Study of BMS-354825 (Dasatinib) in Patients With Chronic Myeloid Leukemia Who Are Either Resistant or Intolerant to Imatinib: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Study of BMS-354825 (Dasatinib) in Patients With Chronic Myeloid Leukemia Who Are Either Resistant or Intolerant to Imatinib (NCT00101660), a non-randomized phase 2 study. The primary outcome is Number of Imatinib-resistant Participants With Major Cytogenetic Response (MCyR).

2. Clinical Question

The study also aimed to assess effects of dasatinib in the stated population, identify side effects, and study drug levels in blood. Listed secondary outcomes include response counts and percentages, time to response, response without progression at specified follow-up times, major molecular response, and change in FACT-G questionnaire scores. Their titles describe planned outcome topics, but numerical results for them are not reported in the registry record.

3. Trial Design

This was a phase II, non-randomized, open-label study using a single-group model. Its title and eligibility description distinguish participants whose disease was resistant to imatinib from participants who were intolerant of it. Those categories are clinically and analytically different, but assignment to them was not randomized. The registry record lists enrollment of 387 and status as completed. The study began in 2005-02, with primary completion in 2006-09.

The intervention was dasatinib. The arm description specifies a starting regimen of 70 mg twice daily and allows escalation to 90 mg twice daily for participants with evidence of progression or lack of response. It also permits up to 2 dose reductions for intolerance. Thus, the regimen was not necessarily identical in dose or exposure for every participant over the study. The registry record does not report how many participants escalated or reduced their dose, the timing of those changes, or how treatment changes were handled in the primary analysis.

The primary endpoint concerns the number of imatinib-resistant participants who received treatment and achieved MCyR within a 2 years timeframe. This defined analysis population is narrower than the overall enrollment description, which includes both resistant and intolerant participants. The record does not provide a numerical primary outcome result or a detailed account of the number included in that endpoint analysis.

Because there was no randomized comparator and no masking, the study design primarily describes outcomes among people receiving dasatinib under the stated dosing rules. Comparisons between the resistant and intolerant groups, if considered, would not be randomized treatment comparisons. Differences could reflect the groups’ baseline characteristics, their reason for entering the study, treatment exposure, or other factors not described in the registry record. The record does not report a protocol, detailed allocation procedures beyond the non-randomized designation, or a full statistical analysis plan.

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: All imatinib-resistant participants who received treatment.

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 Number of Imatinib-resistant Participants With Major Cytogenetic Response (MCyR), measured over 2 years.

The primary endpoint is the number of imatinib-resistant participants with a major cytogenetic response (MCyR). It is defined by examining Philadelphia chromosome-positive (Ph+) metaphases among cells with metaphases in a bone marrow sample. A complete cytogenetic response (CCyR) means 0% Ph+ metaphases; a partial cytogenetic response (PCyR) means 1% to 35% Ph+ metaphases. MCyR combines these response categories.

Cytogenetic response is a way to describe the proportion of examined marrow cells carrying the Philadelphia chromosome. Reporting a response count can convey how many participants in the specified analysis population met the endpoint definition. The meaning of that count depends on knowing who was assessed, how missing assessments were handled, and what denominator was used. Those details, along with the actual response count, are not reported in the registry record.

The endpoint has a timeframe of 2 years and is restricted to imatinib-resistant participants who received treatment. It does not describe the intolerant group’s primary response, and it is not a comparison with a control treatment. A count alone would not show the precision of the estimated response frequency unless the relevant denominator and an uncertainty measure were also available. Neither a numerical result nor a confidence interval for this primary endpoint is reported in the registry record.

Other listed outcomes include hematologic and molecular response measures, response timing, and patient-reported functional assessment. These capture different aspects of disease status and participant experience; they are not interchangeable with the primary cytogenetic endpoint. Their numerical findings are not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does the primary endpoint count?

The primary outcome is a count of imatinib-resistant participants with MCyR, not a continuous measurement of change. The response definition uses the prevalence of Ph+ metaphases among cells with metaphases in a bone marrow sample. CCyR is defined as 0% Ph+ metaphases, and PCyR as 1% to 35%; together, these make up MCyR. The registry record specifies the population as all imatinib-resistant participants who received treatment and sets the timeframe at 2 years.

