Study of Acalabrutinib in Chinese Adult Subjects With Relapsed or Refractory Mantle Cell Lymphoma, Chronic Lymphocytic Leukemia or Other B-cell Malignancies: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Study of Acalabrutinib in Chinese Adult Subjects With Relapsed or Refractory Mantle Cell Lymphoma, Chronic Lymphocytic Leukemia or Other B-cell Malignancies (NCT03932331), a non-randomized phase 1, phase 2 study. The primary outcome is Phase II: Objective Response Rate (ORR) Assessed by Blinded Independent Central Review (BICR).

2. Clinical Question

The broader study aimed to assess safety, tolerability, pharmacokinetics, and clinical efficacy. Its two parts were Phase I and Phase II. The Phase II primary endpoint focuses on whether a participant achieved a qualifying tumor response; it is not a comparison of acalabrutinib with another treatment. The record lists other outcomes, including response and time-to-event measures, but does not report numerical results for the primary ORR endpoint.

This distinction matters for interpretation. A response percentage can describe outcomes among the analyzed participants, but without a control group it cannot by itself separate treatment effects from other explanations for observed outcomes. The registry record also does not report enough detail to assess how the response estimate varied by participant characteristics or how it relates to the separate disease cohorts.

3. Trial Design

This was a Phase 1/2, open-label, multicenter study of acalabrutinib in Chinese adults with relapsed or refractory (R/R) MCL, CLL, or other B-cell malignancies. The study is registered as non-randomized and single-group, with no masking. Overall enrollment is listed as 105. The record gives the study start as 2020-04-29, primary completion as 2022-12-22, and status as active, not recruiting.

The Phase I portion included participants with R/R B-cell malignancies. Phase II separated participants into an MCL cohort and a CLL cohort. The registry describes acalabrutinib as an oral drug to be taken until disease progression or unacceptable toxicity. One participant from Phase I rolled over to the Phase II MCL reporting group, a detail relevant when interpreting the reported analysis populations.

The primary Phase II outcome is ORR assessed by BICR. The assessment schedule listed in the record includes evaluations at the end of Cycles 2, 4, and 6, then every 12 weeks +/- 7 days through Cycle 25, and every 24 weeks +/- 7 days thereafter. The record says assessment continued until 18 December 2023. It does not report the protocol rationale for this schedule.

Because the study has no randomized control group, its design supports description of outcomes in the enrolled groups rather than a controlled estimate of comparative benefit. Open-label describes the study overall; the primary endpoint nevertheless specifies BICR assessment. The registry record does not describe the details of assessor blinding procedures. It also does not report a statistical plan beyond the stated exact method for the ORR confidence interval.

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.

Before assignment: This study was divided into 2 parts: Phase I portion (participants with R/R B-cell malignancies) and Phase II portion (participants with R/R MCL and R/R CLL). Study consists of screening period (28 days), treatment period until PD and a safety and survival follow-up period. A total of 105 unique participants were enrolled in the study, 12 participants in Phase I, 33 participants in Phase II MCL, 60 participants in Phase II CLL. One participant from Phase I entered Phase II MCL reporting group.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: The Safety analysis set included all participants who received at least 1 dose of acalabrutinib.

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.

Population: The Safety analysis set included all participants who received at least 1 dose of acalabrutinib. A total of 105 unique participants were enrolled in the study.

6. Primary Endpoint

The registry lists the primary outcome as Phase II: Objective Response Rate (ORR) Assessed by Blinded Independent Central Review (BICR), measured over Response evaluations performed at the end of Cycles 2, 4 and 6; and then every 12 weeks +/- 7 days through Cycle 25, and then every 24 weeks +/- 7 days thereafter. Assessed until 18 December 2023..

Objective response rate is the percentage of participants who achieved a response meeting the endpoint definition. The registry defines response as complete response (CR), CR with incomplete marrow recovery (CRi), nodular partial response (nPR), or partial response (PR). The assessment is based on International workshop on chronic lymphocytic leukemia 2018 criteria and is performed by blinded independent central review.

