CPX-351 in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia or Myelodysplastic Syndrome: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for CPX-351 in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia or Myelodysplastic Syndrome (NCT02019069), a na phase 2 study. The primary outcome is Response Rate (RR).

2. Clinical Question

3. Trial Design

This was a phase II, single-group study of CPX-351 for AML or higher-risk MDS relapsed or refractory to prior therapy with a hypomethylating agent. The registry lists an enrollment of 11 and identifies CPX-351 as the intervention. The study is marked completed. Its recorded start date is 2014-02-03, and its primary completion date is 2017-12-04. These registry dates describe the study record; they do not supply details about recruitment timing or follow-up for individual participants.

The design has no listed control arm, and allocation is recorded as not applicable. Masking is recorded as none. There is therefore no randomized, masked, or concurrent comparison described in the registry record. The primary endpoint is a participant count for response at Day 42. Secondary outcomes listed include CRi, CR, duration of remission, overall survival, early induction mortality, mortality at Day 60 after first induction, participants experiencing serious adverse events, and serious adverse events. The registry also lists serious adverse-event terms.

The intervention description specifies intravenous induction schedules for a first and second induction. Although it includes a consolidation heading, no consolidation schedule is recorded in that description. The registry record does not report the protocol’s treatment decision rules, eligibility criteria in detail, follow-up procedures, or whether every enrolled participant received each planned treatment phase. It also does not report a statistical analysis plan, sample-size justification, interim analyses, or analysis populations. These omissions limit what can be reconstructed about how the study was conducted and how its outcomes were intended to be analyzed.

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 Response Rate (RR), measured over Day 42.

The primary endpoint is response rate at Day 42, expressed in the registry as a count of participants. It combines complete response (CR) and complete response with incomplete count recovery (CRi). CR requires less than 5% blasts, no blasts with Auer rods, no persistence of extramedullary disease, recovery of blood counts to platelets ≥ 100,000/uL and ANC > 1000/uL, and transfusion independence. CRi uses the CR parameters except that platelets are < 100,000/uL and/or ANC is ≤ 1000/uL.

Combining CR and CRi allows the endpoint to count participants who meet the response criteria despite incomplete platelet or neutrophil recovery. This is a definition of the outcome, not evidence that a response occurred. The registry record does not report the number meeting either definition, so the observed primary endpoint cannot be assessed from the record.

General statistical context: a response endpoint reduces each participant’s outcome to whether the defined response criteria were met by the assessment time. A count communicates how many participants were classified as responders, while a proportion relates that count to the analyzed group. Neither measure conveys precision by itself; an uncertainty interval would help show how much the observed estimate could vary across comparable groups. The registry record reports the endpoint as a count without dispersion and does not provide an uncertainty interval or the analyzed denominator for this endpoint.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

General statistical context: a clinical endpoint needs a clear definition, an assessment time, and a rule for deciding which participants meet it. Here, the primary endpoint is the count meeting either CR or CRi at Day 42. This is a binary classification at the participant level: each participant either meets the combined response definition or does not. The registry describes the definitions but does not report the endpoint count or an uncertainty estimate. Without those results, no observed response proportion or precision can be interpreted.

What does a count show?

A count is the number of participants classified as having an outcome. To understand a count as a rate or proportion, a reader also needs the relevant analysis denominator and a clear account of missing assessments or exclusions. The registry records enrollment of 11, but does not report the denominator used for the primary endpoint, whether all enrolled participants were assessed at Day 42, or how missing response assessments were handled. Enrollment alone should not be assumed to equal the endpoint analysis denominator.

General statistical context: an uncertainty interval around a response proportion describes the range of values compatible with the observed data under a specified method. With limited data, such intervals are often wide, reflecting uncertainty rather than a defect in calculation. No interval is reported for the primary response endpoint. The registry record also does not identify an interval method, model, or inferential procedure for that endpoint.

Why does the study design matter?

This is a single-group study, without a listed comparator. A result from one treatment group is a description of outcomes in that group. It does not directly estimate how outcomes would differ under another treatment, because there is no concurrent comparison group in the registry record. General statistical context: random allocation can help balance measured and unmeasured factors between groups, while masking can reduce some assessment or reporting influences. Neither a randomized allocation nor masking is recorded for this study. The record does not report alternative methods intended to address these limitations.

Allocation is marked not applicable, masking is recorded as none, and the model is single-group. These design descriptions should not be mistaken for evidence that a comparative analysis was conducted. The registry reports zero analyses. It does not report an adjusted analysis, a prespecified statistical model, handling of covariates, or an analysis plan. No treatment-effect estimate or comparative p-value can be interpreted from the registry information.

What do planning calculations mean?

