This page provides an independent statistical analysis and educational interpretation of publicly reported results. ClinicalTrials.gov provides the official trial registry record. Numerical trial results on this page are restricted to the results posted in the ClinicalTrials.gov record; calculations added by Clinical Biostats are labelled as such.
1. Trial at a Glance
This page covers the registry results for Rituximab and Acalabrutinib in Newly Diagnosed B Cell Post Transplant Lymphoproliferative Disorder (NCT04337827), a na phase 2 study. The primary outcome is Overall Response Rate (ORR).
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT04337827 |
| Phase | Phase 2 |
| Condition | Post-transplant Lymphoproliferative Disorder |
| Allocation | Not applicable (single group) |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 6 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Deepa Jagadeesh |
| Results posted | Yes |
2. Clinical Question
Population
Participants with newly diagnosed B cell post-transplant lymphoproliferative disorder (PTLD). The registry record lists an enrollment of 6.
Intervention
Rituximab weekly for 4 weeks together with acalabrutinib twice daily for 4 weeks. Diagnostic CT scans were used for response assessment, which would guide further treatment decisions.
Comparator
There was no comparison group. The study is recorded as single-group, with allocation listed as not applicable and masking as none.
Primary question
What is the overall response rate (ORR) up to 8 weeks after treatment? The registry describes estimating ORR with a 90% confidence interval and comparing it with a null value using an exact binomial test.
The study concerns a treatment combination for newly diagnosed B cell PTLD. The registry summary describes an unmet need for novel therapies and explains that the study team sought to investigate rituximab with acalabrutinib. Its primary endpoint focuses on response during a specified period after treatment, rather than on a direct comparison with another treatment.
Because the design has one group, the central question is descriptive: what response was observed among participants who received the combination and were assessed? A single-group result cannot establish how outcomes would compare with a different treatment or with no treatment. The registry record does not report the observed ORR, the number of participants who responded, or a confidence interval for the endpoint. It therefore does not give a numerical answer to the primary question.
3. Trial Design
This is a Phase II, single-group study of rituximab and acalabrutinib in newly diagnosed B cell PTLD. The registry lists an enrollment of 6 and identifies the status as terminated. The recorded start date is 2020-09-02, and the primary completion date is 2022-06-27. Allocation is listed as not applicable, and masking is listed as none.
Participants were to receive rituximab weekly for 4 weeks and acalabrutinib twice daily for 4 weeks. Diagnostic CT scans were included for response assessment, with that assessment intended to guide further treatment decisions. The registry does not report additional details about how response was assessed, the criteria used, or how decisions about further treatment were made.
The primary outcome is overall response rate, with a timeframe of up to 8 weeks after treatment. The record describes a 90% confidence interval, an exact binomial test against a null value, and a logistic regression model to identify factors associated with response status. It does not report the null value, the factors considered, or results from these analyses.
The registry states that financial support for research activity not associated with active subjects receiving study medication under the IND was terminated. The study team consequently decided to close enrollment and cease long-term follow-up. It also states that zero participants were followed past the end of treatment. No randomized control arm or masked assessment is recorded. The registry record does not report a protocol-level account of the design rationale, planned sample-size justification, or any interim 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
| Stage | Rituximab and Acalabrutinib |
|---|---|
| STARTED | 6 |
| COMPLETED | 6 |
| NOT COMPLETED | 0 |
Analysis population for the primary outcome, as defined in the registry: Sponsor terminated financial support of all research activity not associated with active subjects receiving study medication enrolled under this IND, it has been decided to close enrollment and to cease long-term follow-up of subjects. Zero participants were followed past the end of treatment for several reasons, including removal of funding that prevented follow-up or participants reaching stable disease (per protocol, participant does not get followed). Therefore, no data was collected.
