A Study of Pomalidomide Monotherapy for Children and Young Adults With Recurrent or Progressive Primary Brain Tumors: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Study of Pomalidomide Monotherapy for Children and Young Adults With Recurrent or Progressive Primary Brain Tumors (NCT03257631), a na phase 2 study. The primary outcome is Percentage of Participants With an Objective Response and Long-term Stable Disease.

2. Clinical Question

3. Trial Design

This is a phase 2, single-group study of pomalidomide monotherapy for children and young adults with recurrent or progressive primary brain tumors. The registry lists 53 enrolled participants. The study covered four tumor types: high-grade glioma, medulloblastoma, ependymoma, and diffuse intrinsic pontine glioma. Its brief summary says the study was intended to assess efficacy, safety, and tolerability.

The registry records allocation as NA and masking as none. With a single-group design, the primary endpoint describes outcomes among participants receiving pomalidomide; it does not provide a concurrent control-group estimate. There is consequently no randomized contrast from which to separate treatment effects from the natural course of disease, participant selection, or other influences. This is a design consideration, not a conclusion about the treatment.

Pomalidomide is listed as the intervention, with a starting dose of 2.6 m2/day. The registry describes capsule strengths and an oral suspension formulation. The primary endpoint timeframe was the first 6 cycles, or the first 3 cycles for participants in the DIPG group. The record gives the study status as completed, with a start date of 2017-09-18 and a primary completion date of 2023-09-14.

The registry record does not report a separate control arm, a randomization procedure, or masking beyond the listed designation of none. It does not report a sample-size justification, an interim analysis plan, or a detailed statistical analysis plan. Although secondary outcomes include response, stable disease, response duration, progression-free survival, overall survival, and treatment-emergent adverse events, the record lists 0 analyses and does not report numerical results for the primary endpoint.

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.

Before assignment: In stage 1 approximately 9 participants were to be enrolled in parallel to each group. If two or more participants in a group achieved an objective response or long-term stable disease within the first 6 cycles of treatment (within the first 3 cycles for DIPG) an additional 11 participants were to be enrolled in that group.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: The response population consisted of all enrolled participants receiving at least one cycle of pomalidomide if therapy was not discontinued earlier due to progressive disease (PD)

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.

Population: The intent-to-treat population includes all enrolled participants, regardless of whether they received any treatment or not

6. Primary Endpoint

The registry lists the primary outcome as Percentage of Participants With an Objective Response and Long-term Stable Disease, measured over 6 months (first 6 cycles) or 3 months (first 3 cycles) for participants in the DIPG group.

The primary endpoint is the percentage of participants who achieved either an objective response or long-term stable disease. Objective response was defined as complete response or partial response. Complete response required disappearance of all lesions and no new lesions. Partial response required a reduction of at least 50% in the size of measurable lesions, and/or persistence of non-target lesions without progression or with a decrease in size. Long-term stable disease required stable disease maintained for at least 6 cycles, or at least 3 cycles for participants in the DIPG group.

The endpoint was assessed during the first 6 treatment cycles, or the first 3 cycles for DIPG, measured from the first dose date. The registry’s description also defines stable disease and progressive disease using changes in measurable lesions, new lesions, and progression of non-target lesions. These criteria make the endpoint a combined measure: it counts participants with an early tumor response as well as those meeting the specified duration of stable disease.

A percentage is useful for expressing how common the endpoint was within the defined response population. The registry specifies a 95% confidence interval, which, as a general statistical concept, conveys uncertainty around an estimated percentage. The record does not report the observed percentage, confidence interval, or number of participants meeting the endpoint. The endpoint definition alone therefore does not establish how participants actually fared.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does the primary endpoint estimate?

The endpoint is a percentage: the proportion of the defined response population that met either the objective-response criterion or the long-term stable-disease criterion. The response population consisted of enrolled participants receiving at least one cycle of pomalidomide, except where therapy was discontinued earlier because of progressive disease. This population definition is important because the denominator for a percentage depends on who is included. The registry gives the definition but does not report the endpoint denominator or numerator.

