Safety and Efficacy Study of Pracinostat With Azacitadine in Elderly Patients With Newly Diagnosed Acute Myeloid Leukemia (AML): Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Safety and Efficacy Study of Pracinostat With Azacitadine in Elderly Patients With Newly Diagnosed Acute Myeloid Leukemia (AML) (NCT01912274), a na phase 2 study. The primary outcome is Best Response Rate.

2. Clinical Question

This question concerns response observed during treatment and follow-up, not a comparison of the combination with another treatment. In a single-arm study, the response proportion can describe outcomes among enrolled participants, but it cannot by itself separate treatment effects from other influences, such as the course of AML or differences in who entered the study. The record identifies a planned enrollment of 50 and lists the primary analysis population as the intention-to-treat set. It does not report a numerical response estimate, its precision, or a comparison against a control-group outcome.

3. Trial Design

The registry describes a Phase II, open-label, single-arm, two-stage, multicenter trial sponsored by Helsinn Healthcare SA. It enrolled patients age 65 years or older with newly diagnosed AML and lists an enrollment of 50. The study status is completed. The recorded study start is 2013-12-24, and the primary completion date is 2016-11-08.

All participants were assigned to the combination of pracinostat and azacitidine; no randomized or concurrent control arm is described. The registry lists allocation as not applicable and masking as none. Because treatment and assessment were open-label, participants and study personnel were not masked to the treatment assignment. The record does not report whether response assessments were independently reviewed or blinded.

The regimen description specifies 60 mg of pracinostat by mouth 3 times a week for 3 weeks, followed by 1 week of rest, repeated every 28 days. Azacitidine was specified at 75 mg/m2 for the first 7 days of each 28-day cycle, by subcutaneous injection or intravenous infusion if subcutaneous injections were intolerable. These are the regimen details recorded for the study; the registry record does not report treatment adherence or the amount of treatment participants actually received.

The primary outcome was best response rate, measured as a count of participants meeting one of the specified response categories. The registry also lists secondary outcomes including overall response rate, progression-free survival, overall survival, and duration measures. Their presence in the outcome list does not establish what results were observed. The registry record does not report numerical primary outcome findings or a statistical analysis plan. It also does not explain how the two-stage design was implemented, including any stage-specific decision rules.

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

Analysis population for the primary outcome, as defined in the registry: ITT set

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 Best Response Rate, measured over through study completion up to a maximum of three years.

The primary endpoint, best response rate, is the proportion of participants assessed as achieving complete remission (CR), complete remission with incomplete blood count recovery (CRi), or morphologic leukemia-free state (MLFS), according to the IWG criteria. It is defined over the period through study completion, up to a maximum of three years, and the specified population is the intention-to-treat set.

These categories capture different response states. CR requires morphologic remission and specified blood-count recovery, as well as the other criteria described in the registry. CRi describes morphologic complete remission with residual neutropenia or thrombocytopenia; transfusion independence is not required. MLFS describes a leukemia-free morphologic state meeting the listed marrow and disease criteria, without requiring transfusion independence. Combining these categories means the endpoint counts participants who meet any one of the three definitions, rather than only those meeting the full CR definition.

As a general statistical matter, a response proportion provides a direct summary of how many participants in a defined analysis population met an outcome definition. It is useful for describing activity in a single-arm study, but it does not establish what would have happened to the same participants under a different treatment. The registry record does not report the observed number meeting the endpoint, the resulting proportion, or an uncertainty interval. Accordingly, the endpoint definition is available, while its trial result cannot be assessed from the registry information.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

Statistical interpretation depends on understanding what was measured, which participants were included, and how uncertainty was handled. The registry specifies a binary primary outcome: a participant either met the response definition or did not. It names the intention-to-treat set as the population for that endpoint. The registry record does not report the observed response count or proportion, confidence interval, or method used to estimate uncertainty.

What does a response proportion describe?

As a general statistical explanation, a proportion is a participant-level summary formed from the number meeting a specified outcome relative to the analysis population. Its meaning depends on the outcome definition and denominator. Here, the definition combines CR, CRi, and MLFS under IWG criteria. The record's use of the intention-to-treat set indicates which analysis population was specified, but does not explain how missing or unevaluable response assessments were handled. Without the observed count and denominator used in the analysis, the numerical response result cannot be reconstructed or evaluated.

A confidence interval, as a general concept, expresses uncertainty around an estimate under a statistical model. It helps distinguish an estimate that is precise from one that remains compatible with a broad range of underlying response probabilities. The registry record does not report a confidence interval for best response rate. No precision statement for the primary result can therefore be made from this record.

What does the single-arm design imply?

In general, a single-arm trial can estimate outcomes among participants receiving the study regimen, subject to its outcome definitions and follow-up. It does not provide a randomized estimate of a treatment contrast. Without a concurrent comparison group, differences from external experience can reflect differences in participant characteristics, eligibility, assessment, time period, or other factors, as well as treatment. The trial record identifies a single group and no randomized comparison, so causal comparative claims are not supported by this design alone.

