MIBG With Dinutuximab

Status: Active

Description

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 dose escalation 3+3 design to determine a recommended phase 2 pediatric dose. An expansion cohort of an additional 6 patients may then be enrolled.

Eligibility 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

Locations & Contacts

California

San Francisco
UCSF Medical Center-Mount Zion
Status: Active
Name Not Available

Colorado

Aurora
Children's Hospital Colorado
Status: Active
Name Not Available

Georgia

Atlanta
Children's Healthcare of Atlanta - Egleston
Status: Approved
Name Not Available

Illinois

Chicago
University of Chicago Comprehensive Cancer Center
Status: Active
Name Not Available

Massachusetts

Boston
Boston Children's Hospital
Status: Active
Name Not Available
Dana-Farber Cancer Institute
Status: Active
Name Not Available

Pennsylvania

Philadelphia
Children's Hospital of Philadelphia
Status: Active
Name Not Available

Trial Objectives and Outline

131I-Metaiodobenzylguanidine (131I-MIBG) is one of the most effective therapies utilized for neuroblastoma patients with refractory or relapsed disease. Data from pre-clinical and adult studies suggest that radiation can enhance the efficacy of immunotherapy and targeted therapies such as dinutuximab. This first pediatric phase 1 trial of 131I-MIBG in combination with dinutuximab aims to determine the recommended phase 2 pediatric dose of these two therapies in combination.

Trial Phase & Type

Trial Phase

Phase I

Trial Type

Treatment

Lead Organization

Lead Organization
New Approaches to Neuroblastoma Treatment (NANT)

Trial IDs

Primary ID NANT2017-01
Secondary IDs NCI-2018-01160
Clinicaltrials.gov ID NCT03332667