General statistical context: a sample-size planning calculation estimates how many participants or events might be needed under specified assumptions, such as a target effect, allocation pattern, significance level, and statistical approximation. Such a calculation is prospective planning, not a result observed in participants. The registry’s stated assumptions describe illustrations based on a fraction of an observed effect, a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. For time-to-event outcomes, the stated illustration uses a total number of events; other illustrations are expressed as participants per arm.

Those assumptions describe two-arm planning illustrations, whereas this study is listed as single-group and has no comparator. They cannot be read as the study’s own design justification or as observed power. The registry record does not report a study-specific sample-size justification, the effect assumed for the trial’s design, or an observed power calculation. No planning illustration can replace the missing primary outcome result or provide evidence of comparative efficacy.

How should safety summaries be read?

General statistical context: a participant count for an adverse event indicates how many people experienced at least one event under the record’s reporting definition. It is not necessarily the count of all event episodes. Multiple event terms may occur in the same participant, so percentages for different terms should not automatically be added. The registry does not report whether the listed terms overlap, their event-level counts, or their timing. Serious adverse events and other adverse events are distinct summary categories in the record, and the same person could potentially contribute to more than one category; the registry does not explain participant overlap.

Safety counts are descriptive and do not establish causation. Interpretation of risks would require details about event definitions, exposure, timing, attribution, follow-up, and an appropriate comparison. Those details are not reported in the registry record. The serious-event percentages should therefore be read as registry summaries of reported terms, not as a comparative safety analysis.

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("Liposomal Cytarabine-daunorubicin CPX-351")
n      <- c(11)
events <- c(3)
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  Liposomal Cytarabine-daunorubicin CPX-351  11  3  27.3  6.0  61.0  9.7  56.6  9.9  57.2

11. Multiplicity, Missing Data and Analysis Populations

The registry lists secondary outcomes covering CRi, CR, duration of remission, overall survival, early induction mortality, mortality at Day 60 after first induction, participants experiencing serious adverse events, and serious adverse events. The record identifies 9 secondary outcomes and 0 analyses. It does not report inferential results for these outcomes in the information available, nor does it describe a hierarchy of hypotheses or a multiplicity adjustment.

General statistical context: when researchers test many outcomes, the chance of finding at least one apparently notable result by chance can increase. Prespecified priorities, adjustment procedures, or emphasis on estimation rather than repeated testing can help readers understand multiple results. Whether such procedures were planned for this study is not reported in the registry record. In the absence of an analysis plan and reported analyses, no conclusion about multiplicity control can be drawn.

Missing-data procedures and analysis populations are also not reported in the registry record. The record does not say whether the primary analysis included all enrolled participants, only participants who received treatment, or only those with an evaluable Day 42 assessment. It does not describe how missing response assessments, withdrawals, or incomplete follow-up were handled. Enrollment of 11 should not be treated automatically as the endpoint denominator.

For outcomes such as duration of remission and overall survival, interpretation depends on follow-up, censoring rules, and the population included in the analysis. Those methods and corresponding results are not reported in the registry record. The registry lists early induction mortality at Day 30 and mortality at Day 60 after first induction as outcomes, but does not supply their outcome results in this record. These reporting gaps prevent assessment of the secondary endpoints and of how missing observations or multiple outcomes may have influenced conclusions.

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 0% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: febrile neutropenia (36.4%), pneumonia (18.2%), adult repiratory distress syndrome (ards) (9.1%), cardio-pulmonary arrest (9.1%), respiratory failure (9.1%).

The registry records 5 participants experiencing serious adverse events among 11 at risk, and 11 participants experiencing other adverse events among 11 at risk. It also records 10 deaths for the CPX-351 group. These counts describe the entries in the registry; they do not establish that treatment caused an event or death. The record does not provide details about event attribution, timing, duration, severity grading beyond the serious-event category, or the relationship of deaths to treatment.

Listed serious adverse-event terms include febrile neutropenia (36.4%), pneumonia (18.2%), adult respiratory distress syndrome (ARDS) (9.1%), cardio-pulmonary arrest (9.1%), respiratory failure (9.1%), and chills (9.1%). The registry does not state whether participants could contribute to multiple terms or explain the precise calculation behind each percentage. The percentages should not be added together or interpreted as mutually exclusive participant groups.

General statistical context: safety summaries can count participants with an event, event episodes, or event terms, and these measures are not interchangeable. A comparison of safety between treatments would require comparable groups and consistent follow-up. No comparator is listed in this study. The available safety information is therefore descriptive and does not estimate comparative risk.

