Comparing the Addition of an Anti-Cancer Drug, Pomalidomide, to the Usual Chemotherapy Treatment (Daunorubicin and Cytarabine Liposome) in Newly Diagnosed Acute Myeloid Leukemia With Myelodysplastic Syndrome-Related Changes: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Comparing the Addition of an Anti-Cancer Drug, Pomalidomide, to the Usual Chemotherapy Treatment (Daunorubicin and Cytarabine Liposome) in Newly Diagnosed Acute Myeloid Leukemia With Myelodysplastic Syndrome-Related Changes (NCT04802161), a randomized phase 2 study. The primary outcome is Rate of Complete Response (CR)/Complete Response With Incomplete Hematologic Recovery (CRi).

2. Clinical Question

3. Trial Design

This is a randomized phase II study with a parallel-group design and no masking. Its listed enrollment is 49, and its status is active, not recruiting. The listed start date is 2022-08-24, and the listed primary completion date is 2024-11-21. These registry fields describe the study record; they do not by themselves establish that all follow-up or analyses are complete.

The principal treatment contrast is daunorubicin and cytarabine liposome plus pomalidomide versus daunorubicin and cytarabine liposome alone. The registry also includes safety run-in groups identified by pomalidomide duration. Those groups are separate from the two treatment arms used for the posted primary outcome counts. The primary outcome description specifically states that the outcome was not reported for the safety run-in phase.

Randomization is intended to support a comparison between assigned groups by reducing systematic differences in baseline characteristics. That general benefit depends on how allocation was implemented and how participants were analyzed; those details are not reported in the registry record. The study is unmasked, so participants and study personnel were not blinded according to the registry field. The consequences of unmasked treatment for outcome assessment depend on how the endpoint was determined, and that assessment process is not reported in the registry record.

The record lists the National Cancer Institute as sponsor. It also lists biospecimen collection and bone marrow aspiration and biopsy, in addition to the study drugs. The registry record does not report the allocation procedure, the detailed follow-up schedule, or a statistical analysis plan. The enrollment field and the arm-specific outcome denominators represent different registry summaries and should not be treated as interchangeable.

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: One participant who was consented to the study declined to participate before being randomized to an arm.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: This outcome measure was not reported on for the safety run-in phase

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 Rate of Complete Response (CR)/Complete Response With Incomplete Hematologic Recovery (CRi), measured over Up to 2 years.

The primary endpoint is the rate of complete response (CR) or complete response with incomplete hematologic recovery (CRi), recorded as a count of participants over up to 2 years. CR and CRi are response categories that distinguish a complete response from one in which hematologic recovery remains incomplete. The registry record does not provide a fuller definition of CRi or the assessment rules used to assign either category.

A response endpoint is used to describe whether participants meet a prespecified disease-response category during the stated observation period. Reporting it as a count makes clear how many participants in each posted group met the combined CR/CRi outcome. The posted counts are 9 in the pomalidomide group and 13 in the chemotherapy-alone group. The corresponding group sizes are 16 and 18.

Combining CR and CRi means the primary outcome does not, on its own, separate complete responses with full hematologic recovery from those with incomplete recovery. A secondary outcome is CR with full hematologic recovery, with absolute neutrophil count > 1 x 10^9/L and platelets > 100 x 10^9/L. Another listed secondary outcome is CR without minimal residual disease. These outcomes address different response details and should not be substituted for the primary CR/CRi endpoint.

The record does not report how missing response assessments were handled, when response was assessed within the stated timeframe, or the analysis population for the primary endpoint. Those details are needed to interpret the response counts fully.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The posted primary outcome is binary at the participant level: each participant either meets the combined CR/CRi outcome or does not, according to the study's response criteria. The arm summaries are counts of participants meeting that outcome. This is distinct from a continuous measurement, such as a laboratory value, where a mean and a measure of spread might summarize the data. The registry records the primary endpoint as a participant count, not as a mean.

What do the arm counts tell us?

