Ibrutinib in Treating Patients With Relapsed or Refractory Classical 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 Classical Hodgkin Lymphoma (NCT02824029), a na phase 2 study. The primary outcome is Overall Response Rate (ORR).

2. Clinical Question

In practical statistical terms, the study is intended to describe tumor response among participants treated with ibrutinib and to assess the response rate using a one-sample method. The registry summary frames the study around patients whose classical Hodgkin lymphoma recurs or does not respond to initial treatment, but additional entry criteria are not reported in the registry record.

The registry enrollment is 28. That is the recorded enrollment, not a reported count of participants included in the primary endpoint analysis. The analysis population, the number with response assessments, and the handling of participants without an evaluable assessment are not reported in the registry record. Without those details and the response result, the planned question can be described, but its answer cannot be quantified from the record.

3. Trial Design

NCT02824029 is a phase II, multicenter, single-arm study sponsored by Barbara Ann Karmanos Cancer Institute. Its official title describes an evaluation of the efficacy and safety of single-agent ibrutinib in patients with relapsed or refractory classical Hodgkin lymphoma. The record lists enrollment as 28 and status as completed. The start is recorded as 2016-06, and the primary completion date is 2023-05-12.

All participants were assigned to the treatment group described as ibrutinib. The brief summary specifies 560 mg by mouth daily; the arm description states that ibrutinib is taken orally once daily, with courses repeating every 28 days while there is no disease progression or unacceptable toxicity. The listed interventions also include laboratory biomarker analysis and a pharmacological study. Their specific procedures and their relationship to the primary endpoint are not reported in the registry record.

The allocation field is not applicable, masking is listed as none, and the model is single-group. These features mean the design does not support a direct randomized comparison. The study can describe outcomes among participants receiving the intervention, but it cannot separate treatment-associated changes from other explanations by comparing outcomes with a concurrent control arm. The registry record does not describe a comparator, random assignment, or blinding.

The primary endpoint is overall response rate, with duration of response and progression-free survival listed as secondary outcomes. The primary endpoint timeframe is described as from study entry to progression or death up to 24 months. The record does not report detailed assessment schedules or definitions for the secondary outcomes. It also does not report protocol details beyond the information in the registry record, such as eligibility criteria, the planned recruitment duration, or whether any protocol amendments occurred.

Although the record identifies the study as completed, completion status alone does not establish that all planned endpoint analyses are reported. In particular, the registry record does not report the primary response estimate or its inferential statistics. The design and planned endpoint are therefore identifiable, but the principal efficacy result cannot be reconstructed from the 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

Reasons for not completing this period:

5. Baseline Characteristics

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

6. Primary Endpoint

The registry lists the primary outcome as Overall Response Rate (ORR), measured over From date of study entry to date of progression or death up to 24 months.

The primary endpoint, overall response rate, is defined as the proportion of participants who have either a complete response or a partial response. It is a binary-outcome summary: each participant is classified according to whether a qualifying response occurred, and the endpoint aggregates those classifications as a proportion. The registry record specifies a one-sample binomial test for assessing this rate.

As a general statistical explanation, response rate is useful when a trial aims to describe how often a defined response is observed during treatment. It gives a direct summary of the frequency of the response category, while a confidence interval indicates the uncertainty around the estimated proportion. A one-sample test can evaluate whether an observed proportion is compatible with a prespecified benchmark. The benchmark and the test result are not reported in the registry record, so the test’s target and conclusion cannot be assessed.

The recorded timeframe is from study entry to progression or death up to 24 months. The record does not report the number of participants with complete or partial response, the overall response rate, or its 95% confidence interval. It also does not report how participants without an assessment or with an assessment after progression or death were classified. Those details matter because the response proportion depends on which participants are included and how response status is determined.

