Acalabrutinib, Umbralisib, and Ublituximab for the Treatment of Previously Untreated Mantle Cell Lymphoma: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Acalabrutinib, Umbralisib, and Ublituximab for the Treatment of Previously Untreated Mantle Cell Lymphoma (NCT04783415), a na phase 2 study. The primary outcome is Complete Response (CR) Rate After Induction (Six Cycles).

2. Clinical Question

3. Trial Design

This is a phase II, single-group study sponsored by City of Hope Medical Center. It evaluates acalabrutinib, umbralisib, and ublituximab in previously untreated mantle cell lymphoma. The registry lists an enrollment of 12 participants, no masking, and allocation as not applicable. With only one treatment group described, the design does not include a randomized control group.

The treatment description specifies ublituximab by intravenous infusion over 90 minutes-4 hours on days 1, 8, and 15 of cycle 1 and on day 1 of cycles 2-6. Acalabrutinib is taken orally twice daily, and umbralisib is taken orally once daily on days 1-28. Cycles repeat every 28 days for six cycles, unless disease progression or unacceptable toxicity occurs. The primary assessment is defined at the end of induction, 24 weeks post-baseline.

The study start date is 2021-03-26, and the primary completion date is 2022-07-31. Its registry status is active, not recruiting. The record lists overall response rate as a secondary outcome, in addition to complete response rate after induction as the primary outcome. Although the record describes the primary endpoint and its intended confidence interval, it does not report an outcome estimate. The protocol’s detailed statistical plan, including any additional analysis specifications, is not reported in the registry record.

A single-group design can describe outcomes among participants who receive the regimen, but it cannot by itself separate treatment effects from other explanations for the observed outcomes. Differences in participant characteristics, natural disease course, supportive care, assessment procedures, or follow-up can matter when comparing results across separate studies. No concurrent treatment comparison is available in this 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

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 After Induction (Six Cycles), measured over Participants were assessed at the end of the induction therapy (24 weeks post-baseline). The induction therapy included six 28-day cycles of the study treatment..

The primary endpoint is the complete response rate after induction. It is defined as the proportion of response-evaluable participants who achieve a complete response at the end of induction therapy. The registry specifies assessment at 24 weeks post-baseline, following six 28-day cycles. It also states that the rate is to be estimated as a proportion, with a 95% exact binomial confidence interval.

A response rate expresses how often a defined response was observed in the evaluated group. Complete response is a specific response category, rather than a measure of how long a response lasts or how long participants live. The endpoint is useful for describing tumor response at a defined assessment time; it does not, on its own, establish the durability of response or demonstrate comparative benefit.

The distinction between all enrolled participants and response-evaluable participants matters. The registry uses the latter as the denominator for the primary endpoint, but the criteria for being response-evaluable and the number meeting those criteria are not reported in the registry record. The observed complete response count, rate, and confidence interval are also not reported in the registry record. Overall response rate is listed as a secondary outcome, but its result is not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary measure is a proportion: the number of response-evaluable participants who achieved complete response divided by the number of response-evaluable participants. The registry record says this proportion was to be accompanied by a 95% exact binomial confidence interval. The record does not include the numerator, denominator, calculated proportion, or interval, so the planned method can be described but its numerical output cannot be interpreted.

What does a confidence interval describe?

In general, a confidence interval expresses the statistical uncertainty around an estimate under the assumptions of the method. For a response proportion, it gives a range of values compatible with the observed count under the specified interval procedure. A wider interval indicates less precision; a narrower interval indicates more precision. A confidence interval is not a guarantee that the true value lies in the particular reported range, and it does not account for every possible source of bias, such as incomplete outcome assessment or differences between the study group and a broader population.

An exact binomial interval is a method for estimating uncertainty around a proportion based on a binomial outcome: each evaluated participant either meets the defined response criterion or does not. “Exact” describes the calculation method, not certainty about the endpoint definition, participant selection, or data completeness. The registry names the exact binomial interval for the primary response rate, but does not report the assumptions or implementation details beyond that description.

Why does the analysis population matter?

The stated denominator is the response-evaluable population, not explicitly all enrolled participants. This distinction can affect the interpretation of a response rate. If participants without an assessment are excluded, the estimate describes those who were evaluable; it may not describe all enrolled participants in the same way. The registry does not define response-evaluable status, report the size of that population, or explain how absent, incomplete, or unevaluable assessments were treated. The extent and direction of any resulting bias cannot be inferred from the record.

For an interpretable proportion, the response criteria and assessment process should be specified and applied consistently. The registry defines the endpoint as complete response at the end of induction, but further details about response criteria, assessment review, or adjudication are not reported in the registry record. The record also does not report a confidence interval for the secondary overall response rate.

What can a single-group estimate show?