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.
| Characteristic | Unit | Rituximab and Acalabrutinib |
|---|---|---|
| Participants analysed | 6 | |
| Age, Categorical: <=18 years | Participants | 0 |
| Age, Categorical: Between 18 and 65 years | Participants | 2 |
| Age, Categorical: >=65 years | Participants | 4 |
| Sex: Female, Male: Female | Participants | 3 |
| Sex: Female, Male: Male | Participants | 3 |
| Ethnicity (NIH/OMB): Hispanic or Latino | Participants | 0 |
| Ethnicity (NIH/OMB): Not Hispanic or Latino | Participants | 6 |
| Ethnicity (NIH/OMB): Unknown or Not Reported | Participants | 0 |
| Race (NIH/OMB): American Indian or Alaska Native | Participants | 0 |
| Race (NIH/OMB): Asian | Participants | 0 |
| Race (NIH/OMB): Native Hawaiian or Other Pacific Islander | Participants | 0 |
| Race (NIH/OMB): Black or African American | Participants | 0 |
| Race (NIH/OMB): White | Participants | 6 |
| Race (NIH/OMB): More than one race | Participants | 0 |
| Race (NIH/OMB): Unknown or Not Reported | Participants | 0 |
| Region of Enrollment: United States | participants | 6 |
6. Primary Endpoint
The registry lists the primary outcome as Overall Response Rate (ORR), measured over Up to 8 weeks after treatment.
| Element | Registry entry |
|---|---|
| Result type | N/A |
| Measure of spread | not applicable |
| Unit | not stated |
| Endpoint classification | not reduced to a single comparison |
Overall response rate (ORR) is the primary endpoint, assessed up to 8 weeks after treatment. In general, response-rate endpoints describe the proportion of participants meeting a prespecified definition of response during an assessment period. The registry also lists complete response rate and partial response rate among secondary outcomes, but the detailed response criteria and the exact construction of ORR are not reported in the registry record.
The registry says ORR would be estimated with a 90% confidence interval and compared against a null value using an exact binomial test. In general, a confidence interval conveys the uncertainty around an estimated response rate; its width depends on the amount and pattern of available information. An exact binomial test is a method for assessing a binary outcome rate against a specified reference value, without relying on a large-sample approximation for that test.
The endpoint is relevant to the study’s stated aim of evaluating the combination, but it is not a comparative endpoint in this design. A response rate in one treated group cannot by itself show how the rate differs from outcomes under another treatment. The record does not report an ORR estimate, its confidence interval, or the test result, so the endpoint’s observed result cannot be assessed from the registry record.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The record describes a planned single-group evaluation of rituximab and acalabrutinib for newly diagnosed B cell PTLD. It gives an enrollment of 6 and specifies ORR up to 8 weeks after treatment as the primary endpoint. However, it does not report an observed ORR, a confidence interval, or an exact binomial test result. Thus, the registry record does not provide a numerical estimate of response or its precision.
The described statistical plan includes logistic regression to identify factors associated with response status. No model results, covariate list, or details about model fitting are reported in the registry record. With an enrollment of 6, any attempt to estimate associations would also be based on a very limited amount of information; this is a general statistical concern about fitting models when few observations are available, not a report of what the study actually analyzed.
The single-group design matters for interpretation. Any response estimate, if reported, would describe outcomes among participants in that group. Without a concurrent comparison group, differences in patient characteristics, disease course, or other influences cannot be separated from treatment effects through a randomized comparison. The record lists allocation as not applicable and masking as none, and does not report a control group.
Follow-up is particularly important for outcomes beyond the treatment period. The registry states that the decision was made to close enrollment and cease long-term follow-up after sponsor financial support for research activity not associated with active subjects receiving study medication was terminated. It reports that zero participants were followed past the end of treatment. This limits what the record can establish about longer-term outcomes; it does not supply an estimate of progression-free survival or duration of response.
The adverse-event information is also limited in what it can establish. It records counts for serious adverse events, other adverse events, and deaths, but gives no additional context about event timing, duration, severity grading, attribution, or individual participants. These counts describe what is recorded, not a comparative safety effect. The registry record therefore supports a careful description of the study design and recorded safety counts, but not a conclusion about treatment efficacy or comparative safety.
