LCL161 in Treating Patients With Primary Myelofibrosis, Post-Polycythemia Vera Myelofibrosis, or Post-Essential Thrombocytosis Myelofibrosis: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for LCL161 in Treating Patients With Primary Myelofibrosis, Post-Polycythemia Vera Myelofibrosis, or Post-Essential Thrombocytosis Myelofibrosis (NCT02098161), a na phase 2 study. The primary outcome is Number of Participants With a Response.

2. Clinical Question

The registry record concerns LCL161 as a single-agent treatment in people with primary myelofibrosis, post-polycythemia vera myelofibrosis, or post-essential thrombocytosis myelofibrosis. Its main efficacy question is whether participants met the record’s definition of response after 3 courses of therapy. Response could be complete remission, partial remission, or clinical improvement under International Working Group consensus criteria for myelofibrosis. The posted record does not report how many participants met that definition, so it does not establish the observed response count or its precision.

Because the study has no concurrent control group, its primary question is about outcomes observed among participants receiving LCL161, not a direct estimate of how LCL161 compares with another treatment or with no treatment. A response count in a single group can describe what occurred in that study population, but without a control group it cannot separate treatment-related change from other explanations for observed outcomes. The registry record does not report the primary response result or a comparison with another group.

3. Trial Design

NCT02098161 is registered as an open-label phase II, single-group study of SMAC mimetic LCL161. M.D. Anderson Cancer Center is listed as the sponsor. The registry lists an enrollment of 50, a start date of 2014-12-18, a primary completion date of 2022-05-19, and a completed status. Primary completion is the registry’s stated milestone; the record does not give a separate study-end date in the registry record.

The study was not randomized and had no masking. It is therefore an uncontrolled treatment study rather than a randomized comparison. Participants were assigned to the LCL161 treatment group described in the record. The listed regimen was oral administration on days 1, 8, 15, and 22, with cycles repeating every 28 days unless disease progression or unacceptable toxicity occurred. The registry also lists laboratory biomarker analysis and questionnaire administration as interventions, alongside LCL161.

The main endpoint is a participant count for response after 3 courses of therapy. The record defines response to include complete remission, partial remission, or clinical improvement under International Working Group consensus criteria. Duration of response, time to response, and overall survival are listed as secondary outcomes. The record states that there are 4 outcome measures, but does not report results for the primary response endpoint or provide statistical analysis records.

Enrollment is a registry design characteristic, not confirmation that every enrolled participant contributed data to every outcome. The analyzed population, the number assessed at each time point, and the handling of participants who stopped treatment or lacked response assessments are not reported in the registry record. Those omissions matter when interpreting a count tied to a particular assessment time. The design supports a description of outcomes in the treated group, but not a like-for-like comparison with a control group.

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

5. Baseline Characteristics

The table reproduces the baseline characteristics posted in the registry, which describe the participants analysed at baseline and help show whether the randomized groups were comparable.

6. Primary Endpoint

The registry lists the primary outcome as Number of Participants With a Response, measured over After 3 courses of Therapy.

The primary endpoint is the number of participants with a response after 3 courses of therapy. Response is defined as complete remission, partial remission, or clinical improvement according to International Working Group consensus criteria for myelofibrosis. The endpoint is a count, not a time-to-event measure or a continuous measurement. It combines several clinically defined response categories, each of which can be reached through different criteria.

Complete remission includes bone marrow blasts <5%, hemoglobin >= 10, absolute neutrophil count (ANC) >= 1000, platelets >= 100, <2% immature myeloid cells, and spleen and liver not palpable. Partial response is defined as complete remission plus one or more listed findings: ANC >= 1000, decreased platelets by 50%, hemoglobin >= 8.5 but <10, or <2% immature myeloid cells. Clinical improvement includes a hemoglobin increase of 2g/dl, transfusion independence, reduction in splenomegaly and/or hepatomegaly >= 50%, or a >=50% reduction in MPN-SAF TSS.

