Modified VR-CAP and Acalabrutinib as First Line Therapy for the Treatment of Transplant-Eligible Patients With Mantle Cell Lymphoma: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Modified VR-CAP and Acalabrutinib as First Line Therapy for the Treatment of Transplant-Eligible Patients With Mantle Cell Lymphoma (NCT04626791), a na phase 2 study. The primary outcome is Percentage of Complete Responses to Therapy (Complete Metabolic Response [CMR]).

2. Clinical Question

3. Trial Design

This is a phase II, single-group study of modified VR-CAP and acalabrutinib as first-line treatment for transplant-eligible patients with mantle cell lymphoma. The registry lists the enrollment as 41. The study began on 2021-08-03, has a primary completion date of 2025-08-03, and is listed as active, not recruiting. Those dates describe the registry record; they do not establish that follow-up or analysis is complete.

Allocation is listed as not applicable, masking as none, and the model as single group. Thus, the design does not include a concurrent randomized control arm. The registry summary describes modified VR-CAP as a combination used as standard first-line treatment and acalabrutinib as an additional study drug. The listed interventions also include rituximab and hyaluronidase human. The complete treatment schedule is not reported in the registry record excerpt.

The primary outcome is the percentage of participants with complete metabolic response at the end of treatment, according to Lugano criteria, with a stated timeframe of 29 months. Secondary outcomes include grade 3 or greater adverse events, progression-free survival, overall survival, feasibility of stem cell collection, and successful progression to autologous stem cell transplant. The record lists eight outcome measures overall, but the other outcome details and results are not reported in the registry record.

The single-group structure can describe outcomes among participants receiving the regimen, but it cannot by itself separate treatment effects from other explanations such as patient selection or the natural course of disease. A comparison to another treatment would require evidence beyond this within-study design.

4. Participant Flow and Accounting

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

Overall Study

Reasons for not completing this period:

5. Baseline Characteristics

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

6. Primary Endpoint

The registry lists the primary outcome as Percentage of Complete Responses to Therapy (Complete Metabolic Response [CMR]), measured over 29 months.

The primary endpoint is the percentage of evaluable participants whose objective status at the end of treatment is complete metabolic response (CMR), assessed according to Lugano criteria. The registry defines a success as a CMR and states that the percentage is estimated by dividing the number of successes by the total number of evaluable patients. The stated timeframe is 29 months.

A response endpoint provides a way to describe tumor response at a specified assessment point. CMR is the particular response category selected for this study; it is not the same measure as time to progression or survival. These outcomes address different questions: a response proportion concerns the share meeting a response definition, while time-to-event outcomes concern how long it takes for an event to occur.

The registry says that a 95% confidence interval for the true success proportion will be calculated using the approach of Duffy and Santner. In general, a confidence interval conveys uncertainty around an estimated proportion; its width depends in part on the amount of information available. The registry record does not report the response count, evaluable population, estimated percentage, or confidence interval. It is therefore not possible to assess the magnitude or precision of the primary endpoint from the reported details.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary outcome is a proportion: the number of evaluable participants with complete metabolic response divided by the number evaluable for the endpoint. This gives an estimate of the response share in the study group. The registry specifies Lugano criteria for classifying response and defines success as CMR at the end of treatment. The number of successes and the evaluable denominator are not reported in the registry record, so the estimate cannot be reconstructed.

What does a confidence interval convey?

In general, a confidence interval expresses uncertainty around an estimate. For a proportion, it describes a range of values compatible with the data under the interval method and its assumptions. A narrower interval generally indicates greater precision, while a wider interval indicates more uncertainty. An interval does not guarantee that the true value lies within its endpoints, and it does not resolve limitations in study design such as the absence of a control group.

The registry states that the primary proportion's 95% confidence interval will use the approach of Duffy and Santner. The method name indicates the intended interval procedure, but the interval itself and the response estimate are not reported in the registry record. Without the observed numerator and denominator, readers cannot check the calculation or evaluate the interval's width.

Why does the single-group design matter?

In general, a single-group study can estimate outcomes among people treated under the study conditions. It cannot directly estimate a randomized treatment contrast because there is no concurrent comparison arm assigned to another regimen. Historical or external comparisons may be affected by differences in patient characteristics, assessment practices, follow-up, and calendar time. The registry record does not report a comparative analysis, and it lists no analyses.

Masking is listed as none. In general, masking can reduce the influence of knowledge about treatment assignment on assessments or reporting, depending on the outcome and who is masked. The record does not describe additional procedures to address possible assessment or reporting effects. That absence should not be replaced by assumptions about what occurred in practice.

How should secondary outcomes be distinguished?

The listed secondary outcomes include adverse events, progression-free survival, overall survival, stem cell collection feasibility, and successful progression to autologous stem cell transplant. These are different kinds of outcomes. Adverse-event measures count safety events or affected participants under specified definitions. Progression-free and overall survival are time-to-event outcomes, while transplant feasibility and proceeding to transplant concern treatment pathway outcomes. Their precise definitions, time origins, censoring rules, and analysis populations are not reported in the registry record.