As a general statistical concept, a sample percentage estimates the frequency of an event in the population being studied. Its interpretation depends on a clear event definition and a clearly specified analysis population. Here, the clinical definitions are set out, but the observed percentage and its participant counts are not reported in the registry record.

How should the confidence interval be understood?

The endpoint specifies a 95% confidence interval. In general, a confidence interval describes uncertainty around an estimate under the assumptions of the method used to calculate it. A narrower interval indicates greater precision than a wider interval, but an interval does not explain why an outcome occurred, show individual-level variability, or establish a causal treatment effect.

The actual interval and the method used to calculate it are not reported in the registry record. It is therefore not possible to assess the precision of the primary estimate or to determine whether the calculation accounted for particular features of the data. The confidence level alone does not supply the missing estimate.

What does the single-group design allow?

The study is listed as single-group, with allocation recorded as NA and masking as none. A single-group endpoint can describe the outcomes observed among participants in that group. Without a separate control group, it cannot directly estimate a difference in outcome between pomalidomide and another treatment or control condition. General statistical reasoning also cautions that observed outcomes in an uncontrolled study may reflect influences other than the intervention. This is a limitation of what the design can establish, not a finding about the treatment.

The registry does not report randomization, a comparative analysis, or an adjustment plan. The study’s phase designation does not substitute for those details. A phase 2 label identifies the study phase in the record; it does not establish the endpoint result or the certainty of any treatment effect.

How do the response criteria shape interpretation?

The primary endpoint combines response and durable disease stability. Complete response requires disappearance of all lesions with no new lesions. Partial response includes a reduction of at least 50% in measurable lesions, with the stated conditions for non-target lesions. Stable disease is defined by the specified range of change in measurable lesions and the absence of new lesions, without meeting criteria for response or progressive disease. Progressive disease includes an increase of at least 25% in measurable lesions, new lesions, or unequivocal progression of existing non-target lesions.

As a general matter, combining distinct outcomes into one endpoint can summarize whether participants met at least one of several clinically defined criteria. But the combined percentage cannot reveal the contribution of each component unless the components are reported separately. Those component counts are not reported in the registry record.

What analysis details are missing?

The record lists 0 analyses. The statistical method for the primary confidence interval, any handling of missing assessments, and any detailed analysis plan are not reported in the registry record. The record also does not describe interim analyses or a sample-size justification. These absences limit evaluation of how the outcome was analyzed; they do not demonstrate that a particular method was or was not used outside what the registry records.

As a general concept, missing outcome observations can affect an estimated percentage if the participants with missing assessments differ from those assessed. The response-population definition gives one eligibility rule related to treatment exposure and early discontinuation for progressive disease, but does not explain how other missing endpoint data were handled. It would be inappropriate to infer an imputation method or missing-data assumption from the endpoint definition alone.

The record identifies several secondary outcomes, including time-to-event measures and adverse events. Different outcome types ordinarily require different analytic summaries, and time-to-event estimates commonly account for differing follow-up. The registry names Kaplan-Meier estimates for progression-free survival and overall survival, but does not report their values, confidence intervals, censoring details, or analysis methods. No additional statistical procedures should be inferred from the outcome names alone.

10. Exact Estimates for Each Arm

No two-arm comparison is shown for this trial, but each arm's result can still be summarized with exact interval estimates computed from the posted counts. The Clopper-Pearson interval is exact and conservative; the Wilson interval is a common closer-to-nominal alternative; the Bayesian credible interval uses a uniform Beta(1, 1) prior. For small groups the three can differ noticeably.

R code and output

arm    <- c("Diffuse Intrinsic Pontine Glioma", "Ependymoma", "High-grade Glioma", "Medulloblastoma")
n      <- c(9, 9, 19, 9)
events <- c(0, 1, 2, 0)
for (i in seq_along(n)) {
  ci <- binom.test(events[i], n[i])$conf.int          # Clopper-Pearson exact interval
  cr <- qbeta(c(0.025, 0.975), 1 + events[i], 1 + n[i] - events[i])   # Bayesian, uniform Beta(1,1) prior
  wi <- (function(x, n) { p <- x / n; z <- qnorm(0.975); d <- 1 + z^2 / n
    c((p + z^2 / (2 * n) - z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d, (p + z^2 / (2 * n) + z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d) })(events[i], n[i])
  cat(sprintf("ARM|%s|%d|%d|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f\n", arm[i], n[i], events[i], 100 * events[i] / n[i],
              100 * ci[1], 100 * ci[2], 100 * wi[1], 100 * wi[2], 100 * cr[1], 100 * cr[2]))
}