A single-group response estimate describes the fraction of evaluated participants meeting the response definition after receiving the treatment regimen. It can provide an outcome description for the study cohort. Without a concurrent comparator, however, it cannot directly quantify how outcomes would differ under another treatment or under a different care approach. Comparisons with results from separate studies may be affected by differences in eligibility, disease characteristics, assessment methods, and follow-up; the registry record does not provide a comparative analysis.

The study has one treatment group and no masking. The record does not describe a randomized allocation process or blinded response assessment. These design features do not change the arithmetic definition of a response proportion, but they are relevant when judging how outcomes were generated and how they might compare with outcomes from other settings. More detailed procedures are not reported in the registry record.

How should planning illustrations be distinguished from trial results?

The record describes a sample-size planning illustration based on an observed effect and hypothetical two-arm assumptions, including equal allocation, a two-sided significance level of 0.05, and a normal approximation. Such illustrations are not the design used in this single-group study and are not observed power. They do not supply evidence about the trial’s response outcome. The numerical planning outputs and the effect value used for the illustration are not reported in the registry record. The record also does not report the trial’s own sample-size justification or design assumptions.

More broadly, a planned statistical method and a reported result are different things. Here, the primary endpoint description names a proportion and an exact confidence interval, but the registry record does not report an estimate or interval. Statistical conclusions about the magnitude or precision of the response outcome therefore cannot be drawn from the available endpoint entry.

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 (Ublituximab, Acalabrutinib, Umbralisib)")
n      <- c(12)
events <- c(12)
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 (Ublituximab, Acalabrutinib, Umbralisib)  12  12  100.0  73.5  100.0  75.8  100.0  75.3  99.8

11. Multiplicity, Missing Data and Analysis Populations

The registry lists two outcome measures: complete response rate after induction as the primary outcome and overall response rate as a secondary outcome. It does not report whether the analyses were intended to support formal hypothesis tests, whether an adjustment for multiple outcomes was planned, or how any such adjustment would be applied. A multiplicity strategy is therefore not reported in the registry record. Without that information, the relationship between any potential endpoint-specific tests and an overall confirmatory claim cannot be assessed.

The record lists zero analyses and does not include numerical results for either outcome. It does not report p-values, confidence intervals for the secondary outcome, or a hierarchy for interpreting the endpoints. The primary outcome description does specify a 95% exact binomial confidence interval, but that specification alone does not reveal whether other analyses were planned or how multiple questions would be handled.

Missing-data handling is also not reported in the registry record. In particular, the record does not describe how participants without an end-of-induction assessment would be classified, whether they would be excluded from the response-evaluable population, or how incomplete assessments would be addressed. It names response-evaluable participants as the endpoint population but does not define the criteria for inclusion in that population or report its size.

The statistical analysis populations beyond that description are not reported in the registry record. The record does not specify whether there was an intention-to-treat population or another prespecified analysis set, nor does it explain how participants who discontinued treatment, progressed, or experienced toxicity were treated in the endpoint analysis. These omissions limit assessment of possible selection effects and the correspondence between enrollment and endpoint results.

The registry does not report an interim-analysis plan or stopping rules. Their absence from the record should not be interpreted as evidence that no such procedures existed; their status is simply not reported 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 0% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: supraventricular tachycardia (8.3%), covid-19 (8.3%), meningitis (8.3%), infusion related reaction (8.3%), alanine aminotransferase increased (8.3%).

The serious adverse event summary lists 12 participants at risk and 4 affected. It lists 12 at risk and 12 affected for other adverse events, and records 1 death. These are descriptive counts for the treatment group, not comparisons with an untreated or alternative-treatment group. They do not by themselves establish that the treatment caused the reported events.

The listed serious adverse event terms are supraventricular tachycardia, Covid-19, meningitis, infusion related reaction, alanine aminotransferase increased, and aspartate aminotransferase increased. Each term is reported as 8.3%. The record does not say whether the same participant could have experienced more than one listed term, and these percentages should not be added together. The event-level counts, timing, duration, severity grading, and attribution to study treatment are not reported in the registry record.

A participant count and an event count are not necessarily interchangeable: one participant can potentially experience multiple events, while a summary may count affected participants. The registry’s summary does not provide the detail needed to determine recurrence or the full distribution of events. The cause and timing of the death, and whether it was considered treatment-related, are not reported in the registry record. These limitations mean the safety figures should be read as a brief descriptive account rather than a complete characterization of safety.

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

The registry record describes a phase II study of a three-drug regimen in previously untreated mantle cell lymphoma and defines a primary response endpoint after induction. It does not report the complete response count, rate, or confidence interval. As a result, the posted information cannot establish the observed level of response or how precisely it was estimated. The secondary overall response rate is listed, but its numerical result is also not reported in the registry record.

