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Phase II Study of Lymphocyte-Depleting Nonmyeloablative Preparative Chemotherapy Followed By Autologous Lymphocyte Infusion, ESO-1 Peptide Vaccination Comprising ESO-1:157-165 (165V) Peptide and Montanide ISA-51, and Interleukin-2 in Patients With Metastatic Melanoma
Alternate Title Basic Trial Information Objectives Entry Criteria Expected Enrollment Outcomes Outline Trial Contact Information Registry Information
Alternate Title
Lymphocyte-Depleting Nonmyeloablative Preparative Chemotherapy Followed By Autologous Lymphocyte Infusion, Peptide Vaccine Plus Montanide ISA-51, and Interleukin-2 in Treating Patients With Metastatic Melanoma
Basic Trial Information
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Protocol IDs
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Phase II
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Treatment
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Completed
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16 and over
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NCI
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NCI-04-C-0104 NCI-6233, 6233, NCT00079144
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Objectives Primary - Determine the clinical tumor regression in patients with metastatic melanoma treated with a lymphocyte-depleting nonmyeloablative preparative chemotherapy regimen followed by autologous lymphocyte infusion, ESO-1 peptide vaccination comprising ESO-1:157-165 (165V) and Montanide ISA-51, and interleukin-2.
Secondary - Determine the survival of the infused lymphocytes in patients treated with this regimen.
- Determine the long-term immune status of patients treated with this regimen.
Entry Criteria Disease Characteristics:
- Diagnosis of metastatic melanoma that is refractory to standard therapy (including high-dose interleukin-2)
- Measurable disease
- HLA-A*0201 positive
- Epstein-Barr virus positive
- ESO-1-expressing disease by reverse transcription polymerase chain reaction amplified tissue OR presence of ESO-1 serum antibody
Prior/Concurrent Therapy:
Biologic therapy - See Disease Characteristics
- Prior ESO-1-based vaccination allowed
Chemotherapy - At least 6 weeks since prior nitrosoureas and recovered
Endocrine therapy - No concurrent systemic steroid therapy
Radiotherapy - Recovered from prior radiotherapy
Surgery Other - At least 4 weeks since prior systemic therapy
Patient Characteristics:
Age Performance status Life expectancy Hematopoietic - Absolute neutrophil count > 1,000/mm3
- Platelet count > 100,000/mm3
- Hemoglobin > 8.0 g/dL
Hepatic - Hepatitis B surface antigen negative
- Hepatitis C antibody negative
- AST and ALT < 3 times upper limit of normal
- Bilirubin ≤ 2.0 mg/dL (< 3.0 mg/dL for patients with Gilbert’s syndrome)
- No coagulation disorders
Renal Cardiovascular - No prior myocardial infarction
- No major cardiovascular illness by stress thallium or comparable test
- No cardiac arrhythmias
- LVEF ≥ 45%
- Normal cardiac stress test required for the following conditions:
- Prior EKG abnormalities
- Symptoms of cardiac ischemia
- Arrhythmias
- Age 50 and over
Pulmonary - FEV1 > 60% of predicted (for patients with a prolonged history of cigarette smoking or symptoms of respiratory dysfunction)
- No obstructive or restrictive pulmonary disease
- No other major respiratory illness
Immunologic - HIV negative
- No active systemic infection
- No opportunistic infection
- No major immune system illness
- No form of primary or secondary immunodeficiency
- No known hypersensitivity to study agents
Other - Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception during and for at least 4 months after study participation
Expected Enrollment A total of 24-74 patients (12-37 per stratum) will be accrued for this study within 2-3 years. Outcomes Primary Outcome(s)Clinical tumor regression
Secondary Outcome(s)Survival of infused lymphocytes Long-term immune status
Outline Patients are stratified according to type of lymphocyte infusion (ESO-1-reactive tumor-infiltrating lymphocytes [TIL] vs ESO-1 reactive peripheral blood lymphocytes [PBL]). - Autologous lymphocyte collection and expansion: Autologous PBL or TIL are collected from patients during leukapheresis or biopsy. The cells are sensitized in vitro with ESO-1:157-165 (165V) melanoma antigen and expanded.
- Lymphocyte-depleting nonmyeloablative preparative chemotherapy: Patients receive lymphocyte-depleting nonmyeloablative preparative chemotherapy comprising cyclophosphamide IV over 1 hour on days –7 and –6 and fludarabine IV over 15-30 minutes on days –5 to –1.
- Autologous lymphocyte infusion: Autologous PBL or TIL are reinfused on day 0*. Patients also receive filgrastim (G-CSF) subcutaneously (SC) once daily beginning on day 1 and continuing until blood counts recover.
- ESO-1 peptide vaccination: Patients receive ESO-1 peptide vaccination comprising ESO-1:157-165 (165V) peptide emulsified in Montanide ISA-51 SC on days 0*-4, 11, 18, and 25.
- Interleukin therapy: Patients receive interleukin-2 IV over 15 minutes 3 times daily on days 0*-4.
[Note: *Day 0 is 1-4 days after the last dose of fludarabine.] Patients achieving stable disease or partial response may receive up to 1 retreatment course. Patients with progressive disease after infusion of PBL may receive retreatment with TIL, if available. Patients are followed at 4-5 weeks, every 3-4 months for 2 years, and then annually thereafter.
Trial Contact Information
Trial Lead Organizations NCI - Center for Cancer Research-Medical Oncology | | | Steven Rosenberg, MD, PhD, Protocol chair | | | |
Registry Information | | Official Title | | Treatment Of Patients With Metastatic Melanoma Using Nonmyeloablative But Lymphocyte Depleting Regimen Followed By The Administration Of In Vitro Sensitized Lymphocytes Reactive With ESO-1 Antigen | | Trial Start Date | | 2004-01-28 | | Registered in ClinicalTrials.gov | | NCT00079144 | | Date Submitted to PDQ | | 2004-01-26 | | Information Last Verified | | 2005-05-18 |
Note: The purpose of most clinical trials listed in this database is to test new cancer treatments, or new methods of diagnosing, screening, or preventing cancer. Because all potentially harmful side effects are not known before a trial is conducted, dose and schedule modifications may be required for participants if they develop side effects from the treatment or test. The therapy or test described in this clinical trial is intended for use by clinical oncologists in carefully structured settings, and may not prove to be more effective than standard treatment. A responsible investigator associated with this clinical trial should be consulted before using this protocol. Back to Top |
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