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 Sorafenib for the Treatment of Chronic Lymphocytic Leukemia (CLL) (NCT01510756), a na phase 2 study. The primary outcome is Overall Response Rate.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT01510756 |
| Phase | Phase 2 |
| Condition | Chronic Lymphocytic Leukemia |
| Allocation | Not applicable (single group) |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 4 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Thomas Kipps |
| Results posted | Yes |
2. Clinical Question
Population
Adults with relapsed or refractory chronic lymphocytic leukemia (CLL) who had an iwCLL-WG indication to receive therapy were the intended population. The primary outcome description states that zero participants were analyzed because the study was terminated. The registry record does not report participant-level characteristics or explain how closely the enrolled group matched the intended population.
Intervention
The planned intervention was oral sorafenib at 400 mg twice daily. The record describes treatment for three cycles, with one cycle defined as 28 days, and assessment after three cycles. The brief summary describes treatment continuously for three months and says responding patients could elect to continue for an additional 9 months. Actual treatment received and continuation are not reported in the registry record.
Comparator
There was no comparison group. The study used a single-group design, with no allocation to an alternative treatment or control condition. The registry record therefore does not provide a concurrent estimate of how outcomes under sorafenib compare with outcomes under another treatment or usual care.
Primary question
The primary question was whether sorafenib produced an overall response in previously treated CLL, assessed after three cycles of treatment. Response assessment was described using changes in absolute lymphocyte count, lymphadenopathy, splenomegaly, or leukemia infiltration of the bone marrow. The registry record reports zero participants analyzed for this endpoint because the study was terminated, so it does not provide an observed response rate.
3. Trial Design
This was a Phase II, single-group study of sorafenib for people with CLL. The registry record lists an enrollment of 4 and identifies the study status as terminated. It lists a start date of 2011-12 and a primary completion date of 2014-05. The reason for termination is not reported in the registry record.
There was no random allocation and no masking. The record identifies no control arm, so the planned assessment concerned outcomes in participants receiving sorafenib rather than a randomized comparison between treatments. Allocation is listed as not applicable. In a single-group design, an outcome can describe what happened among participants receiving the study intervention, but it cannot by itself separate an intervention effect from the natural course of illness, other care, or measurement effects.
The planned regimen was sorafenib 400 mg orally twice daily. The arm description specifies three cycles, with each cycle defined as 28 days. The brief summary describes continuous treatment for three months followed by response assessment and notes that responding participants could elect to continue for an additional 9 months. The record also lists response assessment after three cycles. These are descriptions of the intended regimen; actual exposure, dose modifications, treatment completion, and continuation are not reported in the registry record.
The primary outcome was overall response rate, with the stated timeframe of 3 months. Secondary outcomes included iwCLL-WG-defined complete and partial responses and safety and tolerability. The registry record lists 3 outcome measures but no analyses. The primary outcome population field states that zero participants were analyzed because of study termination. Thus the design and planned endpoint can be described, but an efficacy estimate cannot be recovered from the posted results.
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 | Sorafenib |
|---|---|
| STARTED | 4 |
| COMPLETED | 0 |
| NOT COMPLETED | 4 |
Reasons for not completing this period:
| Reason | Sorafenib |
|---|---|
| Death | 1 |
| Lack of Efficacy | 2 |
| Physician Decision | 1 |
Analysis population for the primary outcome, as defined in the registry: Zero participants analyzed due to termination of study
5. Baseline Characteristics
The table reproduces the baseline characteristics posted in the registry, which describe the participants analysed at baseline and help show whether the randomized groups were comparable.
| Characteristic | Unit | Sorafenib |
|---|---|---|
| Participants analysed | 4 | |
| Age, Categorical: <=18 years | Participants | 0 |
| Age, Categorical: Between 18 and 65 years | Participants | 0 |
| Age, Categorical: >=65 years | Participants | 4 |
| Sex: Female, Male: Female | Participants | 1 |
| Sex: Female, Male: Male | Participants | 3 |
| Region of Enrollment: United States | participants | 4 |
6. Primary Endpoint
The registry lists the primary outcome as Overall Response Rate, measured over 3 months.
