Anti-GD2 CAR T Cells in Pediatric Patients Affected by High Risk And/or Relapsed/refractory Neuroblastoma or Other GD2-positive Solid Tumors

Inclusion Criteria:

Phase I The patient must meet the following eligibility inclusion criteria to be enrolled to receive treatment in the Phase I study.

1. Diagnosis of NBL that have been treated with frontline therapy and is judged to beincurable, based upon the following criteria:

2. Relapse after first-line treatment, proved by a positive 123-I-mMIBG-scan

3. Persistence/progression of disease after the initiation of the upfronttreatment

4. Patients must have measurable or evaluable disease at the time of treatmentenrollment, as shown by bone marrow biopsy/aspirate, US or CT/MRI scan or by 123-I-mMIBG scan.

5. Recover from the toxic effect of previous chemotherapies: grade 4 and or 3non-hematologic toxicities must have resolved to grade ≤2; if some effects of thetherapies have become chronic (i.e. treatment associated thrombocytopenia), thepatient must be clinically stable, according to the opinion of the treatingphysicians, and meet all other eligibility criteria.

6. Age: 12 months -18 years.

7. Voluntary informed consent is given. For subjects < 18 years old their legalguardian must give informed consent. Pediatric subjects will be included in ageappropriate discussion and verbal assent will be obtained for those greater than orequal to 12 years of age, when appropriate.

8. Clinical performance status: Patients > 16 years of age: Karnofsky greater than orequal to 60%; Patients less than or equal to 16 years of age: Lansky scale greaterthan or equal to 60%.

9. Patients of child-bearing or child-fathering potential must be willing to practicebirth control from the time of enrollment on this study and for four months afterreceiving the preparative regimen.

10. Females of child-bearing potential must have a negative pregnancy test because ofthe potentially dangerous effects on the fetus.

Phase II

The patient must meet the following eligibility inclusion criteria to be enrolled to receive treatment in the Phase II study.

1. Diagnosis of NBL that have been treated with frontline therapy and is judged to beincurable, based upon the following criteria:

2. Relapse after first-line treatment, proved by a positive MIBG-scan

3. Persistence/progression of disease after the initiation of the upfronttreatment OR

4. Diagnosis of extremely High Risk NBL at high risk of relapse, defined by stageIII/IV and Myc-N amplification, at the end of the first-line treatment according tothe Standard of Care, even if NED. OR

5. Diagnosis of GD2+ tumors other than Neuroblastoma, considered incurable withconventional treatments by the treating physician.

6. Patients with relapsed/refractory disease must have measurable or evaluable diseaseat the time of treatment enrollment, as shown by bone marrow biopsy/aspirate, US orCT/MRI scan or by MIBG-scan.

7. Recover from the toxic effect of previous chemotherapies: grade 4 and or 3non-hematologic toxicities must have resolved to grade ≤2; if some effects of thetherapies have become chronic (i.e. treatment associated thrombocytopenia), thepatient must be clinically stable, according to the opinion of the treatingphysicians, and meet all other eligibility criteria.

8. Age: 12 months - 18 years.

9. Voluntary informed consent is given. For subjects < 18 years old their legalguardian must give informed consent. Pediatric subjects will be included in ageappropriate discussion and verbal assent will be obtained for those greater than orequal to 12 years of age, when appropriate.

10. Clinical performance status: Patients > 16 years of age: Karnofsky greater than orequal to 60%; Patients less than or equal to 16 years of age: Lansky scale greaterthan or equal to 60%.

11. Patients of child-bearing or child-fathering potential must be willing to practicebirth control from the time of enrollment on this study and for four months afterreceiving the preparative regimen.

12. Females of child-bearing potential must have a negative pregnancy test because ofthe potentially dangerous effects on the fetus

Exclusion Criteria:

1. Pregnant or lactating women

2. Severe, uncontrolled active intercurrent infections

3. Active hepatitis B or hepatitis C infection

4. HIV infection

5. Rapidly progressive disease with life-expectancy < 6 weeks

6. History of grade 3 or 4 hypersensitivity to murine protein-containing products

7. Hepatic function: Inadequate liver function defined as total bilirubin > 4x upperlimit of normal (ULN) or transaminase (ALT and AST) > 6 x ULN based on age andlaboratory specific normal ranges

8. Renal function: serum creatinine > 3x ULN for age.

9. Blood oxygen saturation < 90%.

10. Cardiac function: Left ventricular ejection fraction lower than 45% by ECHO.

11. Marrow function: ANC lower than 500/mm3 and/or platelets lower than 20.000 (notreached by transfusion).

12. Congestive heart failure, cardiac arrhythmia, psychiatric illness, or socialsituations that would limit compliance with study requirements or in the opinion ofthe PI would pose an unacceptable risk to the subject.

13. Untreated CNS metastasis; patients with previous CNS tumor involvement that has beentreated and is stable for at least 6 weeks following completion of therapy areeligible.

14. Concurrent or recent prior therapies, before infusion:

15. Systemic steroids (at a dose equivalent to or greater 2 mg/kg prednisone) inthe 2 weeks before infusion. Recent or current use ofinhaled/topical/non-absorbable steroids is not exclusionary.

16. Systemic chemotherapy in the 2 weeks preceding infusion.

17. Immunosuppressive agents less than or equal to 30 days.

18. Radiation therapy must have been completed at least 3 weeks prior toenrollment.

19. I131-MIBG therapy must have been completes at least 6 weeks prior to enrollment

20. Anti-GD2 murine monoclonal antibody (ch14.18 antibody) in the 2 weeks precedinginfusion

21. Other anti-neoplastic investigational agents currently or within 30 days priorto start of protocol therapy;

22. Exceptions:

23. Subjects receiving steroid therapy at physiologic replacement doses only areallowed provided there has been no increase in dose for at least 2 weeks priorto starting apheresis

24. Patient-derived GD2-CART01 production failure.