Trial Outcomes & Findings for Preventative Trial of Difluoromethylornithine (DFMO) in High Risk Patients With Neuroblastoma That is in Remission (NCT NCT02395666)
NCT ID: NCT02395666
Last Updated: 2024-08-06
Results Overview
To evaluate the preventative activity of DFMO as a single agent in patients that are in remission based on: Event free survival (EFS)
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
140 participants
Primary outcome timeframe
2 Years
Results posted on
2024-08-06
Participant Flow
Participant milestones
| Measure |
Stratum 1
Subjects that are in remission at the end of upfront therapy defined as chemotherapy (5-7 cycles), surgery as indicated, consolidation therapy as indicated, radiation therapy as indicated, anti-GD2 antibody therapy with retinoic acid up to 6 cycles.
Subjects will receive twenty-seven (27) cycles of oral DFMO at a dose of 500 to 1000 mg/m2 BID on each day of a 28 day cycle.
|
Stratum 2
Subjects that are in remission after any previous relapse or refractory therapy.
Subjects will receive twenty-seven (27) cycles of oral DFMO at a dose of 500 to 1000 mg/m2 BID on each day of a 28 day cycle.
|
|---|---|---|
|
Overall Study
STARTED
|
101
|
39
|
|
Overall Study
COMPLETED
|
95
|
38
|
|
Overall Study
NOT COMPLETED
|
6
|
1
|
Reasons for withdrawal
| Measure |
Stratum 1
Subjects that are in remission at the end of upfront therapy defined as chemotherapy (5-7 cycles), surgery as indicated, consolidation therapy as indicated, radiation therapy as indicated, anti-GD2 antibody therapy with retinoic acid up to 6 cycles.
Subjects will receive twenty-seven (27) cycles of oral DFMO at a dose of 500 to 1000 mg/m2 BID on each day of a 28 day cycle.
|
Stratum 2
Subjects that are in remission after any previous relapse or refractory therapy.
Subjects will receive twenty-seven (27) cycles of oral DFMO at a dose of 500 to 1000 mg/m2 BID on each day of a 28 day cycle.
|
|---|---|---|
|
Overall Study
Physician Decision
|
3
|
0
|
|
Overall Study
Lost to Follow-up
|
1
|
0
|
|
Overall Study
Withdrawal by Subject
|
2
|
1
|
Baseline Characteristics
Preventative Trial of Difluoromethylornithine (DFMO) in High Risk Patients With Neuroblastoma That is in Remission
Baseline characteristics by cohort
| Measure |
Stratum 1
n=101 Participants
Subjects that are in remission at the end of upfront therapy defined as chemotherapy (5-7 cycles), surgery as indicated, consolidation therapy as indicated, radiation therapy as indicated, anti-GD2 antibody therapy with retinoic acid up to 6 cycles.
Subjects will receive twenty-seven (27) cycles of oral DFMO at a dose of 500 to 1000 mg/m2 BID on each day of a 28 day cycle.
|
Stratum 2
n=39 Participants
Subjects that are in remission after any previous relapse or refractory therapy.
Subjects will receive twenty-seven (27) cycles of oral DFMO at a dose of 500 to 1000 mg/m2 BID on each day of a 28 day cycle.
|
Total
n=140 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
4.4 years
n=99 Participants
|
6.8 years
n=107 Participants
|
5.1 years
n=206 Participants
|
|
Sex: Female, Male
Female
|
44 Participants
n=99 Participants
|
11 Participants
n=107 Participants
|
55 Participants
n=206 Participants
|
|
Sex: Female, Male
Male
|
57 Participants
n=99 Participants
|
28 Participants
n=107 Participants
|
85 Participants
n=206 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
2 Participants
n=99 Participants
|
1 Participants
n=107 Participants
|
3 Participants
n=206 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
|
Race (NIH/OMB)
Black or African American
|
7 Participants
n=99 Participants
|
3 Participants
n=107 Participants
|
10 Participants
n=206 Participants
|
|
Race (NIH/OMB)
White
|
82 Participants
n=99 Participants
|
32 Participants
n=107 Participants
|
114 Participants
n=206 Participants
|
|
Race (NIH/OMB)
More than one race
|
3 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
3 Participants
n=206 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
7 Participants
n=99 Participants
|
3 Participants
n=107 Participants
|
10 Participants
n=206 Participants
|
PRIMARY outcome
Timeframe: 2 YearsPopulation: One subject removed from Stratum 1 due to not fitting study criteria upon review
To evaluate the preventative activity of DFMO as a single agent in patients that are in remission based on: Event free survival (EFS)
Outcome measures
| Measure |
Stratum 1
n=100 Participants
Subjects that are in remission at the end of upfront therapy defined as chemotherapy (5-7 cycles), surgery as indicated, consolidation therapy as indicated, radiation therapy as indicated, anti-GD2 antibody therapy with retinoic acid up to 6 cycles.
