A Phase II Study of Dasatinib in Children and Adolescents With Newly Diagnosed Chronic Phase Chronic Myelogenous Leukemia (CML) or With Ph+ Leukemias Resistant or Intolerant to Imatinib: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Phase II Study of Dasatinib in Children and Adolescents With Newly Diagnosed Chronic Phase Chronic Myelogenous Leukemia (CML) or With Ph+ Leukemias Resistant or Intolerant to Imatinib (NCT00777036), a non-randomized phase 2 study. The primary outcome is Major Cytogenetic Response (MCyR) Rate.

2. Clinical Question

The study asked whether dasatinib could be evaluated in children and adolescents across several leukemia settings: newly diagnosed chronic phase chronic myeloid leukemia (CP-CML), imatinib-resistant or imatinib-intolerant CP-CML, and Ph+ acute lymphoblastic leukemia (ALL) or accelerated- or blast-phase CML. These are distinct clinical groups, not interchangeable populations. The registry describes three cohorts, with Cohort 1 consisting of participants with imatinib-resistant or imatinib-intolerant CP-CML, Cohort 2 covering Ph+ ALL or accelerated- or blast-phase CML, and Cohort 3 covering newly diagnosed, treatment-naïve CP-CML.

The registry’s broad study purpose also refers to safety and to dasatinib use in the different leukemia settings. Its stated primary efficacy question, however, is narrower: MCyR in Cohort 1. Secondary outcomes include response measures in other cohorts, time to and duration of cytogenetic responses, and progression-free survival. The record does not report numerical results for those outcomes in the registry record for this analysis.

3. Trial Design

This was a Phase II, non-randomized, open-label study with a parallel model. The registry reports enrollment of 133 participants and describes three disease-based cohorts. Because allocation was not randomized and all described cohorts received dasatinib, the design does not provide a like-for-like control comparison. Cohort differences in disease status and prior treatment also mean that outcomes across cohorts cannot be interpreted as though the groups differed only in treatment.

Cohort 1 included participants with CP-CML resistant or intolerant to imatinib. The listed regimen was dasatinib 60 mg/m² as a daily tablet or 72 mg/m² as a daily powder for oral suspension. Cohort 2 included participants with Ph+ ALL or accelerated- or blast-phase CML, with listed daily doses of 80 mg/m² for tablets or 96 mg/m² for powder for oral suspension. Cohort 3 was for newly diagnosed, treatment-naïve CP-CML, with listed daily doses of 60 mg/m² for tablets or 72 mg/m² for powder for oral suspension. The cohort descriptions also give maximum doses for participants with high body surface area; some of those descriptions are incomplete in the registry record.

The regimen descriptions state a minimum treatment duration of 24 months and possible continuation while clinical benefit was being derived. The record gives a study start date of 2009-03-20, a primary completion date of 2016-09-01, and completed status. These dates describe the study record and do not establish an individual participant’s exposure or follow-up duration.

The registry lists 21 outcome measures, including the primary MCyR rate and secondary hematologic, cytogenetic, and progression-free-survival measures. It does not report a statistical analysis plan beyond the stated exact confidence-interval method for the primary endpoint. The original sample-size justification, interim analyses, and details of statistical testing are not reported in the registry record. The enrollment total should not be assumed to be the denominator for any particular outcome.

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.

Before assignment: The PK sub-study analysis is not part of the pre-specified primary and secondary outcome measures.

On Treatment

Reasons for not completing this period:

PK Sub-Study

Follow-Up

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Primary efficacy endpoint pre-specified only for participants treated in Cohort 1

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 Major Cytogenetic Response (MCyR) Rate, measured over From first dose of study therapy until 30 days after last dose (Assessed up to September 2016, approximately 90 months).

The primary endpoint is the MCyR rate among treated participants in Cohort 1. A major cytogenetic response is defined as either a complete response, with 0% Ph+ metaphases, or a partial response, with 1%-35% Ph+ metaphases among at least 20 metaphases assessed in bone marrow. The measure is a proportion: the numerator is the number of treated Cohort 1 participants achieving MCyR, and the denominator is all treated Cohort 1 participants. The registry expresses the rate as a percentage and specifies a 95% confidence interval calculated with the Clopper-Pearson exact method.

This endpoint captures a specified cytogenetic response rather than a comparison against another treatment. In general, a response proportion summarizes how often an event occurred in a defined analysis population; its interpretation depends on a clear numerator, denominator, response definition, and assessment window. The registry’s stated timeframe runs from the first dose through 30 days after the last dose, with assessment up to September 2016, approximately 90 months.

