RATIONALE: Biological therapies use different ways to stimulate the immune system and stop cancer cells from growing. Treating a person's white blood cells in the laboratory and then 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: peripheral blood lymphocyte therapy  Procedure: cytokine therapy  Procedure: interleukin therapy  Procedure: leukocyte therapy  Vaccine: non-tumor cell derivative vaccine  Procedure: vaccine therapy  Drug: autologous lymphocytes  Drug: interleukin-2	Phase I

Further Study Details: 

OBJECTIVES: I. Determine the safety and toxicity of cellular adoptive immunotherapy comprising autologous CD8+ cytotoxic T-lymphocyte clones targeting cancer-testis antigens in patients with metastatic melanoma. II. Determine the duration of in vivo persistence of this therapy in these patients. III. Evaluate the antitumor effects of this therapy in these patients.

PROTOCOL OUTLINE: Autologous peripheral blood mononuclear cells are harvested and then CD8+ cytotoxic T-lymphocyte (CTL) clones targeting cancer-testis (CT) antigens are generated ex vivo. Patients receive cellular adoptive immunotherapy comprising autologous CD8+ CTL clones targeting CT antigens IV over 30 minutes on day 1. Patients also receive interleukin-2 subcutaneously every 12 hours on days 1-14 of courses 2-4. Treatment repeats every 3 weeks for 4 courses in the absence of disease progression or unacceptable toxicity. Patients who demonstrate a clinical response after completion of the fourth course are eligible to receive additional T-cell infusions. Patients are followed for 9 months.

PROJECTED ACCRUAL: A total of 20 patients will be accrued for this study within 3 years.

Ages Eligible for Study:  18 Years   -   75 Years

Criteria

PROTOCOL ENTRY CRITERIA:

--Disease Characteristics--

Histologically confirmed metastatic melanoma

• Stage IV disease

HLA-A1, -A2, or -A3 positive

MAGE-1 or MAGE-3 positive by histology

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

No CNS metastases

--Prior/Concurrent Therapy--

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

Chemotherapy:

• At least 3 weeks since prior standard or experimental chemotherapy
• 1-2 courses of prior cytoreductive chemotherapy for bulky disease allowed

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
• No concurrent pentoxyfylline
• No other concurrent investigational agents

--Patient Characteristics--

Age: 18 to 75

Performance status: Karnofsky 80-100%

Life expectancy: More than 6 months

Hematopoietic: Not specified

Hepatic:

• Bilirubin no greater than 1.6 mg/dL
• SGOT no greater than 3 times upper limit of normal
• PT 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 electrocardiogram requiring drug therapy
• Patients with prior cardiovascular disease or the presence of any of the above abnormalities undergo a cardiac evaluation, which may include a stress test and/or echocardiogram

Pulmonary:

• No clinically significant pulmonary dysfunction by medical history or physical examination
• FEV1 at least 1.0 L
• DLCO at least 45% (corrected for hemoglobin)

Other:

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No active infections or oral temperature greater than 38.2 degrees Celsius within the past 72 hours
• No systemic infection requiring chronic maintenance or suppressive therapy

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:  CDR0000256451; FHCRC-1588.00; NCI-H02-0091
Record last reviewed:  May 2003
Last Updated:  October 13, 2004
Record first received:  September 6, 2002
ClinicalTrials.gov Identifier:  NCT00045149
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08