This page provides an independent statistical analysis and educational interpretation of publicly reported results. ClinicalTrials.gov provides the official trial registry record. Numerical trial results on this page are restricted to the results posted in the ClinicalTrials.gov record; calculations added by Clinical Biostats are labelled as such.
1. Trial at a Glance
This page covers the registry results for A Study of the Effect of Hu3F8/GM-CSF Immunotherapy Plus Isotretinoin in Patients in First Remission of High-Risk Neuroblastoma (NCT03033303), a na phase 2 study. The primary outcome is Relapse-free Survival (RFS).
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT03033303 |
| Phase | Phase 2 |
| Condition | Neuroblastoma |
| Allocation | Not applicable (single group) |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 59 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Memorial Sloan Kettering Cancer Center |
| Results posted | Yes |
2. Clinical Question
The study asks about relapse-free survival after consolidation treatment for patients with high-risk neuroblastoma who were in first complete remission or very good partial response. The regimen combined Hu3F8 and GM-CSF with isotretinoin. The registry describes Hu3F8/GM-CSF as given for five cycles and isotretinoin for six cycles, with isotretinoin starting after the second Hu3F8/GM-CSF cycle.
Population
Patients with high-risk neuroblastoma in first complete remission or very good partial response. The registry lists an enrollment of 59; the primary outcome’s population field is blank.
Intervention
Consolidation with Hu3F8/GM-CSF and isotretinoin, as a single treatment regimen.
Comparator
There is no separate comparator group. Allocation is recorded as not applicable, and the study model is single-group.
Primary question
What relapse-free survival is observed after treatment, using the protocol’s stated definitions of response failure and events?
This is not a randomized comparison of the regimen against another treatment or usual care. It therefore describes outcomes in the treated group, but cannot by itself isolate the regimen’s effect from other influences on relapse-free survival. The registry identifies the primary endpoint as median relapse-free survival in months, with a five-year timeframe. It does not report the median value or a comparative estimate. The clinical question can consequently be described from the study design, but the principal numerical answer is not reported in the registry record.
3. Trial Design
The registry classifies this as a phase II, single-group study. The allocation field is not applicable, and masking is listed as none. These features mean that the record does not describe random assignment to distinct treatment groups or blinded assessment. The intervention group is Hu3F8/GM-CSF plus isotretinoin. The regimen description specifies five cycles of Hu3F8/GM-CSF and six cycles of isotretinoin, with isotretinoin beginning after cycle two of Hu3F8/GM-CSF.
The stated study population is patients with high-risk neuroblastoma in first complete remission or very good partial response. Enrollment is recorded as 59. The study status is completed. The listed start date is 2017-01-23, and the listed primary completion date is 2025-09-29. These registry entries describe the study’s structure and timing; they do not establish how many participants contributed to the primary endpoint analysis or how completely follow-up was observed.
The primary outcome is relapse-free survival, expressed as a median in months, with a five-year timeframe. The protocol description defines response failure in a particular way: progressive disease before two years counts as failure, deaths attributed to treatment toxicity count as events, and withdrawal or loss to follow-up before two years is treated as progression. These rules affect how the endpoint is interpreted and differ from simply counting documented relapses alone.
The registry lists one outcome measure and no analyses. It does not report the primary endpoint estimate, its uncertainty, an analysis population, or a statistical analysis plan. The record also does not report a concurrent control group, so the design supports a description of outcomes in this treated group rather than a controlled estimate of comparative treatment effect.
4. Participant Flow and Accounting
The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.
Overall Study
| Stage | Hu3F8/GM-CSF Plus Isotretinoin |
|---|---|
| STARTED | 59 |
| COMPLETED | 59 |
| NOT COMPLETED | 0 |
5. Baseline Characteristics
The table reproduces the baseline characteristics posted in the registry, which describe the participants analysed at baseline and help show whether the randomized groups were comparable.
| Characteristic | Unit | Hu3F8/GM-CSF Plus Isotretinoin |
|---|---|---|
| Participants analysed | 59 | |
| Age, Continuous | years | 3.5 (0.46 to 17.8) |
| Sex: Female, Male: Female | Participants | 27 |
| Sex: Female, Male: Male | Participants | 32 |
| Ethnicity (NIH/OMB): Hispanic or Latino | Participants | 2 |
| Ethnicity (NIH/OMB): Not Hispanic or Latino | Participants | 56 |
| Ethnicity (NIH/OMB): Unknown or Not Reported | Participants | 1 |
| Race (NIH/OMB): American Indian or Alaska Native | Participants | 0 |
| Race (NIH/OMB): Asian | Participants | 5 |
| Race (NIH/OMB): Native Hawaiian or Other Pacific Islander | Participants | 0 |
| Race (NIH/OMB): Black or African American | Participants | 4 |
| Race (NIH/OMB): White | Participants | 42 |
| Race (NIH/OMB): More than one race | Participants | 0 |
| Race (NIH/OMB): Unknown or Not Reported | Participants | 8 |
| Region of Enrollment: United States | Participants | 59 |
6. Primary Endpoint
The registry lists the primary outcome as Relapse-free Survival (RFS), measured over 5 years.
