Phase II Study of Azacitidine and Sargramostim as Maintenance Treatment for Poor-Risk AML or MDS: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Phase II Study of Azacitidine and Sargramostim as Maintenance Treatment for Poor-Risk AML or MDS (NCT01700673), a non-randomized phase 2 study. The primary outcome is Two-year Relapse Free Survival of Patients.

2. Clinical Question

In statistical terms, the study asks how relapse-free survival is described in a group receiving maintenance treatment in remission, rather than whether that treatment outperforms a randomized control. Its clinical setting combines two diseases, AML and MDS, and more than one type of preceding definitive therapy. The registry identifies these as poor-risk diseases but does not provide separate primary-outcome results by diagnosis or prior-treatment group.

The distinction between the question and the available results is important. A stated endpoint indicates what the study intended to evaluate; it is not itself a finding. Although the primary outcome is titled two-year RFS, the posted registry information does not give an RFS estimate or an event count for that endpoint. No conclusion about the observed level of RFS, its precision, or differences among the groups can be drawn from the primary outcome information in the registry record.

3. Trial Design

This is a Phase II study with a parallel-group structure and non-randomized allocation. The registry lists no masking. Its stated enrollment is 25, and its status is completed. The registry lists a start date of 2013-06 and a primary completion date of 2020-06. The sponsor is Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins.

All three groups received azacitidine and sargramostim as maintenance after a preceding treatment pathway. The group descriptions distinguish maintenance after myeloablative bone marrow transplant (BMT), after non-myeloablative BMT, and after standard consolidation. The official study title describes SCT or cytarabine-based chemotherapy as definitive therapy before maintenance. The registry does not report the treatment schedule, dose, duration, or rules for changing or stopping treatment.

Because allocation was non-randomized, the groups should not be treated as interchangeable comparison arms. The prior-treatment pathways distinguish the groups and may also reflect differences in the patients entering each pathway. The registry record does not report how patients were assigned to a pathway or whether statistical methods were used to adjust for differences among groups. It therefore does not establish a causal comparison between the groups or between the maintenance combination and no maintenance treatment.

The study lists four outcome measures, including the primary two-year RFS outcome. Secondary outcomes include hematologic toxicity as determined by anemia, one-year RFS, and overall survival. The registry lists no analyses for these outcomes. A completed study status does not, on its own, establish that all enrolled patients were assessed for every endpoint or that endpoint results were posted.

The registry also lists an enrollment of 25, but does not identify how many participants contributed to each endpoint analysis. The number enrolled should not be assumed to be the number analyzed, the number with complete follow-up, or the denominator for any particular outcome. Those analysis-population details are not reported in the registry record.

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 Two-year Relapse Free Survival of Patients, measured over 2 year.

The primary endpoint is titled “Two-year Relapse Free Survival of Patients.” The registry describes the outcome as evaluating two-year RFS in patients with poor-risk AML or MDS who receive azacitidine with sargramostim during remission after SCT or cytarabine-based consolidation chemotherapy. The listed outcome unit is participants, and its parameter is a count of participants. However, no primary outcome count, RFS estimate, or analysis result is reported in the registry record.

In general, relapse-free survival is a time-to-event concept: it concerns the time during which a patient remains alive without the specified event, such as relapse, under the endpoint definition. It is used in studies where both relapse and the timing of events matter, rather than treating every patient’s follow-up as equivalent. The exact event definition and handling of follow-up are not detailed in the posted primary outcome information, so those details should not be inferred.

A two-year endpoint focuses attention on status over a stated follow-up horizon. To interpret an estimate, readers would ordinarily need to know how events were defined, how participants without an event by the end of observation were handled, and how uncertainty was quantified. Those methods and the resulting estimate are not reported in the registry record. The endpoint name alone does not tell whether the outcome was analyzed as a survival curve, a fixed-time proportion, or another summary.

The registry also lists one-year RFS as a secondary outcome. It does not post a result for that outcome either. Thus the endpoint description establishes the intended subject of measurement, but cannot support a numerical conclusion about relapse-free survival.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry identifies a Phase II, parallel, non-randomized study with no masking. These design terms describe how the study was organized; they do not tell readers what statistical procedures were used for the outcomes. The record lists no analyses, and a statistical analysis plan is not reported in the registry record. The methods below explain general statistical considerations relevant to the stated endpoints, not methods confirmed to have been used in this study.

