Sorafenib Tosylate and Chemotherapy in Treating Older Patients With Acute Myeloid Leukemia: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Sorafenib Tosylate and Chemotherapy in Treating Older Patients With Acute Myeloid Leukemia (NCT01253070), a na phase 2 study. The primary outcome is Overall Survival (OS) Rate.

2. Clinical Question

The clinical question was whether older patients with acute myeloid leukemia could be treated with a regimen combining sorafenib tosylate and chemotherapy, and how overall survival at one year differed between patients with FLT3 ITD and TKD mutations. The registry describes a phase II study and a treatment group receiving daunorubicin, cytarabine, and sorafenib tosylate. It does not describe a separate control group.

The primary endpoint was the percentage of patients alive at one year. The record says the primary analysis was split by FLT3 mutation type and that baseline mutation testing was performed centrally for all patients. It also says that participants who withdrew consent to protocol treatment and follow-up before one year were excluded from the primary endpoint analysis. The registry reports three such withdrawals, identified as two ITD and one TKD.

This endpoint addresses survival status at a specified follow-up time, rather than the length of time each participant lived or the timing of particular events. It therefore offers a clinically interpretable snapshot, but interpretation depends on knowing the observed survival percentages, their uncertainty, the subgroup denominators, and how missing follow-up was handled. Those numerical outcome details are not reported in the registry record.

Because this was a single-group study, the registry does not provide a concurrent control comparison for estimating the difference attributable to the regimen. The available record can describe the treatment context and the intended survival question, but it cannot establish how the observed course compares with another treatment or with an untreated group.

3. Trial Design

The registry describes NCT01253070 as a phase II study of sorafenib tosylate and chemotherapy for older patients with acute myeloid leukemia. Its enrollment is listed as 54, and its status is completed. The recorded start date is 2011-04-01 and the primary completion date is 2014-10-31. The sponsor is the National Cancer Institute.

The design is identified as single-group, with allocation recorded as not applicable and masking recorded as none. Thus, the record describes an open-label treatment group, not a randomized comparison between separately assigned regimens. The treatment group is named daunorubicin, cytarabine, and sorafenib tosylate. The listed induction regimen combines those drugs; the record also lists consolidation therapy, but its description is incomplete in the registry information available for this analysis.

The intervention list includes the three drugs, as well as biopsy, bone marrow aspiration, laboratory biomarker analysis, quality-of-life assessment, and questionnaire administration. These entries indicate procedures and assessments in addition to drug treatment; they do not establish that each listed procedure was performed for every participant.

The registry lists overall survival and event-free survival as secondary outcomes, alongside the primary overall-survival endpoint. It reports three outcome measures but no statistical analysis entries. No treatment allocation concealment or blinding is described, consistent with the recorded allocation and masking fields. The registry record does not report a sample-size justification, interim-analysis plan, or detailed statistical analysis plan. Consequently, the design can be characterized from its single-group structure and listed outcomes, but important operational and analytical details remain unavailable.

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: Three participants withdrew consent to protocol treatment and follow-up prior to 1 year post registration (2 ITD; 1 TKD). These participants have been excluded from the primary endpoint analysis.

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 Overall Survival (OS) Rate, measured over 1 year.

The primary endpoint is the percentage of patients alive at one year after registration. This is a fixed-time survival measure: each included participant is classified according to whether they were alive at the specified follow-up point. It differs from a time-to-event measure, which uses the timing of deaths and can account for differing follow-up durations through a survival analysis.

Overall survival is used because it captures death from any cause and has a direct interpretation as survival status at the selected time. Reporting a percentage makes the endpoint accessible, but the percentage alone does not show how precisely the underlying survival rate has been estimated. The registry identifies a 95% confidence interval as the dispersion measure, although neither the interval limits nor the survival percentages are reported in the registry record.

The analysis was separated by FLT3 ITD or TKD mutation status. The record states that baseline testing was performed centrally for all patients. It also says three participants withdrew consent to treatment and follow-up before one year and were excluded from the primary endpoint analysis. The record does not provide subgroup denominators, the number alive in each subgroup, a method for handling any other incomplete follow-up, or an explanation of how the fixed-time survival percentages were calculated.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does a one-year survival percentage represent?

The endpoint is the percentage of patients alive at one year. In general, a fixed-time survival percentage translates follow-up into a status at a chosen time point. The result depends on how the analysis defines the starting point, which participants are included, and how incomplete follow-up is addressed. The registry describes the endpoint as measured from registration and states that three participants who withdrew consent to treatment and follow-up before one year were excluded from the primary endpoint analysis. It does not give further calculation details.

A fixed-time percentage is not the same as a median survival time or a hazard ratio. Those measures require different summaries of survival information and are not reported as primary results in this record. The outcome description specifies a percentage and a 95% confidence interval; neither the estimate nor the interval values are available in the registry record.

Why does the confidence interval matter?

In general, a confidence interval communicates uncertainty around an estimate. A narrower interval indicates greater precision under the assumptions of the method, while a wider interval indicates less precision. It does not guarantee that the true value lies within the particular interval, nor does it correct for limitations in study design, missing data, or measurement. Here, the record names a 95% confidence interval as the dispersion measure but does not report its bounds. Therefore, the precision of the primary survival estimates cannot be assessed.

