Biological Therapy in Treating Patients With Metastatic Melanoma
Study Details
Study Description
Brief 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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1 |
Detailed Description
OBJECTIVES:
Primary
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Determine the maximum tolerated dose of autologous CD4+ antigen-specific T-cells for cellular adoptive immunotherapy in patients with metastatic melanoma.
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Determine the safety and toxicity of this regimen in these patients.
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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.
Study Design
Outcome Measures
Primary Outcome Measures
Eligibility Criteria
Criteria
DISEASE CHARACTERISTICS:
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Histologically confirmed metastatic melanoma
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HLA type expressing one of the following class II alleles:
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DRB1*0401
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DRB1*0404
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DRB1*1501
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DPB1*0401
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DPB1*0402
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Tumor expresses tyrosinase
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Tumor expressing NY-ESO-1 and are HLA type DP4, DP2, or DR7 allowed
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No CNS metastases
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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
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WBC greater than 4,000/mm^3
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Absolute neutrophil count greater than 2,000/mm^3
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Platelet count greater than 100,000/mm^3
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Hematocrit greater than 30%
Hepatic
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SGOT no greater than 3 times upper limit of normal
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INR no greater than 1.5 due to hepatic dysfunction
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No significant hepatic dysfunction, defined as hepatic toxicity grade 2 or greater
Renal
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Creatinine no greater than 2.0 mg/dL OR
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Creatinine clearance at least 60 mL/min
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Calcium no greater than 12 mg/dL
Cardiovascular
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No significant cardiac abnormalities*, defined by any 1 of the following:
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Congestive heart failure
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Clinically significant hypotension
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Symptoms of coronary artery disease
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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
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No clinically significant pulmonary dysfunction
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FEV1 at least 1.0 L OR
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FEV1 at least 60%
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DLCO at least 55% (corrected for hemoglobin)
Immunologic
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No acquired or hereditary immunodeficiency
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No autoimmune disease
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No active infection
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No oral temperature greater than 38.2 degrees C within the past 72 hours
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No systemic infection requiring chronic maintenance or suppressive therapy
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HIV negative
Other
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No retinitis or choroiditis
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No history of seizures
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Not pregnant or nursing
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Negative pregnancy test
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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
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At least 4 weeks since prior immunosuppressive therapy
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More than 4 weeks since prior experimental drugs and recovered
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No concurrent pentoxifylline
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No other concurrent investigational agents
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Fred Hutchinson Cancer Research Center | Seattle | Washington | United States | 98109-1024 |
Sponsors and Collaborators
- Fred Hutchinson Cancer Center
- National Cancer Institute (NCI)
Investigators
- Study Chair: Cassian Yee, MD, Fred Hutchinson Cancer Center
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- 1585.00
- FHCRC-1585.00
- NCI-H02-0093
- CDR0000256867