What does non-randomized allocation mean?

In a randomized study, chance-based assignment is used to make treatment groups comparable on average at the start of the study. Non-randomized allocation does not provide that same protection. In this study, the groups are defined by the preceding treatment pathway, and the registry does not report an alternative control group. Differences in patient characteristics, disease features, or care pathways could therefore contribute to any observed difference between groups. Statistical adjustment can sometimes address measured differences, but it cannot automatically remove unmeasured differences, and the registry does not report whether adjustment was performed.

The parallel structure means that the groups are described separately rather than as successive treatment periods for the same participants. It does not imply that the groups are directly comparable. With no masking, treatment knowledge may also be available to patients or study personnel; the registry does not describe how outcomes were assessed or whether any outcome assessment was masked.

How should a survival endpoint be interpreted?

As a general statistical concept, time-to-event methods account for both whether an event was observed and when it occurred. They can also make use of follow-up from participants who have not experienced the event by the end of their observation, subject to the method’s assumptions. A fixed-time survival estimate summarizes the probability of remaining free of the defined event through a specified time. A confidence interval expresses uncertainty around an estimate; it is not a guarantee that the true value lies within the interval.

The primary outcome is named two-year RFS, but the registry does not report the estimate, confidence interval, event definition, or method used to calculate it. It would be inappropriate to assume a particular survival estimator, censoring rule, or statistical model from the endpoint name alone. The registry lists the outcome parameter as a count of participants, which also does not by itself specify the analysis method.

What do counts and percentages communicate?

A count records how many events or participants meet a stated condition. A percentage expresses a count relative to a denominator. For a percentage to be interpreted precisely, the population included in its denominator and the event definition need to be clear. Safety records may distinguish serious events from other events and may list events by term; those categories should not be combined unless the record explains how they relate. The serious-event and other-event entries in this study are reported separately by group.

Counts can be especially difficult to compare when group sizes differ or when the groups arise through non-random pathways. A count alone does not convey the precision of an estimate, and a percentage without a clearly stated denominator can leave uncertainty about its interpretation. The record lists group-specific numbers at risk and affected for serious and other events, along with death counts, but does not describe the timing, event ascertainment, or denominators for the listed serious event terms.

What is over-dispersion, and is it relevant?

In general, over-dispersion occurs when observed variability in count data is greater than expected under a statistical model such as a simple Poisson model. Ignoring it can make uncertainty estimates too narrow. Whether over-dispersion is relevant depends on the outcome structure and the model used. The registry does not report a count model or an analysis of repeated event counts, so there is no basis for saying that over-dispersion was assessed in this study. It is a general consideration, not a reported study method.

What does a planning calculation mean?

The planning assumptions describe an illustration based on an observed effect, using a two-sided significance level of 0.05, equal allocation, and a normal approximation. The assumptions say that the effect targeted for detection is a stated fraction of the observed effect. Such a calculation is a planning illustration, not observed power and not evidence that an endpoint result is precise. The record does not report the study’s own sample-size justification or a statistical plan. Nor does the registry information give an observed primary effect from which readers could independently assess the illustration.

In general, a sample-size calculation depends on assumptions about the endpoint, effect, variability, allocation, and desired statistical properties. A result from such a calculation is conditional on those assumptions. It should not be read as the number of participants actually analyzed, nor as a retrospective measure of whether the study had enough information to answer its question.

What do analyses and multiplicity affect?

When a study evaluates multiple outcomes or comparisons, repeated testing can increase the chance of a misleading positive finding if results are interpreted without accounting for the analysis strategy. Multiplicity methods can control that risk, but the appropriate approach depends on which outcomes and comparisons were planned. This registry lists four outcome measures and no analyses. It does not report a hierarchy of endpoints, multiplicity adjustment, or a prespecified analysis strategy. No particular testing procedure should be attributed to the study based on the registry record.

