Bendamustine Plus Rituximab (BR) for Relapsed or Progressive Marginal Zone B-cell Lymphoma (MZBCL): Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Bendamustine Plus Rituximab (BR) for Relapsed or Progressive Marginal Zone B-cell Lymphoma (MZBCL) (NCT02433795), a na phase 2 study. The primary outcome is Overall Response Rate.

2. Clinical Question

This is a response question in a population whose lymphoma had relapsed or progressed. It is not a randomized comparison of BR against another treatment or against a control group. The registry record identifies overall response rate (ORR) as the primary outcome and specifies a 90% confidence interval as its dispersion measure. However, the response-rate estimate and confidence limits are not reported in the registry record, so the magnitude and precision of the posted primary result cannot be described from this record.

Of the 27 eligible patients, 26 were evaluated for response. One patient was not evaluated after early treatment discontinuation following life-threatening pneumonia and acute respiratory failure after the first cycle. The record also identifies progression-free survival and the 3-year survival rate as secondary outcomes, but does not report their results in the listed information.

3. Trial Design

This completed study is listed as phase II and single-group. Its stated purpose was to evaluate bendamustine plus rituximab in patients with relapsed or progressive MZBCL. The registry lists Seoul National University Hospital as the sponsor, enrollment of 27, a start date of 2015-05, and primary completion in 2019-10. No masking was used, and allocation is recorded as not applicable.

All participants were assigned to the BR regimen described in the record. Bendamustine was administered intravenously. Rituximab was administered intravenously at the first cycle and subcutaneously from the second cycle, with treatment continuing to a maximum of the eighth cycle. The record does not give further dosing details in the information available for this analysis.

The primary outcome was ORR, defined as the proportion with a confirmed complete response or partial response. Investigators assessed response using the Revised Response Criteria for Malignant Lymphoma. The recorded timeframe is “Up to disease progression, more than 30.12 months.” The registry also lists progression-free survival and the 3-year survival rate as secondary outcomes.

A single-group design can describe outcomes among treated participants, but it does not estimate a randomized treatment contrast. Without a concurrent control group, differences from another treatment or from the course patients might otherwise have experienced cannot be attributed to BR using this design alone. The registry record does not report the protocol’s sample-size justification, planned interim analyses, or a detailed statistical analysis plan. It also does not report an analysis result for the primary outcome in the information.

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

Analysis population for the primary outcome, as defined in the registry: Of the 27 eligible patients, 26 were evaluated for a response. One patient, a 78-year-old female, was not evaluated because of early treatment discontinuation following the development of life-threatening pneumonia and acute respiratory failure after the first cycle.

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, measured over Up to disease progression, more than 30.12 months.

Overall response rate is the proportion of patients who achieve a confirmed complete response (CR) or partial response (PR). It combines these two response categories into one measure, using the investigator’s assessment under the Revised Response Criteria for Malignant Lymphoma. As a proportion, ORR describes how many patients in the assessed group met the response definition; it does not, by itself, describe how long a response lasted or whether survival changed.

Response rate is used in this study as the primary measure of antitumor activity in patients with relapsed or progressive MZBCL. The record specifies a 90% confidence interval to express uncertainty around the estimate. A confidence interval is a statistical range that reflects the uncertainty associated with an estimated proportion; a narrower interval generally indicates greater precision, while a wider interval indicates less precision. The confidence-interval limits and the ORR estimate are not reported in the registry record, so neither the observed response proportion nor its precision can be assessed from the listed results.

The response population is described as 26 evaluated patients among 27 eligible patients. One eligible patient was not evaluated after early treatment discontinuation associated with life-threatening pneumonia and acute respiratory failure following the first cycle. That distinction matters when interpreting the endpoint: the record describes response evaluation in 26 patients, rather than reporting a response estimate for all 27 eligible patients.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The statistical information in the registry record is limited. It identifies a phase II, single-group study and names ORR as the primary outcome. It defines the outcome and identifies a 90% confidence interval as the dispersion measure, but does not give the response estimate, the interval limits, or a detailed analysis plan. The concepts below explain how such methods are generally interpreted; they should not be taken as evidence that a particular unreported method was used.

What does a response proportion describe?

In general, a response proportion is the number of participants meeting a prespecified response definition relative to the participants included in the response analysis. Here, the definition is a confirmed CR or PR, assessed by the investigator using the Revised Response Criteria for Malignant Lymphoma. The record states that 26 eligible patients were evaluated for response, while one of the 27 eligible patients was not evaluated after early treatment discontinuation. It does not report the number of responders, so the proportion cannot be reconstructed or interpreted from the record.

A response proportion is a summary of whether a response was recorded, not a measure of response duration. It is also distinct from progression-free survival and survival outcomes, which concern time-to-event outcomes. Although those outcomes are listed as secondary measures, their results are not reported in the record information.

How should a confidence interval be read?

