This page provides an independent statistical analysis and educational interpretation of publicly reported results. ClinicalTrials.gov provides the official trial registry record. Numerical trial results on this page are restricted to the results posted in the ClinicalTrials.gov record; calculations added by Clinical Biostats are labelled as such.
1. Trial at a Glance
This page covers the registry results for Study to Evaluate Nilotinib in Chronic Myelogenous Leukemia (CML) Patients With SubOptimal Response (NCT01043874), a na phase 4 study. The primary outcome is MMR Rate at 12 Mos. of Nilotinib Treatment on Study in Patients With Philadelphia Chromosome Positive (Ph+) Chronic Myelogenous Leukemia in Chronic Phase (CML-CP) Who Have a Suboptimal Molecular Response to Imatinib at 18 Months or Later..
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT01043874 |
| Phase | Phase 4 |
| Condition | Philadelphia Chromosome Positive, Chronic Myelogenous Leukemia in Chronic Phase |
| Allocation | Not applicable (single group) |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 45 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Novartis Pharmaceuticals |
| Results posted | Yes |
2. Clinical Question
Population
Adults or other eligibility-defined participants are not specified in the registry record. The stated population is people with Philadelphia chromosome-positive chronic myelogenous leukemia in chronic phase who had a suboptimal molecular response to imatinib at 18 months or later. The primary outcome identifies the Full Analysis Set, but the record does not define that set or state how many participants were included in the endpoint analysis.
Intervention
The intervention was nilotinib, with the listed regimen of 400 mg BID. The study aimed to evaluate the major molecular response rate after 12 months of nilotinib treatment on study.
Comparator
No concurrent comparator is listed. The design is single group, allocation is recorded as NA, and masking is listed as NONE. The study therefore does not provide a randomized, like-for-like comparison with another treatment or with a control group.
Primary question
The primary question was what proportion of the Full Analysis Set achieved major molecular response at 12 months of nilotinib treatment on study. Major molecular response was defined as a BCR-ABL ratio (%) on the International Scale of ≤ 0.1%, corresponding to ≥ 3 log reduction of BCR-ABL transcripts from the standardized baseline value. The registry record does not report the observed proportion or its 95% confidence interval.
This is a question about the response observed in a selected clinical population receiving nilotinib, rather than a question about the difference between treatments. Without a concurrent comparison group, the record cannot establish whether an observed response rate is higher or lower than it would have been under another treatment or no treatment. The eligibility phrase suboptimal molecular response indicates the clinical context for the study, but the registry record does not give further eligibility criteria or explain how suboptimal response was determined.
3. Trial Design
This was a Phase IV, single-group study of nilotinib in Philadelphia chromosome-positive chronic myelogenous leukemia in chronic phase. The registry lists an enrollment of 45 and a nilotinib regimen of 400 mg BID. Allocation is recorded as NA, masking as NONE, and the study model as SINGLE GROUP. These entries describe a study without a randomized allocation or a masked comparison. The listed sponsor is Novartis Pharmaceuticals. The record gives a start of 2009-12, a primary completion of 2013-12, and a status of COMPLETED.
The study population was described as having a suboptimal molecular response to imatinib at 18 months or later. The primary endpoint was the major molecular response rate at 12 months after treatment on study. Secondary outcomes listed in the record are the major molecular response rate at 24 months, time to first major molecular response, and duration of major molecular response. The record lists 4 outcome measures and 0 analyses. It does not provide analysis-specific results for the primary or secondary outcomes.
In general, a single-group design can describe outcomes observed among participants receiving an intervention, but it does not separate the intervention’s effect from other explanations for those outcomes. A comparison with a separate control group is needed to estimate a between-group contrast directly. Because allocation is NA and the model is single group, the registry record does not support a randomized treatment comparison. It also does not report the protocol details needed to assess recruitment procedures, follow-up completeness, treatment changes, or the operational conduct of the study.
The registry identifies the primary analysis population as the Full Analysis Set, but does not define membership in that set or state how many people were included in the analysis. Enrollment alone does not establish the number with an evaluable molecular response at the endpoint. The endpoint estimate, confidence interval, and analysis population count 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.
