A Study Of PF-04449913 In Select Hematologic Malignancies: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Study Of PF-04449913 In Select Hematologic Malignancies (NCT00953758), a non-randomized phase 1 study. The primary outcome is Number of Participants With First Cycle Dose-limiting Toxicities (DLTs).

2. Clinical Question

The central statistical question is therefore descriptive: how many evaluable participants experienced a DLT during the first cycle at each studied dose? In an early-phase study, this kind of outcome can characterize short-term tolerability during dose evaluation. It is not, by itself, a randomized comparison of treatment effects. The registry lists a total enrollment of 47, but the DLT population was restricted to participants without major treatment deviations in Cycle 1. The number meeting that criterion is not reported in the registry record.

The study also listed safety, pharmacokinetic, pharmacodynamic and biomarker outcomes. Their presence indicates that the research questions extended beyond DLT counts, but the registry record does not report results for those measures in the information. The clinical question should thus be read as an early-phase assessment of a single agent across dose groups, not as a test against another treatment or a placebo.

3. Trial Design

This was a Phase 1, nonrandomized, unmasked, sequential study of PF-04449913 as a single agent in select hematologic malignancies. The registry lists 47 participants enrolled. The study started on 2010-03-03, reached primary completion on 2012-09-26, and is marked completed.

The registry identifies ten dose groups: PF-04449913 5 mg, 10 mg, 20 mg, 40 mg, 80 mg, 120 mg, 180 mg, 270 mg, 400 mg and 600 mg. The safety information lists 3 participants at risk in each of the 5 mg and 10 mg groups, 4 in each of the 20 mg and 40 mg groups, 8 in the 80 mg group, 3 in each of the 120 mg and 180 mg groups, 5 in each of the 270 mg and 600 mg groups, and 9 in the 400 mg group. These are dose-specific safety populations; they should not be assumed to be the same as the primary outcome population.

Sequential allocation and multiple dose groups are consistent with a study organized around evaluating doses, but the specific escalation rules, cohort expansion criteria, and dose-selection process are not reported in the registry record. Nor does the record describe a concurrent comparison group. Since allocation was nonrandomized, differences between dose groups could reflect factors other than dose, and the groups are not a like-for-like control comparison.

The registry lists 31 outcome measures and 0 analyses. The primary outcome was DLT count during Cycle 1, defined as Cycle 1 Day 1 through the end of the 28-day cycle. Participants with major treatment deviations in Cycle 1 were not evaluable for this outcome. The specific number excluded or retained under that criterion is 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.

Only the first 6 of 10 groups are shown.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Only participants who did not have major treatment deviations in Cycle 1 were evaluable for DLT.

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.

Only the first 6 of 11 groups are shown.

6. Primary Endpoint

The registry lists the primary outcome as Number of Participants With First Cycle Dose-limiting Toxicities (DLTs), measured over Cycle 1 Day 1 to end of Cycle 1 (28 days).

The primary endpoint counted participants with a dose-limiting toxicity during the first treatment cycle, from Cycle 1 Day 1 to the end of Cycle 1, a period of 28 days. A participant was counted if any qualifying DLT occurred. The registry defines qualifying events as specified severe non-hematologic toxicity, prolonged myelosuppression in a normal bone marrow, or inability to deliver at least 80% of planned doses because of PF-04449913-related toxicities. The detailed criteria also include laboratory thresholds and other conditions described in the registry record.

Only participants without major treatment deviations in Cycle 1 were considered evaluable for this outcome. That restriction matters: the number enrolled is not automatically the denominator for a DLT count. The number evaluable, the number with DLTs, and any dose-specific DLT results are not reported in the registry record.

As general statistical context, a count of participants with an event is a simple way to describe the occurrence of a defined safety outcome in a cohort. It is useful in early-phase dose evaluation because it relates directly to how many participants experienced an event meeting the prespecified definition. A count alone, however, does not show the precision of the underlying event rate or establish that differences across nonrandomized dose groups were caused by dose. Interpretation also depends on clear event criteria and the number actually evaluable.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary outcome is a binary participant-level event summarized as a count: a participant either met the registry definition of a first-cycle DLT or did not. The registry classifies the outcome as a count of participants with an event. It also describes a specific evaluation population: participants with major treatment deviations in Cycle 1 were not evaluable. This distinction is central to interpreting any count or event proportion, because the appropriate denominator is the number actually evaluated for the outcome, not necessarily total enrollment.

