Study of CAR T-Cells Targeting the GD2 With IL-15+iCaspase9 for Relapsed/Refractory Neuroblastoma or Relapsed/Refractory Osteosarcoma
Neuroblastoma, Osteosarcoma
About this trial
This is an interventional treatment trial for Neuroblastoma focused on measuring Autologous Chimeric Antigen Receptor (CAR) T Cells, Interleukin (IL)-15, Disialoganglioside (GD2), Caspase 9, Pediatric, Rimiducid, AP1903, modified T cells, CAR T
Eligibility Criteria
All clinical and laboratory data required for determining eligibility must be available in the subject's medical/research record which will serve as the source document.
Because of the nature of iC9.GD2.CAR.IL-15 T cell product preparation, subjects will be assessed for initial study enrollment eligibility (prior to cell procurement) and then will have to meet criteria prior to starting lymphodepletion and prior to T cell infusion.
Inclusion Criteria for the Study:
- Written HIPAA authorization signed by legal guardian.
- Adequate performance status as defined by Lansky or Karnofsky performance status of ≥ 60 (Lansky for <16 years of age).
- Life expectancy ≥12 weeks.
- Histological confirmation of neuroblastoma or ganglioneuroblastoma at initial diagnosis. Bone marrow samples are acceptable as confirmation of neuroblastoma, confirmation of osteosarcoma at diagnosis
High-risk neuroblastoma with persistent/refractory or relapsed disease, defined as:
- First or greater relapse of neuroblastoma following completion of aggressive multi-drug frontline therapy.
- First episode of progressive neuroblastoma during aggressive multi-drug frontline therapy. Persistent/refractory neuroblastoma as defined by less than a complete response by the revised International Neuroblastoma Response Criteria (INRC) at the conclusion of at least 4 cycles of aggressive multidrug induction chemotherapy on or according to a high-risk neuroblastoma protocol (such as A3973 or ANBL0532).
- Patients must be diagnosed with high risk neuroblastoma at initial diagnosis or if non-high risk at time of initial diagnosis must have had evidence of metastatic progression when >18 months of age as defined in the protocol or relapsed or refractory osteosarcoma that is not responsive to standard treatment.
- Measurable or evaluable disease per Revised INRC for subjects with neuroblastoma or measurable disease by Response Evaluation Criteria In Solid Tumors Criteria (RECIST) v1.1 criteria for subjects with osteosarcoma.
Adequate central nervous system function as defined by:
- No known Central Nervous System ( CNS) disease
- No seizure disorder requiring antiepileptic drug therapy
Exclusion Criteria for the Study Subjects meeting any of the following exclusion criteria will not be able to participate in this study (procurement, lymphodepletion, and cell infusion).
- Pregnant or breastfeeding (NOTE: breast milk cannot be stored for future use while the mother is being treated on study).
- Has a known additional malignancy that is active and/or progressive requiring treatment.
- History of hypersensitivity reactions to murine protein-containing products.
- History of hypersensitivity to cyclophosphamide or fludarabine.
Sites / Locations
- Emory - Winship Cancer Institute
- Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel HillRecruiting
Arms of the Study
Arm 1
Experimental
iC9.GD2.CAR.IL-15 T-cells
The continuous reassessment method (CRM) will be used to estimate the maximum-tolerated dose (MTD) of cells that to be given in dose escalation cohorts comprised of 2-6 subjects. The final MTD will be the dose with estimated probability of dose limiting toxicity (DLT) closest to the target toxicity rate of 20%. Three cell doses will be evaluated: 0.5 x 10^6 cells/kg, 1.0 x 10^6 cells/kg, 1.5 x 10^6 cells/kg. Cohort enrollment will be staggered and each subject must complete at least 2 weeks of the cell treatment without incident of DLT before another subject can be enrolled at that dose level. A minimum of two subjects must complete the 4-week post-infusion DLT period before enrollment at the next higher dose level will be considered. If dose level 1 is determined to be above a tolerable dose, de-escalation would occur to dose level -1 where subjects would receive 0.25 x 10^6 cells/kg.