What does the subgroup description establish?

The primary outcome description separates patients by FLT3 ITD or TKD mutation status and says testing at baseline was centralized for all patients. This establishes the planned reporting distinction, but not the size or balance of the subgroups, the outcome estimates within them, or whether a formal comparison was conducted. A difference between subgroup estimates, if reported, would not by itself establish that mutation type caused a difference in survival. General interpretation of subgroup findings requires attention to the analysis plan, subgroup sizes, uncertainty, and multiplicity; those details are not reported in the registry record.

How should the single-group design be understood?

In general, a single-group study describes outcomes among participants receiving a specified treatment strategy. Without a concurrent comparator, the observed outcome does not quantify a treatment effect relative to another strategy. Differences between this study's outcomes and outcomes from another setting could reflect differences in participants, follow-up, supportive care, eligibility, or measurement, as well as treatment. A single-group design can still document how an enrolled group was treated and what outcomes were recorded, but causal interpretation is limited.

The registry records no random allocation and no masking. It also lists no statistical analysis entries. Accordingly, the statistical model, any adjustment factors, handling of censoring, and formal tests are not reported in the registry record. These omissions prevent reconstruction of the sponsor's analysis from the descriptive endpoint information alone.

What do planning assumptions mean?

General statistical planning uses assumptions about the effect a future study aims to detect, the significance level, allocation, and the method of analysis. The planning assumptions associated with the analysis specify a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. They also describe the effect to detect as a stated fraction of the observed effect. These are planning illustrations computed from the observed effect, not the design of this trial, which is recorded as single-group. The registry does not report the sample-size justification for the trial itself.

Any sample-size figures based on those assumptions are planning illustrations, not observed power. Observed power is not a substitute for an estimate and its confidence interval; it cannot make an unreported endpoint result interpretable. A planning calculation can help frame a hypothetical future comparison, but its assumptions should not be mistaken for evidence that the current study randomized participants or included a control arm.

General consideration of over-dispersion is relevant when count outcomes vary more than a chosen statistical model expects, because standard errors and uncertainty can then be understated. This endpoint is described as a percentage of participants with an event, not as an over-dispersed count outcome. The registry does not report a model that would allow assessment of whether over-dispersion was considered in any 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("ITD Mutated Participants", "TKD Mutated Participants")
n      <- c(37, 14)
events <- c(23, 10)
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  ITD Mutated Participants  37  23  62.2  44.8  77.5  46.1  75.9  46.0  76.0
ARM  TKD Mutated Participants  14  10  71.4  41.9  91.6  45.4  88.3  44.9  88.2

11. Multiplicity, Missing Data and Analysis Populations

The registry identifies overall survival at one year as the primary outcome and lists event-free survival and overall survival among the secondary outcomes. It also describes a primary analysis split between FLT3 ITD and TKD mutation groups. Examining more than one outcome or subgroup can raise multiplicity concerns: when many hypotheses are tested, the chance of at least one apparently unusual result can increase. General statistical practice may address this through prespecified hypotheses, adjusted testing, or emphasis on estimation and uncertainty. The registry record does not report whether any multiplicity strategy was specified or used.

The record does not include statistical analysis entries, and it does not report a detailed analysis plan. It is therefore not possible to determine whether subgroup comparisons were planned as confirmatory or exploratory, whether secondary outcomes were formally tested, or whether any adjustments were made. The absence of those details should not be interpreted as proof that no such procedures were used outside the registry record.

For missing data, the registry states that three participants withdrew consent to treatment and follow-up before one year and were excluded from the primary endpoint analysis. The listed withdrawals are separated by mutation group. The record does not explain whether these participants had any earlier survival information included in another analysis, nor does it describe imputation, censoring rules, sensitivity analyses, or handling of other missing assessments. Their exclusion means the primary analysis population was not necessarily identical to the enrollment population.

The registry's statement about exclusion is not enough to assess the possible direction or magnitude of missing-data bias. That assessment would require the missingness reasons, subgroup denominators, outcome information, and analysis procedures. No additional missing-data assumptions should be inferred.

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 0% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: anemia (40.0%), platelet count decreased (40.0%), neutrophil count decreased (38.0%), diarrhea (28.0%), white blood cell decreased (28.0%).

The safety record separates serious adverse events from other adverse events for the treatment group. It lists 50 participants at risk for each category. Serious adverse events were reported for 21 participants, while other adverse events were reported for 42 participants. These are separate summaries; the record does not state that participants could appear in only one category, so the figures should not be combined or treated as mutually exclusive.

The most frequently listed serious-event terms include anemia and decreased platelet count, each reported as 40.0%; decreased neutrophil count, 38.0%; diarrhea and decreased white blood cell count, each 28.0%; and febrile neutropenia, 26.0%. These percentages describe the terms as recorded in the safety data. The record does not provide event counts for each term in this summary, severity grades, timing, duration, or attribution to a particular drug.