Overall Study
| Stage | Nilotinib |
|---|---|
| STARTED | 45 |
| COMPLETED | 39 |
| NOT COMPLETED | 6 |
Reasons for not completing this period:
| Reason | Nilotinib |
|---|---|
| Adverse Event | 3 |
| Withdrawal by Subject | 1 |
| Lack of Efficacy | 1 |
| Administrative Problems | 1 |
Analysis population for the primary outcome, as defined in the registry: Full Analysis Set
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.
| Characteristic | Unit | Nilotinib |
|---|---|---|
| Participants analysed | 45 | |
| Age, Continuous | years | 49.5 (SD 14.89) |
| Sex: Female, Male: Female | Participants | 16 |
| Sex: Female, Male: Male | Participants | 29 |
6. Primary Endpoint
The registry lists the primary outcome as MMR Rate at 12 Mos. of Nilotinib Treatment on Study in Patients With Philadelphia Chromosome Positive (Ph+) Chronic Myelogenous Leukemia in Chronic Phase (CML-CP) Who Have a Suboptimal Molecular Response to Imatinib at 18 Months or Later., measured over 12 months after treatment.
| Element | Registry entry |
|---|---|
| Result type | Number |
| Measure of spread | 95% Confidence Interval |
| Unit | % participants achieving MMR |
| Endpoint classification | not reduced to a single comparison |
The primary endpoint was the major molecular response rate at 12 months of nilotinib treatment on study among the Full Analysis Set. The outcome was expressed as the percentage of participants achieving major molecular response. The registry definition is a BCR-ABL ratio (%) on the International Scale of ≤ 0.1%, corresponding to ≥ 3 log reduction of BCR-ABL transcripts from the standardized baseline value.
In general, a molecular response endpoint uses a laboratory measure to classify whether a prespecified response threshold has been reached. A rate expresses how often that classification occurs in the population analyzed. A confidence interval describes the uncertainty around an estimated rate; it does not guarantee that the true rate lies within the interval. The registry lists a 95% confidence interval as the endpoint’s dispersion measure, but it does not report the observed rate or interval limits.
The 12-month time point makes the outcome a response assessment at a specified duration of treatment, rather than a measure of response at any time. The listed secondary outcomes address response at 24 months, time to first response, and duration of response. Their results are not reported in the registry record. The record also does not explain how molecular measurements were scheduled, handled when unavailable, or used to determine endpoint status.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record identifies a clinically defined study population and a specific molecular response threshold, but does not report the primary endpoint result. In particular, the number achieving major molecular response, the estimated rate, and the 95% confidence interval are not reported in the registry record. The record names the Full Analysis Set but does not report its size or define which participants it contains. Consequently, the posted information does not allow readers to judge the observed response frequency or the precision of its estimate.
The intended endpoint is a proportion at 12 months, not a comparison between treatment groups. Even if the response rate were available, a single-group result would describe the outcome in the analyzed participants; it would not by itself quantify what would have happened under an alternative treatment. Differences in patient characteristics, disease course, other care, and measurement can affect an outcome observed during follow-up. The registry record contains no concurrent comparator with which to account for such factors.
The design entries reinforce this distinction. The model is SINGLE GROUP, allocation is NA, and masking is NONE. These are not features of a randomized, masked comparison. The study is marked COMPLETED, but completion status does not indicate that the endpoint was met or that the registry contains complete outcome reporting. The record lists 0 analyses, so it does not identify an analysis method or present analysis-level estimates.
The record lists 4 outcome measures. In addition to the primary 12-month response rate, it identifies a 24-month response rate, time to first major molecular response, and duration of major molecular response. No results for these outcomes are reported in the registry record. Their inclusion indicates the outcomes of interest, but does not establish whether they were measured for every participant, how missing observations were treated, or what estimates were obtained.
In general, the width of a confidence interval helps readers assess the precision of an estimate: wider intervals indicate more uncertainty, while narrower intervals indicate greater precision. That assessment cannot be made for this endpoint because the rate and interval are absent. Likewise, a statistical significance judgment cannot be made without a reported statistical test and result. No significance threshold for the primary endpoint analysis is reported in the registry record.
Overall, the record documents the study question, design classification, intervention, endpoint definition, and some safety counts. It does not document an outcome estimate that would support a conclusion about the frequency of major molecular response in the analyzed population. It also does not provide a controlled comparison that could estimate a treatment contrast. These are limits on what the registry record can establish, not evidence for or against a treatment effect.
9. Statistical Methods Explained
What does a response rate describe?
In general, a response rate is the proportion of an analyzed population meeting a defined response criterion at a stated assessment time. The criterion matters because it determines which participants count as responders. Here, the registry defines major molecular response using a BCR-ABL ratio (%) on the International Scale of ≤ 0.1%, corresponding to ≥ 3 log reduction of BCR-ABL transcripts from the standardized baseline value. The primary assessment is described as occurring 12 months after treatment on study.