A response count is used to summarize how many participants met the stated criteria at the specified assessment. The categories and criteria make the endpoint interpretable as a registry-defined clinical response outcome, while the combined definition also means the count does not show which response category or criterion was met. The registry record does not report the count, category breakdown, or an uncertainty interval. Therefore the endpoint’s observed magnitude and precision cannot be assessed from the posted record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry describes a single-group phase II study and a primary outcome expressed as a count of participants with a defined response. It does not report a statistical analysis for this endpoint. The statistical concepts below explain how such outcomes are generally interpreted; they do not describe methods confirmed for this study unless explicitly stated as part of the registry record.

What does a response count represent?

A binary response outcome classifies each assessed participant as meeting or not meeting the response definition. Summing the participants who meet the definition gives a count. To interpret that count as a proportion, readers also need the number of participants included in the relevant assessment population. The registry record does not report the primary response count, the analyzed denominator, or the analysis population. No response proportion should therefore be inferred from enrollment alone.

The endpoint combines complete remission, partial remission, and clinical improvement. This makes the overall count a summary across several categories. The same total response count could arise from different mixtures of those categories, and the record does not give a category-specific breakdown. The endpoint definition states the criteria, but a definition is not an observed result.

What does a confidence interval add?

In general, a confidence interval describes uncertainty around an estimate under a specified statistical method. For a binary response outcome, an interval around a response proportion can communicate how much the estimate might vary because it is based on a finite set of observations. A narrow interval indicates greater precision under the method’s assumptions; a wide interval indicates more uncertainty. An interval does not repair design limitations, such as the absence of a control group, and does not by itself establish causation.

No primary response estimate or confidence interval is reported in the registry record. The method used to calculate an interval is also not reported. Readers therefore cannot assess the estimated response level or its statistical precision from the posted primary outcome information.

Why does the single-group design matter?

A single-group study can document outcomes among participants receiving the study regimen. It does not directly compare those outcomes with outcomes under an alternative. In a randomized controlled study, random assignment is intended to make groups comparable on average, subject to the design and conduct of the trial. There is no such randomized comparator in this record. The registry lists allocation as not applicable and describes a single group with no masking.

That distinction affects interpretation even if a response count is available. A within-group observation may be useful for describing what occurred, but it cannot isolate the intervention’s contribution from other influences in the way a well-conducted randomized comparison is designed to do. This is a general statistical limitation, not a claim about the cause of any particular outcome in this study.

How should planning illustrations be read?

The record describes planning illustrations based on an observed effect and states that they use 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 outcomes other than time-to-event outcomes, the illustrations are expressed as participants per arm; time-to-event illustrations use a total event count. These are hypothetical planning calculations, not outcomes observed in the trial.

The actual study described in the registry is single-group, not a two-arm study with equal allocation. The planning assumptions therefore represent a hypothetical design context rather than the treatment allocation used in NCT02098161. Such calculations can illustrate how a chosen target effect and statistical assumptions influence a future study’s required size, but they do not show how likely the completed study was to find an effect. They are not observed power, and they should not be interpreted as evidence that the primary endpoint reached a particular threshold.

In general, statistical power is a design property tied to assumptions about the effect, variability, analysis method, and chosen error rate. A post hoc calculation using an observed effect cannot establish the probability that a result is true or compensate for a missing outcome analysis. The registry record does not report a protocol-based sample-size justification, planned power, or a statistical analysis plan for the primary endpoint. The assumptions stated for the planning illustrations should not be mistaken for those missing protocol details.

What can safety counts and percentages tell readers?

Counts and percentages describe recorded events in the safety population as defined by the record. They can show which event terms were listed and how frequently they appeared in that group. They do not, on their own, show whether an event was caused by treatment, how risk compares with another treatment, or how event rates vary over time. A comparison would require an appropriate comparator and clearly defined analysis, neither of which is reported for the safety outcomes.

The registry provides serious-event and other-event affected counts, a count of deaths, and selected serious-event terms with percentages. It does not report the time at risk for each participant, event severity grading details beyond the serious-event classification, or causal attribution in the registry record. Those limitations constrain interpretation. A count of participants affected is also distinct from a count of separate event episodes; the record’s figures should be read according to the labels attached to them.

