Treatment With Acalabrutinib Post Blood or Marrow Transplantation in Subjects With Mantle Cell Lymphoma: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Treatment With Acalabrutinib Post Blood or Marrow Transplantation in Subjects With Mantle Cell Lymphoma (NCT04402138), a na phase 2 study. The primary outcome is Progression Free Survival Rate (PFS) at 2 Years Post-Blood or Marrow Transplant (BMT).

2. Clinical Question

The study concerns maintenance following transplantation rather than treatment before or during the transplant procedure. Its central statistical question is descriptive: how the specified progression-free survival measure is estimated in the treated study group. Since no comparator is included, the study cannot estimate a randomized between-group treatment contrast from this design.

3. Trial Design

This is a Phase II, single-group study of acalabrutinib as post-autologous blood or marrow transplant maintenance therapy in people with mantle cell lymphoma. The registry lists an enrollment of 15 and identifies the study status as completed. The study start date is 2020-08-07, and the primary completion date is 2024-04-05.

Participants in the acalabrutinib group were to self-administer the drug orally for up to approximately 2 years after transplantation. The registry lists no randomized allocation and no masking. With a single group and no concurrent control arm, the design describes outcomes among participants receiving the study regimen rather than testing a randomized contrast against another treatment.

The primary outcome is progression-free survival rate at 2 years after each participant’s transplant. It is defined as a Kaplan-Meier estimate of the percentage alive without disease progression, using RECIL 2017 criteria. The outcome population includes participants who received at least one dose and had adequate baseline and post-baseline assessments, as well as those who discontinued because of death or progression before the first assessment.

The registry also lists outcomes concerning conversion from minimal residual disease positive to negative, the association of minimal residual disease with progression-free survival, and the incidence of grade 3 or greater treatment-related adverse events. Numerical results for these outcomes are not reported in the registry record. The record does not report further details of the study protocol, including a sample-size justification, interim analyses, or a fuller statistical analysis plan.

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:

Analysis population for the primary outcome, as defined in the registry: Participants who receive at least one dose of acalabrutinib, who have an adequate baseline disease assessment and an adequate post-baseline assessment, or those who discontinue due to death or PD prior to their first assessment.

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 Progression Free Survival Rate (PFS) at 2 Years Post-Blood or Marrow Transplant (BMT), measured over 2 years after date of BMT procedure for each patient.

The primary endpoint is the progression-free survival rate at 2 years after blood or marrow transplantation. It is defined as the Kaplan-Meier estimate of the percentage of participants who are alive and have not experienced disease progression by the stated time point. Death and disease progression therefore contribute to whether a participant remains progression-free; the registry’s population definition also includes participants who discontinue because of death or progression before their first assessment.

Disease progression is classified according to RECIL 2017. The registry describes progression as an >20% increase in the sum of longest diameters of target lesions. For small lymph nodes measuring <15 mm after therapy, it specifies a minimum absolute increase of 5 mm and that the longest diameter should exceed 15mm, or the appearance of new lesions.

Time-to-event methods are used because participants may have different lengths of follow-up and the event of interest may not be observed for everyone during follow-up. Kaplan-Meier estimation can incorporate the time to an event and account for incomplete follow-up under its assumptions. The registry’s stated endpoint is a rate at a defined post-transplant time, not a simple count of participants with progression.

The registry specifies a 95% confidence interval as the measure of uncertainty around the endpoint. Neither the estimate nor its interval is reported in the registry record, so its magnitude and precision cannot be described from that record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does the primary endpoint estimate?

The registry defines the primary outcome as a Kaplan-Meier estimate of the percentage of participants who are alive and free of disease progression at 2 years after each participant’s transplant. Kaplan-Meier methods are used for time-to-event outcomes, where the relevant information includes both whether an event occurred and when it occurred. In this study, the event definition combines death or disease progression as described in the primary endpoint.

Unlike a simple percentage calculated only among people with complete follow-up, a Kaplan-Meier estimate can incorporate participants whose follow-up ends before the time point without an observed event. Such observations are generally censored at their last known event-free time. This approach relies on assumptions about censoring and the relationship between follow-up ending and the chance of the event. The handling of censoring and the number of events are not reported in the registry record, so the implementation and its assumptions cannot be evaluated from the record.

How should the confidence interval be understood?

The registry specifies a 95% confidence interval for the primary endpoint. General statistical interpretation: a confidence interval gives a range of values compatible with the observed data under the statistical method and its assumptions, and indicates the uncertainty around an estimate. It does not guarantee that the true value lies within the interval, nor does it measure the probability that a treatment works. The endpoint estimate and interval are not reported in the registry record, so neither the result nor its precision can be assessed.

The registry record does not provide the method used to construct the interval, nor whether any adjustments were made. It also does not report a hypothesis test or a p-value for the primary endpoint. Without those details and the numerical estimate, it is not possible to characterize the result as statistically significant or to assess how sensitive it may be to analytic choices.

How does the progression definition affect the endpoint?

