The body has different ways of fighting infections and disease. No single way seems perfect for fighting cancer. This research study combines two different ways of fighting disease: antibodies and T cells. Antibodies are molecules that fight infections and protect your body from diseases caused by bacteria and toxic substances. Antibodies work by sticking to those bacteria or substances, which stops them from growing and causing bad effects. T cells are special infection-fighting blood cells that can kill other cells, including tumor cells or cells that are infected. Both antibodies and T cells have been used to treat patients with cancers. They both have shown promise, but neither alone has been enough to cure most patients.
This multicenter study is designed to combine both T cells and antibodies in order to create a more effective treatment. The treatment that is being researched is called autologous T lymphocyte chimeric antigen receptor cells (CAR) cells targeted against the disialoganglioside (GD2) antigen that express Interleukin (IL)-15, and the inducible caspase 9 safety switch (iC9), also known as iC9.GD2.CAR.IL-15 T cells.
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
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.
Single group
iC9.GD2.CAR.IL-15 T-cells
Biological/VaccineThree dose levels are being evaluated: 0.5 x 10\^6, 1.0 x 10\^6, 1.5 x 10\^6
Cyclophosphamide
Drug500 mg/m\^2 IV dose on days 1-2 for lymphodepletion prior to cell infusion
Fludarabine
Drug30 mg/m\^2 IV dose on days 1-4 for lymphodepletion prior to cell infusion
Number of participants with adverse events as a measure of safety and tolerability of iC9.GD2.CAR.IL-15 T cells administered to pediatric subjects with relapsed or refractory neuroblastoma or relapsed/refractory osteosarcoma
Toxicity will be classified and graded according to the National Cancer Institute's Common Terminology Criteria for Adverse Events (AEs) (CTCAE, version 5.0), a descriptive terminology which can be utilized for AE reporting. A grading (severity) scale is provided for each AE term/symptom: Grade 1 (Mild; asymptomatic); Grade 2 (Moderate; minimal, local or noninvasive intervention indicated); Grade 3 (Severe or medically significant but not immediately life-threatening; hospitalization indicated; disabling); Grade 4 (Life-threatening consequences; urgent intervention indicated); Grade 5 (Death related to AE). Immune effector cell-associated neurotoxicity syndrome (ICANS) symptoms will be graded according to the criteria outlined in the protocol on a scale from 1 (mild) to 4 (critical). Cytokine release syndrome (CRS) will be graded according to criteria outlined in the protocol on a scale from 1 (mild) to grade 5 (death).
Identify the maximum tolerated dose (MTD) of iC9.GD2.CAR.IL-15 T cells administered to pediatric subjects with relapsed or refractory neuroblastoma or relapsed/refractory osteosarcoma
Tolerability of iC9.GD2.CAR.IL-15 T cells will be assessed by NCI-CTCAE criteria and the CRS grading criteria outlined in Section 12.4 and neurotoxicity/ICANS will be graded according to criteria outlined in Section 12.5
Expansion and persistence of iC9.GD2.CAR.IL-15 cells in vivo
Persistence of iC9.GD2.CAR.IL-15 T cells in vivo will be determined by quantitative Polymerase chain reaction (PCR) and flow cytometry in peripheral blood samples
Anti-tumor response rate to iC9.GD2.CAR.IL-15 t cell administration in pediatric subjects with relapsed or refractory neuroblastoma per Revised International Neuroblastoma Response Criteria (INCR) or relapsed/refractory osteosarcoma by RECIST v1.1
The overall response rate (ORR = complete (CR) + partial (PR) + minor (MR) responses) to iC9.GD2.CAR.IL-15 T cell infusion will be determined using the revised International Neuroblastoma Response Criteria (INRC) for subjects with neuroblastoma. The overall response rate (ORR = complete (CR) + partial (PR) responses) for subjects with osteosarcoma will be measured using Response evaluation criteria in solid tumors (RECIST) version 1.1
Overall survival (OS) in pediatric subjects with relapsed or refractory neuroblastoma or relapsed/refractory osteosarcoma treated with iC9.GD2.CAR.IL-15 T cells
OS will be measured from the date of administration of iC9.GD2.CAR.IL-15 T cells to the date of death
Click on the lead sponsor to view all of their trials.
UNC Lineberger Comprehensive Cancer Center
Lead sponsor
United States Department of Defense
Collaborator
Bellicum Pharmaceuticals
Collaborator
National Cancer Institute (NCI)
Collaborator
