A Study That Switched Patients From Imatinib to Nilotinib and Then Was Followed by Treatment Cessation: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Study That Switched Patients From Imatinib to Nilotinib and Then Was Followed by Treatment Cessation (NCT01744665), a na phase 2 study. The primary outcome is Percentage of Participants Without Molecular Relapse Within 6 Months After Starting the TFR Phase.

2. Clinical Question

The study is listed as phase II and completed. The registry describes an approach in which treatment is stopped only after molecular response has been achieved and sustained. The primary question is consequently about outcomes in people reaching the treatment-free phase, rather than in everyone enrolled at the start of the study. The number entering that phase is not reported in the registry record, so the size and characteristics of the endpoint population cannot be determined from the posted information.

3. Trial Design

This is a phase II, multicenter study in chronic-phase chronic myeloid leukemia. The record lists 59 participants as enrolled, identifies nilotinib as the intervention, and classifies the model as single group. Allocation is recorded as NA and masking as none. The study status is completed. Its recorded start date is 2013-08-12 and primary completion date is 2018-09-28.

The title and official title describe switching from imatinib to nilotinib, followed by an assessment of treatment-free remission in patients achieving and sustaining MR4.5. The arm description says patients entered a monitoring phase lasting 2 years and received 300 mg nilotinib bid. Those achieving MR4.5 entered a consolidation phase and received nilotinib for 2 years. If MR4.5 was sustained during consolidation, they were eligible to stop nilotinib. The arm description is truncated at the point where it begins to describe the period after stopping treatment, so further details of that phase are not reported in the registry record.

The official title calls the study randomized, but the registry design fields list allocation as NA and the model as single group. There is no separately described control arm or basis for a between-group comparison. The record’s wording therefore does not establish a randomized comparative design. The registry does not report a protocol-level explanation of the design-field discrepancy, the method used to select participants for each phase, or the number who advanced through the treatment sequence.

The stated aim is to evaluate molecular relapse-free rates 6 months after stopping nilotinib in patients who achieve MR4.5. Secondary outcomes include relapse-free survival after discontinuation, remaining without molecular relapse at later time points, regaining MR4.5 after restarting nilotinib, progression or death, overall survival, symptom burden, health utility, and quality of life. The record lists 14 outcome measures, but does not provide analysis records for these outcomes. Specific analysis populations and the handling of participants who did not reach the treatment-free phase are not reported in the registry record.

4. Participant Flow and Accounting

The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.

Monitoring Phase

Reasons for not completing this period:

Consolidation Phase

Reasons for not completing this period:

Treatment Free Remission Phase

Re-initiation Phase

Reasons for not completing this period:

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 Percentage of Participants Without Molecular Relapse Within 6 Months After Starting the TFR Phase, measured over 6 months after stopping nilotinib therapy.

The primary endpoint is the percentage of participants without molecular relapse within 6 months after starting the treatment-free remission phase. Its intended denominator is participants who entered that phase, not everyone enrolled at the beginning of the study. The endpoint is meant to describe how often the specified molecular-relapse event was not documented during the stated follow-up period after nilotinib discontinuation.

The registry description contains a definition that needs careful reading. It says the percentage is calculated from participants with no documented confirmed loss of MR4 during the first 6 months, while defining molecular relapse as a confirmed BCR-ABL ratio above MMR: 2 consecutive BCR-ABL levels >0.1% IS taken approximately 4 weeks apart. The endpoint title refers to molecular relapse, and the description also uses both MR4 and MMR terminology. The record does not resolve this wording difference, so the precise endpoint threshold cannot be inferred beyond the stated language.

In general, a molecular endpoint can capture a laboratory-defined change before a clinical event such as progression or death. A fixed follow-up window makes the question specific to a particular period after treatment cessation. However, a percentage is interpretable only alongside its numerator, denominator, and method for handling missing or incomplete follow-up. None of those primary endpoint results is reported in the registry record. No confidence interval or other estimate of precision is reported either.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

Statistical interpretation begins by identifying the question, population, outcome, and time horizon. In this study, the primary question concerns the percentage without molecular relapse during the first 6 months after starting the treatment-free remission phase. The target population for that calculation is defined by entry into that phase. It is not automatically the same as the full enrolled population. The registry reports enrollment of 59 but does not report the number entering the treatment-free phase or the number included in an endpoint analysis.

