Phase II Study of Bendamustine and Rituximab Plus Venetoclax in Untreated Mantle Cell Lymphoma Over 60 Years of Age: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Phase II Study of Bendamustine and Rituximab Plus Venetoclax in Untreated Mantle Cell Lymphoma Over 60 Years of Age (NCT03834688), a na phase 2 study. The primary outcome is Complete Response (CR) Rate at End of Induction.

2. Clinical Question

The study also aimed to examine side effects and listed overall response, progression-free survival and overall survival as secondary outcomes. These outcomes address different aspects of treatment experience: response describes disease status, while time-to-event outcomes concern how long it takes for a specified event to occur. The record does not provide numerical results for those secondary outcomes. The main question can therefore be stated from the registered endpoint, but the result needed to answer it is not available in the registry record.

3. Trial Design

This was a Phase II, single-group study sponsored by PrECOG, LLC. The registry record lists the study as completed and reports enrollment of 33 participants. The recorded study start was 2020-01-13, and primary completion was 2022-10-20. These dates describe the registry record’s study timeline; they do not supply outcome follow-up for each participant.

Participants received venetoclax, bendamustine and rituximab as induction therapy for 6 cycles of 28 days. The record states that maintenance rituximab could be administered after induction at physician discretion. That flexibility means the registered treatment approach included a discretionary post-induction component rather than a maintenance regimen specified as mandatory for all participants. The record does not report how many participants received maintenance rituximab or the reasons for individual treatment decisions.

The study had no masking and no randomized allocation. It is therefore an open-label, single-group design in the practical sense that the registry lists no masking and only one treatment group. No concurrent control group is described. This design can describe outcomes observed among participants receiving the regimen, but it cannot by itself separate the regimen’s effect from changes that might occur over time, other care, or differences in who entered and remained in the study.

The primary endpoint was complete-response status at the end of induction. The registry describes assessment after 6 months of induction treatment, plus an additional 2 months for end-of-treatment PET/CT scans. The record lists treatment-related adverse events assessed by CTCAE v5.0, overall response, progression-free survival and overall survival among secondary outcomes. The detailed statistical plan, analysis populations, and methods for handling follow-up and missing outcome assessments are not reported in the registry 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

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 Complete Response (CR) Rate at End of Induction, measured over Complete Response (CR) status was assessed after 6 months of induction treatment, plus an additional 2 months for end of treatment PET/CT scans..

The primary endpoint was the complete-response rate at the end of induction. Complete response is a categorical assessment of whether a participant meets the specified criteria for a complete response; it is not a measure of how long a response lasts. The registry describes assessment under the Lugano Classification Criteria using PET/CT scans at baseline and PET/CT or CT scans during follow-up. A Deauville score of 3 or lower corresponds to complete response under the description in the record.

The record distinguishes complete response from partial response, stable disease and progressive disease. For scores of 4 or 5, the classification depends on the change in lesion measurements and on whether new lesions or bone marrow recurrence are present. A score of 4 or 5 with a decrease of at least 50% in the sum of lesion measurements is described as partial response. A decrease of less than 50% is described as stable disease, while an increase greater than 1.5cm in a single lesion, new lesions, or bone marrow recurrence denotes progressive disease.

A response endpoint is useful because it gives a defined measure of disease status at a specified assessment. The end-of-induction timing makes the assessment refer to a particular point in the treatment course. General statistical interpretation: a response rate needs both a numerator—the number meeting the response definition—and a denominator—the number assessed under the relevant analysis rules. The registry record does not report the complete-response count or the denominator for this primary endpoint, so neither a rate nor its precision can be stated.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

General statistical explanation: a binary endpoint records whether an outcome is present or absent for each participant. The primary complete-response endpoint is binary at the participant level: a participant either meets the complete-response definition at the specified assessment or does not. A rate summarizes the fraction meeting the definition, but its interpretation depends on how the analysis defines the numerator and denominator. The registry identifies the endpoint as a participant count and names it as a rate, but does not report the observed count, denominator, or endpoint analysis rules.