A response rate is not the same as an average change in a laboratory measurement. It classifies participants against a threshold, then describes the frequency of meeting that threshold. The registry lists the outcome unit as the percentage of participants achieving major molecular response. However, it does not report the number meeting the criterion, the number included in the endpoint analysis, or the estimated percentage. The record therefore permits interpretation of the endpoint definition, but not the response rate itself.
What does the confidence interval add?
In general, a confidence interval communicates sampling uncertainty around an estimate. An interval around a response rate gives a range of values that are compatible with the data under the method used to calculate it. Its width depends on factors including the amount of information available and the variability in the observed data. It is not a statement that the effect is certain, and it does not address every source of bias.
The registry specifies a 95% confidence interval as the dispersion measure for the primary outcome. The interval endpoints and the associated response estimate are not reported in the registry record. Without them, the precision of the primary estimate cannot be assessed. The calculation method for the interval is also not reported in the registry record.
What can a single-group design estimate?
In general, a single-group study can describe outcomes observed among people receiving an intervention. Its main limitation for comparative inference is that it does not directly observe outcomes under a separate treatment or control condition in a comparable group. Therefore, it cannot directly estimate a difference between groups. Other explanations for outcomes, including participant characteristics and the course of the condition, cannot be separated from the intervention by a concurrent randomized comparison in this design.
This study is recorded as SINGLE GROUP, with allocation NA and masking NONE. These design entries should not be interpreted as evidence of a randomized comparison. The registry does not report an analysis method for adjusting or otherwise accounting for differences in participant characteristics. More generally, statistical adjustment cannot substitute automatically for random allocation; its validity depends on the available data and assumptions, which are not described in the registry record.
How should the analysis population be understood?
The primary endpoint names the Full Analysis Set as its population. In general, an analysis population is a defined group of participants whose data are used for an outcome estimate. The label alone does not explain inclusion rules. The registry does not define the Full Analysis Set, report its size, or state whether participants without an endpoint measurement were included or excluded. The enrollment of 45 is not necessarily the endpoint denominator.
Missing outcome data can affect an estimate when participants without measurements differ from those with measurements. In general, analysis methods may use assumptions about missingness, imputation, or other rules for handling unavailable observations. None of those choices is reported in the registry record. It is therefore not possible to assess whether incomplete follow-up affected the primary endpoint result.
What do the planning illustrations mean?
In general, sample-size planning asks how much information may be needed to detect a prespecified effect under chosen assumptions. The planning assumptions associated with this record describe a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. They describe an effect to detect as a stated fraction of the observed effect. For time-to-event calculations, the method is identified as Schoenfeld and the quantity is total events; other calculations are expressed as participants per arm.
These are planning illustrations, not the design of the single-group trial and not observed power. A two-arm planning framework does not mean this study enrolled two treatment groups. The record does not report the study’s own sample-size justification or establish that these illustrations were used to plan the trial. Because the primary result is not reported in the registry record, the observed effect used in the planning description cannot be evaluated from the registry information. Planning calculations should not be read as evidence that the study had a particular probability of detecting an effect.
What can be concluded from the recorded analyses?
The registry lists 0 analyses. This means the record does not present analysis-specific results or methods for the named outcomes. It does not establish why those entries are absent, nor does it show whether analyses were conducted outside the registry record. In general, interpretable results require both an estimate and enough information about how it was obtained, including the population analyzed, outcome definition, handling of missing measurements, and uncertainty measure. Several of these details are not reported in the registry record.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists 4 outcome measures: the primary major molecular response rate at 12 months, a major molecular response rate at 24 months, time to first major molecular response, and duration of major molecular response. The record identifies the first as the primary outcome and the others as secondary outcomes. It does not report a statistical analysis plan, an approach to multiplicity, or any analysis-specific results. It is therefore not reported in the registry record whether or how the interpretation of multiple outcomes was addressed.
In general, testing several outcomes can increase the chance of finding an apparently notable result by chance when each is considered separately. Methods for addressing multiplicity may define a hierarchy of outcomes, adjust significance thresholds, or treat secondary analyses as exploratory. The registry information does not indicate that any particular approach was used. No significance claims can be evaluated from the posted record because outcome estimates and test results are absent.
