Phase II Nilotinib With Newly Diagnosed Chronic Phase Chronic Myelogenous Leukemia (CML): Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Phase II Nilotinib With Newly Diagnosed Chronic Phase Chronic Myelogenous Leukemia (CML) (NCT00129740), a na phase 2 study. The primary outcome is Participants With Complete Molecular Response (Molecular CR).

2. Clinical Question

3. Trial Design

This was a Phase II, single-group clinical trial sponsored by M.D. Anderson Cancer Center. It enrolled 148 participants and is marked completed in the registry. The registry lists the study start as 2005-06-27 and primary completion as 2018-07-11. Those dates describe the registered study timeline; they do not, on their own, explain how long each participant was followed.

The intervention was nilotinib, a drug, at a described dose of 400 mg orally twice daily. Allocation is listed as not applicable, masking as none, and the study model as single group. The registry does not list a separate comparator arm. Thus the design is not a randomized comparison, and outcomes should be read as observations from participants in the nilotinib group rather than as a treatment contrast.

The primary outcome measure was the number of participants with complete molecular response at 12 months. A secondary outcome measure was the number of participants with complete cytogenetic response (CCyR). The record lists two outcome measures in total, but does not report results for either outcome or describe the analyses used to produce results. The number of analyses listed is zero.

The study title and brief description frame the population as newly diagnosed chronic phase CML, but detailed eligibility rules, recruitment procedures, and the basis for the planned enrollment are not reported in the registry record. The registry also does not report how treatment exposure or follow-up was handled for participants who stopped treatment, withdrew, or lacked an outcome assessment. These omissions limit what can be concluded about the conduct of the study beyond its registered design and intervention.

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 Participants With Complete Molecular Response (Molecular CR), measured over 12 months.

The primary endpoint counts participants who met the registry definition of complete molecular response at 12 months. That definition is a PCR ratio of BCR-Abl/Abl of 0% after 12 months of nilotinib therapy, by international standard. It is a binary outcome at the participant level: each participant either meets the specified response definition or does not. The endpoint is expressed as a count of participants, rather than as a continuous PCR measurement or a time-to-event outcome.

Molecular response is used as a measure of disease-related molecular findings under the stated assay definition. The specified threshold and assessment time make the endpoint interpretable in principle: the result would indicate how many assessed participants met that definition at the stated time. The registry record does not describe the assay procedures, the handling of results below or above detection limits, or the rules for classifying missing or unevaluable tests.

The endpoint result itself is not reported in the registry record. Consequently, there is no posted count or proportion to interpret, and no estimate of uncertainty for this endpoint can be described from the record. The secondary endpoint is the number of participants with CCyR, but its result is also not reported. These outcome definitions identify what the study intended to measure; they are not evidence of the observed response.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary outcome is a binary participant-level endpoint. Each participant is classified according to whether the PCR ratio meets the complete molecular response definition at 12 months. For a binary endpoint, a basic descriptive summary would report the number meeting the definition and the number assessed. A proportion could then describe the observed frequency among the relevant analysis population. The registry record identifies the outcome as a participant count, but does not report either the response count or the number assessed for that endpoint.

What would an uncertainty interval describe?

In general, a confidence interval gives a range of estimates compatible with the observed data under a specified statistical method and its assumptions. For a response proportion, it would express uncertainty about the underlying frequency represented by the observed participants. Its width depends on the estimate, the amount of outcome information, and the method used. The interval would not remove the limitations of a single-group design, and it would not turn a descriptive response estimate into a controlled treatment effect. No confidence interval or interval method is reported in the registry record.

For binary data, statistical methods commonly begin with the observed count and denominator. The choice of method matters, particularly when counts are sparse or when an estimated proportion is near a boundary. General methods may use different approximations or exact calculations and can yield different interval limits. The registry record does not identify a method for the primary response endpoint, so no specific estimation or interval procedure should be attributed to this trial.

What does the single-group design allow?

A single-group study can describe the outcomes recorded among its participants. It does not provide an internal control group for estimating how those outcomes would have differed under another treatment or no treatment. In general, random allocation to comparison groups helps make groups comparable with respect to both measured and unmeasured factors, on average. That mechanism is absent from the design described in this record: allocation is not applicable, masking is none, and the model is single group. The registry does not report a comparative effect estimate.

Masking can reduce some forms of bias in outcome assessment or participant and clinician behavior, depending on the setting and outcome. Here, masking is listed as none. The record does not explain whether the molecular outcome assessment was performed with any safeguards against knowledge of treatment, or how the assay result was classified. The absence of masking information should therefore be interpreted as a design characteristic, not as evidence that a particular bias occurred.

How should the planning assumptions be read?

