Trial Information

Phase I Study of Cytokine-Gene Modified Autologous or Partially Matched Allogeneic Neuroblastoma Cells for Treatment of Relapsed/Refractory Neuroblastoma

OBJECTIVES: I. Determine the safety in children of recurrent neuroblastoma of two weekly
subcutaneous injections of autologous, or partially HLA-matched allogeneic, neuroblastoma
cells that have been modified by insertion of the interleukin-2 gene introduced by a
retroviral vector. II. Determine whether multiple histocompatibility-restricted or
unrestricted antitumor immune responses are induced by this treatment and the cell dose
required to produce these effects. III. Obtain preliminary data on the antitumor effects of
this regimen.

OUTLINE: Autologous or partially HLA-matched allogeneic neuroblastoma cells are transduced
with a human gene for interleukin-2 production. Patients receive subcutaneous injections of
the gene-modified cells on days 1 and 8, with the second injection containing 10 times more
cells than the first injection. After a 3-4 week rest, stable and responding patients may
receive additional weekly injections at the second dose. Cohorts of 3-6 patients will be
entered at increasing cell doses until the maximum tolerated dose is estimated. Multiple
injection sites may be used at the higher cell-dose levels. Patients are followed every week
for 6 weeks, every other week for 6 weeks, and monthly for 1 year. Additional visits may be
required as clinically indicated.

PROJECTED ACCRUAL: Approximately 12 patients each will be entered into the autologous and
the partially HLA-matched allogeneic tumor cell treatment groups. Accrual is expected to
require 4 years for the autologous tumor cell group and 2 years for the partially
HLA-matched allogenic tumor cell group.