The record identifies the Full Analysis Set for the primary endpoint but does not define it or give its size. It does not report the number with an available 12-month assessment, the number excluded from analysis, or reasons for missing measurements. Missing-data rules and sensitivity analyses are not reported in the registry record. In general, these details matter because estimates can depend on who is included and how unavailable outcomes are handled.
The record also does not report whether participants were analyzed according to a prespecified population definition, whether endpoint assessments were blinded, or whether any analysis decisions changed during the study. Such details are not reported in the registry record. The listed enrollment should not be treated as the denominator for the primary endpoint without an explicitly reported analysis count.
11. Safety Results
The registry reports serious adverse events as affected participants divided by participants at risk.
| Arm | Participants with serious adverse events | Participants at risk | Percentage |
|---|---|---|---|
| Nilotinib | 7 | 45 | 15.6% |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 5% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Nilotinib | 45 of 45 |
Most frequent serious adverse event terms
| Event term | Organ system | Nilotinib |
|---|---|---|
| Anaemia | Blood and lymphatic system disorders | 1 of 45 |
| Bile duct stone | Hepatobiliary disorders | 1 of 45 |
| Pneumonia | Infections and infestations | 1 of 45 |
| Dehydration | Metabolism and nutrition disorders | 1 of 45 |
| Chronic myeloid leukaemia transformation | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | 1 of 45 |
| Malignant neoplasm of renal pelvis | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | 1 of 45 |
| Erythema multiforme | Skin and subcutaneous tissue disorders | 1 of 45 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Nilotinib |
|---|---|---|
| Hyperbilirubinaemia | Hepatobiliary disorders | 24 of 45 |
| Nasopharyngitis | Infections and infestations | 21 of 45 |
| Headache | Nervous system disorders | 17 of 45 |
| Rash | Skin and subcutaneous tissue disorders | 15 of 45 |
| Alanine aminotransferase increased | Investigations | 14 of 45 |
| Hypophosphataemia | Metabolism and nutrition disorders | 13 of 45 |
| Lipase increased | Investigations | 11 of 45 |
| Constipation | Gastrointestinal disorders | 10 of 45 |
| Nausea | Gastrointestinal disorders | 9 of 45 |
| Myalgia | Musculoskeletal and connective tissue disorders | 9 of 45 |
Serious events with the highest arm-level rate: anaemia (2.2%), bile duct stone (2.2%), pneumonia (2.2%), dehydration (2.2%), chronic myeloid leukaemia transformation (2.2%).
The registry lists 45 participants at risk in the nilotinib group for serious adverse events, with 7 affected. For other adverse events, it lists 45 at risk and 45 affected. These are participant counts in separate reporting categories; they do not state the total number of events or establish that every participant experienced the same event. The registry does not give the period over which these counts were collected.
The serious adverse event terms listed are anaemia, bile duct stone, pneumonia, dehydration, chronic myeloid leukaemia transformation, and malignant neoplasm of renal pelvis. Each term is shown with 2.2%. The registry record does not provide further detail about event timing, severity beyond the serious-event classification, outcomes, or attribution to treatment. The death count is not reported in the registry record.
In general, an adverse event occurring during a study is not by itself proof that the intervention caused it. Safety counts also depend on how events were defined, collected, and coded, and on the observation period. With no control group, these counts do not provide a comparative estimate of safety. They should be read as registry-reported observations in this study group, not as a causal comparison.
12. What the Result Does, and Does Not, Mean
The registry record establishes that a Phase IV, single-group study evaluated nilotinib in people with Philadelphia chromosome-positive chronic myelogenous leukemia in chronic phase who had a suboptimal molecular response to imatinib at 18 months or later. It identifies a regimen of 400 mg BID and a primary endpoint based on major molecular response at 12 months. It also provides the molecular response threshold and some adverse event counts.
The record does not report the primary endpoint estimate, its 95% confidence interval, or the number of participants analyzed for that outcome. As a result, the posted information does not show how many participants achieved major molecular response or how precisely a rate was estimated. The secondary response and time-to-response outcomes are listed, but their results are not reported in the registry record.
Even a reported rate from this design would describe outcomes in the study group rather than establish a treatment difference. The study has no concurrent comparator, and its record lists no random allocation. A single-group observation cannot isolate treatment effects from other possible influences on outcomes. This is an important distinction between describing what occurred and estimating what would have occurred under another treatment.
