MIBG With Dinutuximab +/- Vorinostat

• Status: Recruiting
• Trial end date: 2022-03-01
• Target enrollment: 0
• Participant gender: All

Summary

131I-Metaiodobenzylguanidine (131I-MIBG) is one of the most effective therapies utilized for neuroblastoma patients with refractory or relapsed disease. In this pediatric phase 1 trial, 131I-MIBG will be given in combination with dinutuximab, a chimeric 14.18 monoclonal antibody. This study will utilize a traditional Phase I rolling 6 dose escalation design to determine a recommended phase 2 pediatric dose. An expansion cohort of an additional 6 patients will then be enrolled. If tolerable, vorinostat will then be added to the third dose level. A 6 patient expansion cohort may then be enrolled.

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: New Approaches to Neuroblastoma Therapy Consortium
• Collaborator: United Therapeutics
• Treatments: 3-Iodobenzylguanidine; Antibodies; Antibodies, Monoclonal; Antineoplastic Agents, Immunological; Dinutuximab; Immunoglobulins; Vorinostat

Criteria

Inclusion Criteria:

• Patients must have a diagnosis of neuroblastoma either by histologic verification of neuroblastoma and/or demonstration of tumor cells in the bone marrow with increased urinary catecholamines

• Patients must have high risk neuroblastoma according to COG risk classification at the time of study registration. Patients who were initially considered low or intermediate risk, but then reclassified as high risk are also eligible.

• Patients must have at least ONE of the following: 1) Recurrent/progressive disease at any time prior to study enrollment, 2) Refractory disease, 3) Persistent disease

• Patients must have at least ONE of the following: 1) Bone disease, 2) Any amount of neuroblastoma tumor cells in the bone marrow, 3) At least one soft tissue lesion that meets criteria for a TARGET lesion, 4) At least one non-target soft tissue lesion that is not measurable, but had a biopsy positive for neuroblastoma and/or ganglioneuroblastoma at any time prior to enrollment or is MIBG avid

• Patients must have a Lansky (≤16 years) or Karnofsky (> 16 years) score of at least 50

• Patients must have fully recovered from the acute toxic effects of all prior chemotherapy, immunotherapy, or radiotherapy prior to entering this study.

• Patients must not have received any of the specified therapies as stated in the protocol in the time period prior to registration

• Patients must not be receiving any other anti-cancer agents or radiotherapy at the time of study entry or while on study.

• Patients must not be receiving other investigational medications (covered under another IND) within 30 days of study entry or while on study.

• Patients must not be receiving chronic systemic corticosteroids at doses greater than physiologic dosing (inhaled corticosteroids acceptable).

• Patient must meet the organ function and system function requirements as stated in the protocol

Exclusion Criteria:

• Pregnancy, breast feeding, or unwillingness to use effective contraception during the study.

• Patients who, in the opinion of the investigator, may not be able to comply with the safety monitoring requirements of the study.

• Patients with disease of any major organ system that would compromise their ability to withstand therapy.

• Patients who have received prior allogeneic stem cell transplant

• Patients who are on hemodialysis.

• Patients with an active or uncontrolled infection.

• Known history of human immunodeficiency virus (HIV) infection, hepatitis B, or hepatitis C.

• Patients and/or families who are physically and psychologically unable to cooperate with the radiation safety isolation.

• Patients with a history of having to discontinue anti-GD2 antibody therapy due to toxicity are not eligible.

• Prior anti-GD2 therapy is not otherwise an exclusionary criteria unless it was given in combination with therapeutic 131I-MIBG.

• Patient declines participation in NANT 2004-05, the NANT Biology Study