A Study of Therapeutic Iobenguane (131-I) and Vorinostat for Recurrent or Progressive High-Risk Neuroblastoma Subjects

Inclusion Criteria

• •1. Subjects with a diagnosis of iobenguane avid, high-risk neuroblastoma based on Revised INRC criteria at the time of study enrollment with recurrent or progressive disease at any time prior to enrollment, regardless of overall response to frontline therapy, where frontline therapy includes a minimum of 4 cycles of induction therapy at any time prior to enrollment.
• •2. May have had prior 131I-MIBG therapy, provided:
• •1. It has been at least 6 months from the date of last 131I-MIBG ;
• •2. Response was other than progressive disease on first restaging after 131I-MIBG ;
• •3. Prior 131I-MIBG was given as monotherapy and not in combination with systemic anticancer agents;
• •4. Cumulative lifetime dose of 131I-MIBG at enrollment does not exceed 18 mCi/kg.
• •3. All soft tissue lesions identified on CT/MRI scans must be iobenguane avid lesions on an (123I)-iobenguane scan, or
• •1. any progressive non-iobenguane avid lesion is proven by biopsy to be a non-neuroblastoma lesion.
• •2. any other non-avid lesion is comprised of a fibrotic or scarred mass as shown by routine imaging and confirmed by the investigator.
• •4. Adequate cryopreserved autologous peripheral blood stem cells or bone marrow (at least 2 aliquots of 2.0 × 10exp6 CD34/kg at the time of study enrollment).
• •5. If a male, must agree to use an adequate contraception method as deemed appropriate by the Investigator (e.g., vasectomy, condoms) or partner using effective contraception and to not donate sperm during the study and for 90 days after receiving the last dose of study drug.
• •6. If a female of childbearing potential, have a negative serum pregnancy test result prior to each dosing and, if sexually active, be practicing an effective method of birth control \[e.g., intrauterine device, double-barrier method (i.e., diaphragm, or a cervical cap) with intravaginal spermicidal foam, cream or gel\], or male partner sterilization throughout the study.
• •7. Age at study entry ≥1 year.
• •8. Previous platelet transfusions are permitted, as long as the subject has a platelet count ≥50,000/μL without transfusion support for at least 1 week.
• •9. Subjects must have a minimum pulse oximetry measurement of at least 94% at baseline.
• •10. An absolute neutrophil count ≥750/μL without growth factor for 5 days.
• •11. Liver function parameter results: total bilirubin ≤2 × upper limit of normal for age, and Serum alanine aminotransferase (glutamic-pyruvic transaminase) and serum aspartate aminotransferase (glutamic-oxaloacetic transaminase) ≤ 10 times the upper limit of normal (for all sites, the upper limit of normal for alanine aminotransferase is defined as 45 U/L).
• •12. Normal thyroid function as measured by T4 or TSH or have abnormal results that are not considered clinically important by the Investigator or may be receiving levothyroxine.
• •13. Cardiac Function: shortening fraction of ≥ 27% by echocardiogram or ejection fraction ≥ 50% documented by echocardiogram or radionuclide angiogram within 1 month prior to Visit 1 (Baseline).
• •14. Karnofsky Performance Status (for subjects \>16 years of age) or the Lansky Performance Status Performance Status (for subjects 1 to 16 years of age) ≥50%.
• •15. Full recovery from the toxic effects of any prior therapy.
• •16. Coagulation Function:
• •1. International Normalized Ratio (INR) \< 1.5
• •2. Partial thromboplastin time (PTT) \< 1.5 times upper limit of normal.