The design is single-group, so any reported outcome would describe participants receiving the regimen without a concurrent randomized control. Such an outcome would not, on its own, show how the same participants would have fared with another treatment. It would also not establish that the regimen caused an observed response or adverse event. Comparative conclusions require information beyond a within-group response proportion.

The endpoint is measured at the end of induction, at 24 weeks post-baseline. It concerns response at that assessment time, not how long a response continued or a time-to-event outcome. The registry record does not provide enough information about the response-evaluable population or missing assessments to determine whether the endpoint analysis represents all 12 enrolled participants.

The adverse event summary reports serious events affecting 4 of 12 participants, other adverse events affecting 12 of 12, and 1 death. Those figures are important descriptive safety information, but they do not establish causality or permit a comparison of risk against another regimen. Details needed to interpret the circumstances and attribution of these events are not reported in the registry record.

Accordingly, the record supports a description of the study design, planned response measure, treatment schedule, and limited adverse event summaries. It does not support a quantitative conclusion about the primary response result, its precision, or comparative efficacy. It also does not support a complete assessment of missing-data effects, multiplicity, or safety attribution.

14. Why This Trial Matters Statistically

This study illustrates why an endpoint definition and an endpoint result are not the same. The registry specifies complete response after induction as the primary measure and describes a proportion with a 95% exact binomial confidence interval. Yet the numerical response outcome is not reported in the registry record. Without the observed count, denominator, and interval, readers cannot assess either the magnitude of the estimate or its statistical precision.

It also highlights the importance of identifying the analysis population. The primary endpoint is defined among response-evaluable participants, while the registry lists 12 enrolled participants. The number who were response-evaluable and the criteria used to determine evaluability are not reported. When those quantities are unknown, it is difficult to judge how endpoint results would relate to the enrolled cohort or whether incomplete assessments might affect interpretation.

The single-group design makes the distinction between description and comparison especially important. A response proportion can characterize outcomes in the treated group, but it does not supply a randomized contrast. Any comparison with a separate study would require careful consideration of differences in participants, follow-up, and response assessment. Those differences can complicate interpretation even when response definitions appear similar.

The record also lists a secondary response measure and safety summaries, but does not report outcome analyses or a multiplicity strategy. This makes it useful to separate what the registry describes as planned measurement from what it actually reports as analyzed results. Statistical transparency depends not only on naming endpoints and methods, but also on documenting analysis populations, missing-data handling, and numerical estimates with their uncertainty.

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 main limitation for interpreting the primary endpoint is that its result is not reported in the registry record. There is no reported response count, rate, or confidence interval. Although the record specifies a response-evaluable population, it does not report that population’s size or how participants were classified as evaluable. The relationship between enrollment and the endpoint denominator therefore remains unclear.

The single-group design has no concurrent randomized comparator, limiting the conclusions that can be drawn about relative outcomes. The record lists no masking. It does not report details of response assessment procedures, independent review, or the criteria used to define complete response beyond the endpoint description. These details could be important to understanding the consistency of outcome classification.

Follow-up information beyond the end-of-induction assessment is not reported in the registry record. The primary endpoint addresses response at 24 weeks post-baseline, and does not itself describe response duration or later outcomes. The record does not provide results for the secondary overall response rate.

Important analytic details are also absent. The registry record does not report a missing-data method, an interim-analysis plan, multiplicity handling, or a sample-size justification for the trial itself. It does not provide detailed adverse event definitions, event-level data, attribution, or the circumstances of the death. The serious adverse event terms are reported as percentages, but the record does not clarify whether participants may appear under more than one term. These gaps limit both efficacy and safety interpretation.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Acalabrutinib, Umbralisib, and Ublituximab for the Treatment of Previously Untreated Mantle Cell Lymphoma — NCT04783415.
• Registry record last updated 2026-10-06; status last verified 2026-09.
• Results first posted 2023-11-18.
• 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

NCT04783415 is a phase II, single-group study sponsored by City of Hope Medical Center. It evaluates acalabrutinib, umbralisib, and ublituximab in previously untreated mantle cell lymphoma. The registry lists 12 enrolled participants, no masking, and active, not recruiting status. The study start date is 2021-03-26, and the primary completion date is 2022-07-31.

The primary endpoint is complete response rate after six 28-day induction cycles, assessed at 24 weeks post-baseline among response-evaluable participants. The registry describes estimation with a 95% exact binomial confidence interval. Overall response rate is listed as a secondary outcome. Neither outcome result is reported in the registry record.

The safety summary lists serious adverse events affecting 4 participants, other adverse events affecting 12 participants, and 1 death. The record does not provide sufficient detail to determine event attribution or interpret the listed terms beyond their reported frequencies.