In general, a statistical result is most informative when its endpoint definition, analysis population, estimate, uncertainty, and method are all available. Here, the endpoint definition and some safety counts are recorded, but the primary response result and analysis details are not. The statistical interpretation should remain limited to those recorded details.

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 (SMAC Mimetic LCL161)")
n      <- c(50)
events <- c(15)
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 (SMAC Mimetic LCL161)  50  15  30.0  17.9  44.6  19.1  43.8  19.1  43.8

11. Multiplicity, Missing Data and Analysis Populations

The registry lists 4 outcome measures, including the primary response count and the secondary outcomes duration of response, time to response, and overall survival. When a study examines multiple outcomes, statistical multiplicity can arise if several hypotheses are tested and any apparently notable result is emphasized. In general, methods such as a prespecified hierarchy or adjustment can address some multiplicity concerns. The registry record does not report whether any such strategy was planned or used, and no statistical analysis plan is reported.

The primary endpoint is defined for assessment after 3 courses of therapy. The record does not report how participants without an assessment at that point were handled, whether missing outcomes were imputed, or whether a sensitivity analysis was conducted. It also does not report the analysis population or the number assessed for the primary endpoint. These omissions prevent assessment of whether the response count includes all enrolled participants, only participants with an available assessment, or another defined group. The enrollment of 50 cannot be treated as the endpoint denominator without that information.

The registry record has no posted analysis records for the outcomes. It does not report interim analyses, stopping rules, a protocol-based statistical plan, or a method for handling missing data. Each of these details is not reported in the registry record; their absence should not be interpreted as proof that they were not considered outside the posted record. Without the analysis population, missing-data approach, and multiplicity plan, readers cannot evaluate potential effects of selective outcome availability or multiple testing on the reported findings. In this case, the primary response result itself is also not reported, limiting interpretation further.

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: lung infection (18.0%), anemia (10.0%), fever (10.0%), blood and lymphatic system disorders (6.0%), neoplasms benign, malignant and unspecified (incl cysts and polyps) (6.0%).

The safety record lists 50 participants at risk for serious events, with 33 recorded as serious-event affected. It lists 50 participants at risk for other events, with 50 recorded as other-event affected, and reports 2 deaths. These are descriptive registry figures. They do not establish that LCL161 caused an event, and the single-group design offers no concurrent treatment group for a comparative safety estimate.

The listed serious-event terms include lung infection (18.0%), anemia (10.0%), fever (10.0%), blood and lymphatic system disorders (6.0%), neoplasms benign, malignant and unspecified (incl cysts and polyps) (6.0%), and rectal hemorrhage (6.0%). These percentages describe the record’s listed terms; they should not be added together or treated as separate mutually exclusive groups. The record does not provide further details about overlap among events or the time at risk for each participant.

A serious-event count is different from an overall adverse-event count, and a participant affected count is different from a count of event episodes. The registry record does not report causal attribution details in the registry record presented. The figures therefore describe recorded safety experience in this group, not comparative risk or proof of treatment causation.

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

The registry record establishes that NCT02098161 was an open-label, single-group phase II study of LCL161 in patients with specified forms of myelofibrosis. It identifies the dosing schedule and defines a primary response endpoint assessed after 3 courses of therapy. It also records selected safety counts and terms. These details describe the study’s intended question and some of the recorded safety experience.

The record does not report the primary response count, a response estimate, a confidence interval, or a statistical test. Consequently, it cannot show how many participants met the response definition, how precisely response was estimated, or whether a statistical analysis supported a particular interpretation. The treatment schedule and endpoint criteria are not themselves evidence of an observed response.

Even if a response result were available, the design would remain uncontrolled. A single-group result could describe outcomes among participants receiving LCL161, but it would not establish what would have occurred under another treatment. Differences in participant characteristics, disease course, assessments, or other care could contribute to observed outcomes. These are general considerations for interpreting a nonrandomized single-group study, not claims about what happened to particular participants in this trial.

The safety figures similarly describe events recorded in the treatment group. Without a comparator and further information about event attribution and observation time, they do not establish comparative safety or treatment causation. The count of deaths is reported, but the record does not provide details in the registry record that would support attributing those deaths to treatment.