What does a participant count communicate?

As general statistical context, an event count gives the number of observed participants who met the stated definition during the specified observation period. A count is easy to interpret, but it does not by itself describe the probability of an event unless the denominator is also known. Even when both count and denominator are known, the observed proportion is an estimate based on a finite group. It is not an exact measure of the underlying risk in a broader population.

The primary endpoint uses a composite definition: several kinds of toxicity or treatment delivery difficulty can qualify a participant as having a DLT. Composite outcomes can summarize multiple clinically relevant event types, but their interpretation depends on the component definitions. A participant may qualify through any one of the listed criteria; the overall count does not reveal which criterion accounted for each event unless component results are reported. The registry describes the criteria, but the result by criterion is not reported in the registry record.

Why does the evaluation period matter?

The endpoint covers Cycle 1 Day 1 through the end of Cycle 1, stated as 28 days. A fixed window makes the time period for counting events explicit. It also means the endpoint addresses events within that window, rather than all possible events over an unspecified or longer period. The record lists other safety and laboratory outcomes, but their observation windows and results are not all available in the information for this record.

The evaluability restriction also affects interpretation. Participants with major treatment deviations in Cycle 1 were excluded from the DLT-evaluable population. General statistical reasoning cautions that excluding participants can affect a result if the reasons for exclusion are related to health status, treatment exposure, or the chance of an event. The record does not state how many participants had such deviations or why, so the extent or direction of any effect cannot be assessed.

How should confidence intervals be understood?

In general, a confidence interval expresses uncertainty around an estimate, such as an event proportion. It gives a range of values compatible with the observed data under the interval method's assumptions. Wider intervals indicate less precision; narrower intervals indicate greater precision. Small cohorts commonly yield uncertain estimates, even when the observed count is clearly stated. No confidence interval for the DLT outcome is reported in the registry record, so the precision of that primary result cannot be assessed.

For a binary outcome, statistical methods may estimate an event proportion and its interval using assumptions about the sampling process. The choice of method matters, especially with small denominators or event counts. The registry record does not report an analysis method for the primary endpoint, and it does not report a primary analysis result. It would therefore be inappropriate to attribute a particular interval method or infer an unreported estimate.

What can dose groups show in a sequential study?

General statistical context: when participants are assigned sequentially to dose groups without randomization, group summaries can describe what was observed at each dose. They do not automatically estimate the causal effect of changing dose. Groups may differ in timing, participant characteristics, eligibility, or other aspects of care. Random allocation is one way to reduce systematic differences between comparison groups; this study was nonrandomized, and the registry explicitly notes that the arms are not a like-for-like control comparison.

In addition, the dose groups are small and of unequal size, as reflected in the safety populations listed in the registry. A change in a few observations could substantially alter a group summary. Any visual pattern across doses should be treated as descriptive rather than as definitive evidence of a dose-response relationship. The record does not report a formal trend analysis or a model comparing doses.

What do the planning assumptions mean?

General statistical context: sample-size calculations are planning illustrations, not observed power. The stated planning approach uses a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation, with the effect to detect expressed as a fraction of the observed effect. For time-to-event outcomes, the planning convention uses a total event count; for other outcomes, it uses participants per arm. These assumptions describe an illustrative calculation framework, not the design justification for this trial. The trial was nonrandomized and sequential, and its dose groups are not a two-arm randomized comparison. The rationale for the study's enrollment and any original sample-size justification are not reported in the registry record.

Because the primary effect estimate and associated planning outputs are not reported in the registry information, no numerical planning result can be interpreted. General principles still apply: changing the target effect, allocation, significance level, or statistical assumptions changes a calculated sample size. Such calculations do not show the probability that a completed study's result is true, and they should not be described as observed power.