General safety interpretation: a participant-level adverse-event summary is not the same as a count of all event episodes, since a participant may experience more than one event. These data describe reported events in the treatment group; they do not establish that the regimen caused each event. The registry does not report a concurrent control group for comparing safety.

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

The registry record describes a phase II, single-group study combining sorafenib tosylate with chemotherapy for older patients with acute myeloid leukemia. Its primary outcome is overall survival at one year, separated by FLT3 ITD or TKD mutation status. This defines the outcome the study set out to summarize, but the record does not report the observed survival percentages or their 95% confidence intervals.

Accordingly, the posted record does not support a quantitative statement about the level or precision of survival in the analyzed groups. It also does not report a statistical test or numerical comparison between mutation subgroups. The listed enrollment and withdrawal information do not substitute for outcome results and should not be used to calculate or infer survival.

The single-group structure also limits what the study can establish. Without a concurrent control group, the observed outcomes cannot show how survival would have differed under another treatment strategy. Since the regimen combines drugs, the design as described cannot isolate the effect of any one component. These are limits on causal interpretation and do not assert that the regimen did or did not have an effect.

The safety information records adverse events in the treatment group, including serious-event terms and their reported percentages. It is descriptive; without a control group or additional attribution information, it cannot determine whether the regimen caused an event or compare its safety with another regimen.

In general, a study result is best understood by considering the estimate, uncertainty, analysis population, follow-up completeness, and design together. The record provides some of the design and endpoint definitions, but the missing outcome estimates and analysis details leave substantial uncertainty about the numerical findings.

14. Why This Trial Matters Statistically

This trial illustrates the distinction between a clearly named endpoint and a fully interpretable numerical result. The registry specifies overall survival at one year, identifies a 95% confidence interval as the uncertainty measure, and describes separation by FLT3 mutation type. Yet the numerical estimates and interval limits are not reported in the registry record. Without them, readers cannot judge either the size or precision of the survival outcomes.

It also illustrates why design determines the scope of statistical conclusions. The study is recorded as single-group, with no random allocation or masking. Outcomes in such a group can be described, but they do not provide a concurrent estimate of what would have occurred under an alternative regimen. A combination regimen further makes it impossible to assign any observed outcome to a particular component on the basis of this design alone.

Missing follow-up matters even when the stated number of withdrawals appears small in relation to enrollment: exclusion from the primary analysis changes who contributes to the endpoint, and interpretation depends on the reasons and analysis of missing outcomes. The record identifies withdrawals before the endpoint time and their mutation categories, but does not provide subgroup denominators or sensitivity analyses.

Finally, planning assumptions should be distinguished from the actual trial design. The accompanying assumptions use equal allocation between two arms and a normal approximation, whereas this trial is recorded as single-group. A planning illustration can inform hypothetical future study design, but it is neither an observed result nor evidence of observed power. These distinctions are central to reading clinical trial statistics accurately.

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 follow from the registry information. The single-group design has no concurrent control group, so the record cannot support a randomized treatment comparison. No allocation or masking is described, and the combined regimen does not permit the effect of sorafenib tosylate to be separated from the effects of chemotherapy or other aspects of care.

The primary outcome is defined, but its numerical results are absent. The record does not report subgroup survival rates, confidence-interval limits, subgroup denominators, or the number alive at the endpoint. It also does not report the statistical methods used to calculate the endpoint, the handling of censoring, or the analysis population beyond the stated exclusion of three withdrawals.

The registry lists several acute myeloid leukemia condition terms and identifies the study as involving older patients with FLT3-mutated disease. It does not provide enough information in this record to characterize the distribution of the listed disease subtypes or other participant characteristics. Generalizability to patients outside the enrolled study population cannot be assessed from these entries alone.

The safety summary is also limited: it gives participants at risk, affected counts for broad adverse-event categories, and selected serious-event percentages, but not detailed event-level counts, grades, timing, duration, or attribution. There is no comparator for contextualizing those reports.

Finally, the registry record does not report a sample-size justification, interim-analysis plan, multiplicity strategy, or detailed statistical analysis plan. The sample-size assumptions associated with the analysis are planning illustrations and do not describe the single-group trial's own design. These gaps limit evaluation of both the rationale for the study size and the analytical choices behind any results not included in the record.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Sorafenib Tosylate and Chemotherapy in Treating Older Patients With Acute Myeloid Leukemia — NCT01253070.
• Registry record last updated 2022-08-04; status last verified 2022-08.
• Results first posted 2016-02-11.
• 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

NCT01253070 is a completed phase II, single-group study sponsored by the National Cancer Institute. It evaluated sorafenib tosylate with daunorubicin and cytarabine in older patients with acute myeloid leukemia. The registry lists enrollment of 54 and records the study start as 2011-04-01 and primary completion as 2014-10-31.

The primary outcome is the percentage of patients alive at one year, analyzed by FLT3 ITD or TKD mutation status, with a 95% confidence interval specified. The record reports three withdrawals before one year who were excluded from the primary endpoint analysis, but does not provide the survival estimates or interval limits. Event-free survival and overall survival are listed as secondary outcomes. The record also includes descriptive adverse-event information, but no concurrent comparator or statistical analysis entries.