| Element | Registry entry |
|---|---|
| Result type | Median |
| Measure of spread | Full Range |
| Unit | months |
| Endpoint classification | Time-to-Event Analysis |
Relapse-free survival (RFS) is the primary endpoint. In general, a time-to-event endpoint measures the time from a defined starting point to an event of interest. It is used when both whether an event occurs and when it occurs matter. A median summarizes the time by which half of the analyzed population has experienced the event, provided that the data support estimating that point. It is not an average, and it does not describe every participant’s course.
The registry gives the endpoint unit as months and the timeframe as five years. It describes the reported parameter as a median with a full range for dispersion. The record does not state the median, the range, or the number of events used to estimate them. The endpoint population field is blank, so the population included in the reported analysis is not reported in the registry record.
The event definition is important. Progressive disease before two years is considered response failure. Deaths from toxicity attributable to protocol treatment are counted as events. Participants who withdraw or are lost to follow-up before two years are considered to have progressed. Thus, the endpoint is governed by protocol-specific rules and is not simply a count of confirmed relapses. The registry does not explain how withdrawals or loss to follow-up after two years are handled.
In general, time-to-event methods can use information from participants who have not yet experienced an event by the end of observed follow-up, while accounting for their incomplete event time. The registry record does not report the method used to estimate RFS or how censoring was handled. Without the endpoint estimate and its uncertainty, the record does not allow a quantitative assessment of the observed RFS.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry identifies a clinically meaningful time-to-event outcome, but it does not report a numerical result for that outcome. Although the primary endpoint is described as median RFS in months, no median, full range, confidence interval, event count, or analysis population appears in the record. The number of analyses is listed as zero. As a result, the principal outcome cannot be interpreted quantitatively from this registry record.
The study’s single-group structure also limits what any reported outcome could establish. In general, outcomes in a single treated group can describe what occurred among participants receiving that regimen, but they do not show what would have occurred in a comparable group receiving a different treatment or no study regimen. Without a concurrent comparator, differences attributable to treatment cannot be separated from differences in patient characteristics, prior care, follow-up, or other factors. This is a design limitation, not evidence that the regimen did or did not affect outcomes.
The protocol’s event definition needs to remain in view when reading any RFS estimate. Progressive disease before two years is classified as response failure; treatment-attributable toxicity deaths count as events; and withdrawal or loss to follow-up before two years is treated as progression. That last rule means some endpoint events may reflect follow-up status rather than documented progressive disease. The record does not state how withdrawal or loss to follow-up after two years is handled, or provide details on event adjudication.
The listed enrollment is 59, but enrollment alone does not establish how many participants were included in the RFS analysis, how many events occurred, or how precise the estimate would be. Those details are not reported in the registry record. The record also gives no confidence interval or other measure of uncertainty for the primary endpoint. A point estimate without uncertainty would be difficult to judge; here, even the point estimate is absent.
Safety information is listed separately from the RFS endpoint. The record reports participants affected by serious and other adverse events, deaths, and selected serious-event terms. These figures describe reported safety events in the treated group. They do not establish the cause of every event or permit a controlled comparison of safety rates, because the study has no comparator group. The deaths listed should not be assumed to be treatment-related; the registry identifies treatment-attributable toxicity deaths as events for RFS, but does not state that all listed deaths met that definition.
Overall, the record describes the study question, regimen, endpoint definition, and selected safety counts, but does not report the primary outcome estimate or a statistical analysis. It therefore supports an account of the study design and the information recorded, not a conclusion about the magnitude or precision of RFS in this group, and not a comparison of treatment effects.
9. Statistical Methods Explained
Statistical interpretation begins with the design. This is a single-group phase II study, with allocation recorded as not applicable and masking recorded as none. In general, a single-group study can describe outcomes among participants receiving a regimen. It does not create a randomized counterfactual group, so it cannot by itself estimate the difference between outcomes under the regimen and outcomes under an alternative. The record does not report a comparator or an adjusted comparative analysis.
What does a median time-to-event result mean?
