A Pilot Study of Autologous T-Cell Transplantation With Vaccine Driven Expansion of Anti-Tumor Effectors After Cytoreductive Therapy in Metastatic Pediatric Sarcomas
Eradication of low tumor burdens can occur in vivo when T-cell mediated responses are
generated against specific tumor antigens. The Ewing's sarcoma family of tumors (ESFT) and
alveolar rhabdomyosarcoma (AR) display several features which make them candidate diseases
for trials of such immunotherapy. First, intensive cytotoxic chemotherapy is generally able
to eradicate bulk disease in patients with metastatic disease, but tumor relapse eventually
occurs in nearly all patients. Second, tumor-specific chromosomal translocations resulting
in the production of novel fusion proteins have been identified in the great majority of
these tumors. Peptides derived from these fusion proteins have been shown to function as
tumor antigens for cytolytic T cells in animal studies. Third, studies of immune
reconstitution after intensive cytotoxic therapy have provided evidence that
antigen-specific T cells can be generated in vivo when the adoptive transfer of peripheral T
cells and antigen are provided during the period of T cell regeneration. This process can
be augmented in murine models by the use of human immunodeficiency virus (HIV) active
protease inhibitor, indinavir, potentially through inhibition of programmed cell death in
expanding T cells. Merging these concepts, this protocol will attempt to eradicate minimal
residual disease in pediatric patients with metastatic ESFT and AR via vaccination with
tumor-specific peptides undertaken concomitant with autologous T cell transplantation and
indinavir.
Interventional
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Number of Participants With an Immune Response to Tumor-specific and Non-tumor Specific Peptides During a Period of Immune Reconstitution
Immune response was defined as a percent specific lysis of >10% following challenge with peptide pulsed targets, or interferon gamma production following challenge with peptide pulsed targets >2-fold that found with no-peptide controls or a proliferation index >3.0. Tumor specific peptides: Ewings sarcoma Type 1: EF-1 (EWS/FLI-1)*SSSYGQQN/PSYDSVRRGA,Ewing's Sarcoma Type 2: EF-2 (EWS/FLI-2)* SSSYGQ/QSSLLAYNT, Alveolar rhabdomyosarcoma: PXFK (PAX3/FKHR)† TIGNGLSPQ/NSIRHNLSL. Non-tumor specific peptide:HPV16E7 MLDLQPETT-MET-9-THR. See protocol link module for additional information re: peptides.
20 weeks post vaccination
No
Crystal Mackall, M.D.
Principal Investigator
National Cancer Institute, National Institutes of Health
United States: Federal Government
970052
NCT00001566
December 1996
September 2008
Name | Location |
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National Institutes of Health Clinical Center, 9000 Rockville Pike | Bethesda, Maryland 20892 |