ORR is used to summarize whether participants experienced a qualifying tumor response during assessment. It reduces a sequence of response assessments to a participant-level category: response or no qualifying response, according to the defined criteria. The reported percentage and its 95% CI are intended to describe the estimated response proportion and its statistical precision.

The record specifies the tumor response analysis set: participants who received at least 1 dose of acalabrutinib and had an available baseline tumor assessment. One participant from Phase I rolled over to the Phase II MCL reporting group. The record does not give the number in the primary analysis set, the number who met the response definition, the ORR estimate, or its confidence limits. Therefore, the endpoint definition and method are reported, but the primary response result itself is not reported in the registry record.

ORR is not the same as duration of response, progression-free survival, or overall survival. Those measures concern how long outcomes persist or when events occur. The registry lists several such secondary outcomes, but their definitions and numerical findings are not reported in the information available for this analysis.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The methods specified for the primary endpoint combine a binary participant-level outcome with a confidence interval. A participant either meets the defined response criteria or does not, based on the assessment rules. The ORR is the percentage meeting the response definition in the specified analysis set. The registry says the estimate and its 95% two-sided CI were to be calculated using the Clopper-Pearson exact method.

What does the confidence interval describe?

In general, a confidence interval expresses the uncertainty around an estimate under a statistical model and method. For a response percentage, a narrower interval indicates greater precision, while a wider interval indicates more uncertainty. A 95% CI is not a range that contains 95% of individual participant outcomes. It describes uncertainty about the underlying response proportion in the population represented by the analysis, subject to the design and assumptions. The registry record does not report the actual ORR estimate or interval limits, so their width and precision cannot be evaluated.

In general, the Clopper-Pearson exact method is designed for a binomial proportion and uses the discrete nature of response counts. It can be useful when an estimate is based on a limited number of participants or when response counts are near the boundaries of possible values. The method does not correct for design limitations such as the lack of a control arm, selection into the analysis population, or incomplete outcome assessment. Its use determines how uncertainty around a proportion is calculated, not whether the study design supports a causal comparison.

What does central review add?

The primary endpoint is assessed by BICR. In general, independent central assessment can reduce reliance on local investigator judgments for the primary response classification. The study itself is open-label, but the endpoint identifies the central review as blinded. The registry record does not specify who was blinded, how the review was conducted, how disagreements were handled, or whether the reviewers had access to other clinical information. These details are not reported in the registry record.

The endpoint definition includes CR, CRi, nPR, and PR and refers to International workshop on chronic lymphocytic leukemia 2018 criteria. The assessment schedule is specified as the ends of Cycles 2, 4, and 6, followed by every 12 weeks +/- 7 days through Cycle 25 and every 24 weeks +/- 7 days thereafter, with assessment until 18 December 2023. In general, a prespecified schedule helps define when response is evaluated. The registry record does not describe how an assessment outside the stated window, a missed visit, or a change in response classification was handled.

How should the analysis population be read?

The tumor response analysis set includes participants who received at least 1 dose of acalabrutinib and had an available baseline tumor assessment. This is a defined subset, not an automatic synonym for all enrolled participants. In general, requiring treatment exposure and baseline measurement can make the endpoint interpretable for participants with the information needed to assess change, but it can also mean that participants without those data are not represented in the endpoint denominator. The registry record does not report the primary analysis-set size or the reasons any participants may have been excluded.

One participant from Phase I rolled over to the Phase II MCL reporting group. In general, rollover can affect how participant counts are assigned across reporting groups, so the group label should be read as a reporting classification rather than assumed to represent a wholly separate enrollment pathway. The registry does not provide further details about the rollover or how it affects outcome analyses.

What is not specified about the statistical plan?

The registry record reports the CI method for ORR but does not report a sample-size justification, a hypothesis test for the primary endpoint, an interim-analysis plan, or a broader statistical analysis plan. It does not report how missing response assessments were handled, whether any sensitivity analyses were planned, or how multiplicity across outcomes was addressed. These are distinct methodological questions; the stated exact CI method does not answer them.

