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

An observational study of Neuroblastoma, run by United Therapeutics at 18 sites in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Trial summary

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. Read more about this study

Who is it for?: Ages 1 year to 18 years
Conditions the study is for: Neuroblastoma
What is being tested?: Dinutuximab
How many people: 13 participants
Where: 18 sitesUnited States
Study dates: 15 Mar 2016to 19 Dec 2016
Phase: Observational
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 1 year to 18 years
All sexes
No healthy volunteers
Child, Adult

Study population: High-risk neuroblastoma patients prescribed Unituxin

Who may be able to join

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.

Who cannot join

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.

Trial locations and contacts

18 sites in 1 country.

City, postcode or hospital

18 sites in 1 country

United States18 sites

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

Other trials in United States

About this study

Official title: 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.

Read the 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.

Conditions: Neuroblastoma
Being tested: Dinutuximab
Medical subject headings: Neuroblastoma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

DinutuximabDrug
Also called Unituxin®
Unituxin was administered along with cytokines according to the prescribing information

Study groups in NCT02693171
Study group	Role	What they receive
Dinutuximab administered for 5 cycles		High-risk neuroblastoma patient treated with Unituxin as standard of care Receives: Drug: Dinutuximab

What is being measured

The primary outcome is the main question the study is designed to answer.

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)
Measured: Approximately 6 months

Secondary outcomes (3)

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.
Measured: 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.
Measured: 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.
Measured: Approximately 6 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

15 Mar 201619 Dec 2016

First posted26 Feb 2016 (estimated)
Study start15 Mar 2016
Primary completion19 Dec 2016
Study completion19 Dec 2016

Why it stopped: Sponsor decision

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Other trials for NeuroblastomaStudies of the same condition, open and under way.
More trials run by United TherapeuticsThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Observational
Observational model: Cohort
Time perspective: Prospective
Enrolment: 13 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT02693171
Sponsor's protocol ID: DIV-NB-401
Status last verified: Jun 2019
First submitted: 23 Feb 2016
Last updated: 5 Aug 2019
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes
Individual data sharing: No

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

RecruitingPhase 1/2
Testing the Addition of Iberdomide to Therapy in People With Neuroblastoma That Has Come Back, Not Responded to Treatment, or Gotten Worse
Recurrent Ganglioneuroblastoma, Recurrent Neuroblastoma
Active, not recruitingObservational study
Genomic Structural Variation in Cancer Susceptibility
Breast Cancer, Colon Cancer
RecruitingPhase 2
Enasidenib in IDH2-Mutated Malignant Sinonasal and Skull Base Tumors
Metastatic Chondrosarcoma, Locally Advanced Chondrosarcoma
RecruitingObservational study
Prospective Comprehensive Molecular Analysis of Endocrine Neoplasms
Endocrine Tumors, Thyroid Neoplasms
RecruitingPhase 1
PEACH TRIAL- Precision Medicine and Adoptive Cellular Therapy
Neuroblastoma, Diffuse Intrinsic Pontine Glioma

All Neuroblastoma trials

Study at a glance

From the registry record, last updated by the sponsor on 5 Aug 2019. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Post-Marketing Study to Further Assess the Immunogenicity and Safety of Unituxin® in High-Risk Neuroblastoma Patients
ClinicalTrials.gov ID: NCT02693171
Acronym / sponsor ID: DIV-NB-401
Conditions: Neuroblastoma
Study type: Observational
Recruitment status: TerminatedReason stopped: Sponsor decision
Enrolment: 13 participants (actual)
Lead sponsor: United TherapeuticsIndustry (pharma, biotech, devices)
Study start: 15 Mar 2016 (actual)
Primary completion: 19 Dec 2016 (actual)
Study completion: 19 Dec 2016 (actual)
First posted: 26 Feb 2016 (estimated)
Results: Posted 5 Aug 2019

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

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.