In general, time-to-event analysis concerns both the occurrence and timing of an event. The median event time is the point at which an estimated event-free proportion reaches one half, when the available follow-up supports estimation. A median is not the same as the mean, and it does not convey the whole shape of the event-time distribution. The registry calls for median RFS in months and a full range, but does not report either value. It also does not report a confidence interval for the median.
Time-to-event methods commonly account for participants whose event has not been observed by the time their follow-up ends. Such observations are often described as censored: they contribute information up to their last known follow-up without being treated as though an event occurred at that time. This is general statistical context, not a statement about the analysis used in this study. The method for estimating RFS and the censoring rules are not reported in the registry record.
How does the event definition affect interpretation?
The registry states that progressive disease before two years is a response failure. It also counts deaths from toxicity attributable to protocol treatment as events. Participants who withdraw or are lost to follow-up before two years are considered to have progressed. These rules determine which observations contribute as events; they are not interchangeable with a definition based solely on confirmed relapse. In particular, classifying withdrawal or loss to follow-up as progression can make the endpoint reflect both disease status and follow-up status. The handling of withdrawal or loss to follow-up after two years is not reported in the registry record.
In general, endpoint definitions should be considered alongside the estimate because a result only has meaning relative to the event rules used to produce it. The registry gives no details on independent event review, adjudication procedures, or the date from which RFS time was measured. These details are not reported in the registry record.
What can the record say about uncertainty?
A confidence interval, in general, gives a range of values compatible with the data under a specified statistical procedure. It helps readers assess the precision of an estimate; a point estimate alone cannot show how much uncertainty surrounds it. The primary endpoint’s confidence interval and other uncertainty measures are not reported in the registry record. The event count and number included in the endpoint analysis are also not reported, so the information available does not allow readers to assess the statistical precision of an RFS estimate.
Enrollment is recorded as 59. It should not be substituted for the analysis population or the number of participants with complete endpoint information. Enrollment and analysis denominators can differ for reasons including eligibility, follow-up, and missing outcome data. The registry’s endpoint population field is blank, and the analysis population is not reported in the registry record.
What do the planning illustrations represent?
Planning calculations are not observed trial outcomes. In general, sample-size planning explores how many participants or events a future study might need under stated assumptions about the effect to detect, statistical significance, allocation, and analysis method. The assumptions recorded for the illustrations include a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation; the effect to detect is described as a stated fraction of the observed effect. For time-to-event calculations, the stated convention is to report the total number of events using the Schoenfeld method; for other calculations, the convention is participants per arm.
Those assumptions describe planning illustrations, not the design or results of this single-group trial. In particular, a two-arm planning illustration does not turn the study into a randomized two-arm comparison. Planning outputs are not observed power and do not demonstrate that the trial was adequately powered. The registry does not report a trial-specific sample-size justification or statistical plan, and no numerical planning output is stated in the record.
What is missing from the analysis record?
The registry lists one outcome measure and no analyses. It does not report a model, an analysis population, an estimate of RFS, uncertainty around that estimate, or details of adjustment. It also does not report an interim analysis plan, a statistical analysis plan, or methods for handling missing observations beyond the stated event rule for withdrawal or loss to follow-up before two years. These omissions prevent reconstruction of the endpoint analysis from the registry record. General statistical principles can explain how such analyses are often performed, but they cannot establish which procedures were used in this study.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists one outcome measure and no analyses. It identifies RFS as the primary endpoint, but does not provide an endpoint result, analysis population, event count, or statistical method. A multiplicity plan describing how inference across multiple outcomes, time points, or analyses would be controlled is not reported in the registry record. The fact that one outcome measure is listed does not establish that only one analysis was conducted or that no other outcomes were assessed; the record does not provide enough information to make that determination.
Missing-data handling is only partly described. Under the stated endpoint definition, withdrawal or loss to follow-up before two years is considered progression. That is a protocol rule for classifying these cases, rather than a complete account of missing-data methods. The registry does not report how withdrawal or loss to follow-up after two years is handled, the extent of missing follow-up, or any sensitivity analyses evaluating alternative assumptions. It also does not state how missing covariate or other outcome data, if any, were treated.
The primary outcome population field is blank. An intention-to-treat population, per-protocol population, or other analysis population is not reported in the registry record. The enrollment count of 59 therefore cannot be assumed to equal the number analyzed for RFS. The registry does not report participant flow through treatment and follow-up or the number contributing to the endpoint estimate.
