Phase I Study of Donor Derived,Gene Modified, Multi-virus-specific, Cytotoxic T-Lymphocytes Redirected to the Tumor Marker GD2 for Relapsed/Refractory Neuroblastoma Post-allogeneic Stem Cell Transplantation With a Submyeloblative Conditioning Regimen
Neuroblastoma (NB) is the most common extracranial tumor of childhood and prognosis for
patients with relapsed or refractory disease is < 10% and there is no standard therapy for
these patients. Research toward immunotherapeutic agents has intensified as monoclonal
antibody targeting GD2, when incorporated into upfront NB therapy, prolongs survival.
Allogeneic Hematopoietic stem cell transplantation (HSCT) has been utilized in patients with
NB with evidence of a graft versus tumor (GVT) effect but transplant related mortality (TRM)
has nullified the survival benefit. In an effort to harness the GVT effect of allogeneic
transplant and lower TRM, harvested viral specific cytotoxic T-cells from the donor will be
infused early post-HSCT to the HSCT recipient to shorten the recovery of immunity toward the
most significant viral infections. The investigators will also retrovirally transduce the
viral specific CTL with a chimeric antigen receptor (CAR) gene complex such that the tV-CTL
can expand, via their native T-cell receptors in response to viral infections post-HSCT and
carry the capability of killing tumor cells through their transduced receptor which, on the
extracellular component of the CAR, has specificity for GD2 expressed on the surface of NB.
In essence, the investigators intend to take the specificity of the monoclonal antibody to
GD2, already utilized in therapy for NB, and combine this specificity with the cytotoxicity
of T-cells to target NB. The investigators hypothesize that the infusion will be safe and
viral specificity of the tV-CTL will provide long term immunity to both viral infections and
the investigators will see anti-tumor effects.
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Infusional and long term safety and persistence of tumor redirected, genetically modified, donor derived, allogeneic multi-virus specific cytotoxic T-cells (tV-CTL) after allogeneic hematopoietic stem cell transplant in patients with neuroblastoma
Immediate and short term toxicity of infusion will be assessed over 8 weeks. Yearly monitoring for insertional mutagenesis/oncogenesis will be performed for 15 years.
Doug Myers, MD
Children's Mercy Hospital
United States: Food and Drug Administration
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