Ixazomib and Rituximab in Treating Patients With Relapsed or Refractory Mantle Cell Lymphoma: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Ixazomib and Rituximab in Treating Patients With Relapsed or Refractory Mantle Cell Lymphoma (NCT04047797), a na phase 2 study. The primary outcome is Complete Remission Rate at 16 Weeks.

2. Clinical Question

The clinical question is about remission following the combined regimen in a narrowly defined setting: mantle cell lymphoma that has returned or has not responded after BTK inhibitor treatment. The registry record also lists overall response rate, progression-free survival, overall survival, and tolerability as secondary outcomes. Those outcomes describe other aspects of response, disease course, and treatment safety, but the record does not provide their results.

3. Trial Design

This is a phase 2 study of ixazomib and rituximab in patients with BTK inhibitor-resistant mantle cell lymphoma. Its registered title and condition descriptions refer to relapsed or refractory disease. The study uses a single-group model: participants receive the study regimen, and the registry record lists no separate control group. Allocation is not applicable, and masking is listed as none.

The registry record reports enrollment of 3 and a status of terminated. The start date is 2019-08-28, and the primary completion date is 2024-06-01. These are record details; they do not explain why the study was terminated or establish how long individual participants were followed. A reason for termination is not reported in the registry record.

The treatment description lists ixazomib by mouth on days 1, 8, and 15, with treatment repeating every 28 days for up to 12 cycles in the absence of progression or unacceptable toxicity. Rituximab is described as an intravenous infusion on days 1, 8, 15, and 22 of cycle 1. The later rituximab schedule is cut off in the registry record, so it cannot be fully described from that entry.

With a single group, the study can describe outcomes among treated participants but cannot directly compare outcomes between treatment groups. Without a concurrent control, changes in disease status cannot be separated from other explanations using a randomized comparison. The record does not report a statistical analysis plan, sample-size justification, or the reason for the study's termination.

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: All endpoints will be measured on patients that received at least one dose of the study drug

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: Patients that received at least one dose of the study drug

6. Primary Endpoint

The registry lists the primary outcome as Complete Remission Rate at 16 Weeks, measured over 16 weeks.

The primary endpoint is complete remission rate at 16 weeks. The registry describes the measure as a count of participants and states that complete remission is assessed by PET/CT or CT imaging using Lugano Criteria 2014. The endpoint is intended to capture whether treated patients meet the specified imaging-based criteria for complete remission at the stated assessment time.

A remission endpoint is used to describe tumor response at a defined point in follow-up. A count can communicate how many participants met the criteria, while a rate expresses that count relative to an eligible population. The registry record identifies the endpoint time and its assessment method, but does not report the complete remission count, the remission rate, or an uncertainty interval. It is therefore not possible to describe the observed remission result from the registry record.

The endpoint population is described as patients who received at least one dose of study drug. This definition matters because it specifies who is intended to contribute to the endpoint; it is not necessarily identical to every person enrolled. The record does not report how participants with missing imaging, an incomplete assessment, or other unavailable endpoint information were handled. It also does not report whether assessments were centrally reviewed or how disagreements in image interpretation were addressed.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does a count endpoint mean?

The primary outcome is recorded as a count of participants meeting complete remission criteria at 16 weeks. For a binary outcome, each participant is classified according to whether the defined event occurred. The count is the number classified as having the event; a rate relates that count to the number assessed or included under the specified analysis population. The registry record provides the endpoint definition but not the observed count or rate. No numerical efficacy estimate can therefore be reconstructed from this entry.

In general, the denominator matters as much as the count. The registry states that endpoints are measured in patients who received at least one dose of study drug, but it does not explain how missing assessments or other departures from the intended assessment were handled. Without those details and the observed endpoint data, the analysis population and denominator used for a remission rate are not available in the registry record.

How would uncertainty be described?

In general, a confidence interval gives a range of values compatible with the observed data under a specified statistical model and its assumptions. It communicates precision rather than guaranteeing that the true effect lies within a particular interval. For a binary outcome, the width of an interval depends on the number of observed participants and outcomes, as well as the interval method. With limited observations, estimates are often imprecise, and a small change in the observed count can have a substantial effect on the estimated rate.

No confidence interval or primary endpoint result is reported in the registry record. There is thus no interval width or point estimate to explain. A p-value, if reported, would address compatibility of data with a specified null model; it would not measure the size or clinical importance of an effect. No p-value is reported for this endpoint.

What can a single-group design estimate?

