A Pilot Study of Gene Modified Autologous Neuroblastoma Vaccine for the Post-Chemotherapy Treatment of High-Risk Neuroblastoma
Tumor cells from subjects with high-risk neuroblastoma will be obtained at the time of
presentation and initial diagnosis, during routine surveillance of bone marrow disease
status, or at the time of surgical resection of disease during primary chemotherapy. The
tumor cells will be irradiated to prevent the possibility of tumor growth. Autologous
neuroblastoma tumor cells will be used to treat neuroblastoma following the completion of
primary or salvage chemotherapy when peripheral blood lymphocyte counts have recovered to >
500 CD3+ cells/mm3. This preceding chemotherapy may or may not have included bone marrow or
peripheral stem cell rescue. Therefore, following the achievement of best response with
chemotherapy, vaccine will be administered for 6 months. Vaccine modified for secretion of
IL-2 will be used.
Vaccine therapy will commence after complete recovery from the side effects of primary or
salvage chemotherapy, as long as the subject has an absolute CD3+ lymphocyte count and an
absolute neutrophil count greater than 500/mm3. A vaccine consisting of 0.3 x 10 8
cells/patient will be given per injection, based on data from the Phase I studies.
Injections will be given twice monthly for two months, then monthly for four months, for a
total of eight vaccine injections over six months. The immune effects of the vaccine,
toxicity of treatment, and anti-tumor effects will be periodically assessed. Further
evaluation will be done annually.
The first and second vaccine injection sites will be "punch biopsied" one week after the
injection. Several x-rays and various types of scans will also be taken to assist with
monitoring the status of the neuroblastoma. Complete details of the evaluations required by
this study are included in.
Subjects may receive supportive care for any acute or chronic toxicity from the injections,
including blood product support, antibiotics, and other appropriate intervention.
Pneumocystis carinii prophylaxis initiated during chemotherapy may be continued during
vaccine therapy for as long as deemed appropriate by the investigator. As well, subjects
may receive concurrent therapy with cis-retinoic acid at the discretion of the treating
An adenoviral vector is being used to transduce the cells ex-vivo. Subjects will not be
treated with the viral vector.
Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Patients who demonstrate immunological anti-tumor response at any time during, and for up to 12 months from initiation of, treatment with injections of autologous neuroblastoma cells, genetically modified by adenoviral vectors to secrete IL-2
12 months post injections
Heidi V Russell, MD
Baylor College of Medicine
United States: Food and Drug Administration
|Texas Children's Hospital||Houston, Texas|