Duration of response and progression-free survival are listed as secondary outcomes. They address different questions from the primary response proportion, but their definitions, estimates, and analyses are not reported in the registry record. Thus the endpoint definition is clear enough to identify the intended summary, while the actual observed result and its precision remain unreported.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry record identifies overall response rate as the primary endpoint and says that a one-sample binomial test will be used. The endpoint classifies participants according to whether they have a complete or partial response, then expresses the response count as a proportion of the relevant analysis population. Although the endpoint and planned test are named, the registry record does not report the observed count, the denominator used, the response estimate, or the test output.

What does a one-sample binomial test assess?

As a general statistical explanation, a binomial model is commonly used for a set of outcomes that fall into two categories, such as response and no response. A one-sample test compares an observed proportion with a prespecified reference value. The registry record does not report that reference value, so it is not possible to tell what null benchmark the planned test would use or to evaluate a result against it. A test result alone would not describe the size or precision of the response estimate; those require the estimate and an uncertainty measure, such as a confidence interval.

What does a confidence interval add?

As a general explanation, a confidence interval conveys uncertainty in an estimate under the model and method used to calculate it. For a response proportion, its width is influenced by the amount of information and by the observed proportion. A narrower interval indicates greater statistical precision than a wider interval, but an interval does not remove design limitations or establish a causal effect. No response confidence interval is reported in the registry record. The endpoint description names 95% confidence interval as the dispersion measure, but the corresponding estimate is not reported.

Why does the analysis population matter?

The denominator determines the proportion being estimated. A response rate based on all enrolled participants answers a different operational question from a rate based only on participants with an evaluable assessment. As a general matter, exclusions or missing assessments can affect both the estimate and its uncertainty, particularly if their occurrence is related to outcome. The registry record does not report the primary analysis population, response-evaluable count, or rules for handling missing response assessments. Therefore the denominator and the practical meaning of the planned response rate cannot be independently checked.

What can be learned from the planned significance level?

The registry record’s sample-size-assumptions description refers to a two-sided significance level of 0.05 for a planning illustration. This is not a reported result of the primary test and does not establish that the primary analysis used that threshold. The sample-size description also refers to equal allocation between two arms and a normal approximation. Those are planning assumptions; they do not describe the actual single-group design. The stated illustration is explicitly not the trial’s own design. It uses a fraction of an observed effect as the effect to detect, but an observed effect value is not reported in the registry record.

The same planning description distinguishes total event counts for time-to-event illustrations using the Schoenfeld method from participants per arm for other illustrations. Those are generic planning conventions, not reported participant outcomes or evidence of achieved power. Sample-size calculations are prospective planning tools under specified assumptions. They are not observed power, and they cannot substitute for an estimate of the outcome and its uncertainty. No numerical sample-size illustration is reported in the registry record.

How should time-to-event outcomes be distinguished?

Duration of response and progression-free survival are listed as secondary outcomes. As a general explanation, time-to-event methods account for the timing of an event and can accommodate participants whose event has not been observed by the end of follow-up through censoring, when the analysis method and assumptions permit. The registry record does not report the definitions, analysis methods, event counts, follow-up summaries, or estimates for these outcomes. It is therefore not possible to assess how censoring was handled or what the secondary outcome results indicate.

The primary endpoint’s stated timeframe refers to study entry through progression or death up to 24 months, while its definition is a proportion with complete or partial response. The record does not explain the assessment schedule or how this timeframe relates to determining response. That does not permit an assumption about the intended response-assessment rule; the additional detail is not reported in the registry record.

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(21)
events <- c(0)
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)  21  0  0.0  0.0  16.1  -0.0  15.5  0.1  15.4

11. Multiplicity, Missing Data and Analysis Populations

The registry record names overall response rate as the primary endpoint and duration of response and progression-free survival as secondary outcomes. It does not report a multiplicity strategy for interpreting more than one endpoint, nor does it describe any hierarchy, adjustment, or decision rule across outcomes. When multiple hypotheses are tested, the chance of at least one chance-positive result can increase; as a general statistical matter, a prespecified strategy helps clarify how evidence across outcomes is to be interpreted. The registry record does not provide enough information to determine whether or how this issue was addressed.

