Document Detail


A phase I study of nonmyeloablative chemotherapy and adoptive transfer of autologous tumor antigen-specific T lymphocytes in patients with metastatic melanoma.
MedLine Citation:
PMID:  12000866     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
This report describes a phase I clinical trial using nonmyeloablative, lympho-depleting chemotherapy in combination with adoptive immunotherapy in patients with metastatic melanoma. The chemotherapy-conditioning schedule that induced transient lymphopenia consisted of cyclophosphamide (30 or 60 mg/kg per day for 2 days) followed by fludarabine (25 mg/m(2) per day for 5 days). Immunotherapy for all patients consisted of in vitro expanded, tumor-reactive, autologous T-cell clones selected for high avidity recognition of melanoma antigens. Cohorts of three to six patients each received either no interleukin (IL)-2, low-dose IL-2 (72,000 IU/kg intravenously three times a day to a maximum of 15 doses), or high-dose IL-2 (720,000 IU/kg intravenously three times a day for a maximum of 12 doses). The toxicities associated with this treatment were transient and included neutropenia and thrombocytopenia that resolved in all patients. High dose intravenous IL-2 was better tolerated by patients after chemotherapy than during previous immunotherapy cycles without chemotherapy. No patient exhibited an objective clinical response to treatment, although five patients demonstrated mixed responses or transient shrinkage of metastatic deposits. This study established a nonmyeloablative-conditioning regimen that could be safely administered in conjunction with adoptive T-cell transfer and IL-2 in patients with metastatic melanoma.
Authors:
Mark E Dudley; John R Wunderlich; James C Yang; Patrick Hwu; Douglas J Schwartzentruber; Suzanne L Topalian; Richard M Sherry; Francesco M Marincola; Susan F Leitman; Claudia A Seipp; Linda Rogers-Freezer; Kathleen E Morton; Azam Nahvi; Sharon A Mavroukakis; Donald E White; Steven A Rosenberg
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Publication Detail:
Type:  Clinical Trial; Clinical Trial, Phase I; Journal Article; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Journal of immunotherapy (Hagerstown, Md. : 1997)     Volume:  25     ISSN:  1524-9557     ISO Abbreviation:  J. Immunother.     Publication Date:    2002 May-Jun
Date Detail:
Created Date:  2002-05-09     Completed Date:  2002-10-03     Revised Date:  2009-11-18    
Medline Journal Info:
Nlm Unique ID:  9706083     Medline TA:  J Immunother     Country:  United States    
Other Details:
Languages:  eng     Pagination:  243-51     Citation Subset:  IM    
Affiliation:
Surgery Branch, National Cancer Institute, Building 10, Room 2B08, 9000 Rockville Pike, Bethesda, MD 20892, USA. Mark_Dudley@nih.gov
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MeSH Terms
Descriptor/Qualifier:
Adolescent
Adult
Antigens, Neoplasm / immunology*
Female
Humans
Immunotherapy, Adoptive*
Interleukin-2 / therapeutic use
Male
Melanoma / secondary*,  therapy*
Middle Aged
T-Lymphocytes / immunology*
Grant Support
ID/Acronym/Agency:
Z01 SC003811-33/SC/NCI NIH HHS
Chemical
Reg. No./Substance:
0/Antigens, Neoplasm; 0/Interleukin-2
Comments/Corrections

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