Study of CAR T-Cells Targeting the GD2 With IL-15+iCaspase9 for Relapsed/Refractory Neuroblastoma or Relapsed/Refractory Osteosarcoma

Summary

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.

Eligibility

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:

1. Written HIPAA authorization signed by legal guardian.
2. Adequate performance status as defined by Lansky or Karnofsky performance status of ≥ 60 (Lansky for \<16 years of age).
3. Life expectancy ≥12 weeks.
4. Histological confirmation of neuroblastoma or ganglioneuroblastoma at initial diagnosis. Bone marrow samples are acceptable as confirmation of neuroblastoma, confirmation of osteosarcoma at diagnosis
5. High-risk neuroblastoma with persistent/refractory or relapsed disease, defined as:

   1. First or greater relapse of neuroblastoma following completion of aggressive multi-drug frontline therapy.
   2. 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).
   3. 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.
6. 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.
7. Adequate central nervous system function as defined by:

   1. No known Central Nervous System ( CNS) disease
   2. 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).

1. Pregnant or breastfeeding (NOTE: breast milk cannot be stored for future use while the mother is being treated on study).
2. Has a known additional malignancy that is active and/or progressive requiring treatment.
3. History of hypersensitivity reactions to murine protein-containing products.
4. History of hypersensitivity to cyclophosphamide or fludarabine.

Conditions3

Locations2 sites

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