What does an estimate describe?

An estimate is a numerical summary calculated from observed data. For a response endpoint, the estimated rate would describe the observed proportion meeting the criteria among the participants included in the analysis. It would not automatically describe every person with the condition or predict an individual participant’s outcome. In a single-group study, the estimate would describe the studied group under the recorded treatment approach; it would not be a direct estimate of the difference between that approach and an alternative.

The registry record does not report a primary endpoint estimate. Therefore, no interpretation of its magnitude is possible. It would also be inappropriate to treat enrollment as the endpoint denominator without a reported analysis rule. Participants may have different assessment availability or follow-up, and the registry record does not state how those situations were handled.

What would a confidence interval add?

General statistical explanation: a confidence interval gives a range of values compatible with the data under a specified statistical procedure. It helps communicate precision, which is different from the estimate’s direction or clinical relevance. A wider interval indicates greater uncertainty than a narrower interval. Confidence intervals do not eliminate bias from study design, outcome assessment, or missing data, and they do not convert an uncontrolled comparison into a randomized one. No confidence interval for the primary endpoint is reported in the registry record.

What does a hypothesis test address?

General statistical explanation: a hypothesis test compares observed data with a null model defined by the analysis. A p-value measures how unusual the observed data, or data more extreme, would be under that model and its assumptions. It is not the probability that the null hypothesis is true, nor does it measure the size or importance of an effect. The registry record does not report a primary hypothesis test, p-value, or inferential analysis. It is therefore not possible to characterize the primary endpoint as statistically significant or not statistically significant from the recorded information.

Why does the design matter?

The study is registered as single-group, with allocation not applicable and no masking. General statistical explanation: a concurrent randomized comparison helps balance, on average, measured and unmeasured factors between groups, while a single-group study lacks that direct comparison. An observed response can be described, but attributing it specifically to the treatment combination is more difficult. Patient selection, the course of the disease, other care, and how outcomes are assessed can all affect the observed result. The record does not report an external comparator or a design intended to estimate a treatment contrast.

The registered treatment also includes physician-discretionary maintenance rituximab after induction. General statistical explanation: when post-induction care varies by clinical decision, the resulting outcomes may reflect both the induction regimen and subsequent care. Assessing those contributions requires details about who received maintenance, when it was given, and how analyses accounted for it. Those details are not reported in the registry record.

How should planning calculations be read?

The sample-size assumptions describe a planning illustration using 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 calculations, the assumptions describe a total number of events using the Schoenfeld method; other calculations are described in participants per arm. These are planning conventions, not observed trial outcomes. Sample-size calculations estimate the amount of information a proposed design might need under chosen assumptions; they do not show that a completed study had a particular probability of detecting an effect.

The study’s registered design is single-group, whereas the planning assumptions describe equal allocation between two arms. This mismatch makes it important not to interpret a two-arm illustration as the actual design or as a randomized analysis of this trial. The observed effect used for the illustration and the calculated planning values are not reported in the registry record, so no numerical planning result can be interpreted.

General statistical explanation: over-dispersion arises when variability in observed data exceeds what a simple statistical model expects. If present, a model that ignores it can understate uncertainty and make intervals too narrow or tests too optimistic. The registered primary outcome is a participant count for a binary response, and the registry record does not report an over-dispersion assessment or model. No claim about over-dispersion in this study can therefore be made.

Outcome classification is another methodological component. The record specifies the Lugano Classification Criteria and describes imaging modalities and response categories. Consistent application of those criteria is important because classification determines who enters the complete-response numerator. The registry record does not report independent review procedures, assessor masking, or adjudication of disagreements. Those features should not be assumed.

