Imatinib Mesylate and Interferon Alfa in Treating Patients With Chronic Myelogenous Leukemia: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Imatinib Mesylate and Interferon Alfa in Treating Patients With Chronic Myelogenous Leukemia (NCT00015847), a non-randomized phase 2 study. The primary outcome is Complete Cytogenetic Response at 6 and 12 Months (Phase II).

2. Clinical Question

3. Trial Design

This is a Phase 2 study listed as non-randomized, with no masking and a single-group model. The registry record describes a Phase I/II dose-finding study in its official title, while the phase field identifies PHASE2. Its stated focus is the safety, tolerability, and anti-leukemic effects of STI571, also named as imatinib mesylate, in combination with interferon alfa for chronic myelogenous leukemia in chronic phase.

Enrollment is recorded as 25. The registry lists imatinib mesylate and recombinant interferon alfa as interventions. The record does not report dose levels, dose escalation details, treatment schedules, adherence, or the criteria used to select a dose. Those details should not be inferred from the dose-finding wording in the official title.

The study started in 2001-04, had primary completion in 2011-05, and is marked TERMINATED. The registry record does not explain why the study was terminated or how termination affected recruitment, follow-up, or outcome collection. It also does not give a reason for the interval between the listed start and primary completion dates.

Because allocation is non-randomized and the model is single group, this design does not provide a randomized control comparison. The listed safety group is titled Imatinib Mesylate, while the study description concerns the combination; the record does not clarify this labeling. The registry lists six outcome measures and zero analyses. It does not report a statistical analysis plan, a sample-size justification, or details about analysis populations. The planning assumptions described for sample-size illustrations are not evidence that the trial itself used those assumptions.

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 Complete Cytogenetic Response at 6 and 12 Months (Phase II), measured over At 6 and 12 months during phase II.

The primary outcome is the number of participants with complete cytogenetic response at 6 and 12 months during Phase 2. The registry describes cytogenetic response using the percentage of Ph-positive metaphases in bone marrow: complete is defined as 0% Ph-positive cells, partial as 1-34%, minor as 35-95%, and none as 96-100%. These categories provide a way to classify the cytogenetic findings rather than reporting only a broad statement of disease status.

As a general statistical explanation, a cytogenetic endpoint can summarize a biological response using a defined measurement and threshold. A count of participants meeting a prespecified category can be readily interpreted, provided that the denominator, assessment timing, and handling of missing measurements are clear. Reporting results at 6 and 12 months can also distinguish response at different follow-up times; it does not, by itself, show whether the same participants contributed data at both assessments.

The registry gives the endpoint definition and timeframe but does not report the observed counts, denominators at either assessment, or response estimates. It also does not state how missing marrow assessments or participants who discontinued treatment were handled. Thus, the endpoint is described, but the registry record does not provide enough outcome data to estimate the frequency of complete response or its precision.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

Statistical methods can clarify what a clinical trial result would mean, but they cannot replace unreported results. In this record, the outcome definition is present, while outcome counts and analyses are not. The registry records zero analyses. It does not report the statistical plan, the estimator intended for the primary endpoint, or whether any formal hypothesis test was planned. The explanations below are general and should not be mistaken for methods confirmed to have been used in the study.

What does a binary outcome count represent?

The primary endpoint is expressed as a number of participants with an event, where the event is complete cytogenetic response at a specified assessment time. A count is easier to interpret when accompanied by the number of participants eligible for that assessment and a proportion or other estimate. Those denominators and estimates are not reported in the registry record. The enrollment value of 25 cannot be assumed to be the denominator at 6 months or 12 months.

For a binary outcome, an estimate of the response proportion describes the observed frequency in the analyzed group. A confidence interval, when reported, conveys uncertainty around that estimate: it indicates a range of values reasonably compatible with the data under the statistical model. A confidence interval does not remove bias, correct missing outcome data, or create a comparison group. No confidence interval for the primary endpoint is reported in the registry record.

Why does the design matter for interpretation?

Random allocation can help balance measured and unmeasured prognostic factors between comparison groups, on average. This study is identified as non-randomized and single group, so there is no randomized comparison described. A response count from this design would characterize participants observed in the study, but a causal comparison with an alternative treatment would require evidence beyond a single-group count. Differences from historical or external groups, if considered, could reflect differences in participant selection, assessment, follow-up, or care. No such external comparison is reported.

Masking is listed as NONE. In general, masking can reduce the influence of expectations on outcome assessment or participant reporting, depending on the outcome and procedures. The registry does not explain the assessment process or whether outcome assessors were separate from treatment staff. The primary endpoint is defined through bone marrow cytogenetic findings, but the record does not describe laboratory procedures or safeguards against assessment bias.

What can planning assumptions tell a reader?

The sample-size assumptions describe a planning illustration based on an observed effect, with a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. The target effect is described as a stated fraction of the observed effect. For non-time-to-event outcomes, the illustration is expressed as participants per arm for 80% power or 90% power; time-to-event illustrations are described in terms of total events. These are planning conventions, not observed trial outcomes, and they do not establish the design or analysis actually used in this single-group study.