9. Statistical Methods Explained
The registry describes several statistical methods for the primary endpoint, but does not report the corresponding outcome estimates or analysis results. The methods below explain the purpose of those approaches in general and distinguish the planned analyses from results recorded for this study.
What does a confidence interval communicate?
In general, a confidence interval expresses the uncertainty around an estimated quantity. For a response rate, it provides a range of values compatible with the observed data under the method’s assumptions. A narrower interval indicates greater precision than a wider interval, but the interval does not remove design limitations such as the absence of a comparison group. The registry specifies a 90% confidence interval for ORR. It does not report the interval itself, the estimated rate, or details about the confidence-interval method.
When a response rate is based on a small group, uncertainty can be substantial. General methods for proportions account for the fact that a rate is bounded and that the observed response status is binary. The registry’s choice of an exact binomial test is consistent with testing a binary response rate against a reference value without using a large-sample approximation for the test. The null value is not reported in the registry record, so the intended reference for that comparison cannot be identified.
What does an exact binomial test address?
In general, an exact binomial test evaluates how compatible observed binary outcomes are with a specified response probability under a null hypothesis. Its result depends on the number of outcomes in each category and on the null value. A test result alone would not quantify the size or clinical importance of a response rate; that is why the planned confidence interval and the estimated rate are also important. Here, the registry states that the test was planned but does not provide its result or the response count.
What would logistic regression add?
Logistic regression is a general method for modeling a binary outcome, such as response status, in relation to one or more explanatory factors. The registry says this model would be used to identify factors associated with response status. It does not specify the factors, the model form, or any estimates. An association from such a model would not, by itself, demonstrate that a factor caused a difference in response.
Model complexity must also be considered in relation to the available data. In general, a model fitted to sparse data can produce unstable estimates and wide uncertainty, particularly when there are few participants or few outcomes in one category. That is a methodological caution, not a claim that a particular model was successfully fitted or failed in this study. The registry records 0 analyses and does not report a fitted logistic regression model.
Why does the design affect inference?
A single-group analysis estimates outcomes for participants receiving the study treatment. It does not directly estimate a difference between that treatment and an alternative. Random allocation, when used, can help balance known and unknown participant characteristics across groups; no randomized comparison is recorded for this study. The absence of masking may also matter in general when outcomes require judgment, but the registry does not describe the response assessment procedures in enough detail to assess whether or how this affected measurement.
The stated assessment window is up to 8 weeks after treatment. A response endpoint within that period does not answer questions about longer-term disease control. The registry lists duration of response and progression-free survival among secondary outcomes, but does not provide estimates for them. It also reports that zero participants were followed past the end of treatment, which limits the follow-up information available for longer-term outcomes.
How should planning calculations be understood?
In general, sample-size calculations are planning illustrations that depend on assumptions about the effect to detect, significance level, allocation, and statistical method. They are not observed results and should not be presented as observed power. The registry record does not report the study’s own sample-size justification. Any planning illustration based on an observed effect would not replace an actual estimate and uncertainty interval, and it would not transform a single-group study into a comparative trial.
Overall, the methods described indicate how the investigators planned to summarize and test response, but the registry record does not report the numerical inputs or results needed to reproduce or evaluate those analyses. Readers should distinguish the stated analytic intentions from analyses and findings actually recorded.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists multiple outcomes, including repeated entries for complete response rate and partial response rate, as well as duration of response and progression-free survival. It records 14 outcome measures. The primary endpoint is ORR. The registry record does not report a multiplicity-adjustment strategy, a hierarchy among secondary outcomes, or an explanation for the repeated outcome entries. Without that information, it is not possible to determine how the chance of false-positive findings across multiple statistical tests was addressed.
The primary endpoint description specifies an exact binomial test and logistic regression, but the record does not report their results. It records 0 analyses. A planned test is not the same as a reported test result, and the absence of reported analyses should not be interpreted as evidence that the null hypothesis was supported or rejected.