| Element | Registry entry |
|---|---|
| Result type | N/A |
| Measure of spread | not applicable |
| Unit | not stated |
| Endpoint classification | not reduced to a single comparison |
The primary endpoint was overall response rate (ORR) after 3 months. ORR is generally the proportion of an analyzed group meeting a prespecified definition of response. Here, the record describes assessing absolute lymphocyte count, lymphadenopathy, splenomegaly, and/or bone marrow leukemia measured by a 4-color flow minimal residual disease panel after three cycles of study treatment. The response description includes a 50% decrease in absolute lymphocyte count, a 50% decrease in the sum of lymph node products, a 50% decrease in splenomegaly, or a 50% decrease in leukemia infiltration of the bone marrow.
Response criteria are used to translate clinical and laboratory measurements into a defined endpoint. A prespecified threshold can make response classification more consistent and help distinguish a response from smaller changes that may not meet the criterion. The record also names complete response and partial response in the secondary outcome description, but it does not report analyzed counts for either category.
The primary endpoint population is explicitly recorded as zero participants analyzed because the study was terminated. Consequently, no response numerator, analysis denominator, or ORR estimate is reported. The endpoint definition describes what the investigators intended to measure; it is not evidence that a response was observed.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record describes a Phase II study of sorafenib in previously treated CLL, but it does not contain an analyzed primary endpoint result. The enrollment is listed as 4, while the primary outcome population is listed as zero participants analyzed due to termination. These entries refer to different things: enrollment records participants entered into the study, whereas the primary outcome population records participants included in the endpoint analysis. The record does not explain participant-level disposition or why none were analyzed.
Because the endpoint analysis has no participants, there is no reported response count, response proportion, or estimate of uncertainty for ORR. The planned endpoint and its assessment criteria remain informative about the question the study intended to address, but they cannot establish what response outcomes occurred. In particular, zero analyzed is not equivalent to zero responders: it means the record gives no analyzed participants from whom a response rate could be estimated.
The single-group design also limits what an observed outcome could establish even if endpoint results were available. Without a concurrent comparator, an outcome among participants receiving sorafenib would not directly show how the same population would have fared under another treatment or without the study treatment. That limitation concerns causal interpretation, separate from the more fundamental absence of an analyzed primary result.
The posted safety entries describe 4 participants at risk in the serious adverse-event category, with 1 affected, and 4 at risk in the other adverse-event category, with 4 affected. The record lists brain abscess (aspergillus) as a serious adverse event term at 25.0%. Deaths are not reported in the registry record. These entries describe recorded safety counts, not an efficacy result; the record does not provide enough detail to characterize timing, duration, attribution, severity beyond the serious classification, or clinical course.
Study status is listed as terminated, but the reason is not reported in the registry record. The listed dates are 2011-12 for study start and 2014-05 for primary completion. Those dates do not explain the termination, establish how long participants received treatment, or show whether the planned assessments were completed. No detailed analysis results, confidence intervals, or statistical tests are reported. The appropriate interpretation is therefore limited: the record documents an intended response study, an enrollment of 4, termination, and no analyzed primary endpoint population. It does not provide an estimate of sorafenib's response rate in this trial.
9. Statistical Methods Explained
The available record supports a basic description of the design and endpoint, but not a reconstruction of the statistical analysis. The study is identified as a single-group Phase II trial with no masking and no allocation. The primary endpoint is ORR, intended to be assessed after 3 months. The primary outcome population is reported as zero participants analyzed because the study was terminated, and the record lists no analyses. A statistical interpretation must keep the planned analysis question separate from results that were actually reported.
