Neuroblastoma
Conditions
Brief 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.
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.
Interventions
DRUGDinutuximab
Unituxin was administered along with cytokines according to the prescribing information
Sponsors
United Therapeutics
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
1 Years to 18 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| To Determine the Incidence of Human Anti-chimeric Antibody (HACA) in High-risk Neuroblastoma Patients Treated With Unituxin Combination Therapy. | 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) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| To Determine the Incidence of Targeted Immune-related Adverse Events (AEs) During Treatment With Dinutuximab Combination Therapy in High-risk Neuroblastoma Subjects. | Approximately 6 months | The incidence of targeted immune-related adverse events (AEs) during treatment with dinutuximab combination therapy in high-risk neuroblastoma subjects were summarized and listed. |
| To Determine the Incidence of Neutralizing Antibody (NAb) in Patients With Human Anti-chimeric Antibody (HACA) Positive Samples. | Approximately 6 months | Incidence of neutralizing antibody (NAb) in patients with human anti-chimeric antibody (HACA) positive samples was summarized and listed. |
| To Determine the Effect of HACA on Dinutuximab Plasma Concentrations. | Approximately 6 months | 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Dinutuximab Administered for 5 Cycles High-risk neuroblastoma patient treated with Unituxin as standard of care
Dinutuximab: Unituxin was administered along with cytokines according to the prescribing information | 12 |
| Total | 12 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 1 |
| Overall Study | Discontinuation of Study by Sponsor | 8 |
Baseline characteristics
| Characteristic | Dinutuximab Administered for 5 Cycles |
|---|---|
| Age, Continuous | 2.3 years STANDARD_DEVIATION 1.37 |
| Age, Customized Age at Diagnosis | 1.9 years STANDARD_DEVIATION 1.24 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 9 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants |
| Pre-Autologous Stem Cell Transplantation (ASCT) Response Complete response (CR) | 3 Participants |
| Pre-Autologous Stem Cell Transplantation (ASCT) Response Mixed response (MR) | 0 Participants |
| Pre-Autologous Stem Cell Transplantation (ASCT) Response No response (NR) | 0 Participants |
| Pre-Autologous Stem Cell Transplantation (ASCT) Response Partial response (PR) | 3 Participants |
| Pre-Autologous Stem Cell Transplantation (ASCT) Response Progressive disease (PD) | 0 Participants |
| Pre-Autologous Stem Cell Transplantation (ASCT) Response Very good partial response (VGPR) | 6 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 2 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 2 Participants |
| Race (NIH/OMB) White | 8 Participants |
| Region of Enrollment United States | 12 participants |
| Sex: Female, Male Female | 4 Participants |
| Sex: Female, Male Male | 8 Participants |
| Time since Diagnosis | 0.8 years STANDARD_DEVIATION 0.62 |
| Treatment of Neuroblastoma Cancer-related surgery | 10 Participants |
| Treatment of Neuroblastoma Induction chemotherapy treatment | 12 Participants |
| Treatment of Neuroblastoma Other cancer-related treatment | 1 Participants |
| Treatment of Neuroblastoma Radiotherapy treatment | 11 Participants |
| Treatment of Neuroblastoma Single stem cell transplant | 3 Participants |
| Treatment of Neuroblastoma Tandem stem cell transplant | 9 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 12 |
| other Total, other adverse events | 10 / 12 |
| serious Total, serious adverse events | 0 / 12 |
Outcome results
Primary
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)
Time frame: Approximately 6 months
Population: 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).
Secondary
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.
Time frame: Approximately 6 months
Population: 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).
Secondary
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.
Time frame: Approximately 6 months
Population: 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).
Secondary
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.
Time frame: Approximately 6 months
Population: Outcome measure data were not collected. Safety data from the 12 subjects dosed prior to study termination were collected and summary level data were reported (eg, total number of subjects affected and total number of events for dinutuximab-treated subjects). Please refer to the adverse event tables for results.