General sample-size calculations estimate how much information a future study might need under specified assumptions. Their results depend on the assumed effect, variability or event frequency, significance level, allocation, and statistical model. A calculation based on an observed effect is especially uncertain as a planning guide because an observed effect can be imprecise. It is not observed power and does not show that the present study had adequate power. No trial-specific sample-size justification is reported in the registry record.

How should missing data and follow-up be considered?

Missing outcome information can affect both the estimate and its interpretation. If participants with missing assessments differ from those with observed assessments, a complete-case result may not represent the full enrolled group. General approaches include defining an analysis population, stating how missing observations are handled, and examining whether conclusions depend on those choices. The registry record does not report missing-data methods, numbers assessed at each time, or analysis populations. No missingness pattern or sensitivity analysis can be inferred.

Different follow-up assessments may also involve different available participants. A result at 6 months and a result at 12 months should be interpreted with its own denominator and assessment rules. The registry specifies both time points but does not say whether the primary analysis required data at both, how participants who stopped treatment were followed, or whether response classifications were centrally reviewed. These are not minor reporting details: they define which observations contribute to the estimate.

Why do multiple outcomes require care?

The registry lists six outcome measures, but it does not report an analysis plan or multiplicity procedure. In general, examining multiple outcomes or time points can increase the chance of apparently notable findings when many statistical tests are conducted. A prespecified hierarchy, adjustment method, or clear distinction between primary and exploratory outcomes can help readers interpret results. The record identifies a primary outcome and its time points, but does not state how multiplicity was addressed or whether analyses were prespecified. Since no analyses are recorded, no adjustment or unadjusted inference can be assessed.

In short, sound interpretation would require outcome counts with denominators, estimates with uncertainty, clear analysis populations, missing-data handling, and a documented statistical plan. These elements are not reported for the primary endpoint in the registry record. General statistical principles explain why they matter, but do not fill the reporting gaps.

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("Imatinib Mesylate")
n      <- c(25)
events <- c(13)
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  Imatinib Mesylate  25  13  52.0  31.3  72.2  33.5  70.0  33.4  70.1

11. Multiplicity, Missing Data and Analysis Populations

The registry lists six outcome measures, identifies complete cytogenetic response at 6 and 12 months as the primary outcome, and records zero analyses. It does not report a multiplicity strategy, such as an order for testing outcomes, an adjustment procedure, or a distinction between confirmatory and exploratory analyses. General statistical reasoning notes that testing multiple outcomes or time points can complicate interpretation because the chance of a chance finding may increase as more tests are considered. Without a reported analysis plan and results, it is not possible to determine whether or how that issue was addressed.

Missing-data information is also absent for the primary endpoint. The record does not give assessment denominators, counts of missing marrow results, reasons for missingness, or methods used to handle missing observations. It does not state whether participants who discontinued treatment remained under outcome follow-up. Those omissions prevent assessment of whether the observed participants, if any, would represent all enrolled participants.

The registry does not define an analysis population for efficacy, such as which participants would be included in the primary analysis. Enrollment of 25 should not be treated as an outcome denominator. Nor does the record identify a per-protocol, intention-to-treat, or other analysis population. These terms should not be assigned to the study without documentation.

Because the registry reports no primary endpoint analyses, there are no posted analysis estimates to evaluate for multiplicity or missing-data sensitivity. These are reporting limitations, not evidence that a particular method was or was not used outside the registry.

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: elevated aspartate aminotransferase (ast) and alanine aminotransferase (alt) (12.0%), fatigue (4.0%), bone pain (4.0%), diarrhea (4.0%), infection (4.0%).

The registry reports safety figures for a group titled Imatinib Mesylate. For serious events, it lists 25 at risk and 8 affected. For other events, it lists 25 at risk and 15 affected. These are counts in the registry record, not comparative treatment effects. The record does not provide a control group for a like-for-like comparison, and these counts alone do not establish that treatment caused an event.

The serious-event terms listed include elevated aspartate aminotransferase (AST) and alanine aminotransferase (ALT), reported as 12.0%, and fatigue, bone pain, diarrhea, infection, and rash, each reported as 4.0%. These percentages should be read as the registry’s reported figures for the listed terms; the record does not provide further detail about event onset, duration, severity grading, recurrence, or attribution. It also does not clarify how the term-specific percentages relate to the broader affected counts.

General safety interpretation depends on the event definitions, observation period, reporting rules, and number of participants assessed. Those details are not reported in the registry record. The deaths field is null, which is not a reported death count. The intervention list includes both imatinib mesylate and recombinant interferon alfa, while the safety group title names Imatinib Mesylate; the record does not explain this labeling difference.