For time-to-event outcomes, general analysis methods account for follow-up time and censoring, which occurs when an outcome is not observed during a participant's available follow-up. The record does not report whether these outcomes were analyzed, what methods were planned, or any estimates. It would not be appropriate to infer a particular survival method from the outcome names alone.

What can planning calculations say?

In general, sample-size planning calculations describe how much information a future study might need under specified assumptions. They are not observed outcomes and do not establish the probability that a study has detected an effect. The stated planning assumptions describe a two-sided significance level of 0.05, equal allocation between two arms, a normal approximation, and effects defined as a stated fraction of an observed effect. For time-to-event planning, the description refers to a total number of events; other planning illustrations are expressed as participants per arm for 80% power or other stated power levels.

Those assumptions describe a planning illustration, not the design of this trial: this study is single group and has no two-arm allocation. No numerical planning outputs or observed primary effect are reported in the registry record. The planning assumptions therefore cannot be used to infer the trial's sample-size justification, its intended detectable response, or its statistical power. The registry record does not report a sample-size justification or statistical plan.

10. Exact Estimates for Each Arm

No two-arm comparison is shown for this trial, but each arm's result can still be summarized with exact interval estimates computed from the posted counts. The Clopper-Pearson interval is exact and conservative; the Wilson interval is a common closer-to-nominal alternative; the Bayesian credible interval uses a uniform Beta(1, 1) prior. For small groups the three can differ noticeably.

R code and output

arm    <- c("Treatment (Modified VR-CAP, Acalabrutinib)")
n      <- c(41)
events <- c(37)
for (i in seq_along(n)) {
  ci <- binom.test(events[i], n[i])$conf.int          # Clopper-Pearson exact interval
  cr <- qbeta(c(0.025, 0.975), 1 + events[i], 1 + n[i] - events[i])   # Bayesian, uniform Beta(1,1) prior
  wi <- (function(x, n) { p <- x / n; z <- qnorm(0.975); d <- 1 + z^2 / n
    c((p + z^2 / (2 * n) - z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d, (p + z^2 / (2 * n) + z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d) })(events[i], n[i])
  cat(sprintf("ARM|%s|%d|%d|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f\n", arm[i], n[i], events[i], 100 * events[i] / n[i],
              100 * ci[1], 100 * ci[2], 100 * wi[1], 100 * wi[2], 100 * cr[1], 100 * cr[2]))
}

ARM  Treatment (Modified VR-CAP, Acalabrutinib)  41  37  90.2  76.9  97.3  77.5  96.1  77.4  96.0

11. Multiplicity, Missing Data and Analysis Populations

The registry lists eight outcome measures, including the primary CMR endpoint and secondary safety, survival, and transplant-related outcomes. It does not report a multiplicity strategy. In general, when several outcomes or repeated statistical tests are considered, the chance of at least one apparently unusual result can increase if no adjustment or hierarchy is used. A prespecified approach can clarify which outcome is primary and how secondary findings should be interpreted. The record does not report whether such an approach was planned or applied.

Missing-data methods and analysis populations are also not reported in the registry record. The primary endpoint is defined among evaluable patients, but the number evaluable and the handling of participants without an endpoint assessment are not stated. In general, excluding participants without an assessment can affect the estimated proportion if their outcomes differ from those observed. The extent and direction of any such effect cannot be determined without counts and a stated analysis approach.

The registry lists enrollment of 41, but does not establish that all enrolled participants contributed to each outcome analysis. No analysis populations, missingness counts, or sensitivity analyses are reported. These omissions limit assessment of how complete the endpoint data are and how robust any estimate might be. Because no statistical analyses are listed, the record does not support conclusions about how multiplicity or missing observations were addressed.

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: febrile neutropenia (9.8%), anemia (2.4%), blood and lymph sys disorders - oth spec (2.4%), atrial fibrillation (2.4%), cardiac arrest (2.4%).

The safety figures distinguish serious adverse events from other adverse events. In the treatment group, 7 participants are listed as at risk for serious adverse events, while 41 are listed as affected by other adverse events. The record also lists 2 deaths. These are separate entries and should not be combined into a single event rate. The registry does not explain in the summarized details why the serious-event at-risk denominator differs from the other-event denominator.

The most frequently listed serious adverse event term is febrile neutropenia at 9.8%. Anemia, blood and lymph system disorders classified as other specified, atrial fibrillation, cardiac arrest, and gastric hemorrhage are each listed at 2.4%. These percentages describe the registry's reported serious-event terms; they do not provide a full account of event timing, duration, recurrence, severity beyond the serious classification, or attribution.

