Ibrutinib in Treating Patients With Relapsed or Refractory Transformed Indolent B-cell Non-Hodgkin Lymphoma: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Ibrutinib in Treating Patients With Relapsed or Refractory Transformed Indolent B-cell Non-Hodgkin Lymphoma (NCT02207062), a na phase 2 study. The primary outcome is Overall Response Rate (Combined Complete Response + Partial Response).

2. Clinical Question

The clinical question is therefore descriptive: among participants enrolled in this pilot study, what response and safety outcomes were recorded during treatment and follow-up? The registry identifies additional outcomes, including complete response rate, disease control rate, overall survival, progression-free survival, response relative to the underlying B-cell histology, and tolerability of chronic ibrutinib therapy. Those outcomes indicate the range of questions the study planned to examine, but their listing does not establish that results for each were reported. The registry record does not report those results in the information available for this trial summary.

3. Trial Design

This was a phase II pilot study of ibrutinib in participants with relapsed or refractory transformed indolent B-cell non-Hodgkin lymphoma. The registry lists the study as completed, with enrollment of 20 participants. The start is recorded as 2014-10, and primary completion as 2023-11-01. The sponsor was the University of Washington.

The design is identified as single group, with no masking and allocation listed as NA. Participants received ibrutinib by mouth once daily while disease had not progressed and unacceptable toxicity had not occurred. Laboratory biomarker analysis was also listed. Because there was no separate control group, the study is not a randomized comparison. Its data can describe outcomes among the enrolled participants, but cannot by themselves distinguish treatment-associated changes from the course participants might have experienced without ibrutinib or under another treatment.

The primary endpoint was overall response rate, combining complete and partial responses, measured as a count of participants over a timeframe of up to 5 years. The registry also lists several secondary clinical outcomes and tolerability. It records seven outcome measures and zero analyses. The registry record does not report the endpoint assessment schedule, the response criteria, or the analysis population definition. It also does not report whether any interim analyses were planned or conducted.

The term pilot describes the study in its official title and registry summary, but the registry record does not report a sample-size justification or a detailed protocol rationale. A planning illustration elsewhere associated with the posted results is not the trial’s own design justification. Its assumptions should not be read as evidence that the actual study was designed as a two-arm trial: the registered study itself is single 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 Overall Response Rate (Combined Complete Response + Partial Response), measured over Up to 5 years.

Overall response rate combines participants classified as having a complete response with those classified as having a partial response. The registry specifies that the endpoint is a count of participants and gives a timeframe of up to 5 years. It does not report the number achieving either response category, the combined count, or an estimated overall response rate. The response assessment criteria and the precise timing of assessments are not reported in the registry record.

As a general statistical concept, an overall response endpoint condenses response categories into a summary of how many participants meet a defined response threshold. Combining complete and partial responses can be useful when the clinical question concerns any specified degree of tumor response, while retaining the individual categories can distinguish the levels of response. The combined measure does not describe how long a response lasts, whether disease later progresses, or how participants fare overall. Those questions require other outcomes, such as duration of response, progression-free survival, or overall survival; the registry lists some of these as secondary outcomes but does not report their results in the available record.

For a count-based endpoint, interpretation depends on both the count and the number of participants included in the analysis. The enrolled group size is reported as 20, but the registry does not specify whether all enrolled participants were included in the primary endpoint analysis, nor does it report the number evaluable for response. Without the response count and its analysis denominator, the primary endpoint cannot be quantified from the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registered design is single group. This means the study followed participants receiving the listed intervention without a separate randomized control group. In general, a single-group study can describe outcomes in its enrolled participants. It does not provide the protection against measured and unmeasured differences between groups that random allocation can offer. Comparisons with historical experience or other studies require additional assumptions and are not reported in the registry record for this study.

What does a participant count tell us?

