Basic Trial Information
Trial Description
     Summary
     Further Trial Information
     Eligibility Criteria
Trial Contact Information

Basic Trial Information

Trial Description

Summary

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.

Further Study Information

OBJECTIVES:

Primary

• Determine the maximum tolerated dose of autologous CD4+ antigen-specific T-cells for cellular adoptive immunotherapy in patients with metastatic melanoma.

• Determine the safety and toxicity of this regimen in these patients.

• Determine the duration of in vivo persistence of adoptively transferred CD4+ antigen-specific T-cell clones in these patients.

Secondary

• Determine the antitumor effects of this regimen in these patients.

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 on days 1 and 3 post T-cell infusion, and then once weekly for 12 weeks.

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

Eligibility Criteria

DISEASE CHARACTERISTICS:

• Histologically confirmed metastatic melanoma

• HLA type expressing one of the following class II alleles:

• DRB1*0401

• DRB1*0404

• DRB1*1501

• DPB1*0401

• DPB1*0402

• Tumor expresses tyrosinase

• Tumor expressing NY-ESO-1 and are HLA type DP4, DP2, or DR7 allowed

• No CNS metastases

• Prior CNS involvement allowed provided there is no evidence of CNS disease at least 2 months after treatment

PATIENT CHARACTERISTICS:

Age

• 18 to 75

Performance status

• Karnofsky 70-100%

Life expectancy

• More than 16 weeks

Hematopoietic

• WBC greater than 4,000/mm^3

• Absolute neutrophil count greater than 2,000/mm^3

• Platelet count greater than 100,000/mm^3

• Hematocrit greater than 30%

Hepatic

• SGOT no greater than 3 times upper limit of normal

• INR no greater than 1.5 due to hepatic dysfunction

• No significant hepatic dysfunction, defined as hepatic toxicity grade 2 or greater

Renal

• Creatinine no greater than 2.0 mg/dL OR

• Creatinine clearance at least 60 mL/min

• Calcium no greater than 12 mg/dL

Cardiovascular

• No significant cardiac abnormalities*, defined by any 1 of the following:

• Congestive heart failure

• Clinically significant hypotension

• Symptoms of coronary artery disease

• Cardiac arrhythmias present on EKG requiring drug therapy NOTE: *Patients with a history of cardiovascular disease or any of the above abnormalities undergo a cardiac evaluation, including a cardiac stress test and/or echocardiogram

Pulmonary

• No clinically significant pulmonary dysfunction

• FEV1 at least 1.0 L OR

• FEV1 at least 60%

• DLCO at least 55% (corrected for hemoglobin)

Immunologic

• No acquired or hereditary immunodeficiency

• No autoimmune disease

• 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

• HIV negative

Other

• No retinitis or choroiditis

• No history of seizures

• Not pregnant or nursing

• Negative pregnancy test

• Fertile patients must use effective contraception during and for 3 months after study

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 4 weeks since prior chemotherapy (standard or experimental) and recovered

Endocrine therapy

• No concurrent systemic steroids except for toxicity management

Radiotherapy

• At least 4 weeks since prior radiotherapy

Surgery

• Not specified

Other

• At least 4 weeks since prior immunosuppressive therapy

• More than 4 weeks since prior experimental drugs and recovered

• No concurrent pentoxifylline

• No other concurrent investigational agents

Trial Contact Information

Trial Lead Organizations/Sponsors

Fred Hutchinson Cancer Research Center

Cassian Yee

Study Chair

Link to the current ClinicalTrials.gov record.
NLM Identifer NCT00045357
Information obtained from ClinicalTrials.gov on December 14, 2011

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