For a count to be interpreted fully, readers generally need the number meeting the endpoint and the number assessed or otherwise included in the analysis. The denominator matters because a count without its population size cannot show the proportion responding. The registry record does not report the primary result, its denominator, or a confidence interval. Consequently, neither the observed response frequency nor its uncertainty can be reconstructed from the information in the registry record.

What does a confidence interval add?

In general, a confidence interval expresses the statistical uncertainty around an estimate under the assumptions of the analysis. It helps distinguish a relatively precise estimate from one compatible with a broad range of values. It does not eliminate bias, correct an inappropriate comparison, or guarantee that the underlying assumptions hold. No confidence interval for the primary endpoint is reported in the registry record, so its precision cannot be evaluated this way.

What can a single-group design establish?

A single-group study describes outcomes among participants treated according to the study regimen. It lacks a randomized concurrent control group, so it does not directly estimate a treatment contrast against another assigned strategy. Randomization helps balance measured and unmeasured participant characteristics across treatment assignments, on average; that feature is absent. General statistical interpretation therefore separates observed outcomes under treatment from causal claims about what treatment changed.

The resistant and intolerant categories are not randomized arms. They are defined by the participant’s relationship to imatinib. A difference between categories, if reported, could reflect differences in disease history, tolerance, or other characteristics rather than a treatment effect. The registry record does not report a comparative analysis between these categories.

How should dose changes be considered?

The protocol description allows dasatinib escalation from 70 mg twice daily to 90 mg twice daily for evidence of progression or lack of response, and allows up to 2 dose reductions for intolerance. Such changes can make treatment exposure differ across participants. In general, analyses may define whether outcomes are evaluated according to initial treatment assignment, treatment actually received, or another specified population. The registry record does not report the primary analysis method, the handling of dose changes, or the frequency of escalation and reduction. No particular analysis approach should be inferred.

What is known about statistical planning?

The record identifies a phase II study and its primary endpoint but does not report a sample-size justification, target power, or the assumptions used to plan enrollment. It also does not report interim analyses, stopping rules, or a prespecified statistical analysis plan. These omissions mean it is not possible to determine from the registry record how the enrollment target was selected or whether any planned monitoring affected the reported analyses.

In general, sample-size planning depends on the endpoint, the effect the study is intended to detect, variability or event frequency, the chosen error rates, and the analysis design. Those are general considerations, not study-specific details. A study’s enrollment count does not itself show that it had adequate precision for every listed outcome, and power cannot be inferred from enrollment alone. The registry record does not report the assumptions needed for a study-specific assessment.

How should the listed secondary outcomes be read?

The registry lists secondary outcomes covering MCyR among imatinib-intolerant participants, response without progression at follow-up times, time to response, complete hematologic response, major molecular response, and FACT-G score change. The endpoint titles describe distinct estimands. A response count, a response percentage, a time-to-response summary, and a questionnaire score change answer different questions and require different analysis details.

The registry record lists 12 outcome measures and 0 analysis entries. This means numerical analysis results are not available in the record for interpretation; it does not establish that no analyses were conducted elsewhere. Outcome titles alone do not establish the definition of every analysis population, the handling of missing measurements, the censoring rules for time outcomes, or the statistical models used. Those methods are not reported in the registry record.

Why do missingness and follow-up matter?

In general, missing outcome measurements can affect estimates when participants who lack measurements differ from those who are assessed. Analyses may address this with specified assumptions or methods, but different approaches can yield different results. The registry record does not report the extent of missing primary endpoint data or the method used to handle missing assessments. It also does not give enough information to assess whether all participants had comparable follow-up through the 2 years timeframe.

