Phase II Trial of Venetoclax and Rituximab as Initial Therapy in Older Patients With Mantle Cell Lymphoma: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Phase II Trial of Venetoclax and Rituximab as Initial Therapy in Older Patients With Mantle Cell Lymphoma (NCT05025423), a na phase 2 study. The primary outcome is Overall Response Rate (ORR) After Four Cycles of Venetoclax and Rituximab..

2. Clinical Question

The clinical question is about tumor response in a particular treatment setting: initial therapy for older patients with mantle cell lymphoma. Overall response rate combines complete responses and partial responses, as determined by the stated imaging assessment and criteria. The endpoint is defined after four cycles, with a timeframe of 120 days in the registry record.

Because the study has no comparison arm, its primary question is not whether venetoclax plus rituximab produces more responses than another regimen. Instead, the intended assessment is whether the response proportion meets a prespecified acceptability threshold under the study's design. The registry record describes Simon's optimal two-stage design for testing that threshold, but does not report the stage-specific enrollment targets, decision boundaries, or observed response results.

The registry lists enrollment of 7 and a terminated status. It does not report the number of participants who were evaluable for the primary endpoint or their response categories. Consequently, the clinical question is identifiable from the protocol description, but the posted record does not permit an answer about the observed response proportion.

3. Trial Design

This is a phase II, open-label, single-arm study of venetoclax with rituximab as initial therapy for patients over the age of 60 with previously untreated mantle cell lymphoma. The sponsor is Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins. The registry record gives a start date of 2022-06-21, a primary completion date of 2025-05-14, enrollment of 7, and a status of terminated.

Open-label means the study is not masked: the record lists masking as none. The allocation field is NA, consistent with the record's description of a single-arm study rather than a randomized comparison. The model is listed as sequential, and the primary endpoint description says Simon's optimal two-stage design will be used. These details indicate a planned staged approach to assessing the response-rate threshold, but the registry record does not report the stage-specific rules or whether the planned stages were completed.

The treatment arm is described as venetoclax and rituximab. Its registry description indicates venetoclax dose escalation during Cycles 1-4 and later treatment decisions based on response. The remaining dosing description is incomplete in the registry record, so the full treatment schedule cannot be reconstructed from the posted information.

The primary endpoint is overall response rate after four cycles, with complete and partial responses assessed by PET/CT using Lugano criteria. The listed timeframe is 120 days. Secondary outcomes include response categories, response after 8 cycles, progression-free survival, and overall survival. Although these outcomes are named, their results and detailed analysis methods are not reported in the registry record.

The study has no concurrent comparator, so it cannot provide a randomized estimate of the combination's effect relative to another treatment. Its intended statistical question is instead whether the observed response experience meets the stated acceptability criterion. The registry does not report a sample-size justification, stage boundaries, protocol deviations, or reasons for termination.

4. Participant Flow and Accounting

The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.

Overall Study

5. Baseline Characteristics

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

6. Primary Endpoint

The registry lists the primary outcome as Overall Response Rate (ORR) After Four Cycles of Venetoclax and Rituximab., measured over 120 days.

The primary endpoint is overall response rate after four cycles of venetoclax and rituximab. It is defined as the sum of complete responses and partial responses, assessed by PET/CT according to Lugano criteria. The registry gives the endpoint timeframe as 120 days and describes the outcome unit as participants.

Response rate is a binary-outcome summary at the participant level: each evaluated participant is categorized according to whether a qualifying complete or partial response occurred. The resulting proportion is intended to capture tumor shrinkage meeting the specified response criteria. Combining complete and partial responses can provide a broader measure of objective response than counting complete responses alone, while retaining the distinction between response categories for secondary reporting.

The endpoint is used because the trial's primary objective is to determine whether the combination yields a clinically acceptable proportion of overall responses in this population without chemotherapy. The registry states that Simon's optimal two-stage design will test a null hypothesis that the true overall response rate is 50% or less. This threshold defines the planned statistical question; it is not itself an observed result.