Subjects will receive twenty-seven (27) cycles of oral DFMO at a dose of 500 to 1000 mg/m2 BID on each day of a 28 day cycle.
|
Stratum 2
n=39 Participants
Subjects that are in remission after any previous relapse or refractory therapy.
Subjects will receive twenty-seven (27) cycles of oral DFMO at a dose of 500 to 1000 mg/m2 BID on each day of a 28 day cycle.
|
GG, GT or TT
Tests of the association of survival with ODC1 single nucleotide polymorphism rs2302616 genotype.
|
|---|---|---|---|
|
Number of Participants With Event Free Survival (EFS) During Study.
|
84 percentage of subjects without an event
Interval 80.0 to 88.0
|
51 percentage of subjects without an event
Interval 43.0 to 59.0
|
—
|
SECONDARY outcome
Timeframe: 2 YearsTo evaluate the preventative activity of DFMO as a single agent in patients with neuroblastoma who are in remission based on: Overall Survival (OS)
Outcome measures
| Measure |
Stratum 1
n=100 Participants
Subjects that are in remission at the end of upfront therapy defined as chemotherapy (5-7 cycles), surgery as indicated, consolidation therapy as indicated, radiation therapy as indicated, anti-GD2 antibody therapy with retinoic acid up to 6 cycles.
Subjects will receive twenty-seven (27) cycles of oral DFMO at a dose of 500 to 1000 mg/m2 BID on each day of a 28 day cycle.
|
Stratum 2
n=39 Participants
Subjects that are in remission after any previous relapse or refractory therapy.
Subjects will receive twenty-seven (27) cycles of oral DFMO at a dose of 500 to 1000 mg/m2 BID on each day of a 28 day cycle.
|
GG, GT or TT
Tests of the association of survival with ODC1 single nucleotide polymorphism rs2302616 genotype.
|
|---|---|---|---|
|
Percentage of Participants With Overall Survival (OS)
|
97 percentage of subjects without an event
Interval 95.0 to 99.0
|
84 percentage of subjects without an event
Interval 78.0 to 90.0
|
—
|
SECONDARY outcome
Timeframe: 2 yearsPopulation: Stratum 1 and 2 were analyzed together as one safety group as per statistical analysis plan.
To continue to determine the safety and tolerability of DFMO as a single agent and in pediatric and young adult patients with high risk neuroblastoma that is in remission.
Outcome measures
| Measure |
Stratum 1
n=140 Participants
Subjects that are in remission at the end of upfront therapy defined as chemotherapy (5-7 cycles), surgery as indicated, consolidation therapy as indicated, radiation therapy as indicated, anti-GD2 antibody therapy with retinoic acid up to 6 cycles.
Subjects will receive twenty-seven (27) cycles of oral DFMO at a dose of 500 to 1000 mg/m2 BID on each day of a 28 day cycle.
|
Stratum 2
Subjects that are in remission after any previous relapse or refractory therapy.
Subjects will receive twenty-seven (27) cycles of oral DFMO at a dose of 500 to 1000 mg/m2 BID on each day of a 28 day cycle.
|
GG, GT or TT
Tests of the association of survival with ODC1 single nucleotide polymorphism rs2302616 genotype.
|
|---|---|---|---|
|
Number of Participants With Adverse Events as a Measure of Safety and Tolerability
|
57 Participants
|
—
|
—
|
SECONDARY outcome
Timeframe: 2 yearsPopulation: Stratum 1 and 2 were analyzed together as one group as per statistical analysis plan.