What does a percentage estimate?

In general, a percentage is the observed number meeting a condition divided by the number assessed under the stated endpoint definition. Its interpretation depends on both parts of that calculation and on how missing observations are treated. Here, the registry provides the endpoint description but no numerator, denominator, or primary estimate. As a result, neither the value nor its precision can be reconstructed from the posted record. The enrollment count cannot be substituted for the missing endpoint denominator, and no calculation should assume that everyone enrolled reached the treatment-free phase.

How should the molecular event be defined?

For an endpoint to be reproducible, the event rule needs to specify what measurement qualifies, when it is assessed, and whether confirmation is required. The record describes molecular relapse as a confirmed BCR-ABL ratio above MMR, with 2 consecutive BCR-ABL levels >0.1% IS taken approximately 4 weeks apart. It also describes the endpoint numerator as participants with no documented confirmed loss of MR4. The record does not reconcile the MR4 and MMR wording. This matters statistically because changing the event threshold can change who is classified as having relapsed, even when the underlying measurements are the same.

What does uncertainty mean?

In general, a confidence interval describes the range of values reasonably compatible with the observed data under the analysis assumptions. A narrow interval indicates greater precision than a wide interval, though precision does not establish that an endpoint definition is clinically appropriate or that a result is causal. No confidence interval is reported for the primary endpoint. There is also no reported estimate from which to assess whether any interval would be informative. A p-value, if reported, would address compatibility with a specified statistical hypothesis; it would not replace an estimate or describe the magnitude of an outcome. No primary p-value is reported in the registry record.

How does the design affect interpretation?

The registry describes the model as single group and allocation as NA, with masking recorded as none. General statistical principle: a single-group outcome can describe what occurred among participants who received the study strategy, but it does not provide the concurrent counterfactual outcome needed for a direct treatment comparison. Differences from an external expectation could reflect selection, monitoring, follow-up, or other factors, as well as the intervention. No control arm is described in the registry record. The official title’s use of “Randomized” does not by itself supply a comparator or clarify the registry’s design fields.

The study’s sequence also creates distinct populations: those enrolled, those reaching MR4.5, those entering consolidation, those sustaining MR4.5, and those eligible to stop treatment. The registry does not report counts for these transitions. General statistical principle: when analysis is restricted to participants who reach a later treatment phase, the result describes that selected group and cannot be generalized automatically to everyone at initial enrollment. The selection process and the characteristics of the later-phase group would be relevant to interpretation, but those details are not reported in the registry record.

What can be learned from time-to-event outcomes?

One listed secondary outcome is relapse-free survival, defined as time from nilotinib discontinuation to the first documented molecular relapse. In general, time-to-event methods use both whether an event occurred and how long participants were followed. Participants without a recorded event by the end of observation may be censored, meaning their later event status is unknown. Proper interpretation depends on the time origin, event definition, follow-up, and censoring rules. The registry lists the outcome but reports no analysis or results for it. The same limitation applies to the listed overall-survival outcome.

What is the role of a planning calculation?

In general, sample-size planning asks how much information may be needed to estimate or detect an effect under stated assumptions. Such calculations are prospective illustrations, not evidence that a study had a particular probability of detecting an effect after completion. No sample-size justification or planning assumptions for this trial are reported in the registry record. No observed power can be inferred from the enrollment count or from the absence of endpoint results. The record also does not report an interim-analysis plan or a statistical analysis plan.

The registry lists 14 outcome measures, but a list of outcomes does not establish how they were prioritized or analyzed. General statistical principle: when many outcomes or repeated assessments are tested, the chance of at least one chance finding can increase if multiplicity is not addressed. The registry record does not report a multiplicity strategy. Without analysis results, test specifications, and population definitions, there is no basis for a more detailed statistical reconstruction.