The registry describes a sample-size illustration based on a fraction of an observed effect. It specifies a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. These are planning assumptions for a hypothetical two-arm comparison, while the registered trial is single group. They do not describe the actual allocation or analysis of this study. The effect estimate, the chosen fractions, and the resulting participant counts are not reported in the registry record, so no planning values can be evaluated from the information available.

In general, a sample-size calculation estimates how much information may be needed to detect a prespecified effect under stated assumptions. Its output depends on the target effect, variability or event frequency, error rates, allocation, and analysis method. A planning calculation is not an observed result and does not show that a study had a particular probability of detecting an effect after it was completed. No observed-power interpretation is warranted from the registry information. The two-arm illustration should not be read as the study's own design or as evidence that the trial was adequately sized.

What is the role of over-dispersion?

For a binary outcome modeled as a count, standard binomial methods rely on assumptions about the relationship between the count's variability and its denominator. In general, over-dispersion means that variability is greater than a model assumes; if present and ignored, uncertainty estimates can be too narrow. This is a general statistical concept, not a finding about this study. The registry record does not report a model, a dispersion assessment, or enough endpoint data to assess over-dispersion.

Finally, the record lists two outcome measures and zero analyses. It does not report a prespecified statistical analysis plan, an analysis population, a method for missing outcomes, or adjustment for multiple outcome testing. Those details are needed to understand how endpoint results would have been selected, estimated, and interpreted. Their absence does not prove that procedures were not used; it means they are not reported in 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("Nilotinib")
n      <- c(148)
events <- c(23)
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  Nilotinib  148  23  15.5  10.1  22.4  10.6  22.2  10.6  22.3

11. Multiplicity, Missing Data and Analysis Populations

The registry lists two outcome measures: complete molecular response as the primary outcome and complete cytogenetic response as a secondary outcome. It lists zero analyses, and neither outcome result is reported in the registry record. No multiplicity adjustment or testing hierarchy is described. With multiple outcomes, general statistical practice distinguishes a primary question from additional questions and considers how repeated testing can affect the chance of false-positive findings. The record does identify the primary outcome, but does not say whether or how any multiplicity procedure was planned or applied.

Missing-data handling is not reported in the registry record. The record does not state how participants without a 12-month PCR assessment were classified, whether the endpoint was analyzed only among those assessed, or whether any imputation or sensitivity analysis was used. These choices can affect the denominator and interpretation of a binary response count. Without the outcome count, assessment denominator, and missing-data rules, the primary endpoint cannot be reconstructed or evaluated.

The analysis population is also not reported. It is not stated whether outcomes were intended to be analyzed for all enrolled participants, only participants who began or continued treatment, or another defined group. The enrollment count of 148 should not automatically be treated as the denominator for the primary endpoint. The safety record lists 148 participants at risk for both serious and other adverse events, but those safety denominators do not establish the analysis population for molecular response. These are reporting gaps, not evidence about which methods were used.

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: abdoninal pain (5.4%), cardiac chest pain (4.1%), cardiac ischemia/infarction (3.4%), cns ischemia (2.0%), dyspnea (2.0%).

The registry lists 148 participants at risk for serious adverse events, with 47 affected, and 148 at risk for other adverse events, with 148 affected. It also records 7 deaths in the nilotinib group. These figures describe the entries in the safety record. They do not, on their own, establish that nilotinib caused any particular event or death, and there is no comparator group in this study for a direct safety contrast.

The registry lists the following serious adverse event terms and percentages: Abdoninal Pain, 5.4%; Cardiac Chest Pain, 4.1%; Cardiac ischemia/infarction, 3.4%; CNS Ischemia, 2.0%; Dyspnea, 2.0%; and Pain, 2.0%. The spelling of “Abdoninal Pain” is as recorded. The record does not explain whether these percentages use participants or events as their denominator, or whether a participant could appear under more than one term. They should therefore be read as listed category figures, not summed or interpreted as mutually exclusive groups.

Definitions of event collection, follow-up duration, severity grading, and relatedness assessment are not reported in the registry record. The counts alone cannot describe when events occurred, their duration, or how they were judged in relation to treatment.

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

The registry establishes that a Phase II, single-group study evaluated nilotinib in a population described as newly diagnosed chronic phase CML. It specifies the primary outcome as complete molecular response at 12 months, defined by a PCR ratio of BCR-Abl/Abl of 0% by international standard. It also records enrollment of 148 participants and provides some safety counts. These details describe the study question, design, and selected registered results.

The central efficacy result is missing: the number of participants who met the primary endpoint is not reported in the registry record. The secondary CCyR result is also not reported. Consequently, the record cannot establish the observed frequency of either response, quantify uncertainty around those outcomes, or support a conclusion about how the study's participants fared on those endpoints.