The primary endpoint is a count of participants with an overall response, combining complete and partial responses. A count is an absolute summary. To interpret it as a rate, the analysis denominator must also be known and the response assessment must be defined. The registry reports enrollment of 20, but does not report the primary response count or the number included in that analysis. Enrollment alone therefore cannot be used to derive an observed response rate. The registry also does not report response criteria, evaluator procedures, or the assessment schedule.

In general, binary outcomes classify each participant into one of two categories, such as whether a defined event occurred. A count of participants with an event is often accompanied by an estimated proportion and an uncertainty interval. These are distinct quantities: a count describes the observed number, while a proportion relates that count to an analysis denominator. Neither an estimate nor an interval for the primary endpoint is reported in the registry record.

How should uncertainty be understood?

As a general concept, a confidence interval expresses uncertainty around an estimate under a specified statistical model and procedure. A narrower interval indicates greater precision under those assumptions; a wider interval indicates less precision. An interval is not a guarantee that the true value lies within its endpoints, and it does not correct for bias, incomplete outcome assessment, or an inappropriate analysis population. Since the registry does not report a primary endpoint estimate or confidence interval, its precision cannot be assessed from this record.

A p-value, when reported, addresses how compatible data are with a specified null model under the analysis assumptions. It is not a measure of the size or clinical importance of an effect. The registry record lists zero analyses and does not report a primary endpoint p-value. No statistical significance conclusion can be drawn from the listed endpoint definition or from completion status.

What does the planning illustration represent?

The planning illustration is explicitly described as being computed from an observed effect, rather than as the trial’s own design. It specifies a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. The effect to detect is described as a stated fraction of the observed effect. For time-to-event outcomes, the illustration uses the total number of events under the Schoenfeld approach; for other outcomes, it expresses participants per arm.

These are assumptions for a planning exercise, not evidence that the registered pilot had two arms. The registered study is single group, and the planning assumptions of equal allocation between two arms do not describe its allocation. The specific observed effect and the resulting planning values are not reported in the registry entries available for this account. The illustration should not be interpreted as observed power or as the actual sample-size justification. The registry record does not report the trial’s own sample-size calculation or justification.

In general, a sample-size calculation asks what amount of information a proposed design would need to detect a specified effect under stated assumptions. It is conditional on those assumptions, including the endpoint, analysis, allocation, significance threshold, and target power. A planning calculation cannot establish that an effect occurred. It also cannot substitute for an observed estimate and its uncertainty. Where a calculation is based on an observed effect, it may be especially sensitive to uncertainty in that effect; using a fraction of an observed effect changes the planning target, not the observed trial result.

What can be inferred from adverse-event counts?

The registry records 7 participants affected by serious adverse events among 20 at risk, and 20 participants affected by other adverse events among 20 at risk. These are participant counts, not counts of all event episodes. A participant may have experienced more than one event, and the registry information does not establish how the event terms overlap across participants. The listed percentages for individual terms are reported as such; the record does not provide enough detail to reconstruct event-level totals or timing.

As a general statistical matter, adverse-event summaries require attention to the definition of an event, the observation period, the population at risk, and whether the summary counts participants or event episodes. Causal attribution is a separate question from whether an event was recorded during a study. These adverse-event figures describe the registry entries; they do not by themselves demonstrate that ibrutinib caused the events. The record does not report event-level exposure time or a comparative safety analysis.

Finally, a statistical analysis plan determines how outcomes, analysis populations, missing observations, and multiplicity are handled. The registry record does not report a detailed statistical analysis plan. The listed outcome names therefore do not reveal which models or inferential procedures were used, whether adjustments were made, or how uncertainty was calculated.