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("Treatment Free Remission")
n      <- c(32)
events <- c(12)
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  Treatment Free Remission  32  12  37.5  21.1  56.3  22.9  54.7  22.9  54.9

11. Multiplicity, Missing Data and Analysis Populations

The registry lists 14 outcome measures, including the primary molecular-relapse endpoint and secondary measures of relapse-free survival, later molecular status, response after restarting nilotinib, progression or death, overall survival, symptoms, health utility, and quality of life. It does not report how the primary and secondary outcomes were prioritized for statistical testing or whether any multiplicity adjustment was planned. The registry record does not report an analysis plan or interim analyses. Therefore, the interpretation of any potential family of statistical tests cannot be assessed from the posted information.

Missing-data procedures and analysis populations are also not reported in the registry record. In particular, the record does not state how participants with incomplete molecular monitoring, missing assessments, or discontinuation before the endpoint window would be handled. It does not report how many participants entered the treatment-free phase or contributed endpoint data. These omissions prevent assessment of whether the primary percentage would represent all phase entrants or a subset with available observations.

General statistical principle: missingness can affect an estimate if the likelihood of having an observed outcome is related to the outcome itself or to characteristics associated with it. Different assumptions about missing observations can lead to different estimates. No such assumptions or sensitivity analyses are reported. The registry lists 0 analysis records, so there are no posted analysis populations or missing-data results to evaluate. The impact of missingness and multiplicity on the study findings is therefore not quantifiable from the registry record.

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: abdominal pain (3.4%), cardiac failure (1.7%), coronary artery disease (1.7%), myocardial infarction (1.7%), pericardial effusion (1.7%).

The registry safety figures list 59 participants at risk for serious adverse events and 19 affected. It also lists 59 at risk and 59 affected in the other adverse-event category. No deaths are listed. These are aggregate safety counts in the registry record; they do not establish whether events were related to nilotinib or whether an event caused treatment discontinuation. The record does not provide enough detail to determine the observation period or the participant-level distribution of events.

The listed serious adverse-event terms and percentages are abdominal pain, 3.4%; cardiac failure, 1.7%; coronary artery disease, 1.7%; myocardial infarction, 1.7%; pericardial effusion, 1.7%; and hypoaesthesia oral, 1.7%. These entries describe the reported terms and percentages, not a comparison with another group. They should not be added together: participants may have experienced more than one event, and the registry does not provide a rule establishing that the terms are mutually exclusive.

In general, safety counts depend on the event definitions, collection period, and population monitored. The record does not report comparative safety estimates or enough detail to interpret the listed terms as causal effects. The figures should be read as registry-reported observations, not as evidence that an event was caused by treatment or as a complete safety assessment.

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

The registry record establishes that this completed phase II study examined a treatment-free remission strategy involving nilotinib in chronic-phase CML. It describes a primary question about remaining free of molecular relapse during the first 6 months after starting the treatment-free phase and gives a rule for molecular relapse. It also outlines monitoring, consolidation, and eligibility to stop treatment after sustained MR4.5. The record does not report the primary endpoint estimate, so it does not show what percentage met the endpoint or how precisely that percentage was estimated.

The design information matters. The registry identifies a single-group model and allocation as NA, and it does not describe a like-for-like control group. Consequently, the record cannot support a comparative estimate between nilotinib and another treatment strategy. It also cannot establish that an observed outcome, if reported elsewhere, was caused by stopping treatment or by any particular part of the sequence. The official title’s reference to randomization is not enough to resolve the discrepancy with the registry design fields.

The study question applies to participants reaching the treatment-free remission phase, not necessarily to everyone initially enrolled. The registry does not report how many participants reached that phase or the primary analysis denominator. This limits assessment of how broadly any phase-specific outcome might apply. Further, the endpoint description uses both MR4 and MMR terminology without explaining the relationship. The event definition should not be interpreted as more precise than its registry wording allows.

