Study to Assess Effect of Oral Venetoclax Tablet in Combination With Oral Ibrutinib Capsule on Best Overall Response of Complete Response in Adult Japanese Participants With Relapsed/Refractory Mantle Cell Lymphoma: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Study to Assess Effect of Oral Venetoclax Tablet in Combination With Oral Ibrutinib Capsule on Best Overall Response of Complete Response in Adult Japanese Participants With Relapsed/Refractory Mantle Cell Lymphoma (NCT04477486), a na phase 2 study. The primary outcome is Percentage of Participants Achieving Best Overall Response of Complete Response (CR), as Assessed by the Independent Review Committee (IRC).

2. Clinical Question

In statistical terms, the primary question concerns the proportion of a defined study population meeting a response criterion at the stated assessment time. Each participant contributes to the endpoint according to whether their best overall response meets the CR definition under the assessment approach named in the record. The endpoint is not a comparison between treatment groups: all participants were enrolled in the single Ibrutinib + Venetoclax group.

The study also listed outcomes involving CR or partial response, investigator-assessed responses, duration of response, minimal residual disease, and progression-free survival. These related measures address different aspects of response or follow-up, but they do not change the primary question. The registry record does not report results for the primary endpoint or the secondary outcomes.

3. Trial Design

This was a Phase 2 study of venetoclax in combination with ibrutinib in Japanese participants with relapsed or refractory MCL. The registry lists AbbVie as the sponsor and records the study as completed. The recorded start date is 2020-09-23, the primary completion date is 2022-02-09, and enrollment was 13 participants. The brief summary had anticipated around 12 participants in Japan.

The design is classified as single group. Allocation is listed as NA, and masking as none. Thus, the registry describes a study without a randomized allocation or a masked comparator group. The listed arm is Ibrutinib + Venetoclax. Participants were described as receiving venetoclax in various or increasing doses with ibrutinib until a target dose was reached, for up to 104 weeks, followed by ibrutinib monotherapy. The brief summary describes continued ibrutinib after the combination period until disease progression, intolerance, or a participant’s decision to stop participating.

The intervention description gives no exact dose values. Although the study summary characterizes ibrutinib as fixed dose, the arm description names “Ibrutinib Dose A”; further dosing details are not reported in the registry record. The protocol’s dose-escalation schedule and the operational rules for dose changes are also not reported in the registry record.

A single-group study can describe outcomes observed among people receiving the study regimen, but it cannot by itself separate treatment-associated changes from other explanations such as disease course, participant selection, or assessment conditions. Without a concurrent comparison group, the design does not provide a randomized estimate of how outcomes would differ under another treatment. The registry record does not report a sample-size justification, planned interim analyses, or a detailed statistical analysis plan.

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.

Before assignment: The Full Analysis Set (FAS) included all participants who received at least one dose of study drug and was used for all efficacy analyses (except for those based on IRC assessment), safety, and baseline analyses (N=13). The Per-protocol (PP) population excluded participants with non-evaluable disease at baseline (based on IRC assessment). PP population was used for IRC-assessed endpoints (N=12).

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Per-Protocol Population

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.

Population: Full Analysis Set (N=13)

6. Primary Endpoint

The registry lists the primary outcome as Percentage of Participants Achieving Best Overall Response of Complete Response (CR), as Assessed by the Independent Review Committee (IRC), measured over Week 13.

The primary endpoint is the percentage of participants achieving a best overall response of complete response (CR), assessed by an Independent Review Committee (IRC). It is defined using the Revised Criteria for Response Assessment for Malignant Lymphoma following the Lugano classification (Cheson 2014), with Week 13 as the timeframe. The analysis population named for this endpoint is the Per-Protocol Population.

This is a binary outcome at the participant level: a person either meets the CR response criterion or does not. The percentage expresses how common that classification was in the analysis population. The registry specifies a 95% confidence interval as the measure of uncertainty, but the observed percentage and interval are not reported in the registry record.

Generally, a response endpoint provides a structured way to summarize disease status under defined assessment criteria. Use of an IRC can provide an assessment distinct from the investigator’s assessment; the registry also lists investigator-assessed response outcomes. The record does not describe how disagreements between reviewers were resolved or provide further details about assessment procedures.