In general, a confidence interval conveys uncertainty around an estimate. For a response proportion, it indicates a range of values compatible with the data under the interval’s statistical assumptions. Greater precision is associated with a narrower interval; less precision is associated with a wider one. The registry specifies a 90% confidence interval for ORR, but does not report either endpoint or the ORR estimate. It is therefore not possible to assess the interval’s width or use it to judge the precision of the primary outcome.

A confidence interval is not a guarantee that the true value lies within a particular calculated range, and it does not resolve limitations of the design or outcome assessment. In particular, an interval around a single-group response proportion would not create a randomized comparison. It would quantify uncertainty around the estimate for the analyzed group, not the uncertainty around a contrast with an unobserved control group.

What does the design allow?

In general, a single-group study can describe outcomes among participants treated under the study regimen. A randomized comparison instead assigns participants to distinct groups and can estimate differences between those groups, subject to its design and analysis. This study is listed as single-group, with allocation not applicable and no masking. There is no like-for-like control comparison in the record. Thus, the design does not support a randomized estimate of how BR compares with another intervention.

The lack of masking is part of the recorded design. Since the endpoint was investigator-assessed, masking could be relevant in general to the possibility that knowledge of treatment influences assessment. The record does not describe additional safeguards or procedures for response assessment, so none should be assumed.

What can be inferred from the planning illustrations?

Planning sample-size illustrations are not observed results and are not a measure of the probability that a study detected an effect. The stated illustration assumptions are a two-sided significance level of 0.05, equal allocation between two arms, a normal approximation, and an effect defined as a stated fraction of the observed effect. For time-to-event outcomes, the illustrations refer to a total number of events; for other outcomes, they refer to participants per arm. These are planning assumptions, not the design description of this single-group study.

The registry record does not report the study’s own sample-size justification. The planning illustrations cannot be treated as the study’s original rationale, nor do they establish that the study had adequate or inadequate power. The registry’s single-group design also differs from the two-arm equal-allocation assumption used for those illustrations. Sample-size calculations, when available, describe hypothetical planning conditions; they do not replace the missing primary outcome estimate or its interval.

What statistical details remain unknown?

The record does not report the specific method used to calculate the 90% confidence interval, the handling of missing response assessments, or whether any sensitivity analyses were performed. It does not describe interim analyses, the detailed statistical analysis plan, or a sample-size justification. No analyses are listed. General statistical concepts cannot fill those gaps: absent details should not be inferred from the endpoint definition or the study’s phase.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists three outcome measures: ORR as the primary outcome, plus progression-free survival and the 3-year survival rate as secondary outcomes. It reports zero analyses in the information. Results for the secondary outcomes are not reported in the registry record, and the primary response estimate and confidence limits are also not reported.

Multiplicity arises in general when several outcomes, time points, or statistical comparisons are assessed. Unless the analysis plan specifies how these tests are handled, repeated testing can affect how evidence is interpreted. The registry record does not report a multiplicity strategy, such as an adjustment procedure or a hierarchy for testing outcomes. It is therefore not possible to determine whether multiplicity was addressed in the study’s analysis.

For response evaluation, 26 of 27 eligible patients were assessed. One patient was not evaluated following early treatment discontinuation after life-threatening pneumonia and acute respiratory failure after the first cycle. The record does not describe a missing-data method, imputation procedure, sensitivity analysis, or the precise analysis population beyond this account. It is also not reported in the registry record whether other outcome data were missing.

The distinction between eligible and evaluated participants is relevant because the primary outcome is a proportion. The recorded information does not give the response count or an estimate, so the effect of the unevaluated patient on the reported response result cannot be assessed. No assumptions should be made about that patient’s response status or about how the investigators treated the missing assessment in their analysis.

11. 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: lung infection (11.1%), hepatitis b reactivation (3.7%).

The safety record lists 27 participants at risk for both serious and other adverse events in the BR group. Three participants were affected by serious adverse events, and 14 were affected by other adverse events. The record lists zero deaths. These are participant counts, not a comparison of event rates between treatments.

The two most frequent serious adverse-event terms listed are lung infection at 11.1% and hepatitis B reactivation at 3.7%. The record also describes the patient who was not evaluated for response as having developed life-threatening pneumonia and acute respiratory failure after the first cycle, leading to early treatment discontinuation. The registry information does not state whether those specific conditions correspond to one of the listed serious-event terms, so they should not be linked beyond what the record says.

In general, adverse-event counts describe events recorded during a study and do not, by themselves, establish causation. This single-group study has no comparator arm, so these figures cannot show whether event risk was higher or lower than under another treatment. The registry record does not provide further details on event severity beyond the serious-event classification and listed terms.

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

The record establishes that a phase II, single-group study evaluated bendamustine plus rituximab in patients with relapsed or progressive MZBCL. It specifies an investigator-assessed ORR based on confirmed complete or partial responses under the Revised Response Criteria for Malignant Lymphoma. It also reports that 26 of 27 eligible patients were evaluated for response, and gives selected safety counts for the BR group.