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("PF-04449913 5 mg", "PF-04449913 10 mg", "PF-04449913 20 mg", "PF-04449913 40 mg", "PF-04449913 80 mg", "PF-04449913 120 mg")
n      <- c(3, 3, 4, 4, 6, 3)
events <- c(0, 0, 0, 0, 1, 0)
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  PF-04449913 5 mg  3  0  0.0  0.0  70.8  0.0  56.1  0.6  60.2
ARM  PF-04449913 10 mg  3  0  0.0  0.0  70.8  0.0  56.1  0.6  60.2
ARM  PF-04449913 20 mg  4  0  0.0  0.0  60.2  0.0  49.0  0.5  52.2
ARM  PF-04449913 40 mg  4  0  0.0  0.0  60.2  0.0  49.0  0.5  52.2
ARM  PF-04449913 80 mg  6  1  16.7  0.4  64.1  3.0  56.4  3.7  57.9
ARM  PF-04449913 120 mg  3  0  0.0  0.0  70.8  0.0  56.1  0.6  60.2

11. Multiplicity, Missing Data and Analysis Populations

The registry lists 31 outcome measures, including the primary DLT count and secondary safety, laboratory, biomarker, and pharmacokinetic measures. It lists 0 analyses. The individual endpoint definitions indicate that the study gathered or planned to report several kinds of information, but the registry record does not specify how results across multiple outcomes were handled statistically.

As general statistical context, testing or estimating many outcomes creates a multiplicity issue: the more separate questions considered, the greater the chance that at least one result may appear notable by chance when formal tests are used. Common approaches include identifying a primary outcome in advance, adjusting significance levels, or treating secondary outcomes as exploratory. The registry identifies a primary outcome, but any multiplicity adjustment, hierarchy among secondary outcomes, or prespecified testing strategy is not reported in the registry record. No assumption should be made that an adjustment was or was not performed.

Missing-data handling is also not reported in the registry record. For the primary outcome, the record states that participants with major treatment deviations in Cycle 1 were not evaluable, but it does not give the number excluded, reasons for individual exclusions, or how any other incomplete observations were handled. This means the relationship between total enrollment and the DLT analysis population cannot be established from the record.

The record also does not describe interim analyses, the statistical analysis plan, or methods for handling missing safety, biomarker, or pharmacokinetic measurements. Those omissions limit reproducibility and make it difficult to assess whether the reported outcomes were analyzed as planned. The absence of such information is not evidence that a particular procedure was used or omitted; the relevant details are simply not reported in the registry record.

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 (66.7%), fatigue (40.0%), pyrexia (40.0%), respiratory failure (40.0%), thrombocytopenia (33.3%).

The serious adverse-event information is organized by dose group and gives the number of participants at risk and the number affected. For example, the 400 mg group lists 9 participants at risk and 8 affected, while the 80 mg group lists 8 at risk and 5 affected. These are participant counts for each dose group. They are not randomized comparisons, and the group sizes differ.

The registry also lists serious adverse-event terms and percentages: febrile neutropenia, 66.7%; fatigue, 40.0%; pyrexia, 40.0%; respiratory failure, 40.0%; thrombocytopenia, 33.3%; and gastritis haemorrhagic, 33.3%. The denominator for those percentages is not reported in the registry record. The percentages should therefore be read as listed, without inferring the number of participants or events behind them. A participant could potentially contribute to more than one event term, so term percentages should not be assumed to add to a total.

The dose-group information also lists other adverse events: in every group, the number affected is the same as the number at risk. Serious adverse events and other adverse events are distinct summaries in the record and should not be conflated. Death counts are null for the listed groups; death information is not reported in the registry record.

As general context, small safety cohorts provide limited precision, and descriptive counts do not establish that dose caused differences between groups. They also do not replace the missing primary DLT result or convey the full timing, severity, or duration of each event.

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

The record establishes that a Phase 1 study of PF-04449913 was conducted in participants with select hematologic malignancies, using a sequential, nonrandomized design and multiple dose groups. It defines first-cycle DLTs as the primary outcome and provides descriptive safety counts by dose. These details help characterize what the study set out to assess and how some safety information was recorded.

The record does not report the primary DLT count, the number evaluable for that outcome, or a dose-specific DLT analysis. It therefore cannot establish from the posted information how often a DLT occurred during the first cycle. It also cannot show whether DLT frequency changed with dose. The listed serious adverse-event counts and terms describe safety observations, but they are not substitutes for the primary outcome results.

General statistical context: an observed event count is not a causal comparison. In a nonrandomized study, dose groups may differ in ways that affect their outcomes. Without randomization or a reported adjustment strategy, a difference in counts across groups cannot be attributed solely to dose. The unequal, small group sizes also mean that descriptive percentages, where available, may be imprecise.