Tests (p-value) of the association of survival with ODC1 single nucleotide polymorphism rs2302616 genotype. Blood: microRNA analysis as predictor of DFMO effect, ornithine decarboxylase (ODC) single nucleotide polymorphism (SNP) analysis in DNA isolated from nucleated cells
Outcome measures
| Measure |
Stratum 1
n=140 Participants
Subjects that are in remission at the end of upfront therapy defined as chemotherapy (5-7 cycles), surgery as indicated, consolidation therapy as indicated, radiation therapy as indicated, anti-GD2 antibody therapy with retinoic acid up to 6 cycles.
Subjects will receive twenty-seven (27) cycles of oral DFMO at a dose of 500 to 1000 mg/m2 BID on each day of a 28 day cycle.
|
Stratum 2
n=140 Participants
Subjects that are in remission after any previous relapse or refractory therapy.
Subjects will receive twenty-seven (27) cycles of oral DFMO at a dose of 500 to 1000 mg/m2 BID on each day of a 28 day cycle.
|
GG, GT or TT
n=140 Participants
Tests of the association of survival with ODC1 single nucleotide polymorphism rs2302616 genotype.
|
|---|---|---|---|
|
Test the Association of Survival With ODC1 Genotype
|
0.96 p-value
|
0.58 p-value
|
0.67 p-value
|
SECONDARY outcome
Timeframe: Samples drawn at 5 timepoints: (0 (pre dose), 30min, 1 hour, 3 hours, and 6 hours post-dose) on two different daysPopulation: 12 subjects from both Stratum 1 and 2 were analyzed together as one group as per statistical analysis plan.
Pharmacokinetic assay Cmax/D Samples drawn at 5 timepoints: (0 (pre dose), 30min, 1 hour, 3 hours, and 6 hours post-dose) on two different days.
Outcome measures
| Measure |
Stratum 1
n=12 Participants
Subjects that are in remission at the end of upfront therapy defined as chemotherapy (5-7 cycles), surgery as indicated, consolidation therapy as indicated, radiation therapy as indicated, anti-GD2 antibody therapy with retinoic acid up to 6 cycles.
Subjects will receive twenty-seven (27) cycles of oral DFMO at a dose of 500 to 1000 mg/m2 BID on each day of a 28 day cycle.
|
Stratum 2
Subjects that are in remission after any previous relapse or refractory therapy.
Subjects will receive twenty-seven (27) cycles of oral DFMO at a dose of 500 to 1000 mg/m2 BID on each day of a 28 day cycle.
|
GG, GT or TT
Tests of the association of survival with ODC1 single nucleotide polymorphism rs2302616 genotype.
|
|---|---|---|---|
|
Peak Plasma Concentration (Cmax)
|
11958 ng/mL
Interval 5123.0 to 18793.0
|
—
|
—
|
SECONDARY outcome
Timeframe: 0 (pre dose), 30min, 1 hour, 3 hours, and 6 hours post-dose on two different daysPopulation: 12 subjects from both Stratum 1 and 2 were analyzed together as one group as per statistical analysis plan.
Pharmacokinetic assay AUC(0-6 hr)/D Samples drawn at 5 timepoints: (0 (pre dose), 30min, 1 hour, 3 hours, and 6 hours post-dose) on two different days
Outcome measures
| Measure |
Stratum 1
n=12 Participants
Subjects that are in remission at the end of upfront therapy defined as chemotherapy (5-7 cycles), surgery as indicated, consolidation therapy as indicated, radiation therapy as indicated, anti-GD2 antibody therapy with retinoic acid up to 6 cycles.
Subjects will receive twenty-seven (27) cycles of oral DFMO at a dose of 500 to 1000 mg/m2 BID on each day of a 28 day cycle.
|
Stratum 2
Subjects that are in remission after any previous relapse or refractory therapy.
Subjects will receive twenty-seven (27) cycles of oral DFMO at a dose of 500 to 1000 mg/m2 BID on each day of a 28 day cycle.
|
GG, GT or TT
Tests of the association of survival with ODC1 single nucleotide polymorphism rs2302616 genotype.
|
|---|---|---|---|
|
Area Under the Plasma Concentration Versus Time Curve (AUC)
|
47024 hr*ng/mL
Interval 23868.0 to 70180.0
|
—
|
—
|
SECONDARY outcome
Timeframe: 0 (pre dose), 30min, 1 hour, 3 hours, and 6 hours post-dose on two different daysPopulation: 12 subjects from both Stratum 1 and 2 were analyzed together as one group as per statistical analysis plan.