In general, a single-group study can describe outcomes among the participants who received the intervention. It does not have a concurrent randomized group to support a direct treatment contrast. A result from such a study cannot by itself distinguish a treatment-associated outcome from changes that might also occur because of the disease course, participant selection, other care, or measurement processes. These are general interpretive considerations; the registry record does not report information that would quantify their contribution in this study.

Allocation is listed as not applicable, the model is single group, and masking is listed as none. These features mean the design is not a randomized, masked comparison. The record does not describe whether outcome assessment was otherwise blinded, so no claim about that process is warranted.

What do the planning assumptions mean?

In general, power is the probability that a study will meet a prespecified statistical criterion under a specified effect and set of assumptions. A sample-size calculation uses design assumptions to illustrate how many participants might be needed for a planned comparison; it does not describe what was observed in an enrolled study. The planning assumptions associated with the posted sample-size material specify a two-sided significance level of 0.05, equal allocation between two arms, a normal approximation, and an effect expressed as a stated fraction of the observed effect. For time-to-event outcomes, the stated planning convention is to report the total number of events; for other outcomes, it is participants per arm.

Those assumptions are planning illustrations, not evidence that this study had two arms or used those methods in its analysis. The registered trial is single group, and the record does not report the study's own sample-size justification or statistical plan. No planning count is stated in the registry record details, and a planning illustration should not be interpreted as observed power. Observed power is not a substitute for reporting an estimate and its uncertainty.

Why do event counts and time-to-event outcomes differ?

In general, a binary outcome records whether an event occurred by a defined assessment, while a time-to-event outcome also uses information about when an event occurred. Time-to-event methods can account for participants whose follow-up ends before an event is observed, under assumptions about censoring and the analysis. The registry lists progression-free survival and overall survival, but the record does not provide their event counts, follow-up summaries, estimates, or analysis methods. No specific time-to-event analysis can therefore be attributed to this study.

For safety, a count of participants with an event is not the same as a count of every event occurrence: a participant may experience more than one event. The registry's safety entry describes affected participants and lists serious-event terms with percentages. It does not provide event-level timing or a comparative analysis. These figures should be read as descriptive registry data, not as a treatment-effect estimate.

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("Study Drug")
n      <- c(3)
events <- c(3)
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  Study Drug  3  3  100.0  29.2  100.0  43.9  100.0  39.8  99.4

11. Multiplicity, Missing Data and Analysis Populations

The registry record lists several outcomes: complete remission at 16 weeks as the primary endpoint, and overall response rate, progression-free survival, overall survival, and tolerability as secondary outcomes. When a study examines several outcomes, multiplicity can arise because multiple statistical questions are considered. In general, testing many hypotheses without a prespecified strategy can increase the chance of a nominally positive finding occurring by chance. A statistical plan may specify a primary outcome, a testing hierarchy, or an adjustment method, but the registry record does not report whether any such strategy was planned or used.

The record reports no analyses and does not include numerical results for the listed efficacy outcomes. It therefore does not establish which outcomes were analyzed, whether any multiplicity adjustment was applied, or whether results were selected for reporting. These details are not reported in the registry record.

The endpoint population is described as patients who received at least one dose of study drug. The record does not describe an intention-to-treat population or another analysis population, and it does not state how participants with missing, incomplete, or unevaluable assessments were treated. It also does not report imputation methods, sensitivity analyses, or reasons for missing outcome information. These missing-data practices are not reported in the registry record.

In general, missing outcomes can affect both the analysis denominator and the interpretation of an estimated rate. The direction and size of any effect depend on why information is missing and how the analysis handles it. No conclusion about missingness or its impact is possible without those details and the outcome data.

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: respiratory, thoracic, and mediastinal disorders- other, specify (covid-19 pneumonia) (33.3%), pulmonary embolism (33.3%), stroke (33.3%).

The registry record lists one safety group titled Study Drug. It reports 3 participants at risk for serious adverse events and 1 affected, with 0 deaths. For other adverse events, it reports 3 at risk and 3 affected. These are participant counts in the registry entry, not comparative rates against a control group. The serious-event terms listed are COVID-19 pneumonia, pulmonary embolism, and stroke, each shown with 33.3%.

The listed percentages should be read as registry-reported figures. They do not establish that the events were caused by treatment, and the record does not provide event timing, severity details beyond the serious-event classification, or participant-level overlap among terms. It is not possible to infer from the terms alone whether the same participant experienced more than one event. The record also does not state how causality was assessed.

Because the study is single group and enrollment is 3, the safety entries are descriptive. They do not provide a controlled comparison or a stable estimate of event frequency. The registry record does not report an explanation for termination, so the listed safety information should not be treated as evidence of the reason the study ended.