The record does not report how many participants had complete responses, partial responses, or no qualifying response. It also does not report the analyzed denominator, a response-rate estimate, or a confidence interval. Without those results, the stated endpoint and threshold explain what the study intended to evaluate but do not establish whether the observed response experience met the criterion.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry describes a single-arm phase II study and identifies overall response rate as its primary endpoint. The statistical question is whether the true response rate is greater than a stated threshold: the null hypothesis is that it is 50% or less. The record says Simon's optimal two-stage design will be used. The design's detailed operating rules, including the stage-specific enrollment targets and response boundaries, are not reported in the registry record.

What does a response-rate test assess?

A response-rate analysis treats each participant's endpoint status as a category, such as complete response, partial response, or no qualifying response. For the primary endpoint, complete and partial responses are combined into overall response. The observed proportion would be the number of participants meeting that definition divided by the number included in the endpoint analysis. Neither the response count nor the analyzed denominator is reported in the registry record, so no observed proportion can be interpreted.

A hypothesis test compares the observed data with a specified null hypothesis. Here, the null represents response rates considered not clinically acceptable by the study description. A test result would depend not only on the observed response proportion but also on the design's prespecified decision rules. The record gives the null threshold but does not provide a test statistic, p-value, confidence interval, or formal decision. The threshold should therefore be understood as a planned benchmark, not as evidence that the treatment did or did not meet it.

Why use a two-stage design?

In general, a two-stage design can allow a study to stop early when the accumulating response data are inconsistent with a target considered worthwhile. This can limit continued enrollment under a prespecified rule. The operating characteristics depend on the chosen null and alternative response rates, the acceptable error probabilities, and the stopping boundaries. Those design inputs and boundaries are not reported in the registry record. The word “optimal” in the design name does not supply those missing details; it refers to a design-selection criterion that must be specified in the protocol.

The registry also lists the model as sequential. That label is consistent with staged assessment, but it does not reveal whether a planned interim analysis occurred, whether stopping criteria were met, or how the termination decision was made. These details are not reported in the registry record.

What can a confidence interval add?

In general, a confidence interval expresses the uncertainty around an estimated response proportion. A wider interval indicates less precision, while a narrower interval indicates greater precision under the interval's assumptions. For a small study, the estimate can be sensitive to the outcome of individual participants, and interval estimates can remain broad. This is a general statistical consideration, not a result specific to this trial. The registry record does not report an estimated response rate or its confidence interval, so precision cannot be assessed from the posted primary outcome information.

What does the absence of a control group mean?

A single-arm response analysis can describe the proportion of treated participants meeting the endpoint definition. It cannot make a randomized comparison with another therapy. Historical benchmarks can sometimes provide context, but their interpretation depends on how similar the populations, outcome definitions, follow-up, and assessment procedures are. The registry record does not identify a historical control analysis. The stated threshold is part of the planned hypothesis test, not a concurrent control arm.

Open-label status means treatment assignment is not masked in the registry design. For an imaging-based endpoint, consistent assessment rules matter because knowledge of treatment and clinical context can influence some aspects of evaluation. The record specifies PET/CT and Lugano criteria but does not report whether assessments were independently reviewed or masked. This is a limitation of the available description, not evidence that assessments were conducted improperly.

How should the planning illustrations be read?

The registry's planning assumptions describe illustrative calculations based on an observed effect, with a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. They also state that the effect to detect is a specified fraction of the observed effect. These are planning assumptions, not the study's observed results or proof of power. The trial itself is described as single-arm, so an equal-allocation, two-arm illustration does not describe its enrollment design. The observed effect and the calculation outputs are not reported in the registry record. Any sample-size figures generated under those assumptions should be interpreted only as hypothetical planning illustrations, not as observed power or as the actual design of this trial.