For a binary endpoint such as response, an analysis ordinarily classifies each evaluable participant according to whether the prespecified response definition was met. The response count and the denominator analyzed are both needed to estimate an ORR. The denominator matters because it identifies the group to which the estimate applies; the count matters because it determines how many participants met the definition. Neither an analyzed response count nor an analysis denominator is reported for this study. The enrollment of 4 cannot be substituted for an endpoint denominator when the primary outcome field says zero participants were analyzed.
General statistical explanation: a confidence interval expresses uncertainty around an estimate under the assumptions of the method used to construct it. For a response proportion, uncertainty depends on the number analyzed and the observed response count. With no participants in the reported endpoint analysis, there is no trial-specific ORR estimate around which to construct a meaningful confidence interval. No confidence interval is reported in the registry record. This is not evidence that the response rate is a particular value; it is an absence of an endpoint estimate.
General statistical explanation: statistical significance tests address compatibility between observed data and a specified statistical model or null hypothesis. A test result depends on the data, analysis method, and hypotheses. The registry record reports no analyses, test statistics, or p-values. It is therefore not possible to describe a trial-specific significance test, or to infer one from the endpoint definition or enrollment.
The study had no comparator arm. In a randomized comparative trial, random allocation can support a comparison by balancing measured and unmeasured prognostic factors on average, subject to the trial's conduct and size. That framework does not apply to this single-group study. If a response estimate had been reported, it would describe the analyzed participants receiving sorafenib; it would not supply a randomized contrast. Comparisons with external expectations would require an explicit reference and additional assumptions, neither of which is reported in the registry record.
The response definition uses changes in disease measurements. The record describes 50% decreases in absolute lymphocyte count, lymphadenopathy measured by the sum of lymph node products, splenomegaly, or leukemia infiltration of bone marrow. General statistical explanation: prespecified operational definitions can improve reproducibility by specifying which measurements count as an outcome and what threshold qualifies. However, implementation also requires details such as assessment timing, handling of incomplete measurements, and rules for combining components. Those details are not reported in the registry record beyond the stated assessment description and timeframe.
General statistical explanation: over-dispersion is relevant when outcome variability is greater than a model assumes. For count outcomes, for example, a simple model may underestimate variability if observations vary more than expected under its distribution. This record does not report an over-dispersed outcome model or an analysis of count data. ORR is described as a response endpoint, and no model specification or dispersion assessment is reported. Over-dispersion should therefore be understood as a general modeling consideration, not as a method used or a problem demonstrated in this study.
The record includes a planning-illustration assumption statement describing a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation, with the effect to detect expressed as a fraction of the observed effect. It also distinguishes participant counts per arm for non-time-to-event outcomes from total event counts for time-to-event illustrations. These are planning-illustration assumptions, not a reported trial analysis. The study itself is single-group, and the registry record does not report a protocol-based sample-size justification, a target effect, an observed endpoint effect, or the results of any sample-size calculation. The illustration cannot be treated as observed power or as evidence that the trial was adequately powered.
General statistical explanation: a sample-size calculation depends on the endpoint, target effect, variability or event assumptions, error rates, and analysis design. Changing these assumptions changes the planning result. A calculation based on an observed effect is especially dependent on the stability of that estimate; it does not establish that the effect is real or that a future study will reproduce it. Here, no primary response effect was reported, so the record does not offer a trial-specific observed ORR from which to judge precision.
There is no reported interim analysis, stopping rule, covariate adjustment, or statistical analysis plan. The registry record does not report how response data were handled, whether response assessors were independent, or how the secondary outcome of safety and tolerability was analyzed. These omissions should be described as unreported rather than filled in by assumptions. The available statistical reading is consequently descriptive: the endpoint was planned, its broad measurement criteria were stated, and no primary analysis result appears in the record.
10. Multiplicity, Missing Data and Analysis Populations
The registry record lists ORR as the primary outcome and lists complete and partial responses and safety and tolerability as secondary outcomes. It reports 3 outcome measures but no analyses. It does not describe a multiplicity strategy, such as a hierarchy among outcomes or an adjustment for testing several outcomes. With no analyses reported, there is no basis for determining whether multiple statistical tests were performed or how any such tests would have been interpreted.