Time-to-event outcomes, such as time from first dose to response, generally require rules for defining the event, the time origin, and censoring when the event is not observed during follow-up. The titles of the listed outcomes identify some time origins, but detailed analysis rules and numerical results are not reported. These general considerations cannot fill the gaps in the study-specific analysis 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("Dasatinib, 70 mg, Twice Daily (BID)")
n      <- c(288)
events <- c(159)
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  Dasatinib, 70 mg, Twice Daily (BID)  288  159  55.2  49.3  61.0  49.4  60.8  49.4  60.8

11. Multiplicity, Missing Data and Analysis Populations

The registry lists 12 outcome measures, including the primary MCyR count and multiple secondary response, timing, and questionnaire outcomes. When several outcomes are examined, the chance of at least one apparently notable result can increase if each is tested separately without adjustment. In general, multiplicity methods can address a prespecified family of tests, but the choice depends on which outcomes and comparisons are treated as a family.

The registry record does not report whether multiplicity was considered, whether any adjustment was used, or which outcome comparisons were designated as confirmatory. It lists 0 analysis entries, so no outcome-specific numerical analysis results or inferential procedures are available in the record. This absence does not establish that analyses or multiplicity procedures were not conducted; it means they are not reported in the registry record.

Missing-data methods are also not reported. The record does not state how participants without an endpoint assessment were handled, how much primary outcome information was missing, or whether any sensitivity analyses assessed alternative assumptions. For the secondary outcomes, detailed denominators and handling of missing assessments are likewise not reported.

The primary population is described as all imatinib-resistant participants who received treatment, but the record does not give the number of participants included in the primary analysis or clarify how post-enrollment exclusions and missing assessments affected that population. It also does not report the analysis population definitions for the secondary outcomes. These gaps limit assessment of whether the analyses preserve the stated population and how robust the findings would be to missing data. The actual primary result and the statistical plan are 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: pleural effusion (16.2%), pyrexia (9.0%), dyspnoea (8.1%), cardiac failure congestive (5.1%), pneumonia (5.1%).

The safety record separates participants into groups labelled Intolerant and Resistant. For serious adverse events, it reports 99 at risk and 48 affected in the Intolerant group, and 288 at risk and 146 affected in the Resistant group. For the other adverse-event category, it reports 99 at risk and 96 affected in the Intolerant group, and 288 at risk and 287 affected in the Resistant group. These are group-specific counts as recorded; they should not be treated as a randomized comparison.

The listed serious adverse-event terms and percentages are pleural effusion, 16.2%; pyrexia, 9.0%; dyspnoea, 8.1%; cardiac failure congestive, 5.1%; pneumonia, 5.1%; and diarrhoea, 3.5%. The registry record does not state in this summary whether participants could contribute to more than one term, so these percentages should not be added or interpreted as mutually exclusive categories. The record also does not give the event-term denominators or exposure-adjusted rates.

Counts at risk and affected describe reported participants, but do not by themselves show event timing, duration, severity beyond the serious-event classification, or how dose changes relate to events. Death counts are not reported in the registry record. The non-randomized design and lack of a like-for-like control group mean that these figures describe observed safety reporting in the study rather than a comparative estimate of risk.

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

The registry record establishes that a phase II study evaluated dasatinib among participants with chronic-phase Philadelphia chromosome-positive chronic myeloid leukemia who were resistant or intolerant to imatinib. It specifies an MCyR endpoint for the imatinib-resistant treated population, defines the cytogenetic response categories, and describes the dosing regimen and permitted dose changes. It also reports selected adverse-event counts and serious-event terms.

The record does not report the numerical primary endpoint result. It therefore does not establish how many imatinib-resistant participants achieved MCyR, what proportion that count represents, or how precisely a response frequency might be estimated. The fact that the trial is marked completed and has enrollment of 387 does not answer those endpoint questions. The titles of secondary outcomes likewise do not reveal their numerical results.

Even if an outcome estimate were available, the single-group, non-randomized design would not provide a randomized comparison with another treatment. Observed outcomes under the study regimen should not be read as the causal effect of dasatinib relative to an alternative. The resistant and intolerant groups are defined by imatinib status and are not interchangeable randomized groups.

The safety figures show reported counts for the two named groups and selected serious adverse-event terms. They do not establish comparative risk, and the registry record does not report death counts, exposure-adjusted event rates, or enough detail to reconstruct the event-term denominators. Safety interpretation also needs to account for the possibility of dose escalation and reduction, whose frequency and analytical handling are not reported.