The numerical MCyR estimate and confidence interval are not reported in the registry record. Therefore, the endpoint definition and method can be described, but the response frequency and its precision cannot be evaluated from the record information. The endpoint is specified only for Cohort 1; it should not be generalized to all 133 enrolled participants or to the other cohorts.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary outcome is a binary response summarized as a percentage: each treated participant in Cohort 1 either met the MCyR definition or did not. The response criteria distinguish complete cytogenetic response, defined as 0% Ph+ metaphases, from partial response, defined as 1%-35% Ph+ metaphases among at least 20 bone-marrow metaphases. Either category counts toward MCyR. This definition sets the event being counted; it does not state how many participants experienced it.

What does the percentage represent?

In general, a percentage for a binary outcome is calculated from the number of participants meeting the event definition divided by the number in the relevant analysis population. The registry specifies that all treated Cohort 1 participants form the denominator and Cohort 1 participants achieving MCyR form the numerator. It does not report either count or the resulting percentage. Enrollment of 133 applies to the study as a whole and cannot stand in for the Cohort 1 denominator.

The distinction between enrolled, treated, and assessed participants matters. A registry may state a population for an endpoint without giving the actual number included in the analysis. The endpoint definition uses treated participants, but the number treated in Cohort 1 and the number with evaluable cytogenetic assessments are not reported in the registry record. The relationship between those counts, including whether missing assessments were counted as non-response or handled another way, is also not reported.

Why is a confidence interval useful?

The registry states that a 95% confidence interval for the MCyR rate was calculated using the Clopper-Pearson exact method. In general, a confidence interval represents uncertainty around an estimate arising from the observed sample. A narrower interval indicates greater precision under the stated method; a wider interval indicates less precision. For a proportion, an exact method is one approach to constructing an interval that respects the bounded nature of the measure. The numerical interval is not reported in the registry record, so its width and the precision of the endpoint estimate cannot be assessed.

The 95% label is a property of the interval procedure, not a statement that a particular treatment effect has a 95% probability of being true. It also does not resolve design limitations, missing outcome data, or differences in patient characteristics. The confidence interval would describe uncertainty in the Cohort 1 response proportion, not a randomized comparison with another treatment.

How should the endpoint timeframe be read?

The registry defines the assessment window as beginning with the first dose of study therapy and ending 30 days after the last dose. It states that the endpoint was assessed up to September 2016, approximately 90 months. This is a study-level timeframe; it does not mean that every participant received treatment or was followed for the same duration. Individual exposure and observation times are not reported in the registry record. The endpoint window also does not provide the timing of each response or establish response duration.

Other listed outcomes address different questions. Complete hematologic response and best cytogenetic response are response measures; time-to-response outcomes concern when a response was reached; duration outcomes concern how long a response persisted; and progression-free survival concerns time without progression or death as defined by the study. The registry lists these outcomes but does not give their numerical estimates, operational definitions beyond their titles, or analysis details in the registry record. They should not be treated as interchangeable measures.

What does non-randomized allocation imply?

In general, random allocation helps balance measured and unmeasured factors between treatment groups on average. This study is listed as non-randomized, with no masking and a parallel model. Its disease-based cohorts are not randomized arms, and the record does not describe a control treatment. Therefore, an outcome proportion in a cohort is descriptive of that cohort under the study conditions. It does not isolate the effect of dasatinib from differences in disease phase, prior treatment, patient characteristics, or other factors.

Open-label status means masking is listed as none. In general, awareness of treatment assignment can affect reporting, assessment, or decisions, depending on the outcome and study procedures. The record does not report what safeguards or independent assessment procedures, if any, were used for response evaluation. It is not appropriate to assume either that assessments were biased or that they were protected from bias.

What can planning illustrations tell a reader?

The record describes planning illustrations based on an observed effect, with a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. The effect to detect is described as a stated fraction of the observed effect. For time-to-event illustrations, the record says the quantity is total events; for other illustrations, it is participants per arm. These are planning assumptions, not observed trial outcomes or evidence of observed power. The original sample-size justification for the trial is not reported in the registry record, and numerical planning values are not included in the registry record for this analysis.

