Trial Information

Phase I Study to Evaluate the Safety of Cellular Immunotherapy for Recurrent/Refractory Neuroblastoma Using Genetically-Modified Autologous CD8+ T Cell Clones

OBJECTIVES: I. Determine the safety and toxicity of cellular immunotherapy using ex vivo
expanded autologous CD8+ cytotoxic T-lymphocyte clones genetically modified to express the
CE7R scFvFc:zeta chimeric immunoreceptor and the HyTK selection/suicide gene in children
with recurrent or refractory disseminated neuroblastoma. II. Determine the antitumor
activity of this regimen in these patients. III. Determine the duration of in vivo
persistence of adoptively transferred clones and the effect of interleukin-2 on maintaining
the in vivo persistence of these clones. IV. Screen for the development of host
anti-scFvFc:zeta and HyTK immune responses in patients treated with this regimen. V.
Determine the efficacy of ganciclovir in ablating transferred clones in vivo if toxicity
occurs in these patients.

OUTLINE: This is a multicenter study. Patients undergo autologous peripheral blood stem cell
harvest. CD8+ cytotoxic T-lymphocyte (CTL) clones are isolated, genetically modified to
express the CE7R scFvFc:zeta chimeric immunoreceptor and the HyTK selection/suicide gene,
and then expanded ex vivo. While the modified CTL clones are being generated, patients each
receive an individualized salvage chemotherapy regimen that may consist of one of the
following: cyclophosphamide and topotecan; ifosfamide, carboplatin, and etoposide; or
another chemotherapy regimen chosen by the patient's primary oncologist. The first cohort of
5 patients receives escalating doses of modified CTL clones IV over 30 minutes on days 0,
14, and 28 in the absence of disease progression or unacceptable toxicity. Each patient
begins the series of 3 infusions as soon as an adequate number of modified CTL clones are
ready and after the acute side effects of chemotherapy have resolved. In the absence of
unacceptable toxicity in the first cohort, the second cohort of 5 patients receives the same
treatment as cohort 1 plus interleukin-2 subcutaneously every 12 hours on days 15-24 and
29-38. Patients with unacceptable toxicity receive ganciclovir IV every 12 hours for 14 days
(or longer if symptomatic resolution is not achieved in that interval). Patients are
followed at day 100 and then periodically thereafter.

PROJECTED ACCRUAL: A total of 10 patients will be accrued for this study within 3 years.