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("Venetoclax and Rituximab in Patients Over 60 Yrs O")
n      <- c(5)
events <- c(4)
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  Venetoclax and Rituximab in Patients Over 60 Yrs O  5  4  80.0  28.4  99.5  37.6  96.4  35.9  95.7

11. Multiplicity, Missing Data and Analysis Populations

The registry lists multiple secondary outcomes, including complete response, partial response, stable disease, disease progression, response after 8 cycles, progression-free survival, and overall survival. Several are named as distinct outcomes, but the registry record does not report a multiplicity strategy for interpreting results across them. Without a stated approach, separate statistical tests across multiple outcomes can increase the chance of at least one apparently noteworthy result arising by chance. This is a general statistical concern; no such results are reported in the record.

The registry lists 10 outcome measures and 0 analyses. No analysis results, p-values, confidence intervals, or endpoint-level participant counts are reported. The primary endpoint is described with a null hypothesis and a two-stage design, but details of the test and its decision rules are not reported in the registry record.

Missing-data handling and analysis populations are also not reported in the registry record. The entry does not specify how participants without an endpoint scan, those who discontinue treatment, or those whose response cannot be classified would be handled. It does not state whether the primary analysis would include all enrolled participants, treated participants, or only those with an evaluable assessment. Enrollment of 7 does not establish the analysis denominator.

These omissions matter because response-rate estimates depend on both outcome classification and the population used in the denominator. A complete interpretation would require the prespecified analysis population, endpoint ascertainment rules, missing-outcome strategy, and the number analyzed. None is available in the registry record.

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 1% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: tumor lysis syndrome (14.3%), infusion reaction (14.3%).

The registry safety entries describe a group with 7 participants at risk. It lists 1 participant with a serious adverse event, 1 with another adverse event, and 0 deaths. Tumor lysis syndrome and infusion reaction are each listed as top serious terms at 14.3%.

These figures are descriptive counts and percentages in the posted record. They do not establish a comparative safety profile because the study has no control group. The registry does not report the timing, duration, severity grading, clinical course, or attribution of the listed events. It also does not explain whether a participant could contribute to more than one event category or whether the top serious terms overlap with the overall serious-event count. The percentages should therefore be read as registry-reported values, not as a basis for deriving additional counts.

The record does not report exposure duration or a detailed accounting of adverse events by treatment cycle. Without that context, the safety entries cannot characterize event rates over a common observation period or support comparisons with other studies. The listed death count is 0, but the record does not provide further detail about the completeness or duration of death follow-up.

These data describe what the registry records for this small enrolled group; they do not determine whether the combination caused an event or establish the risk for a broader patient population.

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

The registry record establishes that a phase II study was designed to evaluate venetoclax with rituximab as initial therapy for older patients with previously untreated mantle cell lymphoma. Its primary endpoint is overall response after four cycles, defined by complete or partial response on PET/CT using Lugano criteria. The stated statistical aim is to test whether the true response rate exceeds the threshold represented by a null hypothesis of 50% or less.

The record does not report the primary response results. It therefore does not establish how many participants responded, what the response proportion was, or how uncertain that estimate would be. The listed enrollment of 7 is not a substitute for an endpoint result or for the analyzed denominator. The study status is terminated, but the reason is not reported in the registry record.

Even if response results were available, a single-arm study would describe outcomes among participants who received the regimen rather than estimate a randomized treatment difference. The design cannot separate the treatment's contribution from other influences in the way a concurrent randomized comparison can. The stated response threshold defines a planned benchmark; it is not evidence that the regimen met that benchmark.

The safety entries record serious and other adverse-event counts, top serious event terms, and deaths. They provide descriptive information for the enrolled group but do not support a comparative safety conclusion, and details about timing, attribution, and overlap are not reported.

