PHASE I STUDY TO EVALUATE THE SAFETY OF CELLULAR ADOPTIVE IMMUNOTHERAPY USING GENETICALLY MODIFIED AND UNMODIFIED AUTOLOGOUS CD8+ TYROSINASE-SPECIFIC T CELLS FOR PATIENTS WITH METASTATIC MELANOMA
aldesleukin
+ therapeutic tumor infiltrating lymphocytes
Neoplasms+9
+ Neoplasms by Histologic Type
+ Neoplasms by Site
Treatment Study
Summary
Study start date: October 1, 1995
Actual date on which the first participant was enrolled.OBJECTIVES: Assess the safety and toxicity of cellular adoptive immunotherapy using autologous CD8+ antigen-specific T-cell clones in patients with metastatic melanoma. Estimate the duration of in vivo persistence of adoptively transferred CD8+ antigen-specific cytotoxic T-cell clones in these patients. Evaluate the antitumor effects of CD8+ antigen-specific T-cell clones in these patients. OUTLINE: Autologous peripheral blood mononuclear cells are harvested and then CD8+ cytotoxic T-lymphocyte (CTL) clones targeting melanosomal antigens are generated ex vivo. Patients receive cellular adoptive immunotherapy comprising autologous CD8+ CTL clones over 30 minutes on day 1. Patients also receive interleukin-2 subcutaneously every 12 hours on days 1-14 of courses 2-3. Treatment repeats every 3 weeks for 3 courses in the absence of disease progression or unacceptable toxicity. Patients are followed for approximately 1 year after the last infusion. PROJECTED ACCRUAL: Approximately 20 patients will be accrued for this study.
Protocol
This section provides details of the study plan, including how the study is designed and what the study is measuring.20 patients to be enrolled
Total number of participants that the clinical trial aims to recruit.Treatment Study
Eligibility
Researchers look for people who fit a certain description, called eligibility criteria: person's general health condition or prior treatments.Any sex
Biological sex of participants that are eligible to enroll.From 18 to 75 Years
Range of ages for which participants are eligible to join.Healthy volunteers not allowed
If individuals who are healthy and do not have the condition being studied can participate.Conditions
Pathology
Criteria
DISEASE CHARACTERISTICS: Histopathologically proven metastatic melanoma No CNS metastases HLA-A2 positive Bidimensionally measurable disease by palpation on clinical exam or radiographic imaging (x-ray, CT scan, or MRI) Surgically accessible site for tumor cell procurement (skin, subcutaneous nodule, or superficial node) and patient clinically eligible for such surgery PATIENT CHARACTERISTICS: Age 18 to 75 Performance status Karnofsky 80-100% 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 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 FEV_1 at least 1.0 L DLCO at least 45% of predicted Other No active infection or oral temperature greater than 38.2 degrees C within 72 hours of study No systemic infection requiring chronic maintenance or suppressive therapy HIV negative No history of seizures No retinitis or choroiditis Not pregnant or nursing Negative pregnancy test Fertile patients must use adequate contraception Peripheral blood samples available weekly for 4 consecutive weeks PRIOR CONCURRENT THERAPY: 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 Other At least 4 weeks since other prior investigational drug therapy and recovered
Study Centers
These are the hospitals, clinics, or research facilities where the trial is being conducted. You can find the location closest to you and its status.This study has 1 location
Fred Hutchinson Cancer Research Center
Seattle, United StatesOpen Fred Hutchinson Cancer Research Center in Google Maps