Even if a response count were available, the single-group design would limit what it could show. An outcome frequency in participants receiving nilotinib would be descriptive; it would not directly estimate what would have happened to comparable participants under another treatment or no treatment. The study has no registered control group, and the record does not provide a randomized comparison. Any treatment-effect claim would require evidence beyond the comparative design information.

The safety entries should be interpreted with similar care. They document counts and listed serious-event terms, but do not establish causation or allow a relative safety comparison. The registry does not report enough information about event definitions, follow-up, or attribution to resolve those questions.

Overall, the record is more informative about the registered design and endpoint definitions than about efficacy. The study's completion status does not substitute for outcome results. Missing analysis details also prevent assessment of how outcomes, missing observations, or multiple endpoints were handled. Conclusions should remain limited to the registry entries explicitly recorded: a single-group nilotinib study, its planned outcome definitions, and the safety counts that are listed.

14. Why This Trial Matters Statistically

This trial illustrates why outcome definitions and outcome results must be read separately. The registry gives a precise primary endpoint: a participant count based on a specified molecular threshold at 12 months. That definition makes clear what the study intended to measure. Yet the absence of the endpoint count means that the clinical result itself cannot be assessed from the registry record. A well-specified measure is not a substitute for a reported estimate.

The design also matters statistically. A single group can describe outcomes under the study conditions, but it cannot provide a direct within-trial comparison against another treatment. Readers should distinguish a response frequency from a comparative treatment effect. The registered design states there was no randomized comparison, so any causal interpretation would need evidence not contained in this record.

The record further demonstrates that enrollment, analysis, and safety denominators are not interchangeable. Enrollment is 148, and the safety entries use 148 participants at risk. However, the primary response denominator is not reported. Without knowing how many participants had evaluable 12-month assessments or how missing results were handled, the response count and its uncertainty remain unavailable.

Finally, the sample-size assumptions describe a two-arm planning illustration, whereas the registered trial is single group. This distinction is important: planning assumptions are not observed study findings, and hypothetical calculations should not be mistaken for the actual design or evidence of achieved precision. The record's missing analysis details underscore the value of reporting estimates, uncertainty intervals, analysis populations, and missing-data methods alongside endpoint definitions.

15. Limitations

• The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
• Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.

The main limitation for statistical interpretation is the absence of posted outcome results. The primary complete molecular response count and the secondary CCyR count are not reported in the registry record, and no analyses are listed. As a result, there is no efficacy estimate or uncertainty measure to interpret.

The design is single group, with allocation not applicable and no masking. There is no concurrent control group in the registry record, so the study does not provide a randomized treatment contrast. The record also does not report the eligibility criteria in detail, the analysis population, or the rules for handling missing endpoint assessments. These gaps prevent readers from determining who contributed to the primary endpoint denominator and how incomplete follow-up was addressed.

Statistical planning and analysis details are limited. A planning illustration is described using equal allocation between two arms and a normal approximation, but its effect inputs and resulting values are not reported in the registry record. Those assumptions do not match the registered single-group design. The record does not describe the primary analysis method, uncertainty estimation, multiplicity handling, or sensitivity analyses.

Safety interpretation is also constrained. Although participant counts and selected serious-event terms are listed, definitions and collection methods are not reported, nor is the basis for judging whether events were related to treatment. The record does not provide a comparator for safety rates. These limitations concern what can be learned from the registry record; they do not establish that unreported methods or assessments were absent from the trial itself.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Phase II Nilotinib With Newly Diagnosed Chronic Phase Chronic Myelogenous Leukemia (CML) — NCT00129740.
• Registry record last updated 2019-09-24; status last verified 2019-09.
• Results first posted 2019-09-11.
• 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

NCT00129740 is a completed Phase II, single-group study titled “Phase II Nilotinib With Newly Diagnosed Chronic Phase Chronic Myelogenous Leukemia (CML),” sponsored by M.D. Anderson Cancer Center. The registry lists enrollment of 148 participants, nilotinib at 400 mg orally twice daily, no masking, and no comparator group. The study start is recorded as 2005-06-27 and primary completion as 2018-07-11.

The primary outcome was the number of participants with complete molecular response at 12 months, defined by a PCR ratio of BCR-Abl/Abl of 0% by international standard. Complete cytogenetic response was listed as a secondary outcome. Neither outcome result is reported in the registry record, and zero analyses are listed. Safety entries record 47 of 148 participants with serious adverse events, 148 of 148 with other adverse events, and 7 deaths; the record does not establish causation. Analysis populations, missing-data procedures, and multiplicity methods are not reported.