Accordingly, the record supports conclusions about the study's intent, design features, status, and limited recorded safety information. It does not support a claim that the combination was effective or ineffective, that it was superior or inferior to another approach, or that the trial stopped for a particular reason. Those questions require results and context not reported in the registry record.

14. Why This Trial Matters Statistically

This study illustrates how a phase II trial can frame an early clinical question around a response threshold rather than a randomized treatment difference. The registry identifies a specific population, combination regimen, imaging-based endpoint, and null hypothesis. Those elements make the intended question understandable even though the outcome findings are not posted.

The record also highlights the distinction between a design and its results. A stated two-stage design describes a planned method for evaluating accumulating response data; it does not show whether any interim boundary was reached or whether the study completed its planned stages. The status is terminated, but the reason and decision process are not reported in the registry record.

Another important statistical issue is the difference between a benchmark and a comparator. The null threshold of 50% or less is part of the primary hypothesis. It is not a concurrent control group and cannot provide the same basis for causal comparison as random assignment. A response proportion, if reported, would need to be interpreted as an outcome description within the study population.

The small listed enrollment and absence of posted endpoint results make completeness and precision especially important questions. Readers need the number analyzed, response categories, and an uncertainty estimate to understand what the study observed. The registry does not report these details. The safety entries are similarly descriptive and do not permit comparison with another regimen.

For clinical research interpretation, this record is a useful reminder that endpoint definitions, analysis populations, stopping rules, missing-data methods, and final results each contribute to a complete statistical account. The registry describes some elements of the intended design, but the information needed to evaluate the primary response finding is not reported.

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 most consequential limitation of the registry record is that it does not report the primary endpoint results. Response counts, the analyzed denominator, an overall response estimate, and its uncertainty are not available. As a result, the trial's central statistical question cannot be answered from the posted record.

The study is single-arm and open-label, so it does not provide a concurrent randomized comparison. Any response outcomes would be descriptive of the treated group and would not by themselves quantify benefit relative to another regimen. The registry specifies PET/CT and Lugano criteria but does not report assessment masking, independent review, or other safeguards for outcome classification.

Enrollment is listed as 7, while the reason for termination is not reported in the registry record. The record does not clarify whether all enrolled participants began treatment, completed the primary endpoint assessment, or entered an analysis. It also does not report missing-data procedures, analysis populations, protocol deviations, or follow-up completeness.

The primary description names Simon's optimal two-stage design but does not give its stage targets or decision boundaries. The record does not report whether an interim analysis occurred or how the termination status relates to the planned design. It also does not report a sample-size justification. Planning assumptions for illustrative calculations do not establish the actual design rationale or observed power.

Safety information is limited to summary counts and listed serious-event terms. Timing, duration, severity grading, attribution, event overlap, and exposure time are not reported. These limits prevent detailed interpretation of both efficacy and safety and make it important to distinguish the study's stated objective from findings that are not available in the registry record.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Phase II Trial of Venetoclax and Rituximab as Initial Therapy in Older Patients With Mantle Cell Lymphoma — NCT05025423.
• Registry record last updated 2026-06-10; status last verified 2026-06.
• Results first posted 2026-06-09.
• 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

The registry describes a phase II, open-label, single-arm study of venetoclax and rituximab as initial therapy for patients over the age of 60 with previously untreated mantle cell lymphoma. Its primary endpoint is overall response after four cycles, defined as complete plus partial responses by PET/CT using Lugano criteria; the stated timeframe is 120 days. The primary hypothesis concerns whether the true response rate is greater than 50%.

The record lists enrollment of 7, a terminated status, and no posted analysis results. It does not report primary response counts, an analyzed denominator, the reason for termination, or the detailed operating rules for the stated two-stage design. Safety entries list 1 participant with a serious adverse event, 1 with another adverse event, and 0 deaths; tumor lysis syndrome and infusion reaction are each listed among the top serious terms at 14.3%.

The available information describes the study's intent and limited registry safety data, but it does not provide the results needed to assess the primary response question.