The event definition is operational: progression is determined using RECIL 2017 criteria rather than an unspecified clinical impression. The registry describes a >20% increase in the sum of longest diameters of target lesions; for small lymph nodes measuring <15 mm after therapy, it specifies a minimum absolute increase of 5 mm and that the longest diameter should exceed 15mm; appearance of new lesions is also included. This definition establishes which disease changes count as progression for the stated endpoint.

In general, an endpoint depends on how events are defined and assessed. Changes in lesion measurement or assessment timing can affect when progression is recorded. The registry record does not report the assessment schedule, independent review procedures, or further operational details beyond the stated criteria. No assumptions about those procedures can therefore be made.

What can a single-group design estimate?

The study has one treatment group and no randomized comparator. Its primary outcome can describe the group’s progression-free survival estimate, if numerical results are available, but this design does not provide a randomized estimate of the difference between acalabrutinib and another treatment. General statistical explanation: randomization can help balance measured and unmeasured prognostic factors between groups on average. With no randomized comparison group, interpretation of an outcome as caused by the study treatment is more limited.

The registry lists enrollment of 15. That enrollment figure describes the study size, not the number necessarily included in a particular endpoint analysis. The primary endpoint population has eligibility rules based on receipt of at least one dose and disease assessments, with an additional inclusion for participants who discontinue because of death or progression before their first assessment. The number analyzed under this definition is not reported in the registry record.

What do the planning illustrations mean?

General statistical explanation: sample-size calculations depend on assumptions about the effect to be detected, the variability or event process, the significance level, allocation, and the statistical method. A planning illustration is not an observed result and does not show the probability that the completed study detected an effect. The registry record states that its planning illustrations are based on a fraction of the observed effect, use a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation; time-to-event illustrations use total events under the Schoenfeld method, while other illustrations refer to participants per arm.

Those assumptions describe illustrations, not necessarily the study’s original design. The record explicitly does not establish that they were used to plan this single-group trial. The study’s own sample-size justification and any calculation underlying its enrollment are not reported in the registry record. Planning numbers should not be treated as observed power or as evidence that the endpoint was adequately precise.

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("Acalabrutinib")
n      <- c(15)
events <- c(11)
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  Acalabrutinib  15  11  73.3  44.9  92.2  48.0  89.1  47.6  89.0

11. Multiplicity, Missing Data and Analysis Populations

The registry lists one primary outcome and three secondary outcomes: conversion from minimal residual disease positive to negative, the correlation of minimal residual disease with progression-free survival, and the incidence of grade 3 or greater treatment-related adverse events. The listed primary outcome is progression-free survival rate at 2 years after transplantation. No numerical results for these outcomes are reported in the registry record.

When a study evaluates multiple outcomes or conducts multiple statistical tests, the chance of at least one apparently unusual result can increase. General statistical explanation: multiplicity procedures may address this issue by adjusting interpretation or testing thresholds. The registry record does not report a multiplicity strategy, a hierarchy among the secondary outcomes, or planned statistical tests. No adjustment or testing procedure should be inferred.

The record identifies an endpoint population: participants who received at least one dose and had adequate baseline and post-baseline assessments, or participants who discontinued because of death or progression before their first assessment. It does not report the number included in the primary analysis, the number excluded, or how other missing assessments were handled. The reasons for missing data and any imputation method are not reported in the registry record.

The record lists 0 analyses. This means that numerical analysis results are not reported in the registry record; it does not establish that no analysis was conducted. Details such as censoring rules, sensitivity analyses, interim analyses, and the complete statistical analysis plan are not reported in the registry record. As a result, the analytic approach and the potential effect of missingness or multiple testing cannot be fully evaluated.

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 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: coronavirus infection (6.7%), clostridium difficile infection (6.7%), sepsis (6.7%).

The registry lists 15 participants at risk for serious adverse events, of whom 3 were affected. It lists 15 participants at risk for other adverse events, with 15 affected, and lists deaths as 0. These are counts in the record, not estimates from a randomized comparison. They describe events recorded for the acalabrutinib group and should not be interpreted as comparative treatment effects.

The top serious adverse event terms are Coronavirus infection, Clostridium difficile infection, and Sepsis. Each is listed at 6.7%. Those term-specific percentages are registry entries; they do not by themselves describe event duration, severity beyond the serious-event classification, recurrence, or clinical course. The registry record does not report those details.

The primary endpoint and the safety outcomes answer different questions. Progression-free survival concerns survival without disease progression after transplantation; adverse-event summaries describe safety events recorded in the treatment group. The secondary outcome list includes incidence of grade 3 or greater treatment-related adverse events, but a numerical result for that outcome is not reported in the registry record. The listed serious and other adverse-event figures should not be assumed to be the same measure as that secondary outcome. The record does not report the criteria used to judge treatment relatedness.

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

The registry establishes that a completed Phase II study evaluated oral acalabrutinib as maintenance therapy after autologous blood or marrow transplantation for mantle cell lymphoma. It records enrollment of 15, a single treatment group, and a primary endpoint defined as a Kaplan-Meier progression-free survival rate at 2 years after transplantation. It also records several safety figures and identifies secondary outcomes concerning minimal residual disease and treatment-related adverse events.

