Post-Marketing Assessment of Immunogenicity and Safety of Unituxin® in High-Risk Neuroblastoma Patients
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
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 Design
Arms and Interventions
| Arm | 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:
|
Outcome Measures
Primary Outcome Measures
- 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 Outcome Measures
- 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.
Eligibility Criteria
Criteria
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.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | University Of Alabama At Birmingham | Birmingham | Alabama | United States | 35233 |
| 2 | Arkansas Children's Hospital | Little Rock | Arkansas | United States | 72202 |
| 3 | Children's Hospital Los Angeles | Los Angeles | California | United States | 90027 |
| 4 | Children's Hospital of Orange County | Orange | California | United States | 92868 |
| 5 | Rady Children's Hospital- San Diego | San Diego | California | United States | 92123 |
| 6 | University of Chicago | Chicago | Illinois | United States | 60637 |
| 7 | Dana Farber Cancer Institute | Boston | Massachusetts | United States | 02215 |
| 8 | University of Michigan - C S Mott Children's Hospital | Ann Arbor | Michigan | United States | 48109 |
| 9 | Children's Hospitals and Clinics of Minnesota - Minneapolis | Minneapolis | Minnesota | United States | 55404 |
| 10 | Children's Mercy Hospital | Kansas City | Missouri | United States | 64108 |
| 11 | Columbia University Medical Center | New York | New York | United States | 10032 |
| 12 | Carolinas Medical Center / Levine Children's Hospital | Charlotte | North Carolina | United States | 28203 |
| 13 | Duke University Medical Center | Durham | North Carolina | United States | 27710 |
| 14 | Nationwide Children's Hospital | Columbus | Ohio | United States | 43205 |
| 15 | Penn State Hershey Children's Hospital | Hershey | Pennsylvania | United States | 17033 |
| 16 | Vanderbilt-Ingram Cancer Center | Nashville | Tennessee | United States | 37232 |
| 17 | Cook Children's Health Care System | Fort Worth | Texas | United States | 76104 |
| 18 | Seattle Children's Hospital | Seattle | Washington | United States | 98105 |
Sponsors and Collaborators
- United Therapeutics
Investigators
- Study Chair: Ami Desai, MD, Children's Hospital of Philadelphia
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- DIV-NB-401
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | Dinutuximab Administered for 5 Cycles |
|---|---|
| Arm/Group Description | High-risk neuroblastoma patient treated with Unituxin as standard of care Dinutuximab: Unituxin was administered along with cytokines according to the prescribing information |
| Period Title: Overall Study | |
| STARTED | 12 |
| COMPLETED | 3 |
| NOT COMPLETED | 9 |
Baseline Characteristics
| Arm/Group Title | Dinutuximab Administered for 5 Cycles |
|---|---|
| Arm/Group Description | High-risk neuroblastoma patient treated with Unituxin as standard of care Dinutuximab: Unituxin was administered along with cytokines according to the prescribing information |
| Overall Participants | 12 |
| Age (years) [Mean (Standard Deviation) ] | |
| Mean (Standard Deviation) [years] |
2.3
(1.37)
|
| Age, Customized (years) [Mean (Standard Deviation) ] | |
| Age at Diagnosis |
1.9
(1.24)
|
| Sex: Female, Male (Count of Participants) | |
| Female |
4
33.3%
|
| Male |
8
66.7%
|
| Ethnicity (NIH/OMB) (Count of Participants) | |
| Hispanic or Latino |
2
16.7%
|
| Not Hispanic or Latino |
9
75%
|
| Unknown or Not Reported |
1
8.3%
|
| Race (NIH/OMB) (Count of Participants) | |
| American Indian or Alaska Native |
0
0%
|
| Asian |
2
16.7%
|
| Native Hawaiian or Other Pacific Islander |
0
0%
|
| Black or African American |
0
0%
|
| White |
8
66.7%
|
| More than one race |
0
0%
|
| Unknown or Not Reported |
2
16.7%
|
| Region of Enrollment (participants) [Number] | |
| United States |
12
100%
|
| Time since Diagnosis (years) [Mean (Standard Deviation) ] | |
| Mean (Standard Deviation) [years] |
0.8
(0.62)
|
| Treatment of Neuroblastoma (Count of Participants) | |
| Induction chemotherapy treatment |
12
100%
|
| Cancer-related surgery |
10
83.3%
|
| Single stem cell transplant |
3
25%
|
| Tandem stem cell transplant |
9
75%
|
| Radiotherapy treatment |
11
91.7%
|
| Other cancer-related treatment |
1
8.3%
|
| Pre-Autologous Stem Cell Transplantation (ASCT) Response (Count of Participants) | |
| Complete response (CR) |
3
25%
|
| Very good partial response (VGPR) |
6
50%
|
| Partial response (PR) |
3
25%
|
| Mixed response (MR) |
0
0%
|
| No response (NR) |
0
0%
|
| Progressive disease (PD) |
0
0%
|
Outcome Measures
| Title | To Determine the Incidence of Human Anti-chimeric Antibody (HACA) in High-risk Neuroblastoma Patients Treated With Unituxin Combination Therapy. |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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). |