The count of 9 in the pomalidomide arm and 13 in the chemotherapy-alone arm gives a direct description of the posted results. The corresponding arm sizes are 16 and 18. Counts are useful for checking the scale of the observed data, but counts from groups of different sizes are not, by themselves, a fair comparison of response frequency. A rate or proportion would account for the number of participants contributing to each arm. The registry record does not post a calculated comparative effect estimate for this endpoint, and no additional rate should be inferred from the counts in this explanation.

For a binary endpoint, a statistical comparison could describe the difference in response probabilities, a ratio of those probabilities, or another prespecified measure of association. Each measure answers a somewhat different question. A confidence interval would describe the range of effect sizes compatible with the observed data under the chosen model and assumptions. General explanation: a wider interval indicates less precision, while an interval that includes no difference is compatible with no difference as well as with effects in either direction, depending on its limits. No confidence interval or other inferential estimate is reported for the primary comparison.

Why does randomization matter?

General explanation: random assignment aims to make treatment groups comparable, on average, with respect to both measured and unmeasured characteristics. It supports a causal interpretation when assignment is maintained, outcomes are measured consistently, and participants are analyzed in a way aligned with the randomization. The registry identifies the trial as randomized, but does not report the sequence-generation method, concealment of allocation, or analysis population. The absence of those details limits assessment of how the randomization was implemented and used.

The study is described as parallel and unmasked. In a parallel design, groups are assigned to different treatment strategies and followed as separate groups. With no masking, awareness of assigned treatment may affect co-interventions, reporting, or outcome assessment in some settings. General explanation: objective, consistently applied response criteria can reduce some assessment concerns, but the registry record does not describe the response review process or whether assessments were independently reviewed.

What does the sample-size illustration represent?

The sample-size calculations are planning illustrations based on the observed effect, not the trial's original design justification and not observed power. The stated assumptions are a two-sided significance level of 0.05, equal allocation between the arms, and a normal approximation. The illustration considers detecting a stated fraction of the observed effect. For time-to-event outcomes, the planning quantity is the total number of events; for other outcomes, it is participants per arm. These assumptions describe a hypothetical future design calculation. They do not add evidence about the treatment comparison in this trial. The record does not report a protocol-based sample-size justification, and no sample-size planning values are described in the posted results discussed for the primary endpoint.

Why is there no recalculated comparison?

The registry record does not report an inferential two-arm comparison for the binary primary endpoint. The posted information identifies the arm-specific response counts and sizes, but no comparative estimate, uncertainty interval, or test result accompanies them. The record also indicates that a recalculated two-arm comparison is unavailable or not estimable for this binary outcome. Accordingly, interpretation should remain with the arm-level counts rather than imply a recalculated treatment effect. There is no reported discrepancy between a sponsor analysis and a recalculated result; no sponsor inferential result is reported for this comparison.

What statistical details remain unknown?

The analysis plan, choice of effect measure, handling of missing outcomes, and any adjustment for baseline factors are not reported in the registry record. Nor are methods for accounting for outcomes assessed at different times, censoring, or competing events described for the secondary time-to-event outcomes. General explanation: these choices matter because they determine which participants and observations contribute to an estimate and how uncertainty is quantified. Without those details and posted estimates, readers cannot assess model fit, precision, or robustness for the primary comparison.

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("Arm A (Daunorubicin and Cytarabine Liposome, Pomal", "Arm B (Daunorubicin and Cytarabine Liposome)")
n      <- c(16, 18)
events <- c(9, 13)
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  Arm A (Daunorubicin and Cytarabine Liposome, Pomal  16  9  56.2  29.9  80.2  33.2  76.9  32.9  77.0
ARM  Arm B (Daunorubicin and Cytarabine Liposome)  18  13  72.2  46.5  90.3  49.1  87.5  48.8  87.4

11. Multiplicity, Missing Data and Analysis Populations

The registry lists 8 secondary outcomes in addition to the primary CR/CRi outcome. These include CR with full hematologic recovery, adverse-event incidence, CR without minimal residual disease, event-free survival, disease-free survival, overall survival, and the rate of allogeneic stem cell transplantation. The record does not report a multiplicity strategy, such as whether the secondary outcomes were treated as exploratory or whether statistical testing was adjusted to account for multiple comparisons. General explanation: when many outcomes are tested, the chance of at least one apparently notable result can increase, so a prespecified approach to multiplicity helps readers interpret a collection of tests.