In short, this record is useful for understanding the trial’s question, design, endpoint definition, and selected safety reporting. It does not provide the primary efficacy result, a complete statistical analysis, or the information needed for a controlled treatment-effect conclusion. These are limits of what is reported in the registry record, not evidence that unreported outcomes had any particular value.

14. Why This Trial Matters Statistically

The trial illustrates why a clearly defined endpoint and analysis population are essential to interpreting a clinical study. Here, the primary endpoint is not a general statement about disease response: it is a count of imatinib-resistant participants who received treatment and met a specified marrow cytogenetic response definition within a 2 years timeframe. The definition gives a concrete basis for identifying MCyR, using the prevalence of Ph+ metaphases and the stated CCyR and PCyR thresholds.

It also illustrates the distinction between study enrollment and analysis population. The record describes enrollment of 387 participants across resistant and intolerant categories, while the primary question applies to imatinib-resistant participants who received treatment. Without the primary count and its denominator, enrollment alone cannot communicate the response estimate or its precision.

The non-randomized single-group design is another important statistical feature. It can describe outcomes and safety observations under the study regimen, but it does not provide the protection against confounding that random assignment offers for a treatment comparison. Categorizing participants by resistance or intolerance does not create randomized comparator arms.

Finally, this record demonstrates the difference between an outcome being named and a result being reported. The primary endpoint is defined and several secondary outcomes are listed, but numerical findings and statistical analyses are not reported in the registry record. For clinical researchers, that distinction matters: endpoint definitions support understanding of what was intended to be measured, while estimates, denominators, uncertainty intervals, and analysis details are needed to judge what the data show.

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.

A key trial-specific limitation is the absence of the numerical primary MCyR result in the registry record. The endpoint definition and timeframe are present, but the count, denominator, and uncertainty estimate are not. This prevents assessment of the primary result’s size and precision from this record.

The design is non-randomized, unmasked, and single-group. There is no randomized control treatment against which to interpret outcomes, and the Resistant and Intolerant groups do not constitute randomized arms. Comparisons across these groups could be affected by differences associated with their imatinib status.

The intervention description allows escalation to 90 mg twice daily for evidence of progression or lack of response and up to 2 dose reductions for intolerance. The registry record does not report how often these changes occurred, how long participants received each dose, or how such changes were addressed in outcome analyses. This limits understanding of actual treatment exposure.

The record also lacks detailed information on the primary analysis population beyond its stated definition, missing outcome assessments, follow-up completeness, and methods for handling missing data. It does not report the statistical analysis plan, sample-size justification, interim analyses, or multiplicity procedures. Secondary outcome titles are available, but their numerical results and analysis details are not reported.

Safety interpretation is limited by the absence of reported death counts and details on event-term denominators, timing, and exposure-adjusted rates. The listed serious-event percentages cannot be assumed to represent mutually exclusive categories. These limitations describe what is not reported in the registry record; they do not imply a particular direction or magnitude for any unreported efficacy or safety finding.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Study of BMS-354825 (Dasatinib) in Patients With Chronic Myeloid Leukemia Who Are Either Resistant or Intolerant to Imatinib — NCT00101660.
• Registry record last updated 2012-03-02; status last verified 2012-02.
• Results first posted 2010-02-24.
• 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 completed phase II, non-randomized, unmasked, single-group study of dasatinib in chronic-phase Philadelphia chromosome-positive chronic myeloid leukemia among participants resistant or intolerant to imatinib. Enrollment was 387. The study began in 2005-02 and primary completion was in 2006-09. The regimen began at 70 mg twice daily, with escalation to 90 mg twice daily allowed for evidence of progression or lack of response and up to 2 dose reductions allowed for intolerance.

The primary endpoint was the number of imatinib-resistant participants who received treatment and achieved MCyR within 2 years. MCyR combines CCyR, defined as 0% Ph+ metaphases, and PCyR, defined as 1% to 35% Ph+ metaphases. The numerical primary endpoint result is not reported in the registry record. The record lists 12 outcome measures and 0 analysis entries.

Safety counts are reported for Intolerant and Resistant groups, along with selected serious adverse-event terms and percentages. Death counts are not reported. The design does not provide a randomized control comparison, and detailed methods for analysis, missing data, and multiplicity are not reported in the registry record.