The “best overall response” wording refers to the response classification used for the endpoint, while Week 13 identifies its stated timeframe. These details matter when interpreting the measure: it is not a duration measure, a survival measure, or a comparison against another group. The registry’s definition identifies the endpoint, but without a posted result it is not possible to describe the observed CR rate or its precision.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What kind of endpoint is this?

Generally, a percentage endpoint for response is a binary participant-level measure. Each participant is classified according to whether the specified response criterion is met, and the percentage summarizes the fraction meeting it in the chosen analysis population. The primary endpoint in this study is CR assessed by the IRC, and the named population is the Per-Protocol Population. The registry record does not give the number classified as CR or the resulting percentage.

A binary endpoint is different from a continuous measure, such as a laboratory value, and from a time-to-event endpoint, such as duration of response or progression-free survival. It records whether a criterion was met rather than how long a response lasted. Other outcomes in this study address those different questions. The endpoint’s Week 13 timeframe and its use of “best overall response” are part of its definition and should be retained when describing what the result would represent.

What does a confidence interval contribute?

Generally, a confidence interval conveys uncertainty around an estimated quantity. For a response percentage, it gives a range of values compatible with the observed data under the method used to calculate the interval. It does not remove uncertainty, and it is not a guarantee that the true response percentage lies within the particular interval. Its width is affected by the amount of information available and by the number of participants meeting the endpoint.

The registry lists a 95% confidence interval for the primary endpoint, but does not report its bounds or the interval method. Therefore, the interval cannot be interpreted numerically, and its width cannot be assessed. The exact response estimate is also not reported, so there is no basis to discuss whether it is precise or imprecise in this particular study.

Why does the analysis population matter?

The endpoint is assigned to the Per-Protocol Population. Generally, a per-protocol analysis focuses on participants who meet specified study-protocol requirements. The exact membership rules, exclusions, and population size are not reported in the registry record. Without those details, readers cannot determine who was included in that endpoint analysis or how the analysis population relates to all enrolled participants.

Analysis populations can affect estimates because the people included in a calculation define its denominator and may differ from those who enrolled. A per-protocol result should therefore be interpreted according to its own stated population rather than assumed to represent every enrolled participant. The registry record does not report how missing endpoint assessments were handled, whether any participants were excluded from the Per-Protocol Population, or how exclusions were decided.

What does the single-group design allow?

Generally, a single-group study can estimate outcomes observed in the group studied, subject to the endpoint definition, analysis population, and completeness of follow-up. It does not create a randomized contrast between the study regimen and a control regimen. In this study, allocation is listed as NA and the model as single group. Consequently, a response percentage, if reported, would be descriptive of this group rather than a randomized comparative treatment effect.

Randomization is one way to make treatment groups comparable on average, including with respect to measured and unmeasured factors. With no randomized comparator in this design, treatment differences cannot be estimated from a between-group contrast. This is a general limitation of single-group evidence, not a claim about any specific source of bias in the participants enrolled.

How should the other outcomes be distinguished?

The registry lists outcomes assessed by both the IRC and investigators, along with duration of response, minimal residual disease, and progression-free survival. Generally, distinct endpoints can capture different features of a disease course and use different assessment rules. A CR classification does not supply information about how long a response persists. Likewise, an outcome based on investigator assessment need not match one based on independent review, because the assessors and procedures differ.

The registry record lists 10 outcome measures and one analysis. It does not report a complete statistical analysis plan, a multiplicity procedure, or whether any outcomes were designated as supportive or exploratory. No adjustment method should be assumed from the fact that multiple outcomes are listed.

What can sample-size planning figures say?

Generally, a sample-size calculation is a planning exercise that depends on assumptions about the effect to detect, statistical significance level, allocation, and analysis method. It is not an observed result and is not evidence that a study had a particular probability of detecting an effect after the data were collected. The registry record states that planning illustrations use a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation, with effects specified as fractions of an observed effect. It also says that time-to-event illustrations refer to total events, while other illustrations refer to participants per arm.