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("Non-myeloablative BMT", "Myeloablative BMT", "Standard Consolidation")
n      <- c(17, 1, 1)
events <- c(8, 1, 1)
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  Non-myeloablative BMT  17  8  47.1  23.0  72.2  26.2  69.0  26.0  69.2
ARM  Myeloablative BMT  1  1  100.0  2.5  100.0  20.7  100.0  15.8  98.7
ARM  Standard Consolidation  1  1  100.0  2.5  100.0  20.7  100.0  15.8  98.7

11. Multiplicity, Missing Data and Analysis Populations

The registry lists four outcome measures, including two-year RFS, one-year RFS, overall survival, and hematologic toxicity as determined by anemia. It does not report the analysis plan, the order in which outcomes were to be assessed, or whether any adjustment for multiple outcomes or comparisons was used. In general, multiplicity matters when several statistical tests or comparisons are interpreted together, because repeated testing can raise the chance of finding an apparently notable result by chance. Without the analysis strategy, it is not possible to determine how the study addressed that issue.

The record lists no analyses. It does not report whether missing data occurred, how participants lost to follow-up were handled, whether outcomes were imputed, or whether sensitivity analyses were planned or performed. For a survival endpoint, general approaches may account for incomplete follow-up, but the method and assumptions must be specified to interpret an estimate. They are not reported for this primary endpoint.

The enrollment entry is 25, but the registry does not state the number included in each endpoint analysis or the population used for those analyses. It does not identify an intention-to-treat, per-protocol, or other analysis population. The listed enrollment should therefore not be treated as the denominator for the RFS endpoint or the safety entries without further information.

These omissions do not establish that missingness or multiplicity problems occurred. They mean that the registry record does not provide enough information to assess how those issues were handled. Without posted endpoint analyses and analysis-population details, readers cannot evaluate the impact of these choices on the reported results.

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: infections (23.5%), anemia (11.8%), neutropenia (11.8%), leukopenia (11.8%), eosinophilia (5.9%).

The registry reports serious and other event entries separately for each treatment pathway. For non-myeloablative BMT, it lists 17 at risk and 4 affected for serious events, and 17 at risk and 17 affected for other events; deaths are listed as 8. For myeloablative BMT, the corresponding entries are 1 at risk and 0 affected for serious events, 1 at risk and 1 affected for other events, and 0 deaths. For standard consolidation, they are 1 at risk and 0 affected for serious events, 1 at risk and 1 affected for other events, and 0 deaths.

The registry also lists serious event terms with percentages: infections, 23.5%; anemia, 11.8%; neutropenia, 11.8%; leukopenia, 11.8%; eosinophilia, 5.9%; and Graft-vs-host disease, 5.9%. The record does not provide further detail about the denominator for these term-specific percentages or their timing and attribution. They should be read as descriptive entries, not as comparisons with another treatment.

“At risk” and “affected” are registry labels, and the record does not explain their operational definitions in the information presented. Counts of affected participants do not necessarily describe the number of individual event episodes. The death entries also do not establish cause or attribution. Because the study was non-randomized and the groups followed different prior treatment pathways, differences among these safety entries cannot be interpreted as causal treatment effects.

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

The registry establishes that a Phase II study evaluated azacitidine with sargramostim as maintenance treatment in remission after definitive therapy for poor-risk AML or MDS. It identifies two-year RFS as the primary outcome and describes three pathways based on prior treatment. It also records selected serious and other adverse event entries and deaths by group.

The record does not report the primary endpoint result, an RFS estimate, a confidence interval, or an analysis of the listed outcomes. It therefore cannot establish the observed two-year RFS in the study. The absence of a posted result is not evidence that the endpoint was met or not met, nor does it show that the combination was beneficial or ineffective.

The study is non-randomized and does not describe an untreated or alternative-maintenance control group. Its groups are based on different prior treatment pathways. Even if outcome values for each group were available, differences could not automatically be attributed to maintenance treatment, because the design does not ensure comparable groups. The registry does not report adjusted comparative analyses that could clarify this issue.