Information about missing outcome data and analysis populations is also limited. The registry states that zero participants were followed past the end of treatment after enrollment was closed and long-term follow-up ceased. The record does not report how many participants had an evaluable primary endpoint, whether any endpoint assessments were missing within the primary timeframe, how missing values were handled, or which analysis population was intended for each outcome. No imputation or sensitivity-analysis approach is reported.
These gaps matter because response estimates depend on the available assessments and on the rules used to classify participants without an assessment. In general, different missing-data assumptions can lead to different interpretations. The registry record does not provide enough detail to determine whether such assumptions affected the planned or reported analyses.
11. Safety Results
The registry reports serious adverse events as affected participants divided by participants at risk.
| Arm | Participants with serious adverse events | Participants at risk | Percentage |
|---|---|---|---|
| Rituximab and Acalabrutinib | 2 | 6 | 33.3% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Rituximab and Acalabrutinib | 1 of 6 |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 1% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Rituximab and Acalabrutinib | 3 of 6 |
Most frequent serious adverse event terms
| Event term | Organ system | Rituximab and Acalabrutinib |
|---|---|---|
| Lung infection | Infections and infestations | 1 of 6 |
| Dyspnea | Respiratory, thoracic and mediastinal disorders | 1 of 6 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Rituximab and Acalabrutinib |
|---|---|---|
| Fatigue | General disorders | 3 of 6 |
| Neutrophil count decreased | Investigations | 2 of 6 |
| White blood cell decreased | Investigations | 2 of 6 |
| Dizziness | Nervous system disorders | 2 of 6 |
| Headache | Nervous system disorders | 2 of 6 |
| Insomnia | Psychiatric disorders | 2 of 6 |
| Dyspnea | Respiratory, thoracic and mediastinal disorders | 2 of 6 |
| Anemia | Blood and lymphatic system disorders | 1 of 6 |
| Supraventricular tachycardia | Cardiac disorders | 1 of 6 |
| Abdominal pain | Gastrointestinal disorders | 1 of 6 |
Serious events with the highest arm-level rate: lung infection (16.7%), dyspnea (16.7%).
The registry records one group, Rituximab and Acalabrutinib, with 6 listed as at risk for serious adverse events and 2 affected. For other adverse events, it lists 6 at risk and 3 affected. It also records 1 death. The record does not provide additional details about the death, including its timing or relationship to treatment.
The serious adverse-event terms listed most prominently are lung infection and dyspnea, each shown as 16.7%. These figures describe the registry’s recorded safety information; they do not establish that an event was caused by treatment. The record does not report event-level timing, severity grades, duration, attribution, or whether events recurred. It also does not explain how the displayed percentages were calculated.
In general, safety counts in a single-group study are descriptive. They cannot be used to estimate a comparative difference in risk without a suitable comparator and compatible follow-up. The small enrollment and the absence of follow-up past treatment also limit what these entries can convey about less common or later events. The counts should be read as the posted safety record, not as a complete account of safety or as a comparison with another treatment.
12. What the Result Does, and Does Not, Mean
The registry record establishes that a Phase II, single-group study of rituximab and acalabrutinib was conducted for newly diagnosed B cell PTLD, with an enrollment of 6 and a primary endpoint of ORR up to 8 weeks after treatment. It also describes the intended response analyses and records some adverse-event counts. These details characterize the study and the information recorded, but they do not provide the primary efficacy result.
The ORR estimate, its 90% confidence interval, and the exact binomial test result are not reported in the registry record. As a result, the posted information does not show what response rate was observed or how precisely it was estimated. It also does not report results from the planned logistic regression or estimates for the listed time-to-event outcomes.
Even if a response estimate were available, a single-group study would describe outcomes within the treated group rather than establish a treatment difference. No concurrent comparator or randomized allocation is recorded. Therefore, the registry record cannot support a comparative conclusion about whether outcomes differ from those under another treatment.
The safety entries should be interpreted with similar care. They report counts and selected event terms, but do not include the detail needed to assess attribution or timing. The record’s statement that zero participants were followed past the end of treatment also means it does not provide long-term follow-up results.
