CPX-351 and Glasdegib for Newly Diagnosed Acute Myelogenous Leukemia With MDS Related Changes or Therapy-related Acute Myeloid Leukemia: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for CPX-351 and Glasdegib for Newly Diagnosed Acute Myelogenous Leukemia With MDS Related Changes or Therapy-related Acute Myeloid Leukemia (NCT04231851), a na phase 2 study. The primary outcome is Percentage of Participants With Event-Free Survival at 6 Months.

2. Clinical Question

3. Trial Design

This is a phase 2, open-label, single-group clinical trial sponsored by the University of California, Irvine. The registry lists an enrollment of 30 and identifies the population as previously untreated patients with AML with myelodysplasia-related changes or therapy-related AML. The study began on 2020-02-19, has a primary completion date of 2024-06-30, and is listed as active, not recruiting.

All participants are assigned to the CPX-351 and glasdegib combination; the registry lists no randomized allocation and no masking. The regimen description includes induction, re-induction if needed, and consolidation. The record describes intravenous CPX-351 and oral glasdegib, but the available regimen description is incomplete, so it does not establish every treatment detail.

The single-group structure is central to interpreting the findings. The study can report outcomes observed among participants treated with the combination, but it does not include a concurrent control group for estimating how outcomes would differ under another treatment. Open-label status also means participants and investigators are not masked to treatment assignment. That may matter for outcomes involving clinical judgments or reporting, although the record does not say whether or how such effects were assessed.

The primary outcome is the percentage of participants with event-free survival at 6 months. The registry also lists secondary outcomes covering adverse events, response, response durability, overall survival, time to normal hematopoiesis, and receipt of an allogenic hematopoietic stem cell transplant. The registry record does not report the analysis methods, analysis populations, or results for these outcomes. Its listed status and completion date describe the study record; they do not establish that outcome analyses are available.

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

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.

6. Primary Endpoint

The registry lists the primary outcome as Percentage of Participants With Event-Free Survival at 6 Months, measured over 6 months.

The primary outcome is the percentage of participants with event-free survival at 6 months. The registry defines event-free survival as the number of months patients are in a remission state. In this study, the measure is intended to summarize whether participants meet the stated event-free survival outcome at a specified follow-up point.

In general, a fixed-time percentage can make a time-to-event outcome easier to interpret at a clinically specified horizon: it describes the proportion meeting the outcome by that point, rather than presenting only a relative comparison between treatment groups. A confidence interval communicates the statistical uncertainty around an estimated percentage. The registry identifies a 95% confidence interval as the dispersion measure, but does not report the estimate or interval.

The endpoint definition is not fully operational in the registry record. It does not specify which events count, how remission is assessed, how deaths or treatment changes are handled, or how participants without follow-up through 6 months contribute to the estimate. Those details are important because different event definitions and follow-up rules can yield different estimates. The primary endpoint result, its confidence interval, and these analysis details are not reported in the registry record. As a result, the endpoint's intended time point is clear, but the observed outcome and the precision of its estimate cannot be assessed from the record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The record identifies a percentage at a fixed follow-up time as the primary outcome. In general, this kind of endpoint reduces each participant's follow-up information to whether the defined outcome is met at the specified time. The resulting estimate is a proportion in the analyzed group. To interpret it, readers need to know who was eligible for analysis, how the endpoint was defined, and how participants without complete follow-up were handled. Those analysis details are not reported in the registry record.

What does a confidence interval add?

In general, a confidence interval describes the uncertainty associated with an estimate under a specified statistical model and its assumptions. A narrower interval indicates greater precision under those assumptions; a wider interval indicates less precision. An interval is not a guarantee about the true value, and it does not measure whether the study design has controlled confounding or selection bias. The registry names a 95% confidence interval for the primary endpoint, but neither the interval nor the underlying estimate is reported. Its precision therefore cannot be evaluated from the record.

What does a single-group design estimate?

A single-group trial observes outcomes among participants receiving the study regimen. It can describe those outcomes, but it does not directly estimate the contrast between that regimen and a concurrent alternative. In a randomized trial, random assignment is intended to make treatment groups comparable on average, supporting an estimate of a treatment contrast. This trial has no randomized allocation and no separate comparator group. A comparison with historical or external outcomes would require additional assumptions and would not have the same protection from differences between groups. No such comparative analysis is reported in the registry record.

The trial is also open-label. In general, masking can reduce the influence of knowledge of treatment assignment on some assessments or reports. Open-label status does not by itself invalidate an outcome, but it makes the endpoint's objectivity and assessment procedures relevant. The registry record does not report whether outcome assessment was independently reviewed or whether any procedures were used to limit assessment bias.

How should the endpoint definition be assessed?