The study is described as two-stage, but the registry record does not report the statistical rules governing the stages. It does not specify any boundary for continuing or stopping, what information was assessed at a stage, or whether an interim analysis occurred. The existence of a two-stage design label should not be taken as evidence of a particular stopping rule or analysis procedure.

How should the planning illustrations be read?

The recorded planning assumptions describe illustrations computed from an observed effect, with a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation; the effect to detect is expressed as a stated fraction of the observed effect. Time-to-event illustrations use a total event count, while other illustrations use participants per arm. These are planning assumptions, not a description of the trial's own design or proof of its statistical power. In particular, equal allocation between two arms does not match this study's single-group design. The record does not report the trial's own sample-size justification, so the illustrations should not be treated as evidence that enrollment was chosen to achieve a specified power for this trial.

As a general matter, sample-size calculations depend on assumptions about the outcome, target effect, variability, significance level, power, and design. Changing an assumed target effect changes the planning result. A calculation based on a fraction of an observed effect is conditional on that reference effect and does not provide evidence that a future study will observe it. Nor is a planning calculation the same as observed power, which is not a substitute for reporting the effect estimate and its uncertainty.

What do the safety counts mean?

Safety fields report participants at risk and participants affected, which are participant counts rather than necessarily counts of separate episodes. A person can experience more than one event, and an event-term percentage does not show the number of episodes or their duration. General statistical interpretation of adverse-event percentages requires knowing the event definitions, observation period, attribution approach, and whether the figures refer to participants or event occurrences. The registry lists serious adverse-event terms with percentages and provides participant counts, but it does not supply all of those additional details in the record.

Finally, statistical significance and clinical importance are different concepts in general. A small p-value, if available, would not by itself show the size or practical importance of an effect; an estimate and its uncertainty are needed for that assessment. No primary p-value or adjusted analysis is reported in the registry record. The most defensible reading is therefore descriptive: the record defines the planned endpoint and study structure, but does not provide enough primary outcome information to quantify the observed response or its precision.

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("Pracinostat With Azacitadine")
n      <- c(50)
events <- c(26)
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  Pracinostat With Azacitadine  50  26  52.0  37.4  66.3  38.5  65.2  38.5  65.2

11. Multiplicity, Missing Data and Analysis Populations

The registry lists several secondary outcomes, including overall response rate, complete cytogenetic response plus molecular complete remission, progression-free survival, overall survival, and duration measures. When a study examines multiple outcomes, general statistical practice distinguishes a prespecified primary question from secondary or exploratory questions. Testing many outcomes can increase the chance of finding an apparently notable result by chance if no multiplicity strategy is used. The registry record does not report a multiplicity adjustment, a hierarchy for testing outcomes, or a statistical analysis plan. It is therefore not possible to determine whether or how the secondary outcomes were intended to support confirmatory claims.

The record identifies the intention-to-treat set for the primary endpoint, but does not describe missing-data procedures, response-evaluation rules for participants without an assessment, or the handling of withdrawals. These omissions matter because a response proportion can depend on how unevaluable participants are treated. The registry record does not report missingness amounts or reasons, so their impact cannot be assessed.

The listed two-stage design raises a further analysis question: stage-specific decisions can affect how outcomes are interpreted, particularly if results are examined before the study is complete. The registry record does not report stage boundaries, interim analyses, or any associated statistical adjustment. This absence does not establish that no such procedures existed; it means they are not reported in the registry record. Likewise, the record does not provide an analysis plan that could clarify which outcomes and populations were prespecified for each analysis.

12. Safety Results

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

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: febrile neutropenia (32.0%), cellulitis (8.0%), atrial fibrillation (8.0%), pneumonia (6.0%), sepsis (6.0%).

The registry lists one treatment group for safety reporting. Its serious adverse-event fields show 50 participants at risk and 50 affected. The other adverse-event fields show 50 participants at risk and 47 affected. These are participant counts in the registry record, not a count of every event episode. They should not be added together: the record does not establish that the categories are mutually exclusive, and participants may contribute to more than one event term.

The listed serious adverse-event terms include febrile neutropenia at 32.0%, cellulitis at 8.0%, atrial fibrillation at 8.0%, pneumonia at 6.0%, sepsis at 6.0%, and diverticulitis at 4.0%. These percentages identify recorded terms and their reported frequency. They do not indicate how long events lasted, how severe each event was, whether an event was judged related to treatment, or whether participants experienced more than one event. The registry record does not report those details in the information.

Safety data from a single treatment group can describe reported events during the study, but do not provide a randomized comparison of risk against another treatment. The listed serious-event terms should not be interpreted as a complete account of all possible harms or as a comparative safety estimate. The registry record does not report deaths in the safety fields.

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

The record establishes that a completed Phase II study evaluated pracinostat with azacitidine in patients age 65 years or older with newly diagnosed AML. It describes a single-group, open-label design, gives the treatment regimen, and defines best response using CR, CRi, or MLFS according to IWG criteria. It also provides participant counts and selected serious adverse-event terms. These details help explain what the study set out to assess and how some safety information was recorded.