The record reports no analyses for the posted secondary outcomes in the analysis summary, and it does not describe any statistical analysis for the primary outcome. Missing-data rules are not reported in the registry record. In particular, the record does not say how participants without an evaluable response assessment, participants who withdrew, or participants with incomplete follow-up were handled. The analysis population is also not reported: it is unclear whether the primary results include all randomized participants, only participants who received assigned treatment, or another defined group.

These omissions matter because response counts depend on who was included and how unavailable outcome information was treated. For time-to-event outcomes, the handling of censoring and event definitions is important, but those analysis details are not reported either. The registry's outcome description says the primary outcome was not reported for the safety run-in phase; the record does not explain how the run-in participants relate to the analysis population for the randomized treatment comparison.

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: anemia (100.0%), febrile neutropenia (100.0%), neutrophil count decreased (100.0%), platelet count decreased (100.0%), white blood cell decreased (100.0%).

The registry lists serious adverse events, other adverse events, and deaths separately for the safety run-in groups and the two treatment arms. For the pomalidomide-plus-chemotherapy arm, 19 of 20 participants at risk were recorded as having a serious adverse event, and 20 of 20 were recorded as having other adverse events; 11 deaths are listed. For the chemotherapy-alone arm, 19 of 19 participants at risk were recorded as having a serious adverse event, and 18 of 19 were recorded as having other adverse events; 7 deaths are listed.

The safety run-in group identified as DL1 (14 Days Pomalidomide) has 7 participants at risk and 7 affected by serious and other adverse events, with 3 deaths listed. The DL-1 (10 Days Pomalidomide) group has 3 participants at risk and 3 affected by serious and other adverse events, with 2 deaths listed. These groups should be distinguished from the randomized treatment arms.

The listed serious adverse-event terms include anemia, febrile neutropenia, decreased neutrophil count, decreased platelet count, decreased white blood cell count, and hypokalemia. The record lists 100.0% for each of the first five terms and 66.7% for hypokalemia. The denominator and calculation basis for these term percentages are not reported in the registry record. The event counts do not establish that treatment caused an event, and the record does not provide a comparative safety analysis or event-collection timeframe.

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

The posted results establish that the registry records CR/CRi responses in both randomized treatment arms: 9 participants in the arm receiving pomalidomide with daunorubicin and cytarabine liposome, and 13 participants in the arm receiving chemotherapy alone. The corresponding group sizes are 16 and 18. These are descriptive counts for the primary outcome, which is defined over up to 2 years.

They do not establish which regimen has a higher response rate or whether any apparent difference is attributable to treatment. No comparative effect estimate, confidence interval, or test result is reported. Without an uncertainty estimate, readers cannot judge the precision of a treatment contrast. The posted results also do not explain which participants contributed to the response counts or how missing assessments were handled.

The trial's randomized design is relevant because it is intended to support comparison of assigned groups. However, the registry does not report enough analysis detail to determine how randomization was reflected in the primary analysis. The study is unmasked, and the registry does not describe how response was assessed. These features are reasons to interpret the counts in context rather than as a definitive causal estimate.

The result is also not a complete summary of the study's clinical outcomes. The registry lists secondary measures addressing hematologic recovery, minimal residual disease, adverse events, survival, and transplantation, but does not provide analyses for them in the posted results. Safety counts are reported for both run-in and randomized groups, but their timing and comparative interpretation are not specified.