The registry names event-free survival at 6 months as the primary outcome and describes event-free survival as the number of months patients are in remission. The record does not specify the event criteria, the source or timing of remission assessments, or how deaths and incomplete observations enter the calculation. In general, survival endpoints require explicit definitions of the event, time origin, follow-up, and censoring rules. Without those details, readers cannot determine exactly how the stated percentage was derived or whether participants were classified consistently.

General statistical methods for time-to-event outcomes account for differing follow-up times and censoring. A fixed-time percentage may be estimated from a time-to-event curve rather than by simply dividing a count by the enrolled group size. The registry record does not identify the estimator or analysis method, so it would be inappropriate to assume which approach was used. Nor does it report whether the 6-month estimate is based on all enrolled participants or a defined analysis population.

What do the sample-size assumptions mean?

The planning illustration is described as using a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation, with the effect to detect expressed as a stated fraction of the observed effect. These are planning assumptions for an illustration, not the design of this single-group trial: the trial record lists no randomized allocation and no two-arm comparison. In general, sample-size calculations depend on the target effect, variability, analysis, and chosen error rates. An illustration based on an observed effect is not evidence that the trial was powered to detect that effect, and it is not observed power. The record does not report the trial's own sample-size justification or design assumptions.

General concepts such as over-dispersion matter when the variability of observed outcomes exceeds what a simple model assumes. That can make standard errors and confidence intervals too small if the model does not account for the extra variability. The registry record does not identify an over-dispersion assessment or any model for the primary outcome, so this is a general consideration rather than a claim about the analysis used in this trial.

What can the posted safety counts establish?

Counts of participants with adverse events describe how many people in the recorded group experienced events under the record's definitions. They are not necessarily counts of total episodes, and one participant may experience more than one type of event. The listed percentages for serious event terms are descriptive; they do not establish treatment causality or allow a comparative risk estimate without a suitable comparator and a clear analysis. The record does not report the safety analysis methods, event attribution, or time-at-risk details beyond the listed group counts.

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("CPX-351 and Glasdegib")
n      <- c(29)
events <- c(9)
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  CPX-351 and Glasdegib  29  9  31.0  15.3  50.8  17.3  49.2  17.3  49.4

11. Multiplicity, Missing Data and Analysis Populations

The registry lists one primary outcome and several secondary outcomes, including adverse events, response, response durability, overall survival, time to normal hematopoiesis, and receipt of an allogenic hematopoietic stem cell transplant. Testing or estimating many outcomes can raise multiplicity concerns: when many statistical tests are considered, the chance of at least one apparently notable result can increase. In general, a statistical plan may identify a primary hypothesis, testing hierarchy, or adjustment strategy to address this issue.

The registry record does not report a multiplicity strategy, a hierarchy among secondary outcomes, or the statistical analysis plan. It also reports no analysis results for the listed outcomes. It is therefore not possible to determine whether any adjustment was planned or applied, or how any secondary findings should be interpreted in relation to the primary outcome.

Missing data can also affect a fixed-time outcome. In general, participants without an observed outcome by the target follow-up may be excluded, censored, or handled using other assumptions. These choices can influence the estimate, especially if missingness is related to health status or outcome. The record does not report the number with missing primary outcome data, the completeness of follow-up, or the method used to handle missing data.

The analysis population is not reported in the registry record. It is therefore unclear whether the primary analysis included all enrolled participants, only those who received treatment, or another defined group. The record also does not describe exclusions, protocol deviations, or sensitivity analyses. These omissions prevent a full assessment of how robust any outcome estimate would be to decisions about eligibility for analysis and missing observations.

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: sepsis (20.0%), febrile neutropenia (10.0%), intracranial hemmorhage (6.7%), respiratory failure (6.7%), allergic reaction - platelet infusion (3.3%).

The registry lists 16 participants with serious adverse events among 30 at risk in the CPX-351 and glasdegib group. It lists 28 participants with other adverse events among 30 at risk and 18 deaths. The listed serious adverse event terms include sepsis (20.0%), febrile neutropenia (10.0%), intracranial hemorrhage (6.7%), respiratory failure (6.7%), allergic reaction - platelet infusion (3.3%), and extended-spectrum beta-lactamases (3.3%).

These figures are descriptive records for the study group, not comparative estimates. Serious adverse event counts and other adverse event counts refer to different categories in the registry and should not be combined. The listed terms may describe overlapping experiences; the record does not state that categories are mutually exclusive. The term percentages should be read as recorded rather than as evidence of treatment causation.

The registry record does not report whether events were judged related to treatment, how long participants were followed for safety, or the timing of events relative to treatment. The death count alone does not identify causes or establish attribution. Without a comparator and additional safety details, the figures describe observed events but cannot quantify an excess risk attributable to the combination.

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

The record describes a phase 2, open-label, single-group study of CPX-351 with glasdegib in previously untreated patients with AML with myelodysplasia-related changes or therapy-related AML. Its primary outcome is the percentage with event-free survival at 6 months. The study therefore addresses outcomes in a specific treated group and a defined follow-up period.