The record does not report the primary response count or proportion. It therefore cannot show the observed best response rate, nor how precise that estimate was. It also does not report a numerical comparison with another treatment, and the study had no concurrent control group. The record consequently cannot establish that the combination caused a particular response rate or was better or worse than an alternative.

As a general statistical distinction, an outcome observed during treatment is not automatically an effect attributable to treatment. A controlled comparison is designed to estimate a treatment contrast, while a single-arm result describes what occurred in the enrolled group. Other factors, including participant selection, outcome assessment, and the natural course of disease, can influence observed outcomes. The registry information does not allow those influences to be separated.

The safety figures likewise describe reported events in the study group, not comparative risks. The percentages for serious adverse-event terms do not tell how many episodes occurred or whether the events were attributed to treatment. Nor do they provide a complete basis for weighing benefits and harms. A balanced interpretation would require the missing response results, additional safety detail, and information about analysis procedures and missing assessments. Those items are not reported in the registry record.

Thus, the study record is informative about design, eligibility framing, regimen, and endpoint definitions, but its posted information is insufficient to assess the magnitude or precision of the primary response outcome. No treatment recommendation follows from these data alone.

14. Why This Trial Matters Statistically

This trial illustrates why a registry entry needs to be read at two levels: the study question and the information actually reported. The study asks about response and safety for a defined combination in older patients with newly diagnosed AML. Its endpoint definition is specific enough to distinguish CR, CRi, and MLFS, and the record identifies the intended primary analysis population. These details give statistical readers a basis for understanding what would count as a response.

At the same time, the primary result is not reported in the registry record. That gap is consequential: design and endpoint information cannot substitute for the observed response count, estimate, or uncertainty. A transparent report of the outcome and its analysis is needed to assess what was observed rather than only what was planned.

The single-arm, open-label structure also provides a useful example of the boundary between describing outcomes and estimating comparative effects. An outcome proportion can characterize participants in the study, but a concurrent randomized comparator would be needed for a direct randomized treatment contrast. In the absence of that comparison, interpretation must remain descriptive.

The safety record offers another statistical lesson: participant counts and term-specific percentages answer different questions from total event counts, event severity, attribution, or comparative risk. Understanding what each number represents is essential before drawing conclusions from safety summaries. Finally, a two-stage label and planning illustrations do not reveal the full statistical plan. Stage rules, missing-data handling, multiplicity decisions, and the reasoning behind planned enrollment are not reported in the registry record. The trial therefore matters as an example of how design labels and endpoint definitions inform interpretation, while incomplete outcome and analysis reporting limits it.

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 trial-specific limitation for interpreting efficacy is that the registry record does not report the primary best response result. It gives the outcome definition and names the intention-to-treat set, but does not provide the observed count, proportion, or uncertainty interval. The primary endpoint therefore cannot be quantified from the registry information.

The design is single-arm and open-label, with no concurrent control group. This prevents a direct randomized comparison and makes it difficult to separate outcomes associated with the treatment regimen from other influences. The record does not state whether response assessments were independently reviewed or blinded, so the assessment process cannot be evaluated from the information reported.

Although the study is described as two-stage, the registry record does not report stage-specific decision rules or whether interim analyses were conducted. It also does not report the sample-size justification or a statistical analysis plan. Missing-data rules, the handling of participants without an evaluable response assessment, and details of the secondary-outcome analyses are not reported in the registry record.

The safety information is limited to participant counts and selected serious adverse-event terms. The record does not provide the additional detail needed to assess event duration, attribution, episode counts, or comparative risks. It also does not report deaths in the safety fields. These reporting gaps should be distinguished from evidence that an event did or did not occur: an item not reported in the registry record cannot be treated as a confirmed absence.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Safety and Efficacy Study of Pracinostat With Azacitadine in Elderly Patients With Newly Diagnosed Acute Myeloid Leukemia (AML) — NCT01912274.
• Registry record last updated 2021-02-09; status last verified 2021-01.
• Results first posted 2021-02-09.
• 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

NCT01912274 is a completed Phase II, open-label, single-arm, two-stage, multicenter study of pracinostat with azacitidine in patients age 65 years or older with newly diagnosed AML. The registry lists an enrollment of 50, a start date of 2013-12-24, and a primary completion date of 2016-11-08. No concurrent comparator is described.

The primary outcome is best response rate, defined by achievement of CR, CRi, or MLFS according to IWG criteria, in the intention-to-treat set. The endpoint timeframe is through study completion, up to a maximum of three years. The registry record does not report the observed primary response result, its precision, or the statistical analysis plan.

Safety reporting lists serious adverse-event terms, including febrile neutropenia at 32.0%, and participant counts for the treatment group. The record also lists secondary outcomes, but the information does not include their numerical results. Overall, the registry documents the study structure and endpoint definitions more fully than its outcome and analysis details.