ARM  Diffuse Intrinsic Pontine Glioma  9  0  0.0  0.0  33.6  -0.0  29.9  0.3  30.8
ARM  Ependymoma  9  1  11.1  0.3  48.2  2.0  43.5  2.5  44.5
ARM  High-grade Glioma  19  2  10.5  1.3  33.1  2.9  31.4  3.2  31.7
ARM  Medulloblastoma  9  0  0.0  0.0  33.6  -0.0  29.9  0.3  30.8

11. Multiplicity, Missing Data and Analysis Populations

The registry lists a primary endpoint and 7 secondary outcome measures. The secondary outcomes cover objective response, long-term stable disease, duration of response, Kaplan-Meier estimates of progression-free survival and overall survival, and treatment-emergent adverse events. The record lists 0 analyses, and numerical results for these outcomes are not reported in the registry record.

When a study evaluates several outcomes, general statistical practice recognizes that the chance of at least one apparently unusual result can depend on how many tests are conducted and how those tests are interpreted. Researchers may address this through a prespecified hierarchy or other multiplicity strategy. The registry record does not report whether such a strategy was planned or used, so no claim about multiplicity adjustment is warranted.

The primary endpoint defines a response population: participants enrolled and receiving at least one cycle, except when therapy was discontinued earlier because of progressive disease. That definition does not specify how missing endpoint assessments were treated, whether participants with incomplete assessments were excluded, or whether any sensitivity analyses were conducted. Those details are not reported in the registry record.

As a general statistical matter, missingness can affect a percentage estimate when availability of an outcome is related to the likelihood of meeting the endpoint. A clear account of the analysis population and missing-data handling helps readers understand the denominator and the assumptions behind the estimate. Here, the registry supplies the population definition but no numerator, denominator, missing-data method, or analysis output. It is not possible to assess the impact of missing data or multiplicity from the recorded information.

12. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Deaths

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: headache (22.2%), hydrocephalus (22.2%), general physical health deterioration (18.2%), hemiparesis (13.6%), pain (11.1%).

The registry reports serious adverse-event figures by tumor group. For each group, the record gives the number at risk for serious adverse events and the number affected, as well as corresponding at-risk and affected counts for other adverse events. The serious-event figures are: DIPG, 11 at risk and 9 affected; ependymoma, 9 at risk and 4 affected; high-grade glioma, 22 at risk and 14 affected; and medulloblastoma, 10 at risk and 4 affected. The registry also lists deaths by group, without further context in the recorded information.

Listed serious-event terms and percentages include headache, 22.2%; hydrocephalus, 22.2%; general physical health deterioration, 18.2%; hemiparesis, 13.6%; pain, 11.1%; and encephalitis, 10.0%. The registry record does not report the denominator or timeframe associated with these listed percentages, nor does this information establish whether an event was caused by pomalidomide. These figures describe safety information recorded in the registry; they are not a comparison with another treatment group. The record does not provide enough detail to assess event timing, severity beyond the serious-event classification, or clinical attribution.

13. What the Result Does, and Does Not, Mean

The registry record can establish the study’s design, population, intervention, endpoint definition, and certain safety counts. It describes a phase 2, single-group study of pomalidomide monotherapy in children and young adults with recurrent or progressive primary brain tumors, including four tumor types. It also defines the primary endpoint as a percentage achieving objective response or long-term stable disease over the specified cycle-based timeframe.

It cannot establish the observed primary endpoint result from the information recorded. The percentage and its 95% confidence interval are not reported, and the record lists 0 analyses. It is therefore not possible to state how frequently participants met the endpoint or how precise that estimate was. The endpoint’s component results are also not reported, so the combined measure cannot be separated into objective response and long-term stable disease.