The listed safety information is descriptive and does not establish that an event was caused by study treatment. The record does not provide additional detail about safety-event timing, attribution, or term-specific denominators. Death counts are reported, but the registry information does not establish their causes or relationship to treatment.

In general, an estimate is more informative when accompanied by an uncertainty interval, a clear endpoint definition, an analysis population, and a description of missing-data handling. These details are not reported for the primary outcome. Readers can therefore use the registry to understand the study’s question and design, but not to quantify or compare its primary efficacy results from the information recorded.

14. Why This Trial Matters Statistically

This study is statistically instructive because it puts a survival endpoint in a non-randomized, multi-pathway setting. The primary question concerns two-year RFS after maintenance treatment, while the three groups differ according to prior definitive therapy. That design makes it essential to distinguish a description of outcomes from a causal comparison. A group label is not equivalent to randomized assignment, and separate group outcomes would not by themselves show that the maintenance treatment caused any difference.

The record also illustrates why endpoint labels and endpoint findings are not interchangeable. A registry can state that an outcome is planned and define its timeframe, yet still lack a posted estimate, event count, or uncertainty measure. Here, the primary outcome is named, but its results and analyses are not reported in the registry record. Readers should not infer a result from the title of the endpoint or from the completed study status.

Safety entries further show why counts, denominators, and definitions matter. The record distinguishes serious events from other events and gives group-level counts, while also listing selected serious event terms as percentages. Without more information about definitions, timing, and denominators for those percentages, they remain descriptive registry entries rather than complete comparative estimates.

For biostatistical interpretation, the central issues are the non-randomized allocation, the distinct prior-treatment pathways, the absence of posted primary results, and unreported analysis details. These features do not make the study question unimportant. They define what can be concluded from the registry record and what would require fuller outcome and methods reporting.

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 affect interpretation of the registry record. The study is non-randomized, has no masking, and describes groups formed around different prior treatment pathways. The registry explicitly cautions that the arms are not a like-for-like control comparison. There is no described comparison with no maintenance treatment or an alternative maintenance regimen. As a result, the design recorded does not support a direct causal estimate of the maintenance combination’s effect.

The primary outcome is named, but its results are not reported. The record provides no two-year RFS estimate, event count, confidence interval, or primary analysis. It also lists no analyses for the four outcome measures. This prevents assessment of the primary result’s magnitude or precision and means that secondary outcome findings cannot be evaluated from the registry information either.

The registry does not report detailed eligibility criteria, the treatment schedule, endpoint definitions beyond the primary description, follow-up procedures, analysis populations, missing-data methods, or the statistical analysis plan. It does not identify how participants entered the three pathways or whether analyses accounted for differences among them. These omissions prevent readers from assessing key sources of bias and uncertainty.

Enrollment is listed as 25, but the number contributing to each outcome is not reported. The safety entries include group-specific at-risk and affected counts, term-specific percentages, and death counts, but the registry does not provide all context needed to interpret the denominators, timing, or attribution. In particular, the safety data should not be read as comparative treatment effects.

The listed completion status indicates the study is recorded as completed; it does not establish that all outcomes were analyzed or posted. These limitations apply to interpretation of the registry record and should not be taken as evidence about results that are not reported.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Phase II Study of Azacitidine and Sargramostim as Maintenance Treatment for Poor-Risk AML or MDS — NCT01700673.
• Registry record last updated 2022-10-18; status last verified 2021-08.
• Results first posted 2021-09-02.
• 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

NCT01700673 is a completed Phase II, parallel, non-randomized study with no masking. The registry lists enrollment of 25 and describes azacitidine plus sargramostim as maintenance treatment after definitive therapy for poor-risk AML or MDS in remission.

Three treatment pathways are described: maintenance after myeloablative BMT, after non-myeloablative BMT, and after standard consolidation. The primary outcome is two-year RFS. Secondary outcomes include hematologic toxicity as determined by anemia, one-year RFS, and overall survival.

The record lists four outcome measures and no analyses. It does not report the primary endpoint results, analysis populations, or missing-data methods. Group-specific serious and other event counts and deaths are listed, along with selected serious event terms and percentages. The record does not provide further context needed for a comparative interpretation of those safety entries.