MIBG 2014-01, A Phase II Single-Arm Study of Therapeutic Iobenguane (131I) for Relapsed, High-Risk Neuroblastoma Subjects (OPTIMUM Trial)

Study ID: STU 042016-029

Summary

The study will be a single-arm, single-agent, nonrandomized, open-label study in subjects with iobenguane avid, relapsed high-risk neuroblastoma. The study will not include subjects with non-iobenguane avid high-risk neuroblastoma. Thus, subjects with a partial response or complete response to previous therapy will be included in the study. if a subject is symptomatic and for logistical reasons cannot be treated immediately with MiBG 131i, 1 to 2 cycles of [Quote]bridging chemotherapy[Quote] or immunotherapy will be permitted. if a subject receives [Quote]bridging chemotherapy[Quote] or immunotherapy, the baseline eligibility testing must be repeated in order for the subject to continue in the study and receive MiBG 131i treatment.

Participant Eligibility

1. Subjects with a diagnosis of iobenguane avid, relapsed, high-risk neuroblastoma based on INRC (International Neuroblastoma Response Criteria) criteria who have completed at least one cycle of induction and consolidation therapy with an INRC criterion of partial response or better, and then showed new progressive disease (INRC criteria progressive disease) as described in the NANT 2007-03 consortium criteria. This may include one or more of the following drugs: cyclophosphamide or ifosfamide, cisplatin or carboplatin, vincristine, doxorubicin (adriamycin), etoposide, topotecan, and/or busulfan and melphalan (sometimes used during stem cell transplant) and/or immunotherapy. (If a subject is symptomatic and for logistical reasons cannot be treated immediately with MIBG 131I, 1 to 2 cycles of * bridging chemotherapy * or immunotherapy will be permitted.). If * bridging chemotherapy * or immunotherapy is applied, approximately 4 weeks will be required for reassessment of the baseline including tumor assessment. 2. Must be therapeutic M-iodo-benzylguanidine -MIBG 131I naive. 3. All soft tissue lesions identified on CT/MRI (computerized tomography/magnetic resonance imaging)scans must be iobenguane-avid lesions on an iobenguane (123I) scan or any non-iobenguane avid lesions biopsy proven to be non-tumor lesions. 4. Adequate cryopreserved autologous peripheral blood stem cells or bone marrow (calculated dose at the time of study enrollment of at least 2.0 x 106 CD34/kg; preferably in 2 or more aliquots). 5. If a man, 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 women of childbearing potential, have a negative pregnancy test result prior to each dosing and, if sexually active, be practicing an effective method of birth control [e.g., intrauterine device, 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 mL 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 [MICRO-SYMBOL]L without growth factor for 5 days. 11. Liver function parameter results: total bilirubin <=1.5 x normal for age, and serum glutamic-pyruvic transaminase (alanine aminotransferase) [SGPT (ALT)] and serum glutamic-oxaloacetic transaminase (aspartate aminotransferase) [SGOT (AST)] <3 x upper limit of normal (note that for ALT, the upper limit of normal for all sites is defined as 45 U/L). 12. Normal thyroid function as measured by T4 and TSH (thyroid stimulating hormone) or have abnormal results that are not considered clinically important by theInvestigator or may be receiving levothyroxine. 13. Cardiac Function: Ejection fraction (>=55%) documented by echocardiogram within 1 month prior to Visit 2 (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.

Cancer Related: Yes
Healthy Volunteers: No
UT Southwestern Principal Investigator: TANYA CARENS WATT

Contact:

Beverly Kleiber

beverly.kleiber@childrens.com

The primary objective is the following: To determine the efficacy of MiBG 131i treatment in subjects with iobenguane avid, relapsed high-risk neuroblastoma as measured by the overall response (Yes / no) based on the revised international neuroblastoma Response Criteria (inRC) 6 weeks after the last MiBG 131i treatment as calculated from the blind read of the inRC components. The revised inRC criteria are as described in Park, et al. (2017) (appendix a of the protocol). There will be a blind read of the iobenguane (123i) scans, a blind read of the CT or MRi scans, and a blind read of the bone marrow biopsies (and aspirates).] The secondary objectives in order of importance are as follows: To determine the efficacy of MiBG 131i treatment in subjects with iobenguane avid, relapsed high-risk neuroblastoma as measured by the overall response (Yes/no) based on the inRC 6 weeks after the last MiBG 131i treatment as calculated from the blind reads of the inRC components. To determine Durability of effect of MiBG 131i treatment in subjects with iobenguane avid, relapsed high-risk neuroblastoma as measured by the response (Yes / no) based on the inRC for all tumor assessment data available and any data collected at time of data cut-off for the primary analysis beyond 12 weeks after the last MiBG 131i treatment as calculated from the blind reads of the inRC components. To determine the efficacy of MiBG 131i treatment in subjects with iobenguane avid, relapsed high-risk neuroblastoma as measured by the response (Yes / no) based on the blind read Relative Curie extension Score defined as less than or equal to 0.5, 6 weeks after the last MiBG 131i treatment which will either be the first treatment or the second treatment; and To determine Durability of effect of MiBG 131i treatment in subjects with iobenguane avid, relapsed high-risk neuroblastoma as measured by the response (Yes / no) based on the blind read Relative Curie extension Score defined as less than or equal to 0.5 for all tumor assessment data available and any data collected at time of data cut-off for the primary analysis beyond 12 weeks after the last MiBG 131i treatment which will either be the first treatment or the second treatment. The Safety objectives are as follows: To assess the short-term safety (18 weeks after the first MiBG treatment); and To assess radiation safety of the thyroid gland as assessed by free thyroxine (T4), thyroid stimulating hormone (TSH), and whole body radiation dose; and the effects on the bone marrow compartment as assessed by the CBC and platelet count. although iobenguane (131i) has been widely used to treat relapsed or refractory neuroblastoma as an investigational radiopharmaceutical, it is not approved for this indication in the united States. This study has been designed to provide the data required to demonstrate efficacy and safety of MiBG 131i for the treatment of subjects with iobenguane avid, relapsed high-risk neuroblastoma.