The study's Phase 1 setting and dose-specific structure make its information different from evidence generated by a randomized efficacy trial. The outcomes listed include safety, pharmacokinetic and pharmacodynamic measures, but results for those measures are not reported in the registry information. No treatment benefit, lack of benefit, or comparative effectiveness conclusion follows in the registry record recorded.

The appropriate interpretation is limited: the registry documents the design, endpoint definition, enrollment, and some adverse-event summaries, while important analysis results and methods are absent. Those gaps leave the primary statistical question unresolved in the registry record. The posted counts should be read as descriptive observations in the listed study groups, not as proof that PF-04449913 does or does not work.

14. Why This Trial Matters Statistically

Early-phase studies raise statistical questions that differ from those in large randomized comparisons. This study makes those issues concrete: it was Phase 1, sequential, nonrandomized, and organized across ten dose groups. Its primary endpoint was a defined first-cycle DLT count, a safety measure tied to a specified observation window. Understanding the endpoint definition and the population considered evaluable is necessary before interpreting any count.

The record also illustrates why denominator reporting matters. Total enrollment was 47, while the primary outcome applied only to participants without major treatment deviations in Cycle 1. The number meeting that criterion is not reported in the registry record. Without it, a reader cannot know the primary analysis denominator or assess the precision of a DLT estimate, even if a count were available.

Another statistical issue is the distinction between description and comparison. Multiple dose groups can help organize observations across exposure levels, but nonrandomized groups do not provide a like-for-like control comparison. Dose patterns may be informative descriptively, yet they should not be interpreted as causal evidence without design and analysis support. Small group sizes make uncertainty especially important.

Finally, the record lists many outcomes but no analyses. This makes transparent reporting of endpoint results, analysis populations, missing-data handling, and multiplicity methods particularly important. These details would help readers distinguish planned questions from reported findings and assess how robust the conclusions are. The case underscores a general lesson: a carefully defined endpoint is useful, but interpretation also requires its results, denominators, and analysis methods.

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 primary limitation for interpreting the study statistically is that the registry record does not report the primary DLT result. It also does not state the number evaluable for that endpoint, despite defining an evaluability restriction for participants with major treatment deviations in Cycle 1. Consequently, neither a primary event proportion nor its precision can be assessed from the recorded information.

The study was nonrandomized and sequential, with no concurrent control group listed. The dose groups are not a like-for-like comparison, so differences in observed safety counts cannot be attributed to dose alone. The record does not describe the allocation rules, dose-escalation criteria, or any statistical approach to adjust for group differences.

The safety populations are small and vary in size across dose groups. Such counts can be sensitive to a small number of observations. Serious adverse-event terms are accompanied by percentages, but their denominator is not reported in the registry record. Death information is also not reported. These gaps limit interpretation of the adverse-event summaries.

The registry lists 31 outcome measures but 0 analyses. It does not report results for the primary outcome or the listed secondary measures in the information available for this record. The statistical analysis plan, missing-data methods, multiplicity strategy, interim analyses, and sample-size justification are not reported in the registry record. These limitations prevent assessment of whether results followed a prespecified analysis strategy and restrict conclusions to the design details and descriptive safety information recorded.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: A Study Of PF-04449913 In Select Hematologic Malignancies — NCT00953758.
• Registry record last updated 2024-04-25; status last verified 2023-11.
• Results first posted 2024-04-25.
• 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

NCT00953758 is a completed Phase 1 study of PF-04449913 in select hematologic malignancies. It was nonrandomized, unmasked, and sequential, with 47 participants enrolled. The study started on 2010-03-03, and primary completion was 2012-09-26.

The primary outcome counted participants with a DLT from Cycle 1 Day 1 through the end of Cycle 1, a 28-day period. Participants with major treatment deviations in Cycle 1 were not evaluable for that outcome. The primary DLT result and evaluable population are not reported in the registry record.

The registry lists ten dose groups and serious and other adverse-event participant counts by group, along with several serious adverse-event terms and percentages. It also lists 31 outcome measures and 0 analyses. The record does not report a randomized comparison, primary outcome analysis, or the statistical plan and missing-data methods.