The registry also describes a sample-size planning illustration based on an observed effect, with 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. Time-to-event illustrations use a total event count, while other illustrations refer to participants per arm. In general, such illustrations are planning exercises, not observed trial findings or observed power. Their two-arm assumptions do not change the registered study's single-group, non-randomized design, and the registry record does not identify them as the trial's own design justification.

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("Phase II MCL", "Phase II CLL")
n      <- c(34, 60)
events <- c(28, 52)
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  Phase II MCL  34  28  82.4  65.5  93.2  66.5  91.7  66.4  91.6
ARM  Phase II CLL  60  52  86.7  75.4  94.1  75.8  93.1  75.8  93.0

11. Multiplicity, Missing Data and Analysis Populations

The registry record lists 29 outcome measures and identifies ORR assessed by BICR as the Phase II primary endpoint. It also lists secondary outcomes, including investigator-assessed response, duration of response, progression-free survival, time to response, time to next treatment for CLL, and minimal residual disease negativity for CLL. The record does not report a multiplicity procedure or explain how interpretation across these outcomes was controlled.

In general, when many outcomes or repeated statistical tests are considered, the chance of at least one apparently notable result can increase. A prespecified hierarchy, adjustment method, or distinction between confirmatory and exploratory outcomes can clarify interpretation. No such plan is reported in the registry record. The record also lists 0 analyses, so it does not provide inferential results across the outcomes to evaluate.

The primary endpoint description specifies the response analysis set and exact CI method, but does not state how missing post-baseline assessments, unevaluable responses, or withdrawal before assessment were handled. The required available baseline assessment does not resolve how missing follow-up outcomes were treated. The number of participants with missing outcome data, reasons for missingness, and any sensitivity analyses are not reported in the registry record.

In general, missing outcomes can affect a response percentage if participants with unobserved outcomes differ from those with observed outcomes. The direction and extent of any effect cannot be determined without the missing-data pattern and analysis rules. The registry record also does not report whether the primary analysis followed a separate prespecified statistical analysis plan.

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: covid-19 (10.0%), pneumonia fungal (8.3%), febrile neutropenia (8.3%), covid-19 pneumonia (8.3%), pneumonia (6.7%).

The safety figures are reported separately for Phase I, Phase II MCL, and Phase II CLL. The serious adverse event counts are 2 of 12 participants in Phase I, 6 of 34 in Phase II MCL, and 21 of 60 in Phase II CLL. The corresponding other adverse event counts are 12 of 12, 28 of 34, and 56 of 60. Deaths are listed as 0, 7, and 2 for those groups, respectively.

These are counts of participants affected, not event totals or exposure-adjusted rates. The registry record does not report follow-up duration by group in this safety summary, so the counts should not be treated as directly comparable rates. They also do not establish that the study drug caused an event or death. Attribution, severity detail, timing, and individual clinical context are not included in these figures.

The listed serious adverse event terms include Covid-19 at 10.0%, Pneumonia fungal at 8.3%, Febrile neutropenia at 8.3%, Covid-19 pneumonia at 8.3%, Pneumonia at 6.7%, and Thrombocytopenia at 2.9%. These percentages describe the listed terms in the registry record; they should not be added together or interpreted as mutually exclusive categories. The record does not provide further detail on overlap, duration, or causal attribution for these terms.

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

The registry record establishes that this was a Phase 1/2, single-group study of acalabrutinib in Chinese adults with R/R MCL, CLL, or other B-cell malignancies. It specifies a Phase II primary endpoint based on ORR assessed by BICR, defines qualifying responses, gives a tumor response analysis-set definition, and states the CI method. It also reports selected adverse-event and death counts across the study groups.

What the record does not establish is the observed primary response rate: no numerical ORR estimate or 95% CI is reported. It therefore does not allow a reader to judge the size or precision of the primary endpoint result. The absence of a reported numerical result is not evidence that no responses occurred; the registry record simply does not report the outcome value.

Even a reported response percentage from this design would be an outcome description for the analyzed participants, not a randomized estimate of the difference between acalabrutinib and another treatment. There is no concurrent comparator, and the study is non-randomized. A response estimate alone would not establish a causal treatment effect. Nor would it answer questions about how long responses lasted, how outcomes differed between disease groups, or how participants would have fared under another treatment.

