Overview

The purpose of this study is to test the safety and efficacy of GD2-CART01, a CAR T cell treatment targeting GD2 in paediatric or young adult patients with High Risk and/or relapsed/refractory Neuroblastoma.

A small exploratory cohort of patients with GD2-positive tumors other than Neuroblastoma has also been included.

Eligibility

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 be
             incurable, based upon the following criteria:
               1. Relapse after first-line treatment, proved by a positive 123-I-mMIBG-scan
               2. Persistence/progression of disease after the initiation of the upfront treatment
          2. Patients must have measurable or evaluable disease at the time of treatment
             enrollment, as shown by bone marrow biopsy/aspirate, US or CT/MRI scan or by
             123-I-mMIBG scan.
          3. Recover from the toxic effect of previous chemotherapies: grade 4 and or 3
             non-hematologic toxicities must have resolved to grade ≤2; if some effects of the
             therapies have become chronic (i.e. treatment associated thrombocytopenia), the
             patient must be clinically stable, according to the opinion of the treating
             physicians, and meet all other eligibility criteria.
          4. Age: 12 months -18 years.
          5. Voluntary informed consent is given. For subjects < 18 years old their legal guardian
             must give informed consent. Pediatric subjects will be included in age appropriate
             discussion and verbal assent will be obtained for those greater than or equal to 12
             years of age, when appropriate.
          6. Clinical performance status: Patients > 16 years of age: Karnofsky greater than or
             equal to 60%; Patients less than or equal to 16 years of age: Lansky scale greater
             than or equal to 60%.
          7. Patients of child-bearing or child-fathering potential must be willing to practice
             birth control from the time of enrollment on this study and for four months after
             receiving the preparative regimen.
          8. Females of child-bearing potential must have a negative pregnancy test because of the
             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 be
             incurable, based upon the following criteria:
               1. Relapse after first-line treatment, proved by a positive MIBG-scan
               2. Persistence/progression of disease after the initiation of the upfront treatment
             OR
          2. Diagnosis of extremely High Risk NBL at high risk of relapse, defined by stage III/IV
             and Myc-N amplification, at the end of the first-line treatment according to the
             Standard of Care, even if NED.
             OR
          3. Diagnosis of GD2+ tumors other than Neuroblastoma, considered incurable with
             conventional treatments by the treating physician.
          4. Patients with relapsed/refractory disease must have measurable or evaluable disease at
             the time of treatment enrollment, as shown by bone marrow biopsy/aspirate, US or
             CT/MRI scan or by MIBG-scan.
          5. Recover from the toxic effect of previous chemotherapies: grade 4 and or 3
             non-hematologic toxicities must have resolved to grade ≤2; if some effects of the
             therapies have become chronic (i.e. treatment associated thrombocytopenia), the
             patient must be clinically stable, according to the opinion of the treating
             physicians, and meet all other eligibility criteria.
          6. Age: 12 months - 18 years.
          7. Voluntary informed consent is given. For subjects < 18 years old their legal guardian
             must give informed consent. Pediatric subjects will be included in age appropriate
             discussion and verbal assent will be obtained for those greater than or equal to 12
             years of age, when appropriate.
          8. Clinical performance status: Patients > 16 years of age: Karnofsky greater than or
             equal to 60%; Patients less than or equal to 16 years of age: Lansky scale greater
             than or equal to 60%.
          9. Patients of child-bearing or child-fathering potential must be willing to practice
             birth control from the time of enrollment on this study and for four months after
             receiving the preparative regimen.
         10. Females of child-bearing potential must have a negative pregnancy test because of the
             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 upper
             limit of normal (ULN) or transaminase (ALT and AST) > 6 x ULN based on age and
             laboratory 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 (not
             reached by transfusion).
         12. Congestive heart failure, cardiac arrhythmia, psychiatric illness, or social
             situations that would limit compliance with study requirements or in the opinion of
             the PI would pose an unacceptable risk to the subject.
         13. Untreated CNS metastasis; patients with previous CNS tumor involvement that has been
             treated and is stable for at least 6 weeks following completion of therapy are
             eligible.
         14. Concurrent or recent prior therapies, before infusion:
               1. Systemic steroids (at a dose equivalent to or greater 2 mg/kg prednisone) in the
                  2 weeks before infusion. Recent or current use of inhaled/topical/non-absorbable
                  steroids is not exclusionary.
               2. Systemic chemotherapy in the 2 weeks preceding infusion.
               3. Immunosuppressive agents less than or equal to 30 days.
               4. Radiation therapy must have been completed at least 3 weeks prior to enrollment.
               5. I131-MIBG therapy must have been completes at least 6 weeks prior to enrollment
               6. Anti-GD2 murine monoclonal antibody (ch14.18 antibody) in the 2 weeks preceding
                  infusion
               7. Other anti-neoplastic investigational agents currently or within 30 days prior to
                  start of protocol therapy;
               8. Exceptions:
               9. Subjects receiving steroid therapy at physiologic replacement doses only are
                  allowed provided there has been no increase in dose for at least 2 weeks prior to
                  starting apheresis
         15. Patient-derived GD2-CART01 production failure.