-cell clones.

PROTOCOL OUTLINE: Patients undergo leukapheresis to collect CD8+ cells, and surgery to harvest autologous tumor cells. CD8+ T-cells that demonstrate antigen specific cytotoxicity in vitro are transduced in vitro with the HyTK retrovirus containing a suicide marker gene. Patients receive 2 IV infusions of transduced CD8+ T-cell clones 1 week apart. In the absence of toxicity after a 2 week observation period, patients receive 3 additional infusions of nontransduced CD8+ T-cell clones given 3 weeks apart with increasing doses of low dose interleukin-2 subcutaneously. Patients are followed for approximately 1 year after the last infusion.

PROJECTED ACCRUAL: Approximately 20 patients will be accrued for this study.

Ages Eligible for Study:  18 Years   -   75 Years

Criteria

PROTOCOL ENTRY CRITERIA:

--Disease Characteristics--

Histopathologically proven melanoma that is metastatic

• No CNS metastases

Bidimensionally measurable disease by palpation on clinical exam or radiographic imaging (x-ray, CT, or MRI)

Surgically accessible site for tumor cell procurement (skin, subcutaneous nodule, or superficial node) and patient clinically eligible for such surgery

--Prior/Concurrent Therapy--

At least 4 weeks since other prior investigational drug therapy and recovered

Biologic therapy At least 4 weeks since other prior immunotherapy

Chemotherapy:

• 1 or 2 courses of cytoreductive chemotherapy allowed for bulky disease
• At least 4 weeks since prior standard or investigational chemotherapy

Endocrine therapy: At least 4 weeks since prior steroid therapy

Radiotherapy: At least 4 weeks since prior radiotherapy

Surgery: Not specified

--Patient Characteristics--

Age: 18 to 75

Performance status: Karnofsky 70-100%

Life expectancy: Greater than 16 weeks

Hematopoietic:

• WBC greater than 4,000/mm3
• Absolute neutrophil count greater than 2,000/mm3
• Platelet count greater than 100,000/mm3
• Hematocrit greater than 30%

Hepatic:

• Bilirubin no greater than 1.6 mg/dL
• SGOT no greater than 150 IU (or no greater than 3 times normal)
• Prothrombin time no greater than 1.5 times control

Renal:

• Creatinine no greater than 2.0 mg/dL
• Calcium no greater than 12 mg/dL

Cardiovascular:

• No congestive heart failure
• No clinically significant hypotension
• No symptoms of coronary artery disease
• No arrhythmia on EKG requiring drug therapy

Pulmonary:

• No severe chronic obstructive pulmonary disease
• FEV1 at least 1.0 L
• DLCO at least 45% predicted

Other:

• No active infection or oral temperature greater than 38.2 C within 72 hours of study
• No systemic infection requiring chronic maintenance or suppressive therapy
• HIV negative
• No history of seizures
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use adequate contraception
• Peripheral blood samples available weekly for 4 consecutive weeks

Washington
      Fred Hutchinson Cancer Research Center, Seattle,  Washington,  98109-1024,  United States

Study chairs or principal investigators

Cassian Yee,  Study Chair,  Fred Hutchinson Cancer Research Center   

Study ID Numbers:  CDR0000064846; FHCRC-1017.01; NCI-V96-0920
Record last reviewed:  May 2003
Last Updated:  October 13, 2004
Record first received:  November 1, 1999
ClinicalTrials.gov Identifier:  NCT00002786
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08