A serious adverse event is not automatically an event caused by study treatment. The record does not report causal attribution for these figures. Likewise, the two deaths should not be assumed to be treatment-related based on the count alone. The safety figures describe reported events in the registry record, not a comparative estimate of risk against another regimen.

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

The registry record establishes that this phase II study evaluates modified VR-CAP and acalabrutinib as first-line therapy for transplant-eligible patients with mantle cell lymphoma. It specifies CMR at the end of treatment, assessed using Lugano criteria, as the primary endpoint, with a stated timeframe of 29 months. It also lists safety, survival, and transplant-related secondary outcomes.

The record does not report the primary response count, evaluable denominator, response percentage, or confidence interval. As a result, it does not show the observed primary response result or how precisely that result was estimated. The listed enrollment of 41 cannot substitute for the endpoint denominator, which is defined as evaluable patients.

Because the trial is single group and has no concurrent control arm, its design cannot provide a randomized comparison with usual treatment or another regimen. The study description includes a rationale for combining the treatments, but that rationale is not evidence of a comparative benefit. No conclusion about treatment effectiveness relative to another option follows from the design information alone.

The registry does list adverse-event counts and serious event terms. These describe reported safety information, but they do not establish causation or comparative safety. The definitions and results for the listed survival and transplant-related outcomes are not reported in the registry record. Overall, the available information supports understanding what the study set out to measure and some of the posted safety data; it does not establish the primary outcome result or a treatment effect.

14. Why This Trial Matters Statistically

This trial is statistically notable for the contrast between a clearly specified primary response question and the absence of a reported primary result in the registry record. The endpoint is defined as a proportion of evaluable participants with CMR according to Lugano criteria, and the record names an interval approach. Yet the numerator, denominator, estimated proportion, and confidence interval are not reported. Those elements are needed to describe both the observed response and its uncertainty.

The design also shapes what can be learned. A single-group study can describe outcomes in the treated cohort, but it does not provide a randomized estimate of differences between treatments. This distinction is important when a study rationale mentions comparison with usual treatment: a rationale and a concurrent controlled comparison answer different evidentiary questions.

The listed secondary outcomes span safety, survival, and transplant-related measures. Each requires clear definitions, follow-up information, and analysis populations to support interpretation. Those details are not reported in the registry record, and no analyses are listed. The safety entries give some descriptive counts and event terms, but without comparative data or attribution they cannot establish relative safety or causation.

For biostatistical interpretation, the key lesson is that endpoint definitions and design information are not substitutes for outcome estimates. The available record identifies what the study aims to evaluate and provides some safety figures; it does not provide enough information to assess the primary response magnitude or precision.

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 primary limitation is the absence of a reported CMR count, evaluable denominator, estimated response percentage, and confidence interval. Although the registry defines the endpoint and its timeframe, the principal outcome cannot be assessed from those details alone. The listed enrollment of 41 is not identified as the analysis denominator.

The single-group design has no concurrent control arm. Consequently, outcomes in the treatment group cannot by themselves quantify a difference from usual treatment or another regimen. The record also lists no masking, which may matter for some outcome assessments; the information summarized does not describe any additional measures related to assessment.

The registry lists eight outcome measures but does not report analysis results for them in the record. Definitions and analysis details for secondary outcomes, including survival and transplant-related outcomes, are not available. Missing-data handling, analysis populations, multiplicity procedures, and a statistical plan are not reported in the registry record.

The safety information includes distinct at-risk and affected counts, but the reason for the different denominators is not reported in the details summarized. Event attribution, timing, and follow-up are also not reported. The registry status is active, not recruiting, and the listed primary completion date is 2025-08-03; the status and date alone do not establish that all outcomes have been collected or analyzed.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Modified VR-CAP and Acalabrutinib as First Line Therapy for the Treatment of Transplant-Eligible Patients With Mantle Cell Lymphoma — NCT04626791.
• Registry record last updated 2026-08-25; status last verified 2026-06.
• Results first posted 2026-07-22.
• 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.

19. Record Summary

The registry identifies a phase II, single-group study of modified VR-CAP and acalabrutinib as first-line treatment for transplant-eligible patients with mantle cell lymphoma. Enrollment is listed as 41; the study is active, not recruiting, with a primary completion date of 2025-08-03. Allocation is not applicable and masking is none.

The primary endpoint is the percentage of evaluable participants with CMR at the end of treatment according to Lugano criteria, with a stated timeframe of 29 months. The registry specifies a 95% confidence interval approach but does not report the primary result or its interval. Secondary outcomes include adverse events, progression-free survival, overall survival, stem cell collection feasibility, and successful proceeding to autologous stem cell transplant.

Safety entries list 7 participants at risk for serious adverse events, 41 affected by other adverse events, and 2 deaths. The record lists serious adverse event terms and percentages but does not establish event causation. No analyses are listed, and further outcome results and statistical analysis details are not reported in the registry record.