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 (Ibrutinib)")
n      <- c(18)
events <- c(6)
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 (Ibrutinib)  18  6  33.3  13.3  59.0  16.3  56.3  16.3  56.6

11. Multiplicity, Missing Data and Analysis Populations

The registry lists the primary overall response endpoint and secondary outcomes that include complete response rate, disease control rate, overall survival, progression-free survival, response relative to underlying B-cell histology, and tolerability of chronic ibrutinib therapy. It also records seven outcome measures and zero analyses. The registry record does not report a multiplicity strategy, such as whether a primary endpoint was tested as the sole confirmatory outcome or whether any adjustment was planned for evaluating multiple outcomes. Without that information, the strength of any collection of inferential claims could not be assessed; in this record, the primary endpoint result and analysis are not reported.

Missing-data handling and analysis populations are not reported in the registry record. In general, missing outcome data can affect an estimate if the availability of an assessment is related to participants’ outcomes. The direction and size of any such effect depend on why data are missing and on the analysis approach. The registry does not state how participants without an evaluable response assessment were handled, whether all enrolled participants were analyzed, or how withdrawals and incomplete follow-up were treated.

The registry record also does not report a statistical analysis plan, interim-analysis methods, or the response assessment criteria. It is not possible to infer these procedures from the endpoint name, the pilot designation, or the study’s completed status. These omissions limit assessment of how outcome definitions and analysis decisions were specified in advance and how the reported participant counts, if available, would relate to the enrolled group.

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: atrial fibrillation (10.0%), acute myocardial infarction (10.0%), nausea (5.0%), pericarditis (5.0%), groin pain (5.0%).

The registry reports 7 participants affected by serious adverse events among 20 at risk in the treatment group. It separately reports 20 participants affected by other adverse events among 20 at risk, and records 14 deaths. These are registry counts and should be read as distinct entries; they do not state that all events were caused by ibrutinib. The registry record does not provide the causal assessments, timing, exposure-adjusted rates, or detailed event narratives needed for a fuller safety interpretation.

The serious adverse-event terms listed include atrial fibrillation at 10.0% and acute myocardial infarction at 10.0%. Nausea, pericarditis, groin pain, and arthralgia are each listed at 5.0%. Those percentages are presented as recorded and should not be converted into a count or interpreted as mutually exclusive categories without further information. One participant may contribute to more than one event term, and the record does not describe overlap.

In general, adverse-event summaries distinguish the number of participants with at least one event from the number of event episodes. They also depend on the time period and definitions used for collection. The available entries do not establish how long each participant was observed or whether the percentages refer to participants or events under a more detailed convention. The figures describe reported safety information in this single-group study; without a concurrent comparator, they do not estimate a comparative excess risk.

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

The registry record establishes that a completed phase II pilot study enrolled 20 participants with relapsed or refractory transformed indolent B-cell non-Hodgkin lymphoma and evaluated single-agent ibrutinib. It specifies overall response rate, combining complete and partial responses, as the primary endpoint over a timeframe of up to 5 years. It also records selected adverse-event counts and terms. These details describe the study’s scope and some recorded outcomes.

The record does not report the primary response count or rate, response uncertainty, or results for the listed survival and disease-control outcomes. It therefore does not show how many participants responded, how precisely response was estimated, or what the survival outcomes were. The outcome names and planned timeframe are not substitutes for outcome results. Nor does a completed status mean that a particular clinical outcome was achieved.

The design limits the kinds of conclusions that can be drawn even if descriptive outcomes are available. Because there was no separate comparison group, the study does not directly compare ibrutinib with another treatment or with no treatment. Observed outcomes in a single group cannot establish the outcome that would have occurred under an alternative approach. No treatment recommendation follows from these registry entries.

The safety counts also require restrained interpretation. The record reports participants affected and named adverse-event terms, but does not establish causality, event timing, severity details beyond the serious-event classification, or comparative risk. The entries are not enough to determine whether a particular event was related to treatment.

In statistical terms, the main limitation is not simply that the enrolled group was small; it is that the primary result and its uncertainty are not reported in the registry record. Without those, the magnitude and precision of the primary outcome cannot be evaluated. The record is useful for identifying the study design, endpoint, enrollment, and selected safety entries, but it does not support a quantitative conclusion about response or comparative effects.