The primary outcome population is stated to include zero participants analyzed because the study was terminated. The record does not report a missing-data method, an imputation approach, or rules for classifying participants without complete response assessments. It also does not provide participant-level disposition, reasons for non-analysis, or a count of participants with incomplete endpoint measurements. These details are important because endpoint estimates can depend on who is included and how missing assessments are treated.
Analysis populations such as intention-to-treat or per-protocol groups are not specified in the registry record. The enrollment of 4 should not be interpreted as an analysis population, given the explicit statement that zero participants were analyzed for the primary outcome. No sensitivity analysis is reported to examine the effect of alternative analysis populations or missing-data assumptions. As a result, the record does not support evaluating robustness to missingness, endpoint eligibility, or participant exclusions.
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 |
|---|---|---|---|
| Sorafenib | 1 | 4 | 25.0% |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 0% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Sorafenib | 4 of 4 |
Most frequent serious adverse event terms
| Event term | Organ system | Sorafenib |
|---|---|---|
| Brain abscess (aspergillus) | Infections and infestations | 1 of 4 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Sorafenib |
|---|---|---|
| Diarrhea | Gastrointestinal disorders | 3 of 4 |
| Hand foot syndrome | Skin and subcutaneous tissue disorders | 3 of 4 |
| anorexia | Metabolism and nutrition disorders | 2 of 4 |
| Fatigue | General disorders | 2 of 4 |
| Polyuria | Renal and urinary disorders | 2 of 4 |
| thrombocytopenia | Blood and lymphatic system disorders | 2 of 4 |
| Abdominal pain | Gastrointestinal disorders | 1 of 4 |
| alopecia | Skin and subcutaneous tissue disorders | 1 of 4 |
| Amylase elevation | Metabolism and nutrition disorders | 1 of 4 |
| Arthralgia | Musculoskeletal and connective tissue disorders | 1 of 4 |
Serious events with the highest arm-level rate: brain abscess (aspergillus) (25.0%).
The safety entries list 4 participants at risk for serious adverse events and 1 affected. The record identifies brain abscess (aspergillus) as a serious adverse event term at 25.0%. It also lists 4 participants at risk for other adverse events and 4 affected. These are safety counts in the registry record; they are not response outcomes.
The serious-event count describes participants recorded as affected, not necessarily the total number of event episodes. The record does not state whether the listed serious term was the only serious event, whether an individual had more than one event, or how events were timed. It does not report the seriousness criteria, the investigators' assessment of relationship to sorafenib, clinical course, or outcome for the listed event. Deaths are not reported in the registry record.
The safety entries should be read as limited descriptive reporting, not as a complete comparative safety analysis. There is no control group, and the record does not provide exposure duration or detailed follow-up. The listed counts therefore do not establish comparative risk or causation.
12. What the Result Does, and Does Not, Mean
This record establishes that a Phase II single-group study was intended to assess sorafenib in previously treated CLL, with ORR as the primary endpoint after 3 months. It also records enrollment of 4, study termination, and zero participants analyzed for the primary outcome. The response criteria and planned treatment schedule describe the intended assessment, but the registry record does not report an analyzed response result.
That distinction is central. A terminated study with zero participants analyzed cannot be interpreted as having no responses, because no analyzed response count is reported. Nor can a response rate be estimated from enrollment alone. The posted results do not establish whether participants experienced response, progression, stable disease, or another outcome under the study regimen.
Even a reported outcome from a single-group study would not by itself establish how outcomes compare with another treatment, because no concurrent comparator was included. In this record, the lack of an analyzed endpoint adds a more immediate limitation: there is no efficacy estimate to interpret. The safety counts provide limited descriptive information, but they do not establish that an event was caused by sorafenib or quantify comparative risk.
