Testing a New Immune Cell Therapy, GD2-Targeted Modified T-cells (GD2CART), in Children, Adolescents, and Young Adults With Relapsed/Refractory Osteosarcoma and Neuroblastoma, The GD2-CAR PERSIST Trial
This phase I trial investigates the side effects and determines the best dose of an immune
cell therapy called GD2CART, as well as how well it works in treating patients with
osteosarcoma or neuroblastoma that has come back (relapsed) or does not respond to treatment
(refractory). T cells are infection fighting blood cells that can kill tumor cells. The T
cells given in this trial will come from the patient and will have a new gene put in them
that makes them able to recognize GD2, a protein on the surface of tumor cells. These
GD2-specific T cells may help the body's immune system identify and kill GD2 positive tumor
I. Determine the feasibility of producing T cells modified to express a GD2-specific chimeric
antigen receptor (GD2-CAR-expressing autologous T-lymphocytes [GD2CART]) meeting established
release criteria using a dasatinib containing culture platform and retroviral vector in the
Miltenyi CliniMACS Prodigy system II. Determine the safety and maximum tolerated dose (MTD)
or recommended phase 2 dose (RP2D) via administration of escalating doses of autologous
GD2CART in children and young adults with relapsed/refractory osteosarcoma and neuroblastoma
following cyclophosphamide-fludarabine based lymphodepletion.
III. Determine clinical activity in a preliminary fashion of autologous GD2CART in children
and young adults with relapsed, refractory osteosarcoma and neuroblastoma.
I. Measure persistence of adoptively transferred GD2CART and correlate this with antitumor
II. If unacceptable toxicity occurs that is possibly, probably, or likely related to GD2CART,
assess the capacity for rimiducid (AP1903), a dimerizing agent, to mediate clearance of the
genetically engineered cells and resolve toxicity.
III. Describe the feasibility and tolerability of a second infusion of GD2CART in select
I. Compare persistence of GD2CART administered in this trial to that observed in a previous
trial using GD2.OX40.28.z.iCasp9 CAR T cells (NCI 14-C-0059) and assess features of the T
cell product and the expanded T cells in vivo that correlate with persistence.
II. Conduct exploratory studies measuring levels of circulating myeloid cells including
myeloid derived suppressor cells (MDSCs) in patients treated on this trial and compare levels
to those observed in NCI 14-C-0059.
III. Explore GD2 expression in patients with neuroblastoma and osteosarcoma, including
patients who have previously received anti-GD2 antibodies, from tissue and/or bone marrow
samples at study entry and if available, after cell infusion.
OUTLINE: This is a dose-escalation study of GD2CART.
LYMPHODEPLETION CHEMOTHERAPY: Patients receive fludarabine phosphate intravenously (IV) daily
on days -5 to -2 and cyclophosphamide IV daily on days -4 to -2.
GD2CART: Patients receive GD2CART cells IV on day 0.
After completion of study treatment, patients are followed up three times weekly until day
14, twice weekly until day 28, at months 2, 3, 6, 9, and 12, every 3 months until the end of
the second year, then annually for up to 10 years.
If you are confirmed eligible after full screening, you will be required to understand and sign the informed consent if you decide to enroll in the study. Once enrolled you may be asked to make scheduled visits over a period of time.
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