Pharmacokinetic assay- tmax, hr Samples drawn at 5 timepoints: (0 (pre dose), 30min, 1 hour, 3 hours, and 6 hours post-dose) on two different days
Outcome measures
| Measure |
Stratum 1
n=12 Participants
Subjects that are in remission at the end of upfront therapy defined as chemotherapy (5-7 cycles), surgery as indicated, consolidation therapy as indicated, radiation therapy as indicated, anti-GD2 antibody therapy with retinoic acid up to 6 cycles.
Subjects will receive twenty-seven (27) cycles of oral DFMO at a dose of 500 to 1000 mg/m2 BID on each day of a 28 day cycle.
|
Stratum 2
Subjects that are in remission after any previous relapse or refractory therapy.
Subjects will receive twenty-seven (27) cycles of oral DFMO at a dose of 500 to 1000 mg/m2 BID on each day of a 28 day cycle.
|
GG, GT or TT
Tests of the association of survival with ODC1 single nucleotide polymorphism rs2302616 genotype.
|
|---|---|---|---|
|
Time to Reach Peak Plasma Concentration (Tmax)
|
3.3 hours
Interval 1.9 to 4.7
|
—
|
—
|
Adverse Events
All Study Subjects
Serious events: 23 serious events
Other events: 41 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
All Study Subjects
n=140 participants at risk
All subjects that received at least one dose of DFMO. Since both arms received the same exact treatment, they were combined into one reporting group.
|
|---|---|
|
Infections and infestations
Infection
|
5.7%
8/140 • Number of events 8 • Through study completion plus 30 days, an average of 2 years.
All subjects that received at least one dose of DFMO. Since both arms received the same exact treatment, they were combined into one reporting group.
|
|
Gastrointestinal disorders
Vomiting
|
2.1%
3/140 • Number of events 3 • Through study completion plus 30 days, an average of 2 years.
All subjects that received at least one dose of DFMO. Since both arms received the same exact treatment, they were combined into one reporting group.
|
|
General disorders
Pain
|
0.71%
1/140 • Number of events 1 • Through study completion plus 30 days, an average of 2 years.
All subjects that received at least one dose of DFMO. Since both arms received the same exact treatment, they were combined into one reporting group.
|
|
Gastrointestinal disorders
Diarrhea
|
2.1%
3/140 • Number of events 3 • Through study completion plus 30 days, an average of 2 years.
All subjects that received at least one dose of DFMO. Since both arms received the same exact treatment, they were combined into one reporting group.
|
|
General disorders
Fever
|
0.71%
1/140 • Number of events 1 • Through study completion plus 30 days, an average of 2 years.
All subjects that received at least one dose of DFMO. Since both arms received the same exact treatment, they were combined into one reporting group.
|
|
Investigations
Hyponatremia
|
0.71%
1/140 • Number of events 1 • Through study completion plus 30 days, an average of 2 years.
All subjects that received at least one dose of DFMO. Since both arms received the same exact treatment, they were combined into one reporting group.
|
|
Vascular disorders
Benign vascular lesion
|
0.71%
1/140 • Number of events 1 • Through study completion plus 30 days, an average of 2 years.
All subjects that received at least one dose of DFMO. Since both arms received the same exact treatment, they were combined into one reporting group.
|
|
Eye disorders
Swelling of Eye
|
0.71%
1/140 • Number of events 1 • Through study completion plus 30 days, an average of 2 years.
All subjects that received at least one dose of DFMO. Since both arms received the same exact treatment, they were combined into one reporting group.
|
|
Metabolism and nutrition disorders
Hypoglycemia
|
0.71%
1/140 • Number of events 1 • Through study completion plus 30 days, an average of 2 years.
All subjects that received at least one dose of DFMO. Since both arms received the same exact treatment, they were combined into one reporting group.
|
|
Skin and subcutaneous tissue disorders
Urticaria
|
0.71%
1/140 • Number of events 1 • Through study completion plus 30 days, an average of 2 years.