Those assumptions describe planning illustrations, not the design of this single-group study. The registry record does not report the trial’s own sample-size justification or a planned two-arm comparison. Any planning illustration should therefore be kept separate from the actual enrollment of 13 and from the unreported primary endpoint result. It is not observed power.

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("Ibrutinib + Venetoclax")
n      <- c(12)
events <- c(10)
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  Ibrutinib + Venetoclax  12  10  83.3  51.6  97.9  55.2  95.3  54.6  95.0

11. Multiplicity, Missing Data and Analysis Populations

The registry lists 10 outcome measures, including the primary IRC-assessed CR endpoint and secondary outcomes involving response, duration of response, minimal residual disease, and progression-free survival. When multiple outcomes are examined, there can be more than one opportunity to observe a result that appears notable by chance. Generally, a prespecified multiplicity approach can control or describe this issue, depending on the study’s goals and analysis plan.

A multiplicity adjustment or hierarchy for interpreting these outcomes is not reported in the registry record. The record lists one analysis, but this does not specify which comparisons or endpoints were analyzed, the order in which they were assessed, or whether any adjustment was applied. No particular statistical strategy can be inferred from the list of outcomes alone.

The primary endpoint is defined for the Per-Protocol Population, but the population size, participant-level endpoint availability, and handling of missing assessments are not reported in the registry record. The record does not say whether missing data were excluded, treated as non-response, imputed, or handled by another method. These choices can affect the denominator and the estimated response percentage, so they are important to understanding a reported result.

The registry record also does not describe the protocol’s analysis-set rules, sensitivity analyses, or procedures for departures from the planned analysis. For a small single-group study, transparency about who contributed to each endpoint and how incomplete follow-up was handled is particularly useful for judging how much the result depends on those decisions. Since the primary result itself is not reported in the registry record, its analysis and missing-data handling cannot be evaluated.

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 0% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: pyrexia (15.4%), covid-19 pneumonia (15.4%), neutropenia (7.7%), glaucoma (7.7%), haemorrhoids (7.7%).

For the Ibrutinib + Venetoclax group, the registry records 13 participants at risk for serious adverse events and 7 affected. It records 13 participants at risk for other adverse events and 13 affected. Five deaths are recorded for the group. These figures describe the study group; they should not be treated as evidence that the regimen caused each event or death.

The registry lists pyrexia and COVID-19 pneumonia at 15.4% each among the top serious adverse-event terms. Neutropenia, glaucoma, haemorrhoids, and lower gastrointestinal haemorrhage are each listed at 7.7%. These are the recorded percentages for the named terms, not measures of treatment effect. The record does not report additional context such as event timing, duration, severity details, or attribution to study treatment.

Generally, safety counts depend on how events are defined, collected, and coded. A participant may experience more than one event, so event-term percentages should not be added together to infer a number of distinct participants. The registry does not provide a comparator group in this study, so these figures cannot be used to estimate a difference in risk versus another treatment. The details recorded do not establish whether the deaths were related to adverse events or treatment.

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

The registry record describes a Phase 2, single-group study in adult Japanese participants with relapsed or refractory MCL. It identifies a specific primary endpoint: the percentage achieving best overall response of CR at Week 13, assessed by an IRC under the stated response criteria. It also records enrollment, the intervention, and selected safety information. These registry entries help define what the study set out to assess.

The primary response result is not reported in the registry record. Neither the observed CR percentage nor its 95% confidence interval is available in the record. Therefore, the record does not support a statement about the frequency of CR in the primary analysis population or the precision of that estimate. Absence of a result in the record is not a zero response and does not establish that no responses occurred.

Because the design has one treatment group and no randomized comparator, even a reported response proportion would not establish how outcomes differ from another treatment. It would describe the participants included in the analysis, under the assessment criteria and follow-up described. General limitations of single-group studies include the inability to use randomization to address differences between treatment groups; no claim about the magnitude of such differences can be made from this record.

The listed secondary outcomes could describe other aspects of response and follow-up, but their numerical results are also not reported in the registry record. In particular, a response endpoint, a duration endpoint, and a survival endpoint answer different questions and should not be substituted for one another. Investigator-assessed outcomes are also distinct from IRC-assessed outcomes.