The record does not explain why the study was terminated, whether participants received the planned treatment, or why none were included in the primary endpoint analysis. It does not report the protocol's statistical plan, sample-size justification, missing-data procedures, or inferential results. These unknowns should remain unknown rather than being inferred from the study status or the enrollment count.
Accordingly, this trial record is informative about the research question, intended regimen, response definition, and the fact that the planned primary analysis was not reported with participants analyzed. It does not show a response rate or provide evidence for a treatment comparison. No conclusion about clinical benefit or lack of benefit follows from the absence of an endpoint estimate.
13. Why This Trial Matters Statistically
This trial illustrates why a registered endpoint and an analyzed endpoint are not interchangeable. The record defines ORR and describes the measurements and thresholds intended to classify response, but it reports zero participants analyzed for that outcome. A well-described endpoint can clarify the scientific question without supplying the result needed to answer it.
The distinction between enrollment and analysis is also important. Enrollment is listed as 4, but the primary outcome population is listed as zero. Reporting both makes clear that the count entered into the study is not automatically the count contributing to an endpoint estimate. Without participant disposition or an explanation for non-analysis, readers cannot determine how the trial moved from enrollment to the reported analysis population.
The single-group design provides another statistical lesson. A response proportion, if available, would describe outcomes in the treated group, while a randomized comparator would be needed for a direct treatment contrast. In this record, there is neither a reported response estimate nor a comparator. Statistical interpretation must therefore avoid converting a planned objective into a result or a descriptive safety entry into a causal conclusion.
The record also demonstrates the limits of planning illustrations. General sample-size assumptions do not replace the study's own design rationale or an observed effect estimate. The registry record does not report a protocol-based sample-size justification or any primary analysis. Statistical planning and completed evidence answer different questions, and planning quantities should not be read as observed study findings.
Finally, the terminated status makes transparent reporting of disposition, analysis populations, and endpoint availability especially valuable. Those details would help readers understand why no primary endpoint population was analyzed. Their absence does not permit a conclusion about the reason for termination, but it does define how narrowly the posted results can be interpreted.
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 most important limitation is that the registry record reports zero participants analyzed for the primary outcome. There is no reported ORR, response count, analysis denominator, confidence interval, or test result. The study's intended endpoint therefore cannot be used to characterize observed response in this trial.
Enrollment is listed as 4, but participant flow from enrollment to the primary analysis is not described. The reason for termination is not reported in the registry record, nor are reasons for non-analysis, treatment exposure, dose changes, treatment completion, or endpoint assessment completion. The relationship between the stated treatment schedule and what participants actually received is not reported.
The single-group design has no comparator, so it cannot provide a randomized treatment contrast. No adjustment strategy, statistical analysis plan, or protocol-based sample-size justification is reported. The record also does not describe missing-data handling, analysis populations, interim analyses, stopping rules, or multiplicity procedures. These limitations preclude assessing how the analysis was planned or whether any reported estimate would have been robust to analytic choices.
Safety reporting is limited to counts and a listed serious event term. The record does not report event timing, duration, attribution, detailed clinical course, or deaths. The reason for study termination and the context of the serious adverse event are not described, so neither should be inferred.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Sorafenib for the Treatment of Chronic Lymphocytic Leukemia (CLL) — NCT01510756.
- Registry record last updated 2016-01-21; status last verified 2015-12.
- Results first posted 2015-10-05.
- 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.
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18. Record Summary
NCT01510756 is a Phase II single-group study of sorafenib for previously treated CLL. The registry record lists enrollment of 4, a start date of 2011-12, a primary completion date of 2014-05, and status as terminated. The planned regimen was sorafenib 400 mg twice daily, with response assessment after three cycles or 3 months as described in the record.
The primary endpoint was ORR. Its description specifies disease measurements and response thresholds, but the primary outcome population is recorded as zero participants analyzed because of termination. No primary response estimate or analysis is reported. The record lists limited adverse-event counts, including a serious event term of brain abscess (aspergillus) at 25.0%. The reason for termination, actual treatment exposure, and detailed statistical methods are not reported in the registry record.