All subjects that received at least one dose of DFMO. Since both arms received the same exact treatment, they were combined into one reporting group.
|
|
Gastrointestinal disorders
Constipation
|
0.71%
1/140 • Number of events 1 • Through study completion plus 30 days, an average of 2 years.
All subjects that received at least one dose of DFMO. Since both arms received the same exact treatment, they were combined into one reporting group.
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory Disorder
|
0.71%
1/140 • Number of events 1 • Through study completion plus 30 days, an average of 2 years.
All subjects that received at least one dose of DFMO. Since both arms received the same exact treatment, they were combined into one reporting group.
|
|
Cardiac disorders
Hypotension
|
0.71%
1/140 • Number of events 1 • Through study completion plus 30 days, an average of 2 years.
All subjects that received at least one dose of DFMO. Since both arms received the same exact treatment, they were combined into one reporting group.
|
|
Ear and labyrinth disorders
hearing loss
|
0.71%
1/140 • Number of events 1 • Through study completion plus 30 days, an average of 2 years.
All subjects that received at least one dose of DFMO. Since both arms received the same exact treatment, they were combined into one reporting group.
|
|
Musculoskeletal and connective tissue disorders
Fracture
|
0.71%
1/140 • Number of events 1 • Through study completion plus 30 days, an average of 2 years.
All subjects that received at least one dose of DFMO. Since both arms received the same exact treatment, they were combined into one reporting group.
|
|
Infections and infestations
Influenza
|
0.71%
1/140 • Number of events 1 • Through study completion plus 30 days, an average of 2 years.
All subjects that received at least one dose of DFMO. Since both arms received the same exact treatment, they were combined into one reporting group.
|
|
Infections and infestations
Bacteremia
|
0.71%
1/140 • Number of events 1 • Through study completion plus 30 days, an average of 2 years.
All subjects that received at least one dose of DFMO. Since both arms received the same exact treatment, they were combined into one reporting group.
|
|
Gastrointestinal disorders
Obstruction
|
0.71%
1/140 • Number of events 1 • Through study completion plus 30 days, an average of 2 years.
All subjects that received at least one dose of DFMO. Since both arms received the same exact treatment, they were combined into one reporting group.
|
Other adverse events
| Measure |
All Study Subjects
n=140 participants at risk
All subjects that received at least one dose of DFMO. Since both arms received the same exact treatment, they were combined into one reporting group.
|
|---|---|
|
Blood and lymphatic system disorders
Neutrophil count decrease
|
7.9%
11/140 • Number of events 11 • Through study completion plus 30 days, an average of 2 years.
All subjects that received at least one dose of DFMO. Since both arms received the same exact treatment, they were combined into one reporting group.
|
|
Blood and lymphatic system disorders
Anemia
|
4.3%
6/140 • Number of events 6 • Through study completion plus 30 days, an average of 2 years.
All subjects that received at least one dose of DFMO. Since both arms received the same exact treatment, they were combined into one reporting group.
|
|
Hepatobiliary disorders
ALT elevation
|
10.0%
14/140 • Number of events 14 • Through study completion plus 30 days, an average of 2 years.
All subjects that received at least one dose of DFMO. Since both arms received the same exact treatment, they were combined into one reporting group.
|
|
Hepatobiliary disorders
AST elevation
|
7.1%
10/140 • Number of events 10 • Through study completion plus 30 days, an average of 2 years.
All subjects that received at least one dose of DFMO. Since both arms received the same exact treatment, they were combined into one reporting group.
|
|
Gastrointestinal disorders
Diarrhea
|
6.4%
9/140 • Number of events 9 • Through study completion plus 30 days, an average of 2 years.
All subjects that received at least one dose of DFMO. Since both arms received the same exact treatment, they were combined into one reporting group.
|
|
Ear and labyrinth disorders
Hearing Loss
|
6.4%
9/140 • Number of events 9 • Through study completion plus 30 days, an average of 2 years.
All subjects that received at least one dose of DFMO. Since both arms received the same exact treatment, they were combined into one reporting group.
|
|
Infections and infestations
Otitis Media
|
4.3%
6/140 • Number of events 6 • Through study completion plus 30 days, an average of 2 years.
All subjects that received at least one dose of DFMO. Since both arms received the same exact treatment, they were combined into one reporting group.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: LTE60