The central efficacy quantity is not reported in the registry record. Neither the ORR estimate nor its 90% confidence limits are listed. As a result, the record information does not show how many evaluated participants had a confirmed response, how large the response proportion was, or how precisely it was estimated. The listed secondary outcomes—progression-free survival and the 3-year survival rate—also have no reported results in the information.

Even if a response estimate were available, the study design would constrain its interpretation. A single-group study describes outcomes within its enrolled group; it does not provide a randomized comparison against another intervention or a control condition. The record therefore cannot establish comparative benefit or harm from these data alone. No treatment recommendation follows from the posted information.

The safety counts show that serious and other adverse events were recorded in the group, including the listed serious-event terms of lung infection and hepatitis B reactivation. They do not establish that BR caused those events or indicate how the counts compare with another treatment. The unevaluated patient’s early discontinuation after life-threatening pneumonia and acute respiratory failure is also part of the record and should be considered when reading the response population and safety context.

In short, the registry describes the question, regimen, design, endpoint definition, evaluable population, and selected adverse-event counts. It does not report the numerical efficacy results or enough statistical detail to assess the planned analysis fully. The appropriate interpretation is bounded by those reported details.

13. Why This Trial Matters Statistically

This study is statistically informative as an example of the distinction between a clearly defined endpoint and a reportable endpoint result. The registry identifies ORR, defines confirmed CR and PR, specifies investigator assessment under the Revised Response Criteria for Malignant Lymphoma, and names a 90% confidence interval. Yet the estimate and interval limits are not reported in the registry record. Without them, readers cannot assess either the response proportion or its precision.

The response population also makes the denominator an important part of interpretation. The record identifies 27 eligible patients and 26 evaluated for response, and explains why one patient was not evaluated. That information helps readers distinguish enrollment from response assessment, but it does not supply the response count or explain how the unevaluated patient was handled analytically.

The single-group design highlights the difference between describing outcomes and estimating a comparative treatment effect. This study can be understood as evaluating outcomes in a treated cohort, but it does not include a randomized control group. A response estimate, if reported, would not by itself show how outcomes compare with another treatment.

Finally, the record lists secondary outcomes and selected safety figures but does not report secondary outcome results, a multiplicity strategy, or a detailed statistical analysis plan. Those gaps matter because they limit the ability to assess the complete analysis and the scope of conclusions. The study therefore illustrates why endpoint definitions, analysis populations, uncertainty estimates, and design context all matter alongside outcome counts.

14. Limitations

• The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
• Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.

The most direct limitation for statistical interpretation is that the registry record does not report the primary ORR estimate or its 90% confidence limits. The response definition and evaluated population are described, but the number of participants with confirmed CR or PR is not. This prevents assessment of the primary outcome’s magnitude and precision.

The study is single-group, with no comparator and no masking. Its results cannot provide a randomized comparison with another treatment. Because the endpoint was investigator-assessed, lack of masking is part of the context for interpreting response, but the record does not report further assessment safeguards or procedures.

One of the 27 eligible patients was not evaluated for response after early treatment discontinuation following life-threatening pneumonia and acute respiratory failure after the first cycle. The record does not report a missing-data strategy or explain how that patient was treated in the primary analysis. It also does not say whether there were other missing assessments.

Although progression-free survival and the 3-year survival rate are listed as secondary outcomes, their results are not reported in the listed information. The record also does not report a detailed statistical analysis plan, a sample-size justification, interim analyses, or a multiplicity strategy. These details are important for assessing how outcomes were planned and interpreted, but should not be inferred.

The adverse-event information is limited to counts, zero deaths, and two listed serious-event terms with percentages. Without a comparator, the counts do not provide comparative safety estimates. Overall, the record supports a description of study design and selected observations, but the missing efficacy results and analysis details limit statistical conclusions.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Bendamustine Plus Rituximab (BR) for Relapsed or Progressive Marginal Zone B-cell Lymphoma (MZBCL) — NCT02433795.
• Registry record last updated 2026-04-22; status last verified 2021-09.
• Results first posted 2026-04-22.
• 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.

18. Record Summary

NCT02433795 is a completed phase II, single-group study sponsored by Seoul National University Hospital. It enrolled 27 patients with relapsed or progressive MZBCL and evaluated bendamustine plus rituximab. The study began in 2015-05 and reached primary completion in 2019-10. No masking was used, and allocation is recorded as not applicable.

The primary outcome was investigator-assessed ORR, defined as confirmed CR or PR under the Revised Response Criteria for Malignant Lymphoma, with a 90% confidence interval specified. Of 27 eligible patients, 26 were evaluated for response. The ORR estimate and confidence limits are not reported in the registry record. Progression-free survival and the 3-year survival rate are listed as secondary outcomes, without results in the information.

The safety record reports 3 participants with serious adverse events, 14 with other adverse events, and zero deaths. Lung infection and hepatitis B reactivation are listed serious-event terms. No randomized comparator is included, and the record does not report a detailed statistical analysis plan or sample-size justification.