In general, a treatment-free remission percentage describes an outcome in a defined group over a defined period; it does not answer every question about long-term disease control, quality of life, or comparative benefit. Those topics appear among the listed secondary outcomes, but their results are not reported in the registry record. The posted safety counts and event terms provide descriptive information only and do not establish causality. Thus, the registry supports understanding the study’s question and broad design, but not a conclusion about the magnitude, precision, or comparative meaning of its primary outcome.

14. Why This Trial Matters Statistically

Statistically, this study raises an important distinction between the population enrolled at the beginning of a treatment sequence and the population eligible for a later treatment-free phase. The primary endpoint is defined among people who entered that phase. Reporting the number enrolled alone cannot show how many reached the endpoint population, what proportion had evaluable monitoring, or how representative later-phase participants were of the initial group. Those transition counts are not reported in the registry record.

The study also illustrates why endpoint definitions need consistent terminology. Its primary endpoint title refers to molecular relapse, the description refers to confirmed loss of MR4, and the relapse rule specifies a threshold above MMR. Statistical classification depends on the operational event rule. When terminology differs within a record, readers cannot assume that the measures use the same threshold or resolve the wording without further documentation.

A single-group design can be useful for describing outcomes within a treatment strategy, but its interpretation differs from a randomized comparison. Without a control group, a result would not by itself quantify what would have occurred under an alternative strategy. Here, the registry’s single-group and allocation fields make that limitation especially relevant, despite the official title’s use of “Randomized.”

Finally, this registry record separates the existence of an outcome definition from the availability of an outcome analysis. It lists a primary endpoint and numerous secondary outcomes, but no analysis records or primary result. That distinction is central to evidence appraisal: a clearly stated question does not itself provide an estimate, precision, or basis for causal interpretation. The record is informative about the intended study structure, while leaving the quantitative outcome assessment unavailable.

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.

Several trial-specific limitations follow from the registry information. First, the registry describes a single-group model with allocation listed as NA, but the official title includes “Randomized.” No protocol-level explanation of this difference is reported. There is no described control group for a like-for-like comparison, so the design cannot be interpreted as a comparative treatment trial on the basis of these fields.

Second, the primary endpoint wording is not fully consistent. The endpoint title concerns absence of molecular relapse; the description refers to no confirmed loss of MR4; and the relapse definition uses a confirmed BCR-ABL ratio above MMR. The registry does not clarify the intended threshold or reconcile these terms. This affects the interpretation of what counts as an event.

Third, the arm description is truncated during its explanation of the period after treatment cessation. The registry record does not provide a complete account of the treatment-free phase, monitoring procedures, or subsequent treatment rules. It also does not report how many participants passed through the successive treatment stages or entered the primary endpoint population.

Fourth, the primary outcome result, denominator, confidence interval, and analysis population are not reported. The registry lists 0 analysis records. Missing-data handling, multiplicity procedures, sample-size justification, interim analyses, and the statistical analysis plan are not reported in the registry record. Consequently, readers cannot evaluate precision, robustness to incomplete follow-up, or the analysis choices behind the intended endpoint. The completion status does not fill these reporting gaps.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: A Study That Switched Patients From Imatinib to Nilotinib and Then Was Followed by Treatment Cessation — NCT01744665.
• Registry record last updated 2020-03-10; status last verified 2020-02.
• Results first posted 2020-03-10.
• 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

This completed phase II, multicenter study concerns a nilotinib treatment sequence and treatment-free remission in chronic-phase CML. The registry lists 59 enrolled participants, a single-group model, allocation as NA, and no masking. The primary question is the percentage without molecular relapse within 6 months after starting the treatment-free phase.

The record describes monitoring and consolidation before eligibility to stop nilotinib, but the arm description is truncated. The endpoint description uses both MR4 and MMR terminology. No primary endpoint result, denominator, confidence interval, or analysis record is reported. The record lists secondary outcomes across molecular, survival, symptom, health-utility, and quality-of-life measures, without quantitative analyses. Safety figures list 19 participants affected by serious adverse events, 59 affected in the other adverse-event category, and no deaths; listed serious-event terms are descriptive and do not establish causality.