Missing-data methods and analysis populations are also not reported in the registry record. In particular, it does not state how participants without a response assessment were handled, whether any participants were excluded from the primary analysis, or what population was used for the response-rate denominator. Without these details, readers cannot establish whether the reported enrollment corresponds to the primary endpoint population; in any case, the primary result itself is not reported.

The record does not describe interim analyses, stopping rules, or any procedures for adjusting inference if results were examined during the study. Those details are not reported in the registry record, and none should be inferred from the phase or completion status. The registry record also does not report the analysis plan for the secondary outcomes or the relationship between those analyses and the primary endpoint.

These omissions limit assessment of the planned statistical evidence, but they do not imply that any particular analysis was or was not conducted outside what is recorded. The registry record provides the endpoint labels and a planned one-sample binomial test for overall response rate; it does not provide the additional information needed to evaluate multiplicity, missingness, or analysis-set decisions.

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: infection (11.5%), dental: teeth (3.8%), obstruction, gi (3.8%), pleural effusion (3.8%), pleural effusion (non-malignant) (3.8%).

The safety record lists 26 participants at risk for serious adverse events and 5 affected. These are participant counts, not a comparison with a control group. The listed serious event terms include infection at 11.5%, dental: teeth at 3.8%, obstruction, GI at 3.8%, pleural effusion at 3.8%, and pleural effusion (non-malignant) at 3.8%. The registry record does not provide further detail about how these terms were grouped or whether the categories overlap.

The record also lists 26 participants at risk for other adverse events and 25 affected. It lists 8 deaths. The record does not state in these figures whether deaths were attributed to treatment, nor does it establish that a particular adverse event caused a death. Event attribution, severity grades, timing, duration, and the specific observation period for these safety figures are not reported in the registry record.

As a general statistical point, a participant count describes how many people were affected, while an event-term percentage describes the reported frequency for a listed term; one participant may potentially contribute to more than one type of event. The record does not provide enough detail to determine event overlap or to interpret these summaries as causal effects. The figures should be read as descriptive safety reporting in a single treatment group, not as comparative estimates of risk.

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

The registry record establishes that NCT02824029 was a completed, phase II, multicenter, single-arm study of ibrutinib in relapsed or refractory classical Hodgkin lymphoma. It specifies an intended primary outcome, overall response rate, defined as the proportion of participants with complete or partial response, and states that a one-sample binomial test will be used. It also lists duration of response and progression-free survival as secondary outcomes.

What the record does not establish is the magnitude or precision of the primary response result. The response count, response proportion, confidence interval, and test output are not reported in the registry record. The benchmark for the one-sample test is also not reported. Without these items, there is no basis for describing the observed response rate, its uncertainty, or whether it met a statistical criterion.

The single-group design also limits causal interpretation. Without a randomized comparison group, outcomes observed among participants cannot provide a like-for-like estimate of what would have occurred under another treatment. The record’s allocation and masking entries reinforce that this is not a randomized, blinded comparison. It is therefore important to distinguish a description of outcomes in the treatment group from evidence of comparative treatment effect.

The enrollment count is 28, but the primary endpoint analysis denominator is not reported. This prevents confirmation of how many participants contributed to the response estimate or how incomplete assessments were handled. The secondary outcomes are named, but their results and analysis details are not reported either. Thus the available record is informative about study structure and outcome definitions but not about the quantitative efficacy results.

The safety figures report serious and other adverse event counts, selected serious event terms, and deaths. They are descriptive counts within the treatment group. They do not by themselves identify cause, establish a treatment relationship, or quantify risk relative to a comparator. The record does not report the additional attribution and follow-up details needed for those interpretations.

In short, the record supports a description of the trial’s design, planned outcomes, and selected safety reporting. It does not support a conclusion about the size of the response, its statistical precision, or comparative treatment effects. Those conclusions require results and analysis details that are not reported in the registry record.