The primary result is not reported in the registry record. There is no posted percentage or 95% confidence interval to assess. Accordingly, the record cannot establish the observed level of event-free survival at the stated time point or the precision of that estimate. The lack of a reported result is different from a result showing no event-free survival; it means the result is unavailable in the record.

Even if the estimate were reported, a single-group design would not provide a randomized comparison with another treatment. It could describe what happened among participants in the study, but it would not alone establish what would have happened to comparable participants under a different regimen. Differences in patient characteristics, disease course, other care, follow-up, and outcome assessment could affect comparisons with external data.

The safety counts and listed serious adverse event terms provide descriptive information about events recorded in the group. They do not establish that treatment caused those events, and without a comparator they do not quantify how event frequency differs from another treatment. The registry record also does not report the primary outcome analysis population, missing-data handling, endpoint event criteria, or statistical analysis plan.

The study's contribution can therefore be described only within these limits: it records a clinical investigation of the combination in the specified population and identifies outcomes of interest, while the registry information available does not include the primary efficacy estimate or enough methodological detail for a complete statistical appraisal. No conclusion about comparative benefit or harm follows from the design and counts alone.

14. Why This Trial Matters Statistically

This trial is statistically notable because it studies a defined combination in a population described as previously untreated patients with AML with myelodysplasia-related changes or therapy-related AML, while using a single-group design. Such a design can document outcomes and safety observations in the treated group, but it does not create a randomized benchmark. Keeping that distinction clear prevents descriptive results from being mistaken for evidence of a treatment contrast.

The fixed-time primary outcome also makes endpoint specification important. The registry gives a 6-month horizon and identifies a 95% confidence interval as the measure of uncertainty, but the event definition and analysis method are not reported. For a time-related outcome, details such as the event criteria, follow-up rules, and treatment of incomplete observations shape what an estimate means. Without the estimate and those definitions, readers cannot evaluate either the result or its precision.

The record's safety counts illustrate a further statistical distinction: frequency within one group is not the same as causal attribution or comparative risk. Counts and percentages can be useful for describing observed events, but interpretation depends on definitions, follow-up, attribution, and an appropriate comparison. Those details are not reported in the registry record.

Finally, the listed outcomes raise questions about analysis planning. The registry record does not describe how multiple outcomes were prioritized, how missing data were handled, or which participants were included in each analysis. These are not minor reporting details: they determine how estimates should be read and how much confidence to place in them. The record thus offers a useful example of why design, endpoint definition, and analysis transparency are all necessary for statistical interpretation.

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.

The main limitation for interpreting efficacy is that the registry record does not report the primary outcome estimate or its 95% confidence interval. The study identifies event-free survival at 6 months as its primary outcome, but the result's magnitude and precision cannot be assessed. The record also does not provide analysis results for the listed outcomes.

The single-group design has no concurrent control and no randomized allocation. Any observed outcomes would describe the treated group rather than estimate a randomized contrast with another treatment. The open-label design may also matter for subjective assessments or reports; the record does not describe masking of outcome assessment or procedures to reduce bias.

The primary endpoint definition is incomplete in the registry record. It describes event-free survival in terms of months in remission but does not specify event criteria, assessment methods, the time origin, or handling of deaths and incomplete follow-up. The analysis population and missing-data methods are also not reported. These gaps make it difficult to determine precisely what a reported percentage would represent, even if one were available.

The safety information is limited to group counts and listed serious event terms. The record does not report event attribution, timing, duration, or comparative data. The counts therefore cannot establish treatment causality or comparative safety. The registry record also does not report the statistical analysis plan, multiplicity procedures, or the trial's own sample-size justification. The planning assumptions described elsewhere are illustrations, not evidence of the study's design or power.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: CPX-351 and Glasdegib for Newly Diagnosed Acute Myelogenous Leukemia With MDS Related Changes or Therapy-related Acute Myeloid Leukemia — NCT04231851.
• Registry record last updated 2026-07-16; status last verified 2025-10.
• Results first posted 2026-03-06.
• 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 record describes a phase 2, open-label, single-group study of CPX-351 and glasdegib in previously untreated patients with AML with myelodysplasia-related changes or therapy-related AML. Enrollment is listed as 30. The study is sponsored by the University of California, Irvine, began on 2020-02-19, has a primary completion date of 2024-06-30, and is listed as active, not recruiting.

The primary outcome is the percentage of participants with event-free survival at 6 months, with a 95% confidence interval specified. The primary result and interval are not reported in the registry record. The record lists secondary outcomes and descriptive adverse event counts, but does not report analysis methods, missing-data handling, or analysis populations. With no randomized comparator, the study describes outcomes in its treatment group rather than a randomized treatment difference.