The safety counts and listed serious adverse-event terms provide descriptive information about events recorded in the study group. They do not by themselves establish causation or comparative safety. The record does not provide a control group or detailed event attribution. Overall, the available information identifies the study’s design and endpoints, but does not provide the primary efficacy result needed to quantify the CR outcome.

14. Why This Trial Matters Statistically

This study illustrates why the endpoint definition, analysis population, and design need to be considered together. The primary outcome is not simply a general claim of response: it is the percentage achieving best overall response of CR, assessed by an IRC using specified criteria, at Week 13, in the Per-Protocol Population. Each of those details sets the scope of the quantity the study intended to estimate.

The single-group design is also central to interpretation. Enrollment of 13 participants allows the registry to describe a small treated group, but the design does not provide a randomized comparison. The study can address the observed experience of participants meeting its analysis criteria if results are available; it cannot, by itself, estimate a randomized contrast against another treatment.

The record further demonstrates that naming a confidence interval is not the same as reporting one. A 95% confidence interval is specified for the primary endpoint, but its numerical bounds and the underlying endpoint result are not reported in the registry record. Without those values, readers cannot assess the estimate’s uncertainty. Reporting the planned endpoint and uncertainty measure is useful, but result transparency is also needed for statistical interpretation.

Finally, the collection of secondary outcomes shows why outcomes should be kept distinct and why multiplicity and missing-data procedures matter. Response, duration, minimal residual disease, and progression-free survival do not measure the same thing. The registry record does not describe how multiple outcomes were handled statistically or how missing assessments were treated. These design and reporting details shape what can responsibly be concluded from a clinical trial record.

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 limitation for interpreting efficacy is that the registry record does not report the primary endpoint result. It names the CR response measure and its 95% confidence interval, but gives neither the percentage nor the interval bounds. Without those quantities, the response rate and its precision cannot be evaluated. Numerical results for the listed secondary outcomes are also not reported in the registry record.

The study is single group, with allocation listed as NA and masking as none. There is no randomized control group for comparison. Therefore, a result from this study would not provide a randomized estimate of the difference between venetoclax plus ibrutinib and another treatment. The registry record does not report a comparative analysis.

Enrollment was 13 participants, while the brief summary anticipated around 12. The record does not provide the sample-size justification for the trial. The Per-Protocol Population is named for the primary endpoint, but its size and membership rules are not reported. Nor are the handling of missing assessments, exclusions, or sensitivity analyses described.

The registry lists multiple outcomes, but does not report a complete statistical analysis plan or any multiplicity procedure. Details about endpoint assessment, the relationship between IRC and investigator assessments, and the handling of incomplete follow-up are not reported in the registry record. Safety information is also limited: counts and selected event terms are listed, but event timing, duration, attribution, and further clinical context are not reported. These limitations constrain interpretation of both the efficacy question and the descriptive safety record.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Study to Assess Effect of Oral Venetoclax Tablet in Combination With Oral Ibrutinib Capsule on Best Overall Response of Complete Response in Adult Japanese Participants With Relapsed/Refractory Mantle Cell Lymphoma — NCT04477486.
• Registry record last updated 2026-08-28; status last verified 2026-08.
• Results first posted 2025-01-14.
• 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

This completed Phase 2 study enrolled 13 adult Japanese participants with relapsed or refractory MCL. It is recorded as a single-group, unmasked study with allocation listed as NA. Participants received venetoclax with ibrutinib, with the combination described for up to 104 weeks and ibrutinib monotherapy afterward.

The primary endpoint was the percentage achieving best overall response of CR at Week 13, assessed by an IRC in the Per-Protocol Population. A 95% confidence interval was specified. The numerical primary result and results for the listed secondary outcomes are not reported in the registry record.

The safety record lists 7 of 13 participants affected by serious adverse events, 13 of 13 affected by other adverse events, and 5 deaths. These are descriptive group figures and do not establish causation. The registry record does not report a randomized comparator, the trial’s sample-size justification, or detailed missing-data and multiplicity methods.