In general, over-dispersion matters when variability in the data is greater than a model assumes; ignoring it can make uncertainty appear too small. That concept is not a reported feature of this binary endpoint analysis, and the registry does not report an over-dispersion model. The primary endpoint instead has a stated exact binomial interval method. No additional inferential model, covariate adjustment, or hypothesis-testing procedure for the endpoint is 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("Cohort 1")
n      <- c(29)
events <- c(26)
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  Cohort 1  29  26  89.7  72.6  97.8  73.6  96.4  73.5  96.2

11. Multiplicity, Missing Data and Analysis Populations

The registry lists 21 outcome measures and identifies a primary MCyR rate for Cohort 1. It also lists secondary outcomes covering MCyR in Cohort 2, complete hematologic response in Cohorts 1 and 3, best cytogenetic response, time to and duration of MCyR and complete cytogenetic response, and progression-free survival. The multiplicity strategy for interpreting results across these outcomes is not reported in the registry record. In general, testing or estimating many outcomes raises the possibility of chance findings; without a stated adjustment or hierarchy, the record does not show how that issue was addressed.

The registry describes the primary endpoint’s numerator and denominator and names the Clopper-Pearson exact method for its 95% confidence interval. It does not report the numerical result, the number treated in Cohort 1, or the number with assessable response data. Nor does it state how missing or unevaluable cytogenetic assessments were handled. The handling of withdrawals, treatment discontinuations, or other incomplete follow-up for the endpoint is not reported in the registry record.

The analysis population is specified as all treated Cohort 1 participants for the primary endpoint. Other analysis populations, including any intention-to-treat-like population, per-protocol population, or safety population definition, are not reported in the registry record. The registry also gives no analysis entries, and details of interim analyses or a fuller statistical analysis plan are not reported. These omissions limit the ability to verify the analysis denominator, reproduce the endpoint estimate, or understand whether planned analyses differed from the posted results.

In general, missing data can affect an estimate when participants without an observed outcome differ from those with an observed outcome. The direction and magnitude of any such effect depend on the missingness pattern and analytic handling. Neither the amount nor the handling of missing endpoint data is available, so no specific effect of missingness can be inferred.

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: febrile neutropenia (33.3%), neutropenia (25.0%), pyrexia (25.0%), oral herpes (25.0%), chronic myeloid leukaemia transformation (25.0%).

The safety summary reports, for each listed group, the number at risk and the number affected by serious adverse events and other adverse events, as well as deaths. In Cohort 1, 16 of 29 participants were affected by serious adverse events and 27 of 29 by other adverse events; 1 death is listed. For Cohort 2: BP-CML Only, the corresponding counts are 7 of 8 and 7 of 8, with 4 deaths. For Cohort 2: Ph + ALL Only, the counts are 6 of 9 and 9 of 9, with 7 deaths. Cohort 3a lists 21 of 51 with serious adverse events and 50 of 51 with other adverse events, with 0 deaths. Cohort 3b lists 12 of 33 and 33 of 33, with 0 deaths. The PK Sub-Study lists 0 of 7 in each adverse-event category and 0 deaths.

The registry also lists febrile neutropenia at 33.3%, and neutropenia, pyrexia, oral herpes, chronic myeloid leukaemia transformation, and malignant neoplasm progression at 25.0% each among its top serious-event terms. The term-level denominators and cohort attribution are not reported in the registry record.

These are descriptive safety counts. They do not establish causality, compare risk against a control group, or account for differences in exposure time. The groups are small and differ in disease setting; the counts should not be read as a randomized comparison. Event timing, duration, severity details, and the relationship of deaths to treatment are not reported in the registry record.

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

The registry record makes clear which primary efficacy measure was intended: the proportion of treated Cohort 1 participants with complete or partial cytogenetic response, assessed from first dose through 30 days after the last dose. It also names the method used for a 95% confidence interval. Those definitions support an understanding of the planned endpoint, but they do not supply its observed result.

Without the response numerator, denominator, percentage, and confidence interval, the MCyR frequency and its statistical precision cannot be judged. There is no basis in the record information for saying how frequently participants achieved the endpoint, whether an estimate was precise, or how it compares with a threshold or another treatment. The absence of a numerical result is not evidence of no response; it means the result is not reported in the registry record.

Even if the cohort response estimate were available, the non-randomized design would limit causal interpretation. A response proportion in a treated group is not the same as a treatment-versus-control effect. Differences between Cohorts 1, 2, and 3 would reflect distinct disease and treatment-history groups as well as any other group differences, so they cannot be interpreted as randomized comparisons.