The registry lists secondary outcomes that address some of those different questions, but their numerical results are not reported in the record. The safety counts likewise do not establish drug causality and lack exposure-adjusted context in the reported summary. These boundaries are important: endpoint definitions and safety counts can inform how a study was structured and what was observed, while conclusions about comparative effects require evidence suited to that question.

Accordingly, the record supports an account of the study design and the planned primary endpoint, but it does not support a conclusion about the magnitude of response or comparative clinical benefit. Interpretation should remain limited to the information actually reported.

14. Why This Trial Matters Statistically

This trial is statistically informative as an example of how design and endpoint definition constrain interpretation. The primary outcome is a binary response proportion with an exact confidence interval, while the overall study is open-label, non-randomized, and single-group. Those features allow a descriptive estimate in the defined population but do not create a controlled comparison.

The distinction between the overall open-label design and BICR assessment is also relevant. Independent central review is the named assessor for the primary endpoint, while the registry does not detail the blinding procedures or how central and investigator assessments relate. A careful statistical reading separates the endpoint's assessor from the study's overall masking status.

The record also separates disease cohorts and identifies a rollover participant, illustrating why analysis populations and reporting groups need clear definitions. The primary response set is based on treatment exposure and an available baseline tumor assessment, rather than being stated as all enrolled participants. Without the set size, participant flow, or missing-outcome rules, the population represented by an eventual response estimate cannot be fully reconstructed from the record.

Finally, the gap between a specified method and an available result matters. The registry states the Clopper-Pearson exact method and a 95% CI, but does not give the ORR or interval. A well-defined statistical method cannot substitute for the numerical estimate needed to assess response frequency and precision. This case underscores the importance of reading design, estimand population, endpoint definition, and reported results together.

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.

Several limitations specific to this registry record restrict interpretation. First, the primary Phase II ORR estimate and its 95% CI are not reported. The response count and primary analysis-set size are also absent, preventing evaluation of the estimate's magnitude or precision.

Second, the study is single-group and non-randomized, with no control arm. The record therefore does not support a direct comparative estimate. Phase II MCL and CLL are separate cohorts, not randomized treatment groups. The Phase I rollover participant is assigned to the Phase II MCL reporting group, but the record does not give enough participant-flow detail to assess the consequences for group reporting.

Third, the record does not report the sample-size justification, interim-analysis plan, comprehensive statistical analysis plan, multiplicity approach, or missing-data rules. It does not give the number or reasons for missing response assessments, nor sensitivity analyses addressing missing outcomes. These omissions limit assessment of whether the planned analysis adequately addressed uncertainty and incomplete follow-up.

Fourth, although BICR is specified for the primary endpoint, operational details of reviewer blinding and adjudication are not reported. The record also does not provide numerical efficacy results for the listed secondary outcomes. Safety summaries give participant counts and selected event terms, but do not provide exposure-adjusted rates or detailed event context in the information reported.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Study of Acalabrutinib in Chinese Adult Subjects With Relapsed or Refractory Mantle Cell Lymphoma, Chronic Lymphocytic Leukemia or Other B-cell Malignancies — NCT03932331.
• Registry record last updated 2026-04-20; status last verified 2026-04.
• Results first posted 2025-03-20.
• 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

NCT03932331 is an open-label, non-randomized, single-group Phase 1/2 study sponsored by AstraZeneca. It enrolled 105 participants and studied oral acalabrutinib in Chinese adults with R/R MCL, CLL, or other B-cell malignancies. Phase II included MCL and CLL cohorts. The registry lists the study as active, not recruiting; start is 2020-04-29 and primary completion is 2022-12-22.

The Phase II primary endpoint is ORR assessed by BICR, with a 95% CI calculated using the Clopper-Pearson exact method. The response definition and assessment schedule are stated, but the numerical ORR result and confidence limits are not reported in the registry record. Selected adverse-event counts and deaths are reported by group, without sufficient information to establish causality or compare exposure-adjusted safety rates.