Post-Marketing Assessment of Immunogenicity and Safety of Unituxin® in High-Risk Neuroblastoma Patients

A Post-Marketing Study to Further Assess the Immunogenicity and Safety of Unituxin® in High-Risk Neuroblastoma Patients

The purpose of this study was to assess the incidence of human anti-chimeric antibody (HACA) in high-risk neuroblastoma patients treated with Unituxin combination therapy.

Study Overview

• Status: Terminated
• Conditions: Neuroblastoma
• Intervention / Treatment: Drug: Dinutuximab

Detailed Description

This was a multi-center, non-randomized, open-label study in patients with high-risk neuroblastoma to assess the immunogenicity, safety and tolerability of Unituxin combination therapy. Patients enrolled in the study were prescribed Unituxin for the treatment of high-risk neuroblastoma.

• Study Type: Observational
• Enrollment (Actual): 13

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35233
      • University of Alabama at Birmingham
  • Arkansas
    • Little Rock, Arkansas, United States, 72202
      • Arkansas Children's Hospital
  • California
    • Los Angeles, California, United States, 90027
      • Children's Hospital Los Angeles
    • Orange, California, United States, 92868
      • Children's Hospital of Orange County
    • San Diego, California, United States, 92123
      • Rady Children's Hospital- San Diego
  • Illinois
    • Chicago, Illinois, United States, 60637
      • University of Chicago
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Dana Farber Cancer Institute
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • University of Michigan - C S Mott Children's Hospital
  • Minnesota
    • Minneapolis, Minnesota, United States, 55404
      • Children's Hospitals and Clinics of Minnesota - Minneapolis
  • Missouri
    • Kansas City, Missouri, United States, 64108
      • Children's Mercy Hospital
  • New York
    • New York, New York, United States, 10032
      • Columbia University Medical Center
  • North Carolina
    • Charlotte, North Carolina, United States, 28203
      • Carolinas Medical Center / Levine Children's Hospital
    • Durham, North Carolina, United States, 27710
      • Duke University Medical Center
  • Ohio
    • Columbus, Ohio, United States, 43205
      • Nationwide Children's Hospital
  • Pennsylvania
    • Hershey, Pennsylvania, United States, 17033
      • Penn State Hershey Children's Hospital
  • Tennessee
    • Nashville, Tennessee, United States, 37232
      • Vanderbilt-Ingram Cancer Center
  • Texas
    • Fort Worth, Texas, United States, 76104
      • Cook Children's Health Care System
  • Washington
    • Seattle, Washington, United States, 98105
      • Seattle Children's Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 year to 18 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

High-risk neuroblastoma patients prescribed Unituxin

Description

Inclusion Criteria:

• Patient had been diagnosed with high-risk neuroblastoma.
• Patient had been prescribed Unituxin and plans to start Unituxin therapy within 30 days of study entry.
• Patient started Unituxin therapy no later than 200 days after Autologous Stem Cell Transplantation (ASCT).
• Written informed consent / assent was obtained in accordance with institutional and International Conference on Harmonisation (ICH) guidelines.

Exclusion Criteria:

• Patient had received prior anti-disialoganglioside (anti-GD2) antibody therapy.
• Patient had participated in an investigational clinical trial with tumor therapeutic intent within 30 days of informed consent.
• Patient underwent Autologous Stem Cell Transplantation (ASCT) more than 200 days prior to receiving Unituxin therapy.

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Dinutuximab administered for 5 cycles; High-risk neuroblastoma patient treated with Unituxin as standard of care	Drug: Dinutuximab; Unituxin was administered along with cytokines according to the prescribing information; Other Names: Unituxin®

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To Determine the Incidence of Human Anti-chimeric Antibody (HACA) in High-risk Neuroblastoma Patients Treated With Unituxin Combination Therapy.	Seven blood samples were collected at the following time points for the evaluation of HACA levels: Course 1- Prior to the first Unituxin infusion; Course 2- Prior to the first Unituxin infusion; Course 3- Prior to the first Unituxin infusion; Course 4- Prior to the first Unituxin infusion; Course 5- Prior to the first Unituxin infusion; Course 6- Prior to the first dose of 13-cis-retinoic acid (RA); Study termination (approximately 2 weeks following the final 13-cis-retinoic acid dose)	Approximately 6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To Determine the Incidence of Targeted Immune-related Adverse Events (AEs) During Treatment With Dinutuximab Combination Therapy in High-risk Neuroblastoma Subjects.	The incidence of targeted immune-related adverse events (AEs) during treatment with dinutuximab combination therapy in high-risk neuroblastoma subjects were summarized and listed.	Approximately 6 months
To Determine the Incidence of Neutralizing Antibody (NAb) in Patients With Human Anti-chimeric Antibody (HACA) Positive Samples.	Incidence of neutralizing antibody (NAb) in patients with human anti-chimeric antibody (HACA) positive samples was summarized and listed.	Approximately 6 months
To Determine the Effect of HACA on Dinutuximab Plasma Concentrations.	Ten blood samples were collected at the following time points for the evaluation of dinutuximab plasma concentrations: Course 1- Prior to the first Unituxin infusion; Course 2- Prior to the first Unituxin infusion; Course 3- Prior to the first Unituxin infusion; Course 4- Prior to the first Unituxin infusion; Course 5- Prior to the first Unituxin infusion; Course 6- Prior to the first dose of 13-cis-retinoic acid (RA); Study termination (approximately 2 weeks following the final 13-cis-retinoic acid dose). An additional 3 blood samples were obtained for the evaluation of dinutuximab plasma concentrations. Each of these blood samples was obtained immediately following the fourth dinutuximab infusion in Courses 1, 3, and 5.	Approximately 6 months

Collaborators and Investigators

• Sponsor: United Therapeutics
• Investigators: Study Chair: Ami Desai, MD, Children's Hospital of Philadelphia

Study record dates

Study Major Dates

• Study Start (Actual): March 15, 2016
• Primary Completion (Actual): December 19, 2016
• Study Completion (Actual): December 19, 2016

Study Registration Dates

• First Submitted: February 23, 2016
• First Submitted That Met QC Criteria: February 25, 2016
• First Posted (Estimate): February 26, 2016

Study Record Updates

• Last Update Posted (Actual): August 5, 2019
• Last Update Submitted That Met QC Criteria: June 11, 2019
• Last Verified: June 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Neuroectodermal Tumors, Primitive; Neuroectodermal Tumors, Primitive, Peripheral; Neuroblastoma; Antineoplastic Agents; Dinutuximab
• Other Study ID Numbers: DIV-NB-401

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No