| Arm/Group Title | Dinutuximab Administered for 5 Cycles |
|---|---|
| Arm/Group Description | High-risk neuroblastoma patient treated with Unituxin as standard of care Dinutuximab: Unituxin will be administered along with cytokines according to the prescribing information |
| Measure Participants | 0 |
| Title | To Determine the Incidence of Targeted Immune-related Adverse Events (AEs) During Treatment With Dinutuximab Combination Therapy in High-risk Neuroblastoma Subjects. |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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. |
| Arm/Group Title | Dinutuximab Administered for 5 Cycles |
|---|---|
| Arm/Group Description | High-risk neuroblastoma patient treated with Unituxin as standard of care Dinutuximab: Unituxin will be administered along with cytokines according to the prescribing information |
| Measure Participants | 0 |
| Title | To Determine the Incidence of Neutralizing Antibody (NAb) in Patients With Human Anti-chimeric Antibody (HACA) Positive Samples. |
|---|---|
| Description | Incidence of neutralizing antibody (NAb) in patients with human anti-chimeric antibody (HACA) positive samples was summarized and listed. |
| Time Frame | Approximately 6 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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). |
| Arm/Group Title | Dinutuximab Administered for 5 Cycles |
|---|---|
| Arm/Group Description | High-risk neuroblastoma patient treated with Unituxin as standard of care Dinutuximab: Unituxin will be administered along with cytokines according to the prescribing information |
| Measure Participants | 0 |
| Title | To Determine the Effect of HACA on Dinutuximab Plasma Concentrations. |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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). |
| Arm/Group Title | Dinutuximab Administered for 5 Cycles |
|---|---|
| Arm/Group Description | High-risk neuroblastoma patient treated with Unituxin as standard of care Dinutuximab: Unituxin will be administered along with cytokines according to the prescribing information |
| Measure Participants | 0 |
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. | |
|---|---|---|
| Adverse Event Reporting Description | ||
| Arm/Group Title | Dinutuximab Administered for 5 Cycles | |
| Arm/Group Description | High-risk neuroblastoma patient treated with Unituxin as standard of care Dinutuximab: Unituxin was administered along with cytokines according to the prescribing information | |
All Cause Mortality |
||
| Dinutuximab Administered for 5 Cycles | ||
| Affected / at Risk (%) | # Events | |
| Total | 0/12 (0%) | |
Serious Adverse Events |
||
| Dinutuximab Administered for 5 Cycles | ||
| Affected / at Risk (%) | # Events | |
| Total | 0/12 (0%) | |
Other (Not Including Serious) Adverse Events |
||
| Dinutuximab Administered for 5 Cycles | ||
| Affected / at Risk (%) | # Events | |
| Total | 10/12 (83.3%) | |
| Blood and lymphatic system disorders | ||
| Thrombocytopenia | 1/12 (8.3%) | 1 |
| Cardiac disorders | ||
| Tachycardia | 8/12 (66.7%) | 15 |
| Eye disorders | ||
| Mydriasis | 1/12 (8.3%) | 1 |
| Gastrointestinal disorders | ||
| Abdominal pain | 1/12 (8.3%) | 1 |
| Lip swelling | 1/12 (8.3%) | 1 |
| Vomiting | 1/12 (8.3%) | 2 |
| General disorders | ||
| Pyrexia | 8/12 (66.7%) | 20 |
| Adverse drug reaction | 1/12 (8.3%) | 2 |
| Face oedema | 1/12 (8.3%) | 4 |
| Oedema | 1/12 (8.3%) | 1 |
| Immune system disorders | ||
| Anaphylactic reaction | 1/12 (8.3%) | 1 |
| Drug hypersensitivity | 1/12 (8.3%) | 1 |
| Investigations | ||
| Alanine aminotransferase increased | 1/12 (8.3%) | 1 |
| Platelet count decreased | 2/12 (16.7%) | 15 |
| Respiratory, thoracic and mediastinal disorders | ||
| Tachypnoea | 6/12 (50%) | 6 |
| Allergic cough | 4/12 (33.3%) | 6 |
| Dyspnoea | 3/12 (25%) | 4 |
| Stridor | 2/12 (16.7%) | 3 |
| Cough | 1/12 (8.3%) | 3 |
| Hypoxia | 1/12 (8.3%) | 1 |
| Wheezing | 1/12 (8.3%) | 1 |
| Skin and subcutaneous tissue disorders | ||
| Pruritus | 6/12 (50%) | 10 |
| Urticaria | 5/12 (41.7%) | 8 |
| Drug eruption | 4/12 (33.3%) | 4 |
| Angioedema | 1/12 (8.3%) | 2 |
| Rash | 1/12 (8.3%) | 1 |
| Vascular disorders | ||
| Hypotension | 6/12 (50%) | 10 |
| Capillary leak syndrome | 1/12 (8.3%) | 1 |
Limitations/Caveats
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
Institution and/or Principal Investigator agree not to publish or publicly present any interim results of the Study without the prior written consent of Sponsor, not to be unreasonably withheld or delayed. Institution and/or Principal Investigator further agree to provide Sponsor with drafts of any such publication or presentation for review and approval no less than 30 days prior to submission for publication or the date of public presentation.
Results Point of Contact
| Name/Title | Odette Jordan, MD, PMP |
|---|---|
| Organization | United Therapeutics Corp. |
| Phone | 919-425-5606 |
| ojordan@unither.com |
- DIV-NB-401