Detailed description

Study design

Observational model: Cohort
Time perspective: Prospective
Number of arms: 1

Arm	Type	Receives
Dinutuximab administered for 5 cycles	–	Drug: DinutuximabHigh-risk neuroblastoma patient treated with Unituxin as standard of care

Who may qualify

Ages: 1 year to 18 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Child, Adult
Study population: High-risk neuroblastoma patients prescribed Unituxin

Key inclusion criteria (4 listed)

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.

Key exclusion criteria (3 listed)

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.

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
DinutuximabAlso: Unituxin®Unituxin was administered along with cytokines according to the prescribing information	Drug	Dinutuximab administered for 5 cycles

Primary outcome

To Determine the Incidence of Human Anti-chimeric Antibody (HACA) in High-risk Neuroblastoma Patients Treated With Unituxin Combination Therapy.
Time frame: Approximately 6 months
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)

3 secondary outcomes

To Determine the Incidence of Targeted Immune-related Adverse Events (AEs) During Treatment With Dinutuximab Combination Therapy in High-risk Neuroblastoma Subjects.
Time frame: Approximately 6 months
To Determine the Incidence of Neutralizing Antibody (NAb) in Patients With Human Anti-chimeric Antibody (HACA) Positive Samples.
Time frame: Approximately 6 months
To Determine the Effect of HACA on Dinutuximab Plasma Concentrations.
Time frame: Approximately 6 months

Results and safety

Results posted to the registry on 5 Aug 2019, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Dinutuximab Administered for 5 Cycles	12	3

Primary outcome: To Determine the Incidence of Human Anti-chimeric Antibody (HACA) in High-risk Neuroblastoma Patients Treated With Unituxin Combination Therapy.

Time frame: Approximately 6 months

Population analysed: Outcome measure data were not collected. Sponsor was required to run this Phase 4 study for EU marketing approval. However, Sponsor terminated the study 15 Dec 2016 and application withdrawn (accepted by European Commission 20 Mar 2017).

3 secondary outcomes are reported in the full results.

Adverse events

Time frame: The Treatment Phase of the study lasted on average approximately 180 days. From Screening until the completion of study termination assessments, subjects participated in the study for approximately 220 days. However, the Sponsor terminated Study DIV-NB-401 on 15 December 2016; all safety data were collected for each subject from screening until the subject's last scheduled visit.. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Dinutuximab Administered for 5 Cycles	0 of 12 (0%)	10 of 12 (83.3%)	0 of 12

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 5 Aug 2019.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Individual participant dataSharing planned: No

Related trials for Neuroblastoma

RecruitingPhase 1/2
Testing the Addition of Iberdomide to Therapy in People With Neuroblastoma That Has Come Back, Not Responded to Treatment, or Gotten Worse
Recurrent Ganglioneuroblastoma, Recurrent Neuroblastoma
Active, not recruitingObservational study
Genomic Structural Variation in Cancer Susceptibility
Breast Cancer, Colon Cancer
RecruitingPhase 2
Enasidenib in IDH2-Mutated Malignant Sinonasal and Skull Base Tumors
Metastatic Chondrosarcoma, Locally Advanced Chondrosarcoma
RecruitingObservational study
Prospective Comprehensive Molecular Analysis of Endocrine Neoplasms
Endocrine Tumors, Thyroid Neoplasms
RecruitingPhase 1
PEACH TRIAL- Precision Medicine and Adoptive Cellular Therapy
Neuroblastoma, Diffuse Intrinsic Pontine Glioma

Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Ami Desai, MD study chair

Children's Hospital of Philadelphia

18 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

An observational study of Neuroblastoma, run by United Therapeutics at 18 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 4 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 5 Aug 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 18 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

Yes. Results are posted in the registry (first posted 5 Aug 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

To Determine the Incidence of Human Anti-chimeric Antibody (HACA) in High-risk Neuroblastoma Patients Treated With Unituxin Combination Therapy. (time frame: Approximately 6 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02693171.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Aug 2019.