Those design and outcome definitions do not supply the primary result. The numerical progression-free survival estimate and its 95% confidence interval are not reported in the registry record. Therefore, the record does not establish the observed rate, its precision, or the number of participants who experienced progression or death for the primary analysis. Nor does it support a conclusion that the intervention did or did not affect progression-free survival.

The single-group design is another important boundary on interpretation. Even if a group outcome estimate were reported, it would describe outcomes in this study population; without a randomized comparator, it would not by itself quantify how outcomes differ from those under another treatment or no maintenance therapy. The registry record does not report a comparative benchmark or analysis.

The safety information is also descriptive. The record lists serious and other adverse-event counts, three top serious event terms with their percentages, and no deaths. It does not provide the clinical details or treatment-relatedness assessments needed to interpret those entries beyond their registry classification. The listed figures should not be treated as a complete characterization of safety.

In general, clinical evidence is interpreted by considering the outcome definition, analysis population, precision, missing data, and study design together. Here, several of those details—including the endpoint estimate, confidence interval, number analyzed, and handling of missing data—are not reported in the registry record. The available record supports a description of the study’s design and planned questions, but not a full quantitative assessment of its primary or secondary outcome results.

14. Why This Trial Matters Statistically

This trial illustrates the distinction between a defined clinical question and a reported statistical result. The registry gives a specific time-to-event endpoint: the Kaplan-Meier estimate of the percentage alive and free of progression at 2 years after transplantation. It also specifies RECIL 2017 progression criteria and a 95% confidence interval. These details help clarify what the endpoint is intended to measure, but the estimate and interval themselves are not reported in the registry record.

The distinction matters because an endpoint definition cannot substitute for the outcome data. Without a numerical estimate and its uncertainty, readers cannot assess the observed progression-free survival level or its precision. Likewise, enrollment of 15 describes study size but does not show how many participants contributed to the primary analysis or how events and incomplete follow-up affected the estimate.

The design makes interpretation especially dependent on keeping descriptive and comparative claims separate. A single-group study can describe outcomes in the participants treated under its protocol. It does not include a randomized control group for estimating a between-treatment difference. This matters when considering whether observed outcomes can be attributed to the maintenance regimen rather than other factors.

The registry also names secondary questions about minimal residual disease and treatment-related adverse events, but does not report their numerical results. The record’s safety counts offer some descriptive information, while leaving important contextual and analytic details unreported. Overall, the study is statistically informative as an example of a post-transplant maintenance question with a defined time-to-event endpoint, while the missing results and single-group design limit what can be concluded quantitatively.

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 central limitation for interpreting the registry record is that it does not report a numerical result for the primary endpoint or its 95% confidence interval. The primary outcome’s magnitude and precision therefore cannot be assessed. Event counts, the number included in the endpoint analysis, and the distribution of follow-up are also not reported in the registry record.

The single-group design has no randomized comparator, so it cannot provide a randomized estimate of the difference between acalabrutinib and another treatment. The registry lists enrollment of 15, but that figure alone does not establish the analysis sample or the amount of information available for a time-to-event estimate. The registry record does not report a sample-size justification for the study.

Important details of the primary analysis are not reported in the registry record, including censoring rules, handling of missing assessments, sensitivity analyses, and the analysis method used for the confidence interval. The record defines an endpoint population, but does not say how many participants met that definition or how other departures from the planned assessment process were treated.

Although the registry lists secondary outcomes, it does not report their numerical results or a strategy for multiplicity. It also does not report the assessment schedule or further procedures for evaluating disease progression beyond the RECIL 2017 criteria stated in the endpoint description. The safety figures are limited to listed counts and selected serious-event terms; event timing, duration, clinical course, and treatment-relatedness assessment are not reported in the registry record.

These limitations concern what can be concluded from the registry record. They do not establish whether additional analyses or protocol details exist outside that record.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Treatment With Acalabrutinib Post Blood or Marrow Transplantation in Subjects With Mantle Cell Lymphoma — NCT04402138.
• Registry record last updated 2025-05-13; status last verified 2025-05.
• Results first posted 2025-05-13.
• 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 record describes a completed Phase II, single-group study of oral acalabrutinib as maintenance therapy after autologous blood or marrow transplantation in people with mantle cell lymphoma. Enrollment is listed as 15. The study start date is 2020-08-07, and the primary completion date is 2024-04-05.

The primary outcome is the Kaplan-Meier progression-free survival rate at 2 years after transplantation, with progression defined using RECIL 2017 criteria and a 95% confidence interval specified. The record lists secondary outcomes involving minimal residual disease and treatment-related adverse events. The primary estimate, confidence interval, and secondary numerical results are not reported in the registry record.

The record lists 3 participants affected by serious adverse events among 15 at risk, 15 affected by other adverse events among 15 at risk, and 0 deaths. Coronavirus infection, Clostridium difficile infection, and Sepsis are each listed as serious adverse event terms at 6.7%. No randomized comparator is part of the study design.