14. Why This Trial Matters Statistically

This trial is statistically notable for the contrast between a clearly named binary primary endpoint and the absence of a reported primary result in the registry record. Overall response rate is defined in terms of complete and partial response, and the planned method is a one-sample binomial test. These details identify the intended form of analysis, but they are not enough to evaluate the evidence without the observed proportion, denominator, confidence interval, test benchmark, and test result.

The single-arm design also highlights a central distinction in clinical-trial interpretation: an outcome observed in a treated group is not the same as a comparative treatment effect. A single-group study can characterize outcomes among enrolled participants, but it does not have a concurrent randomized arm to provide a like-for-like control comparison. That distinction remains important regardless of the statistical method used to summarize the response rate.

The record additionally illustrates why enrollment should not be treated as the endpoint analysis sample size. Although enrollment is 28, the number included in the primary analysis and the handling of missing response assessments are not reported in the registry record. A response proportion cannot be interpreted fully without knowing its denominator and the rules that define who is analyzed.

The study also lists time-to-event outcomes and safety measures, but their labels or descriptive counts alone do not supply complete analyses. Definitions, event handling, analysis methods, and results are needed to understand those outcomes. For safety, descriptive event counts should remain distinct from claims of treatment causation or comparisons of risk.

The statistical importance is therefore methodological rather than a quantified efficacy finding: the record makes the design and intended endpoint identifiable, while leaving key results and analysis details unreported. That distinction helps prevent an endpoint plan, a completed-study status, or a safety count from being mistaken for a complete body of inferential evidence.

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 principal trial-specific limitation in the registry record is that the overall response rate result is not reported. There is no response count, proportion, confidence interval, or one-sample test result, and the test benchmark is not reported. Consequently, the primary efficacy outcome cannot be quantitatively evaluated using this record.

The enrollment is listed as 28, but the record does not identify the number of participants included in the primary endpoint analysis. It does not state how response assessments were scheduled, how participants without an assessment were treated, or what analysis population was used. These omissions make it impossible to check the endpoint denominator or judge the potential effect of missing outcome information.

The single-arm design has no randomized control group. Outcomes in the treatment group therefore do not provide a direct comparison against another intervention or control condition. The record lists no masking, and it does not report additional procedures for limiting assessment bias. Further eligibility details, participant characteristics, and treatment histories are not reported in the registry record, limiting assessment of how broadly the enrolled group can be characterized.

Duration of response and progression-free survival are listed as secondary outcomes, but their operational definitions, analytic methods, results, and precision are not reported. The primary endpoint timeframe mentions follow-up up to 24 months, but the record does not explain assessment timing or how that timeframe determines response status.

Safety reporting is also limited to the listed at-risk and affected counts, selected event terms, and deaths. The registry record does not report detailed event attribution, observation windows, or whether event categories overlap. These limitations do not establish that the study lacked analyses or procedures; they identify information not reported in the registry record.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Ibrutinib in Treating Patients With Relapsed or Refractory Classical Hodgkin Lymphoma — NCT02824029.
• Registry record last updated 2025-02-17; status last verified 2025-01.
• Results first posted 2025-02-17.
• 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

NCT02824029 is a completed phase II, multicenter, single-arm study sponsored by Barbara Ann Karmanos Cancer Institute. The registry enrollment is 28. The study evaluated single-agent ibrutinib for relapsed or refractory classical Hodgkin lymphoma; the summary specifies 560 mg by mouth daily, with treatment courses repeating every 28 days as described in the treatment arm.

The primary endpoint is overall response rate, defined as the proportion of participants with complete or partial response. A one-sample binomial test is specified. Duration of response and progression-free survival are listed as secondary outcomes. The primary response result, its confidence interval, and the test result are not reported in the registry record.

The safety record lists 26 participants at risk for serious adverse events, with 5 affected, and 26 at risk for other adverse events, with 25 affected. It lists 8 deaths and several serious adverse event terms. These are descriptive figures; treatment attribution and a comparative safety analysis are not reported in the registry record.