In general, multiplicity and missingness affect how confidently results can be interpreted: testing many outcomes can increase the chance of false-positive findings if not addressed, while incomplete follow-up can affect estimates when its causes relate to outcome risk. These are general considerations, not evidence that either issue biased this study’s results. With no analysis results or detailed analysis plan recorded, their impact cannot be assessed.
11. Safety Results
The registry reports serious adverse events as affected participants divided by participants at risk.
| Arm | Participants with serious adverse events | Participants at risk | Percentage |
|---|---|---|---|
| Hu3F8/GM-CSF Plus Isotretinoin | 6 | 59 | 10.2% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Hu3F8/GM-CSF Plus Isotretinoin | 10 of 59 |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 5% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Hu3F8/GM-CSF Plus Isotretinoin | 59 of 59 |
Most frequent serious adverse event terms
| Event term | Organ system | Hu3F8/GM-CSF Plus Isotretinoin |
|---|---|---|
| Fever | General disorders | 2 of 59 |
| Infections and Infestations - Other, specify | Infections and infestations | 2 of 59 |
| Sinus tachycardia | Cardiac disorders | 2 of 59 |
| Dehydration | Metabolism and nutrition disorders | 1 of 59 |
| Duodenal obstruction | Gastrointestinal disorders | 1 of 59 |
| Hypertension | Vascular disorders | 1 of 59 |
| Hyponatremia | Metabolism and nutrition disorders | 1 of 59 |
| Hypotension | Vascular disorders | 1 of 59 |
| Vomiting | Gastrointestinal disorders | 1 of 59 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Hu3F8/GM-CSF Plus Isotretinoin |
|---|---|---|
| Lymphocyte count decreased | Investigations | 33 of 59 |
| White blood cell decreased | Investigations | 31 of 59 |
| Platelet count decreased | Blood and lymphatic system disorders | 28 of 59 |
| Neutrophil count decreased | Investigations | 21 of 59 |
| Alanine aminotransferase increased | Investigations | 19 of 59 |
| Pain | General disorders | 9 of 59 |
| Hypotension | Vascular disorders | 7 of 59 |
| Hyponatremia | Metabolism and nutrition disorders | 6 of 59 |
| Aspartate aminotransferase increased | Investigations | 4 of 59 |
| Bronchospasm | Respiratory, thoracic and mediastinal disorders | 4 of 59 |
Serious events with the highest arm-level rate: fever (3.4%), infections and infestations - other, specify (3.4%), sinus tachycardia (3.4%), dehydration (1.7%), duodenal obstruction (1.7%).
The registry reports safety information for the Hu3F8/GM-CSF plus isotretinoin group. It lists 6 participants with serious adverse events among 59 at risk and 59 with other adverse events among 59 at risk. It also lists 10 deaths. The record does not state that these categories are mutually exclusive, so they should not be added or treated as separate sets of participants. The deaths should not be assumed to be caused by treatment; the record does not provide their causes or attribution.
The listed serious adverse-event terms include Fever at 3.4%, Infections and Infestations - Other, specify at 3.4%, and Sinus tachycardia at 3.4%. Dehydration, Duodenal obstruction, and Hypertension are each listed at 1.7%. These percentages are registry entries for the named terms. The record does not provide additional detail on event severity, duration, recurrence, or the number of events per affected participant.
In general, serious adverse events are a safety category and should not be confused with all adverse events or with events judged related to treatment. The registry’s RFS definition counts deaths from toxicity attributable to protocol treatment as events, but it does not state that all deaths in the safety listing were attributed to treatment. Because the study has no comparator group, these figures describe reported events in the treated group rather than comparative safety rates.
12. What the Result Does, and Does Not, Mean
The study record describes a phase II evaluation of a combined consolidation regimen in patients with high-risk neuroblastoma in first complete remission or very good partial response. It identifies median RFS as the primary endpoint and gives protocol-specific rules for defining events. It also records adverse-event information for the treated group. These details clarify what the study set out to observe and how some outcomes were classified.
The record does not report the median RFS, its full range, a confidence interval, or the number of endpoint events. It therefore does not provide a numerical estimate of the primary outcome or show how precise such an estimate might be. The listed enrollment of 59 is not a substitute for the number analyzed or the number with sufficient follow-up. Those details are not reported in the registry record.
Even if a single-group outcome estimate were available, it would describe outcomes in the group receiving the regimen, not establish how outcomes compare with another treatment. In general, a controlled comparison is needed to distinguish a treatment contrast from differences due to patient characteristics, other care, or time. This study’s single-group design does not provide that comparison. That limitation should not be interpreted as evidence for or against treatment benefit.