The safety entries similarly describe participants recorded as affected, without a comparative group or details sufficient to assess causation. The serious event terms and percentages are registry observations. They do not by themselves show that nilotinib caused the events, nor do they provide a comparative safety estimate.
Thus, the registry record supports a description of the study design, intended response question, response definition, and recorded safety counts. It does not support a numerical conclusion about the primary response rate or a controlled estimate of treatment benefit or harm. These limitations concern what is available in this record; they should not be mistaken for a finding that the study did or did not observe responses.
13. Why This Trial Matters Statistically
This study is statistically informative as an example of the difference between a well-defined endpoint and a reported endpoint result. The registry specifies the population context, the assessment time, the molecular response threshold, and the intended confidence interval. Those details tell readers what the primary outcome was meant to represent. But without an estimate, interval, and analysis denominator, the outcome cannot be interpreted quantitatively.
The design also illustrates why study structure determines the scope of inference. A single-group study can report the experience of participants receiving nilotinib, but it cannot estimate a randomized treatment contrast. This remains true even when an outcome is objective in definition. Measurement precision and causal identification are distinct issues: a laboratory criterion can be explicit while the comparative effect remains unknown.
The registry’s identification of a Full Analysis Set raises another general statistical point. An analysis population label needs a definition and count to make an estimate reproducible and interpretable. Enrollment and endpoint analysis populations may differ, especially if outcomes are unavailable, but the record does not describe such differences or how they were handled. The endpoint denominator and missing-data approach are therefore central reporting gaps.
The listed safety counts likewise show why adverse event summaries need context. Participant counts, event terminology, observation periods, and attribution all shape interpretation. Without comparative data, counts can describe events recorded during the study but cannot establish whether their frequency differs from another treatment setting.
Finally, planning calculations and observed results answer different questions. Planning illustrations describe assumptions for a hypothetical calculation; they are not evidence about the trial’s achieved precision or power. The record does not report the trial’s own sample-size justification or primary result. Keeping those distinctions clear prevents a design label, an endpoint definition, or a planning assumption from being mistaken for evidence of an outcome.
14. 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 principal limitation for interpreting the study from the registry record is that the primary response result is not reported. The response estimate, 95% confidence interval, endpoint denominator, and number meeting the response criterion are all not reported in the registry record. The Full Analysis Set is named but not defined, so its relationship to the enrollment of 45 cannot be assessed.
The single-group design has no concurrent comparator, and the record lists allocation as NA and masking as NONE. It therefore does not provide a randomized comparison. The registry does not report adjustment methods, other than the fact that 0 analyses are listed, so the record cannot establish whether potential differences or other influences were addressed in any analysis.
Additional study details relevant to interpretation are not reported in the registry record, including full eligibility criteria, the definition of suboptimal molecular response, the schedule and handling of molecular assessments, the method for calculating the confidence interval, missing-data rules, and sensitivity analyses. The record does not state whether endpoint assessments were complete or how participants without an assessment were classified.
The record lists secondary outcomes but does not report their results or analysis methods. It also does not report a multiplicity approach or the trial’s sample-size justification. Planning illustrations are not a substitute for those details and do not establish achieved power. Safety reporting includes counts and serious event terms, but the observation period, event-level detail, and attribution are not reported in the registry record. These gaps restrict conclusions to the design and information explicitly recorded.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Study to Evaluate Nilotinib in Chronic Myelogenous Leukemia (CML) Patients With SubOptimal Response — NCT01043874.
- Registry record last updated 2016-04-08; status last verified 2016-03.
- Results first posted 2015-02-09.
- 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.
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18. Record Summary
NCT01043874 is a completed Phase IV, single-group study sponsored by Novartis Pharmaceuticals. It enrolled 45 participants and evaluated nilotinib at 400 mg BID in Philadelphia chromosome-positive chronic myelogenous leukemia in chronic phase with suboptimal molecular response to imatinib at 18 months or later. The recorded study start is 2009-12 and primary completion is 2013-12.
The primary outcome was major molecular response rate at 12 months, defined using a BCR-ABL ratio (%) on the International Scale of ≤ 0.1%, corresponding to ≥ 3 log reduction of BCR-ABL transcripts from the standardized baseline value. The record identifies a 95% confidence interval and the Full Analysis Set, but the result, interval, and analysis population size are not reported in the registry record. Secondary outcomes cover response at 24 months, time to first response, and response duration. The record lists 0 analyses. Safety entries report 7 participants affected by serious adverse events and 45 by other adverse events, among 45 at risk in each category.