10. Multiplicity, Missing Data and Analysis Populations

The registry record lists a primary complete-response endpoint and secondary outcomes that include treatment-related adverse events, overall response, progression-free survival and overall survival. It does not report a statistical plan for controlling multiplicity across these outcomes or across any additional analyses. When several outcomes are tested, the chance of at least one apparently unusual result can increase if no adjustment or hierarchy is used. That is a general statistical concern; the record does not establish whether an adjustment was planned or performed.

Missing-data methods and the primary analysis population are not reported in the registry record. The record does not state how participants without an end-of-induction scan, incomplete assessments, or other unavailable outcome data were handled. It also does not identify whether the primary endpoint used all enrolled participants, only participants with an evaluable scan, or another defined population. These details matter because changing who is included can change both the estimated response rate and its precision.

The registry record does not report an interim analysis plan, a prespecified statistical analysis plan, or a method for handling deviations from the intended treatment. The study’s completion status does not answer these methodological questions. Without the analysis rules, it is not possible to determine whether the posted endpoint was analyzed as originally intended, or to assess sensitivity to alternative assumptions about missing assessments. General statistical interpretation: transparent reporting of analysis populations, missing-data handling and multiplicity procedures helps readers distinguish prespecified analyses from exploratory ones and judge how robust conclusions may be.

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 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: covid-19 pneumonia (9.1%), tumour lysis syndrome (6.1%), acute kidney injury (3.0%), acute respiratory failure (3.0%), clostridium difficile colitis (3.0%).

The safety figures describe participants with serious adverse events and participants with other adverse events during induction. The registry record reports 33 participants at risk for serious events and 10 affected, and 33 at risk for other events and 19 affected. These are participant counts; they should not be added together because the record does not state that the groups are mutually exclusive. The record also lists 10 deaths, but does not report their timing, causes, or relationship to treatment.

The listed serious adverse-event terms and percentages are COVID-19 pneumonia, 9.1%; tumour lysis syndrome, 6.1%; acute kidney injury, 3.0%; acute respiratory failure, 3.0%; Clostridium difficile colitis, 3.0%; and nausea/vomiting, 3.0%. These are selected terms in the registry record, not a complete account of each participant’s clinical course. The record does not provide comparative rates, event timing, or a breakdown of how many events each affected participant experienced.

General statistical explanation: “serious” is a classification of adverse-event seriousness and should not be treated as interchangeable with a simple rating of symptom intensity. Counts and percentages summarize events in the recorded group; without a comparator and further context they do not establish causation or quantify relative risk. The record does not report enough information to attribute the deaths or listed events to the regimen.

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

The result this study was designed to measure is the number of participants with a complete response at the end of induction, assessed under the Lugano Classification Criteria. The registry record does not report that count, the endpoint denominator, or the resulting rate. It therefore does not establish a numerical primary response result in the information reported. The study’s completed status and enrollment of 33 participants do not fill that gap.

Even if an observed response rate were available, a single-group study would describe outcomes in the group receiving the registered regimen rather than establish what would have happened to comparable participants receiving another treatment. Without a concurrent control group, differences from other settings cannot be interpreted as a treatment effect on the basis of this study alone. The record also does not report a confidence interval or hypothesis test for the primary endpoint, so statistical precision and compatibility with a specified statistical model cannot be evaluated.

The safety counts and selected serious-event terms provide descriptive information about adverse events recorded during induction. They do not, on their own, show that treatment caused an event or death. The registry record does not supply comparative safety data, event timing, or detailed attribution information. Likewise, the listed secondary outcomes do not have numerical results reported in the record, so their magnitude and precision cannot be assessed.

General statistical interpretation: a study result is most informative when the endpoint definition, analysis population, estimate, uncertainty, missing-data approach and study design are considered together. Here, the endpoint definition and broad design are described, but the primary numerical result and several analysis details are not reported in the registry record. The appropriate conclusion is limited to what the record documents: a completed, single-group Phase II study evaluated the specified induction regimen and registered a complete-response endpoint, while the numerical primary outcome is unavailable in the record.