The trial record therefore supports a limited conclusion: arm-specific response counts were posted, while the precision and statistical significance of a between-group effect remain unreported in the registry record. The results do not, by themselves, establish benefit, lack of benefit, or comparative safety.

14. Why This Trial Matters Statistically

This trial raises a central design and interpretation question in clinical biostatistics: how should a randomized phase II study's response counts be understood when the record does not provide an inferential comparison? The registry identifies a treatment contrast and posts arm-specific primary endpoint counts, but does not report the effect estimate or its uncertainty. That distinction matters because a descriptive result and a statistical comparison are not interchangeable.

The endpoint also combines CR with CRi. Combining response categories can provide a broader measure of response, while secondary outcomes such as CR with full hematologic recovery and CR without minimal residual disease address more specific features. Interpreting the primary outcome therefore requires attention to its definition and to the related outcomes, not just the numerical count. The registry does not provide the full response-assessment rules.

The randomized, parallel design is a useful framework for comparing treatment strategies, while the unmasked status and missing analysis details leave important questions about conduct and analysis. The record does not report the analysis population, missing-data approach, or multiplicity plan for the secondary outcomes. These are not merely reporting formalities: they affect what the estimates mean, which participants they represent, and how confidently results from multiple endpoints can be interpreted.

Finally, the safety information illustrates why event counts need context. Serious and other adverse events are listed in both run-in and randomized groups, but the record does not report a comparative safety analysis or event-collection period. A careful statistical reading separates the randomized efficacy comparison from safety summaries and avoids treating counts from different study groups as if they answered the same question.

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 registry record leaves several limitations specific to interpretation of this study. Although it describes the study as randomized, it does not report the allocation method or concealment procedures. The trial is unmasked, and the record does not describe how response outcomes were assessed or whether assessment was independently reviewed. Those gaps limit evaluation of potential bias in assigning treatment and classifying response.

The primary endpoint is reported as arm-specific counts, but no comparative effect estimate, confidence interval, or inferential test is reported. The analysis population, handling of missing response assessments, and treatment of participants who discontinue are not reported in the registry record. These omissions make it difficult to determine how representative the counts are of all randomized participants.

The primary outcome timeframe is up to 2 years, but the record does not provide the response assessment schedule or follow-up completeness. It also does not provide analysis details for the listed survival outcomes, including event definitions, censoring rules, or the time origin used. The secondary outcomes are numerous, and a multiplicity plan is not reported.

The record lists an enrollment of 49, while the posted primary outcome groups have sizes of 16 and 18 and the safety summaries include separate run-in groups. The registry does not explain how those summaries relate to one another or how participants flowed through the study. The primary outcome description explicitly excludes reporting for the safety run-in phase, but further analysis-population details are not reported.

Finally, the posted safety information does not include event timing or a comparative analysis. The basis for the percentages attached to serious adverse-event terms is also not reported in the registry record. These limitations restrict conclusions about both the precision of the response comparison and the comparative safety profile.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Comparing the Addition of an Anti-Cancer Drug, Pomalidomide, to the Usual Chemotherapy Treatment (Daunorubicin and Cytarabine Liposome) in Newly Diagnosed Acute Myeloid Leukemia With Myelodysplastic Syndrome-Related Changes — NCT04802161.
• Registry record last updated 2026-06-30; status last verified 2026-05.
• Results first posted 2025-12-19.
• 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 a randomized, parallel, unmasked phase II study of daunorubicin and cytarabine liposome with or without pomalidomide in newly diagnosed AML with MDS-related changes. Listed enrollment is 49; the status is active, not recruiting. The listed primary completion date is 2024-11-21.

The primary endpoint is the count of participants with CR/CRi over up to 2 years. The posted randomized-arm counts are 9 of 16 with pomalidomide and 13 of 18 with chemotherapy alone. No inferential comparison or uncertainty interval is reported. The record also lists 8 secondary outcomes and safety-event summaries, including separate safety run-in groups. Statistical analysis details, missing-data methods, analysis populations, and a multiplicity approach are not reported in the registry record.