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

The record establishes that a Phase 2 study was registered to examine imatinib mesylate with interferon alfa in chronic myelogenous leukemia in chronic phase. It describes a non-randomized, unmasked, single-group design and identifies complete cytogenetic response at 6 and 12 months as the primary endpoint. It also records enrollment of 25, a TERMINATED status, and selected safety counts.

It does not establish the frequency of complete cytogenetic response. Although the response categories and assessment times are defined, the registry record does not report response counts, denominators, estimates, or analyses. Therefore, the posted information cannot show the size or precision of an observed primary outcome. A defined endpoint is not itself evidence that a response occurred, and a registry status does not substitute for a results analysis.

The design also does not support a randomized comparison with another treatment or a control condition. General statistical interpretation of an uncontrolled group cannot separate treatment effects from other possible influences. Even if a response estimate were available, it would describe the observed group; it would not by itself demonstrate what would have happened under a different treatment.

The safety entries report affected counts and selected event-term percentages, but do not provide comparative estimates or detailed event definitions. They should be read as registry-reported observations, not proof of causation or a complete account of the safety profile. The registry does not report why the study was terminated, the extent of follow-up, or whether all planned outcomes were collected.

Overall, the record is informative about the study question, design, endpoint definition, and some safety reporting. It is insufficient for judging the primary efficacy outcome, its uncertainty, or a comparative benefit-risk balance. Missing results should not be interpreted as evidence that the intervention succeeded or failed.

14. Why This Trial Matters Statistically

This trial is statistically notable because its question and endpoint are stated more clearly than its results. The registry identifies a cytogenetic response definition and assessment times, allowing readers to understand what the primary outcome was intended to measure. At the same time, it reports no response counts or analyses. This contrast illustrates why a registered endpoint and a reported result are different parts of the evidence record.

The single-group, non-randomized design is another important feature. Such a design can describe outcomes among treated participants, but it does not create a randomized counterfactual. Statistical estimates from a single group may be useful descriptively, yet they cannot alone identify how outcomes would differ under another treatment. Recognizing that distinction prevents a within-group observation from being mistaken for a comparative effect.

The registry also illustrates the role of denominators. Enrollment is recorded as 25, but the endpoint is assessed at 6 and 12 months, and the number with evaluable measurements at each time is not stated. Without denominators and missing-data information, readers cannot know how much outcome information supports a response estimate or whether the assessed group differs from the enrolled group.

Finally, the record lists safety counts and term-specific percentages while leaving several interpretive details unreported. Event counts can be useful, but their meaning depends on definitions, follow-up, attribution, and comparison context. Taken together, these features make the study a useful example of how design, endpoint specification, analysis reporting, and completeness of registry results jointly shape statistical interpretation.

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 this trial from the registry record is the absence of posted primary endpoint results. The record specifies complete cytogenetic response at 6 and 12 months but does not report counts, denominators, effect estimates, uncertainty intervals, or analyses. The listed enrollment of 25 does not resolve this gap because the number assessed at either time point is not reported.

The single-group, non-randomized design limits comparative inference. No randomized control condition is described, so the registry record cannot support a like-for-like estimate of how outcomes compare with another treatment. The absence of masking is recorded, but assessment procedures and any safeguards against bias are not described.

Several features of the study conduct remain unclear. The official title describes dose-finding, but dose levels, schedules, escalation decisions, and dose-specific results are not reported. The registry does not explain the TERMINATED status, the effect of termination on follow-up, or whether all planned outcomes were collected. It also does not report eligibility details, participant characteristics, treatment adherence, or concomitant care.

Outcome interpretation is further limited by missing information on analysis populations, missing assessments, and the handling of participants who discontinued treatment. The registry lists six outcome measures but does not report a multiplicity strategy or statistical analysis plan. Safety reporting includes counts and selected percentages, but does not clarify event definitions, severity grading, attribution, observation periods, or the relationship between the safety group label and the combination described in the study purpose.

These limitations concern what can be concluded from the registry record. They do not establish that the unreported methods or results were absent from other study documents.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Imatinib Mesylate and Interferon Alfa in Treating Patients With Chronic Myelogenous Leukemia — NCT00015847.
• Registry record last updated 2025-08-22; status last verified 2025-08.
• Results first posted 2012-08-20.
• Data retrieved from ClinicalTrials.gov on 2026-11-09.
• Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.

19. Record Summary

The registry record describes a Phase 2, non-randomized, unmasked, single-group study of imatinib mesylate with interferon alfa in chronic myelogenous leukemia in chronic phase. Enrollment is 25. The study started in 2001-04, primary completion is listed as 2011-05, and status is TERMINATED.

The primary outcome is complete cytogenetic response at 6 and 12 months, with response categories defined by the percentage of Ph-positive metaphases in bone marrow. The record lists six outcome measures and zero analyses, but gives no primary response counts or estimates. Safety entries list 8 affected among 25 at risk for serious events and 15 affected among 25 at risk for other events. The reason for termination, analysis plan, missing-data methods, and detailed safety assessment procedures are not reported in the registry record.