13. Why This Trial Matters Statistically

This trial is statistically notable for the distinction between a registered clinical question and a reported numerical result. The primary endpoint is clearly named and its response-classification framework is described, but the registry record does not report the complete-response count, denominator, rate, or uncertainty interval. Readers therefore cannot judge the endpoint’s observed magnitude or precision from the record. This illustrates why registration details and results reporting serve different purposes: defining an outcome does not itself provide the result.

The single-group design is also important. It can characterize outcomes among participants treated under the study approach, but it does not supply a concurrent randomized comparator. That limits causal interpretation, even if descriptive results are available. The physician-discretionary use of maintenance rituximab adds another feature of care that may vary after induction; the record does not state how often it was used or how it was addressed analytically.

The safety record illustrates a related interpretive distinction. Counts of participants with serious and other adverse events, selected terms and deaths are useful descriptive information, but they are not comparative estimates of harm and do not establish attribution. Without detailed timing, treatment exposure and event attribution, the counts cannot answer whether the regimen caused a particular event.

Finally, the stated planning assumptions describe a two-arm sample-size illustration, while the registered trial is single-group. This makes the distinction between a planning calculation and the actual study design especially important. Planning values are not observed outcomes or observed power. The registry record does not report the observed effect used for the illustration or its calculated values. Together, these features make transparent reporting of endpoint results, analysis populations and statistical methods central to interpreting this study.

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.

Several limitations specific to this study follow from the information reported in the registry record. First, the primary complete-response count, denominator, rate and uncertainty estimate are not reported. The endpoint is described, but its observed result cannot be evaluated. The record also does not state how participants without an end-of-induction assessment were handled, so the relationship between enrollment and the primary analysis population is unclear.

Second, the design is single-group, with no masking and no concurrent control group. The findings, if numerical results were available, would describe outcomes under the study approach rather than provide a randomized comparison. The record does not report an external control analysis. The discretionary option for maintenance rituximab after induction introduces variation in subsequent treatment that cannot be characterized from the information recorded.

Third, the registry record does not report the statistical analysis plan, analysis populations, missing-data methods, multiplicity procedures, or any interim analysis plan. It does not report the numerical results for the listed secondary outcomes. These omissions limit assessment of how the analysis was conducted and how complete the outcome reporting is.

Finally, the adverse-event record provides participant counts, selected serious-event terms, percentages and a death count, but does not report event timing, detailed attribution, or comparative rates. It cannot support causal conclusions about adverse events or deaths. The planning assumptions describe equal allocation between two arms despite the trial’s single-group design; the observed effect and planning values are not reported, further limiting interpretation of that illustration.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Phase II Study of Bendamustine and Rituximab Plus Venetoclax in Untreated Mantle Cell Lymphoma Over 60 Years of Age — NCT03834688.
• Registry record last updated 2025-08-11; status last verified 2025-08.
• Results first posted 2024-01-23.
• 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

NCT03834688 is a completed Phase II, single-group study sponsored by PrECOG, LLC., evaluating venetoclax, bendamustine and rituximab in untreated mantle cell lymphoma in people over 60 years of age. The registry reports enrollment of 33 participants, no masking, and induction treatment for 6 cycles of 28 days. Maintenance rituximab could be given after induction at physician discretion.

The primary endpoint was complete-response status at the end of induction, assessed under the Lugano Classification Criteria after 6 months of induction treatment, with an additional 2 months for end-of-treatment PET/CT scans. The primary count, denominator, rate and statistical analysis are not reported in the registry record. Secondary outcomes include treatment-related adverse events, overall response, progression-free survival and overall survival, but numerical results for those outcomes are not reported in the registry record.

The record reports serious and other adverse-event participant counts, selected serious-event terms and 10 deaths. It does not provide sufficient detail to attribute events or deaths to treatment. The single-group design supports descriptive interpretation only and does not provide a randomized comparison.