The endpoint itself also requires careful reading. Early progressive disease counts as failure; treatment-attributable toxicity deaths count as events; and withdrawal or loss to follow-up before two years is treated as progression. Consequently, RFS under this protocol incorporates these rules and is not simply the time until a documented relapse. The registry does not report further details on event adjudication or handling of later loss to follow-up.
The safety listing gives counts, percentages for selected serious-event terms, and a death count, but does not establish the cause of all reported events. Nor can it provide a comparative safety assessment without a control group. Taken together, the record supports a description of the study design, endpoint definition, and recorded safety data. It does not support a conclusion about the magnitude of RFS, its precision, or a comparative treatment effect.
13. Why This Trial Matters Statistically
This trial is statistically notable for the distinction between a clearly named endpoint and an unavailable endpoint result. The registry defines RFS as the primary outcome, specifies months as the unit, gives a five-year timeframe, and describes the event rules. Yet it does not report the median, full range, uncertainty, event count, or analysis population. The endpoint definition alone is not enough to assess the observed outcome.
The single-group design is another important feature. It can be useful for describing outcomes after a regimen, particularly when the study question is focused on a defined patient group and treatment sequence. But without a separate comparator group, the design cannot estimate a treatment contrast. Statistical interpretation must distinguish descriptive follow-up from evidence about what would have happened under an alternative. This distinction remains important regardless of whether a future numerical outcome appears in another record.
The response-failure rules also matter for interpretation. The endpoint counts early progressive disease, specified toxicity-attributable deaths, and withdrawal or loss to follow-up before two years as events or failures. That makes the operational definition central to understanding any eventual estimate. Readers need the estimate, follow-up information, and analysis methods together to judge what it represents.
Finally, the registry illustrates why enrollment and safety summaries should not be mistaken for a primary efficacy analysis. Enrollment is recorded as 59, and safety events are listed, but neither supplies an RFS estimate or its precision. Statistical reporting is most informative when the endpoint result is accompanied by an analysis population, event information, uncertainty, and enough method detail to interpret the estimate. Those elements are not reported in the registry record.
14. Limitations
- The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
- Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.
The principal limitation for interpretation is that the registry does not report the primary endpoint result. Although it specifies median RFS, a five-year timeframe, and a full range for dispersion, the numerical estimate, range, confidence interval, and event count are absent. The endpoint population field is blank, and the number of analyses is listed as zero. These omissions prevent assessment of the magnitude or precision of the primary outcome.
The single-group design provides no concurrent control. Outcomes among participants receiving Hu3F8/GM-CSF plus isotretinoin therefore cannot be compared within this study against outcomes under another regimen. The allocation field is not applicable and masking is listed as none. The record does not report an adjusted comparative analysis or other method that would supply a controlled contrast.
The endpoint rules introduce further interpretive considerations. Withdrawal or loss to follow-up before two years is considered progression, while the handling of such cases after two years is not reported. The record also does not explain the time origin for RFS, the method of estimation, event adjudication, or the amount and pattern of missing follow-up. The analysis population and participant flow are not reported.
Safety information has limits as well. The registry lists serious and other adverse-event counts, selected serious-event terms, and deaths, but does not provide causes for all deaths or detailed attribution for every event. With no comparator group, these data do not support a comparative safety rate. The listed sample-size assumptions describe planning illustrations rather than the trial’s own design justification; a trial-specific sample-size justification and statistical plan are not reported in the registry record.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: A Study of the Effect of Hu3F8/GM-CSF Immunotherapy Plus Isotretinoin in Patients in First Remission of High-Risk Neuroblastoma — NCT03033303.
- Registry record last updated 2026-10-30; status last verified 2025-09.
- Results first posted 2026-10-30.
- Data retrieved from ClinicalTrials.gov on 2026-11-09.
- Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.
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18. Record Summary
This completed phase II study is recorded as a single-group evaluation of Hu3F8/GM-CSF plus isotretinoin for patients with high-risk neuroblastoma in first complete remission or very good partial response. Enrollment is listed as 59. The regimen description specifies five cycles of Hu3F8/GM-CSF and six cycles of isotretinoin, starting isotretinoin after the second Hu3F8/GM-CSF cycle.
The primary endpoint is median relapse-free survival in months, with a five-year timeframe. The registry defines early progressive disease, treatment-attributable toxicity deaths, and certain losses to follow-up as events or failures. It does not report the median RFS, its range, uncertainty, analysis population, or statistical method. The record lists safety counts, selected serious-event terms, and deaths, but gives no comparative safety analysis. With no control group and no primary endpoint result, the registry describes the study structure and recorded events but does not establish a comparative treatment effect or the precision of RFS.