The adverse-event counts provide a separate descriptive view of safety reporting. They indicate how many participants in each listed group were affected, but do not establish that dasatinib caused the events. There is no randomized control group for a comparative safety estimate, and event timing, exposure-adjusted rates, and attribution details are not reported in the registry record. The death counts likewise should not be interpreted as treatment-related deaths without reported attribution.

In general, statistical precision and clinical importance are different considerations. A confidence interval can help describe uncertainty around an estimate, while clinical importance depends on context and the consequences of the outcome. Neither can be fully evaluated for the primary efficacy endpoint without its numerical result and relevant comparison context. The record supports a description of the design, endpoint, and available safety counts, but not a conclusion about comparative efficacy or causation.

14. Why This Trial Matters Statistically

This study is statistically notable because it addresses several pediatric leukemia settings within one non-randomized Phase II study while defining the primary efficacy question for only one cohort. The distinction between the broad enrolled population and the endpoint population is essential: the registry reports enrollment of 133, but states that the MCyR denominator consists of all treated Cohort 1 participants. Those populations should not be conflated.

The endpoint definition is relatively explicit about the cytogenetic response categories, the minimum metaphase assessment, the response denominator, and the named exact confidence-interval method. This illustrates why reporting a measure’s operational definition is important: readers need to know what counted as an event and who was counted before interpreting a percentage. Yet the numerical estimate and interval are not reported in the registry record, leaving the endpoint’s observed frequency and precision unknown.

The non-randomized design is also central. Distinct disease settings and prior-treatment histories are represented in the cohorts, and no randomized control group is described. The study can therefore be read as a set of cohort observations, not a controlled estimate of differences attributable to treatment. Open-label status and unreported response-assessment safeguards further define what can be assessed from the registry entry.

Finally, the record shows how outcome definitions and safety counts may be available while key analysis details remain absent. The registry lists numerous outcomes but does not report a multiplicity strategy, missing-data handling, or a fuller analysis plan. For clinical researchers, these gaps underscore the value of reporting denominators, uncertainty intervals, analysis populations, and outcome handling alongside point estimates.

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 efficacy result is not reported in the registry record. The MCyR percentage, confidence interval, numerator, and treated Cohort 1 denominator are absent, preventing assessment of the observed response frequency and precision. Total enrollment of 133 does not resolve this because the endpoint population is narrower and defined by treatment in Cohort 1.

The study is non-randomized and has no stated control group. Consequently, the record does not support a direct comparative treatment-effect estimate. Its disease-based cohorts differ in clinical setting and prior treatment, so contrasts between them would not isolate treatment effects. The study is also open-label, while response-assessment masking or independent review procedures are not reported in the registry record.

Handling of missing or unevaluable endpoint data is not reported. The analysis populations for outcomes other than the defined primary endpoint, as well as the original sample-size justification, interim analyses, and a full statistical analysis plan, are not reported in the registry record. A multiplicity approach for the 21 listed outcomes is also not given. These gaps constrain reproducibility and interpretation of any endpoint estimates not included in the record.

Safety figures are presented by listed groups, but the registry information does not give exposure-adjusted rates, detailed event timing, full severity information, or treatment attribution for deaths and adverse events. Top serious-event terms are listed with percentages, but their denominators and cohort attribution are not reported. The group counts are descriptive and do not substitute for a controlled safety comparison.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: A Phase II Study of Dasatinib in Children and Adolescents With Newly Diagnosed Chronic Phase Chronic Myelogenous Leukemia (CML) or With Ph+ Leukemias Resistant or Intolerant to Imatinib — NCT00777036.
• Registry record last updated 2025-08-29; status last verified 2025-08.
• Results first posted 2018-01-05.
• 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

NCT00777036 is a completed, non-randomized, open-label Phase II study of dasatinib in children and adolescents with several leukemia settings. The registry reports enrollment of 133 and describes three cohorts: imatinib-resistant or imatinib-intolerant CP-CML; Ph+ ALL or accelerated- or blast-phase CML; and newly diagnosed, treatment-naïve CP-CML. The primary efficacy endpoint is MCyR rate in treated Cohort 1, with a 95% confidence interval specified by the Clopper-Pearson exact method.

The record lists secondary response, response-time, response-duration, and progression-free-survival outcomes, as well as cohort-level adverse-event counts and deaths. The numerical primary efficacy result, its confidence interval, and several key analysis details are not reported in the registry record. The available information supports describing the design and endpoint definition, but does not establish a comparative treatment effect or causal interpretation of safety events.