These distinctions separate what the registry does show—the design, treatment schedule, stated endpoint, termination context, and recorded safety counts—from what remains unavailable. They do not imply that a result was favorable or unfavorable. The absence of a reported efficacy estimate is not itself evidence for either conclusion.
13. Why This Trial Matters Statistically
This study illustrates why design and reporting details are essential to interpreting clinical statistics. A response rate from one group is a description of outcomes among participants who received the regimen. Without a comparison group, it cannot directly estimate how those outcomes differ from another treatment or from an alternative course of care. The registry’s single-group designation and lack of masking define important limits on the conclusions that could be drawn from any response estimate.
Precision is also central. The record describes a confidence interval for ORR, but does not report the estimated rate or interval. A point estimate alone would not show how uncertain the result is, and a confidence interval would not resolve the lack of a comparator. Reporting both design and uncertainty is necessary for readers to understand what the data can support.
The registry states that enrollment was closed and long-term follow-up ceased after sponsor financial support for research activity not associated with active subjects receiving study medication was terminated. It also reports zero follow-up past the end of treatment. This makes clear why follow-up duration and analysis populations matter: short-term response and longer-term outcomes address different questions, and incomplete follow-up constrains the latter.
Finally, the record distinguishes planned methods from posted findings. It describes an exact binomial test and logistic regression but records 0 analyses and no numerical primary result. This is a useful reminder that a statistical plan is not a finding. Clear reporting of estimates, uncertainty, missing-data handling, and analysis populations is needed before readers can assess the strength and scope of the evidence.
14. 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 study has no recorded comparison group, and allocation is listed as not applicable. This prevents a direct treatment comparison and limits causal interpretation. Masking is listed as none. The registry does not provide details about response assessment procedures, so the possible influence of unmasked assessment cannot be evaluated from the record.
Enrollment was 6, and the primary ORR estimate and confidence interval are not reported. The registry also records 0 analyses. Consequently, the primary endpoint cannot be quantitatively assessed, and the planned logistic regression and exact binomial test cannot be reviewed. The registry does not report the null value for the test, the factors considered in regression, or the response criteria.
The record states that financial support for research activity not associated with active subjects receiving study medication was terminated, leading to a decision to close enrollment and cease long-term follow-up. It reports that zero participants were followed past the end of treatment. This restricts interpretation of outcomes requiring longer follow-up, including the listed duration of response and progression-free survival; estimates for these outcomes are not reported in the registry record.
Further limitations include missing detail about analysis populations, missing primary endpoint assessments, and how any missing data were handled. The registry does not report a multiplicity strategy despite listing several outcomes, including repeated entries for some response outcomes. Safety reporting lacks details about event timing, severity, attribution, and the death. These are limitations of the information recorded and should not be taken as evidence that particular analyses or assessments were or were not performed outside the registry record.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Rituximab and Acalabrutinib in Newly Diagnosed B Cell Post Transplant Lymphoproliferative Disorder — NCT04337827.
- Registry record last updated 2024-04-10; status last verified 2024-03.
- Results first posted 2024-04-10.
- 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.
Continue through the Clinical Biostats statistical pathway
Use this trial's endpoint as a starting point for deeper study of effect measures, confidence intervals, and sample-size planning.
18. Record Summary
NCT04337827 is a Phase II, single-group study of rituximab and acalabrutinib for newly diagnosed B cell PTLD. The registry lists an enrollment of 6, no masking, and allocation as not applicable. Treatment was described as rituximab weekly for 4 weeks and acalabrutinib twice daily for 4 weeks, with CT scans used for response assessment.
The primary endpoint was ORR up to 8 weeks after treatment. The record describes a 90% confidence interval, an exact binomial test, and logistic regression, but does not report an ORR estimate or analysis results. The study is listed as terminated. The record says enrollment was closed and long-term follow-up ceased after sponsor financial support was terminated, and that zero participants were followed past the end of treatment.
Safety entries include serious and other adverse-event counts and 1 death. No comparative efficacy or safety conclusion can be drawn from the registry record.