The appropriately limited conclusion is that the registry documents the design, response criteria, and selected safety information, while leaving the primary efficacy result and its statistical uncertainty unreported. The record therefore does not permit a conclusion about the magnitude or precision of the primary response outcome, nor does it support a causal claim about treatment effect.

14. Why This Trial Matters Statistically

This trial is statistically important to read as a single-group study with an explicitly defined response count, rather than as a controlled comparison. The design determines what the data could answer: outcomes in the treated group can be described, but the record has no randomized comparator from which to estimate a treatment contrast. That distinction remains essential even when a study is phase II and has a clearly specified endpoint.

The endpoint also illustrates why definitions and results must be kept separate. The registry gives detailed criteria for complete remission, partial remission, and clinical improvement, and specifies an assessment after 3 courses of therapy. Those details make the intended outcome understandable. They do not report the number meeting the criteria. Without that count, the primary endpoint cannot be statistically summarized from the registry record.

The posted safety figures offer another statistical lesson: counts and percentages are descriptive, and their meaning depends on the population at risk, event definitions, and whether the groups can be compared. The record gives affected counts and selected serious-event terms but does not supply a controlled comparison or all contextual details needed for causal interpretation.

Finally, planning calculations should be distinguished from trial results and from the trial’s own design. The record describes illustrations based on a hypothetical equal-allocation, two-arm setup, while the actual registered study is single-group. Recognizing that difference prevents planning assumptions from being mistaken for observed power or for evidence about the primary outcome. The main statistical lesson is to match each claim to the design, endpoint, and results actually recorded.

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 most consequential limitation for interpreting efficacy is that the registry record does not report the primary response count, an estimate, or an uncertainty interval. Although the response definition and assessment time are specified, the outcome’s observed value and precision cannot be assessed. The registry also does not report the number assessed or the analysis population, so enrollment cannot safely be substituted for the endpoint denominator.

The single-group, open-label design has no concurrent control and no masking. It can describe outcomes in the treated group but cannot provide a direct randomized treatment comparison. The registry entries reported in the registry record do not describe independent or blinded response assessment, so the influence of assessment procedures cannot be evaluated from this record.

The registry lists secondary outcomes, but their results and analysis details are not reported. The handling of missing outcome data, multiplicity, interim analyses, and the statistical analysis plan is also not reported in the registry record. The record’s planning illustrations use hypothetical two-arm assumptions, which differ from the actual single-group design and should not be read as observed trial findings.

Safety interpretation is limited by the absence of a comparator and by missing details about event attribution, timing, and overlap among listed terms. The reported counts and percentages are descriptive and do not establish causality. These limitations describe what the registry record leaves unclear; they do not establish that the underlying study documents or analyses lacked additional information.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: LCL161 in Treating Patients With Primary Myelofibrosis, Post-Polycythemia Vera Myelofibrosis, or Post-Essential Thrombocytosis Myelofibrosis — NCT02098161.
• Registry record last updated 2023-06-06; status last verified 2023-05.
• Results first posted 2023-06-06.
• 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

NCT02098161 is a completed, open-label phase II single-group study sponsored by M.D. Anderson Cancer Center. It evaluated SMAC mimetic LCL161 in patients with primary myelofibrosis, post-polycythemia vera myelofibrosis, or post-essential thrombocytosis myelofibrosis. The registry lists enrollment of 50 and an oral schedule on days 1, 8, 15, and 22, with cycles repeating every 28 days in the absence of progression or unacceptable toxicity.

The primary endpoint is the number of participants with complete remission, partial remission, or clinical improvement after 3 courses of therapy under the stated consensus criteria. Duration of response, time to response, and overall survival are listed as secondary outcomes. The primary response result and outcome analysis details are not reported in the registry record.

Safety information includes 33 serious-event affected participants among 50 at risk, 50 other-event affected participants among 50 at risk, and 2 deaths, along with selected serious-event terms and percentages. These figures are descriptive and do not establish treatment causation or comparative risk.