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

The record identifies a phase 2, single-group study of ixazomib and rituximab in relapsed or refractory mantle cell lymphoma, with a primary endpoint of complete remission at 16 weeks. It also reports enrollment of 3, terminated status, and limited descriptive adverse-event information. These details establish what the study set out to evaluate and what safety counts the registry lists.

The primary remission result is not reported in the registry record. Without the observed count, rate, and an uncertainty measure, the record does not show how many treated participants achieved complete remission or how precisely that outcome was estimated. The secondary efficacy outcomes are listed but their results are not reported either. Consequently, the available record does not answer whether the prespecified response outcomes were observed.

Even a reported outcome from this design would describe participants in a single group rather than establish a comparative treatment effect. No randomized control group is listed, so the study cannot directly estimate how outcomes differed from another treatment. This limitation is distinct from the absence of endpoint results: a missing result cannot be interpreted, and an uncontrolled result would still require cautious interpretation.

The safety counts describe events recorded in the registry, but they do not establish cause, comparative risk, or why the trial was terminated. The reason for termination and the handling of missing data are not reported in the registry record. The findings therefore should not be extended beyond the limited design and descriptive record information.

In general, a study record is most informative when it reports outcome definitions, analysis populations, observed results, uncertainty, and the methods used to handle missing information. Here, the endpoint and some design details are available, but the primary and secondary efficacy results and statistical analysis details are not. The available evidence supports describing the study's design and registry entries, not drawing a conclusion about treatment efficacy.

14. Why This Trial Matters Statistically

This trial matters statistically because its design and registry record make clear the difference between a clinical question and an answer supported by reported data. The study asks about complete remission at 16 weeks after ixazomib and rituximab in a defined patient group. The record specifies how remission was to be assessed, but does not report the observed remission outcome. A clear endpoint definition is useful, yet it cannot replace the result itself.

The single-group model is also central to interpretation. It can organize observations about treated participants, but it does not create a randomized comparison. Readers should distinguish descriptive outcomes from estimates of a comparative treatment effect. The record lists no comparator and does not report masking, allocation, or a statistical plan that would alter this basic design feature.

Enrollment of 3 and terminated status are relevant context, but neither explains the cause of termination or the missing efficacy results. The registry record does not report those explanations. This illustrates why a status label and participant count should not be treated as substitutes for outcome reporting.

Finally, the safety entries show why denominators and the distinction between participant counts and event terms matter. Descriptive counts can be read as recorded, while causal and comparative claims require information the record does not provide. The central statistical lesson is to keep the endpoint, design, precision, and reporting limitations separate when interpreting a small, uncontrolled study.

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 most important limitation for interpreting efficacy is that the registry record does not report the primary endpoint result. It gives no complete remission count, rate, confidence interval, or p-value. The secondary outcomes are listed without results in the record, so their findings cannot be assessed either.

The study is single group, with no randomized comparator. Even if outcome estimates were available, they would not provide a direct comparison with another treatment. Enrollment is 3, and the record lists the study as terminated. It does not state why it was terminated, whether recruitment stopped as planned, or how termination affected follow-up and outcome collection.

The record's endpoint population is patients who received at least one dose of study drug, but it does not describe the analysis population in detail. Handling of missing assessments, incomplete follow-up, and unevaluable imaging is not reported in the registry record. Nor does the record describe the statistical analysis plan, sample-size justification, or any multiplicity strategy.

The treatment description is incomplete for later rituximab administration: the schedule text ends after beginning in cycle 3. The record also does not provide further details on outcome review, event attribution, or the safety assessment process. The serious adverse-event figures are descriptive and are not accompanied by a control group or comparative analysis. These limitations constrain interpretation to the design and registry information that is reported.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Ixazomib and Rituximab in Treating Patients With Relapsed or Refractory Mantle Cell Lymphoma — NCT04047797.
• Registry record last updated 2025-04-20; status last verified 2025-04.
• Results first posted 2024-12-16.
• 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 phase 2, single-group study of ixazomib and rituximab for BTK inhibitor-resistant mantle cell lymphoma, including relapsed or refractory disease. Allocation is listed as not applicable and masking as none. The record reports enrollment of 3, a start date of 2019-08-28, a primary completion date of 2024-06-01, and terminated status.

The primary endpoint is complete remission at 16 weeks, assessed by PET/CT or CT using Lugano Criteria 2014, in patients who received at least one dose of study drug. The registry record does not report the remission result or results for the listed secondary outcomes. It reports descriptive safety counts, including 1 participant affected by a serious adverse event and 0 deaths. The reason for termination, statistical plan, missing-data handling, and analysis results are not reported in the registry record.