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

The registry record describes a phase II, single-group study of CPX-351 in patients with relapsed or refractory AML or MDS following prior hypomethylating-agent therapy. It specifies a Day 42 primary response endpoint that combines CR and CRi, provides the clinical criteria for those classifications, and lists safety outcomes. It also records enrollment of 11 and gives descriptive adverse-event information.

The record does not report the primary response count, a response proportion, or an uncertainty interval. Consequently, it does not show how many participants met the endpoint or how precisely a response rate can be estimated. This absence should not be interpreted as a zero response or as evidence that the intervention did or did not produce responses. The primary result is not reported in the registry record.

The design has no listed comparator and no masking. Outcomes among participants in a single treatment group cannot, by themselves, establish how outcomes compare with another treatment or what would have happened to similar participants under a different condition. The record also does not provide a reported analysis plan, outcome-specific denominators, missing-data methods, or analysis populations, which further limits interpretation.

The serious adverse-event and other adverse-event counts and listed terms are useful as descriptive safety information. They do not establish causation, and they do not provide a comparative safety estimate. The recorded deaths likewise should not be interpreted as treatment-caused without attribution and relevant context, neither of which is reported in the registry record.

Overall, the registry offers study design and endpoint definitions alongside limited descriptive safety counts, but not the primary response result or inferential analyses needed to evaluate response precision or compare treatment outcomes. It supports a description of what was planned and what safety counts were recorded, not a conclusion about comparative benefit or harm.

14. Why This Trial Matters Statistically

This trial illustrates why endpoint definitions and outcome reporting must be considered together. The registry gives detailed criteria for CR and CRi and states that the primary response endpoint combines them at Day 42. Those definitions allow readers to understand what would count as a response. However, without the observed count, denominator, and uncertainty estimate, the endpoint cannot answer how often response was observed or how precise that estimate might be.

The single-group design also matters statistically. A treatment-group outcome can be described, but a control group is needed for a direct comparison within a trial. Because no comparator is listed, the registry cannot provide a randomized estimate of a difference between CPX-351 and another condition. The absence of masking and the absence of a reported analysis plan further limit what can be inferred about outcome assessment and analysis choices.

Safety reporting demonstrates a related distinction: participant counts and event-term percentages are descriptive summaries, not causal or comparative estimates. Without event attribution, timing, overlap information, and a comparator, these summaries cannot determine how much of the observed safety experience is attributable to treatment or how it compares with another option.

For biostatisticians and clinical researchers, the record is a useful example of the limits of interpreting registry entries when key outcome results are missing. A defined endpoint is not the same as a reported result; enrollment is not necessarily the analysis denominator; and a planning assumption is not observed power. These distinctions help prevent over-reading incomplete descriptive data.

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 trial-specific limitations arise from the information recorded. The study is listed as single-group, with allocation not applicable and no masking. No comparator is listed, so the record cannot support a randomized between-group estimate. The registry reports enrollment of 11, but does not describe participant characteristics, detailed eligibility criteria, or the primary endpoint denominator. The extent to which enrolled participants represent the intended population is therefore not reported in the registry record.

The most important reporting limitation is that the primary response result is absent. Although the Day 42 endpoint and CR/CRi criteria are described, the record does not give the number meeting the combined endpoint, an analyzed denominator, a response proportion, or an uncertainty interval. The record also reports zero analyses. Consequently, the efficacy outcome and its statistical precision cannot be assessed from the registry entry.

For safety, the record gives participant counts, a death count, and selected serious adverse-event terms, but does not report attribution, timing, event-level details, or whether terms overlap. Follow-up duration and handling of incomplete observation are not reported. The record also does not provide the treatment exposure received by individual participants. The intervention description leaves the consolidation schedule blank, and does not indicate whether all participants received the induction schedules as written.

Finally, the statistical plan, sample-size justification, interim analyses, multiplicity approach, analysis populations, and missing-data methods are not reported in the registry record. These omissions mean that neither design rationale nor analytic choices can be independently assessed from this information.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: CPX-351 in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia or Myelodysplastic Syndrome — NCT02019069.
• Registry record last updated 2019-01-22; status last verified 2019-01.
• Results first posted 2019-01-15.
• 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 NCT02019069 as a completed phase II study of CPX-351 in patients with relapsed or refractory AML or MDS after prior hypomethylating-agent therapy. It is a single-group study with no listed comparator and no masking. Enrollment was 11. The primary endpoint is the count of participants meeting CR or CRi criteria at Day 42.

The registry record does not report the primary response result or statistical analyses. It lists secondary outcomes and gives descriptive safety counts and serious adverse-event terms. No study-specific statistical plan, analysis populations, missing-data methods, or multiplicity procedures are reported. The record therefore describes the study design and endpoint definitions but does not provide the primary outcome evidence needed to assess response or its precision.