14. Why This Trial Matters Statistically

This study is statistically informative as an example of why a registered endpoint, a completed study, and an outcome result are different kinds of information. The registry defines overall response rate as the combined complete and partial response count and gives a follow-up timeframe of up to 5 years. Yet it does not report the observed response result. Readers therefore need to separate what the study set out to measure from what the registry record makes available for interpretation.

The single-group design also illustrates the boundary between descriptive and comparative evidence. A single group can be used to describe outcomes among enrolled participants, but it does not provide a concurrent control for estimating a treatment contrast. Without random allocation to distinct groups, differences attributable to treatment cannot be isolated through a randomized comparison. This is a design limitation, not a failure of a particular statistical test.

The record also shows why safety counts require context. Counts of affected participants, term-specific percentages, and deaths communicate recorded events, but do not by themselves establish causation or comparative risk. A fuller statistical reading would need clearly defined populations and observation periods, event definitions, and analysis methods. Those details are not reported in the registry record.

Finally, the planning illustration is not a substitute for a trial’s design rationale or observed results. Its two-arm assumptions differ from the registered single-group design, and it is identified as a planning exercise based on an observed effect. Keeping that distinction clear prevents a hypothetical sample-size calculation from being mistaken for evidence of observed treatment performance. The study’s statistical importance lies in recognizing these limits while accurately describing the information that is 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 primary limitation for interpreting efficacy is that the registry record does not report the primary overall response result. It identifies the endpoint and its timeframe but gives no response count, rate, confidence interval, or p-value. The response criteria, assessment schedule, and number of participants evaluable for response are also not reported. As a result, neither the magnitude nor the precision of the primary outcome can be assessed.

The single-group design has no randomized concurrent comparator. It can describe outcomes among enrolled participants, but it does not estimate a randomized treatment contrast. The registry record does not report an external comparator or comparative adjustment. The enrollment of 20 participants also defines the recorded study size, but does not itself reveal the number included in each outcome analysis or the amount of missing follow-up.

Additional details relevant to interpretation are not reported in the registry record: the analysis population, handling of missing outcomes, statistical analysis plan, interim-analysis procedures, multiplicity approach, response criteria, and sample-size justification. The record lists secondary outcomes but does not provide their results in the information available for this account. Listing an outcome does not establish that its analysis was completed or reported.

Safety entries are limited to participant counts, deaths, and selected event terms with percentages. They do not give the event-level timing, participant overlap, exposure duration, detailed causal assessments, or comparative rates needed for a fuller safety analysis. Because the study is single group, the recorded events cannot be interpreted as comparative risk estimates. These limitations are specific to the design and to the information reported in the registry record.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Ibrutinib in Treating Patients With Relapsed or Refractory Transformed Indolent B-cell Non-Hodgkin Lymphoma — NCT02207062.
• Registry record last updated 2025-01-07; status last verified 2024-11.
• Results first posted 2025-01-07.
• 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

NCT02207062 is a completed phase II pilot study sponsored by the University of Washington. It enrolled 20 participants with recurrent or refractory transformed B-cell non-Hodgkin lymphoma. The study used a single-group design with no masking and evaluated ibrutinib taken by mouth once daily in the absence of disease progression or unacceptable toxicity. Laboratory biomarker analysis was also listed.

The primary endpoint was overall response rate, combining complete and partial responses, reported as a participant count over a timeframe of up to 5 years. The registry record does not report that endpoint’s result. It lists secondary outcomes that include response, disease control, survival, response by underlying histology, and tolerability, and records seven outcome measures and zero analyses.

For safety, the registry reports 7 participants with serious adverse events among 20 at risk, 20 with other adverse events among 20 at risk, and 14 deaths. Named serious adverse-event terms include atrial fibrillation, acute myocardial infarction, nausea, pericarditis, groin pain, and arthralgia. The registry entries do not establish causality or provide a comparative safety estimate.