The single-group design also limits comparative interpretation. Without a listed control group, these data do not provide a randomized comparison with another treatment or control condition. An outcome observed in a single group cannot, on its own, identify what would have happened to comparable participants under a different condition. This design feature does not determine whether the treatment had an effect; it sets a boundary on the conclusions supported by the record.

The serious adverse-event counts and listed event terms offer some safety information, but do not by themselves establish causation or comparative risk. Context such as the event timeframe, detailed attribution, and a control-group rate is not reported in the registry record. Overall, the registry information supports a description of the planned endpoint and recorded safety figures, but not a conclusion about efficacy or a comparative benefit-risk balance.

14. Why This Trial Matters Statistically

This study raises several statistical issues that are useful when reading clinical research. Its primary endpoint is not a single response category: it combines objective response with stable disease maintained for a specified duration. The combined measure can communicate whether participants met either criterion, but its interpretation depends on the clinical definitions and the population used as the denominator. Without component counts, readers cannot tell which route contributed to the endpoint.

The assessment window is also tumor-group specific. The registry defines the first 6 cycles for participants generally and the first 3 cycles for DIPG. That distinction should remain visible in any description of the endpoint; treating all participants as if they had the same assessment duration would misstate the registry definition.

The study’s single-group structure is another important statistical feature. It can describe outcomes within the treated group, but it does not provide a randomized contrast. This distinction helps prevent overinterpretation of an outcome percentage as a causal comparison. The registry record does not report a primary outcome estimate, so no conclusion about the size or precision of the result can be drawn from the recorded information.

Finally, the record’s safety information is organized by tumor group, while efficacy results and analysis details are absent. Readers need to distinguish the existence of a defined outcome or listed adverse-event count from the availability of a complete analysis. Attention to the denominator, assessment period, endpoint components, and comparative design is central to statistically careful interpretation of this trial record.

15. 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.

Several limitations specific to interpreting this registry record should be kept in view. The study is single-group, with allocation listed as NA and masking as none. It therefore has no listed randomized comparator, and its outcomes cannot be interpreted as a direct treatment-versus-control contrast. The study is recorded as completed, but completion status does not mean that outcome estimates are present in the record.

The primary endpoint is defined, including its response criteria, population, and assessment window, but its observed percentage and 95% confidence interval are not reported. The registry lists 0 analyses. It also does not report the primary endpoint’s numerator and denominator, separate results for the response and stable-disease components, or subgroup results for the four tumor types.

The registry record does not report a detailed statistical analysis plan, sample-size justification, interim-analysis plan, or method for handling missing endpoint assessments. It is therefore not possible to evaluate the planned confidence-interval procedure, missing-data assumptions, or whether the analyses followed a prespecified hierarchy. The listed secondary outcomes do not substitute for reported estimates or methods.

The safety information has limits as well. Serious adverse-event counts are given by tumor group, but details such as event timeframe and attribution are not reported in the record information. The listed serious-event percentages have no accompanying denominator information in the record. Accordingly, they should not be treated as comparative rates or as evidence that the study drug caused a particular event.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: A Study of Pomalidomide Monotherapy for Children and Young Adults With Recurrent or Progressive Primary Brain Tumors — NCT03257631.
• Registry record last updated 2024-04-16; status last verified 2024-04.
• Results first posted 2019-12-10.
• 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.

19. Record Summary

The registry describes NCT03257631, a phase 2, single-group study of pomalidomide monotherapy in children and young adults with recurrent or progressive primary brain tumors. It lists 53 enrolled participants and four tumor groups: DIPG, ependymoma, high-grade glioma, and medulloblastoma. Allocation is recorded as NA, masking as none, and status as completed.

The primary endpoint is the percentage achieving objective response or long-term stable disease during the first 6 cycles, or the first 3 cycles for DIPG, with a specified 95% confidence interval. The endpoint result and confidence interval are not reported in the registry record. The record lists 7 secondary outcome measures and 0 analyses.

Serious adverse-event counts are reported by tumor group, along with selected event terms and percentages. The record does not include the contextual details needed to interpret those percentages as comparative or causal findings. Overall, it documents the design and outcome definitions, but does not report the primary efficacy estimate or its precision.