RATIONALE: Biological therapies use different ways to stimulate the immune system and stop tumor cells from growing. Treating a person's white blood cells in the laboratory and reinfusing them may cause a stronger immune response and kill more tumor cells. PURPOSE: Phase I 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: leukocyte therapy  Drug: autologous lymphocytes	Phase I

Further Study Details: 

OBJECTIVES: I. Determine the maximum tolerated dose of autologous CD4+ antigen-specific T cells for cellular adoptive immunotherapy in patients with metastatic melanoma. II. Determine the safety and toxicity of this regimen in these patients. III. Determine the duration of in vivo persistence of adoptively transferred CD4+ antigen-specific T-cell clones in these patients. IV. Determine the antitumor effects of this regimen in these patients.

PROTOCOL OUTLINE: This is a dose-escalation study. Patients undergo leukapheresis to collect peripheral blood mononuclear cells. CD4+ antigen-specific T-cell clones are generated over the next 2-3 months using immunogenic peptides MART1, tyrosinase, or gp100. Patients receive autologous CD4+ antigen-specific T cells IV over 30 minutes. Cohorts of 3-6 patients receive escalating doses of autologous CD4+ antigen-specific T cells until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. Patients are followed twice weekly for 12 weeks.

PROJECTED ACCRUAL: A total of 3-18 patients will be accrued for this study within 2-3 years.

Ages Eligible for Study:  18 Years   -   75 Years

Criteria

PROTOCOL ENTRY CRITERIA:

--Disease Characteristics--

Histologically confirmed metastatic melanoma

• No prior therapy OR
• Refractory disease

HLA type expressing one of the following class II alleles:

• DRB1*0401
• DRB1*1501

Tumor expresses tyrosinase

Bidimensionally measurable disease by palpation, x-ray, or CT scan

No CNS metastases

Orbital metastasis not involving the optic nerve or CNS is allowed

--Prior/Concurrent Therapy--

Biologic therapy: No other concurrent immunotherapy (e.g., interleukins, interferons, melanoma vaccines, IV immunoglobulin, or expanded polyclonal tumor-infiltrating lymphocytes or lymphokine-activated killer therapy)

Chemotherapy: At least 3 weeks since prior chemotherapy (standard or experimental)

Endocrine therapy: No concurrent systemic steroids except for toxicity management

Radiotherapy: At least 3 weeks since prior radiotherapy

Surgery: Not specified

Other:

• At least 3 weeks since prior immunosuppressive therapy
• At least 3 weeks since prior interval therapy of any type
• More than 3 weeks since prior experimental drugs and recovered
• No concurrent pentoxifylline
• No other concurrent investigational agents

--Patient Characteristics--

Age: 18 to 75

Performance status: Karnofsky 70-100%

Life expectancy: More 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:

• SGOT no greater than 150 IU OR
• SGOT no greater than 3 times upper limit of normal
• Bilirubin no greater than 1.6 mg/dL
• 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 cardiac arrhythmias on EKG requiring drug therapy

Pulmonary:

• No clinically significant pulmonary dysfunction
• FEV1 at least 1.0 L
• FEV1/FVC at least 50%
• DLCO at least 45% (corrected for hemoglobin)

Other:

• No retinitis or choroiditis
• No active infection
• No oral temperature greater than 38.2 degrees C within the past 72 hours
• No systemic infection requiring chronic maintenance or suppressive therapy
• No history of seizures
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception during and for 3 months after study

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:  CDR0000256867; FHCRC-1585.00; NCI-H02-0093
Record last reviewed:  July 2003
Last Updated:  October 13, 2004
Record first received:  September 6, 2002
ClinicalTrials.gov Identifier:  NCT00045357
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08