Pembrolizumab, Ixazomib Citrate, and Dexamethasone in Treating Patients With Relapsed Multiple Myeloma: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Pembrolizumab, Ixazomib Citrate, and Dexamethasone in Treating Patients With Relapsed Multiple Myeloma (NCT03506360), a na phase 2 study. The primary outcome is Overall Response Percentage.

2. Clinical Question

The clinical question is therefore about the observed response proportion in this treated group, not about a randomized treatment contrast. Without a comparator, any response observed in the group cannot by itself establish how outcomes would have differed under another treatment or without the study regimen. The registry record’s brief summary presents the combination as being studied in relapsed disease; it does not establish a comparative benefit.

3. Trial Design

This was a Phase 2 study with a single-group model. The registry record identifies Mayo Clinic as the sponsor, lists enrollment of 13, and marks the study as completed. The recorded start date is 2018-06-19, and the primary completion date is 2019-11-14. Allocation is listed as NA and masking as NONE. These design features mean the record does not describe random assignment or masking, nor a control arm against which to estimate a between-group treatment effect.

The treatment group received ixazomib citrate, pembrolizumab, and dexamethasone. The regimen description specifies oral ixazomib citrate on days 1, 8, 15, 29, 36, 43, 57, 64, and 71; pembrolizumab intravenously over 30 minutes on days 1, 22, 43, and 64; and oral dexamethasone on days 1, 8, 15, 29, 36, 43, 57, 64, and 71. The description says dexamethasone cycles repeat every 84 days for up to 1 year, but the final wording of the cycle description is incomplete in the registry record. The record also lists laboratory biomarker analysis as an intervention.

The primary outcome is overall response percentage, defined as partial response or better on two consecutive evaluations, with a timeframe of up to 9 months. Secondary outcomes include response thresholds of at least very good partial response and complete response, survival time, progression-free survival, and incidence of adverse events. The registry lists 9 outcome measures but no analyses. Further protocol details, including eligibility criteria, treatment discontinuation rules, and the planned analysis population, are not reported in the registry record.

4. Participant Flow and Accounting

The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.

Overall Study

5. Baseline Characteristics

The table reproduces the baseline characteristics posted in the registry, which describe the participants analysed at baseline and help show whether the randomized groups were comparable.

Population: This study is permanently closed early due to slow accrual.

6. Primary Endpoint

The registry lists the primary outcome as Overall Response Percentage, measured over Up to 9 months.

The primary endpoint is the percentage of evaluable participants who achieved an objective response within up to 9 months. An objective response is defined as a partial response or better recorded on two consecutive evaluations. Requiring confirmation on consecutive evaluations makes the endpoint depend on a sustained recorded response rather than a single evaluation. The registry record describes the planned proportion as the number of successes divided by the total number of evaluable patients.

A response proportion is a binary-outcome summary: each evaluable participant either meets the response definition or does not. Reporting the proportion together with a confidence interval is intended to convey both the estimated response frequency and uncertainty about the underlying response probability. The registry record says the confidence interval was to be calculated according to the approach of Duffy and Santner. It does not report the resulting response proportion, interval limits, or number of evaluable participants.

This endpoint is suitable for describing tumor response in a single treatment group, but it does not by itself provide a comparison with an alternative. The absence of a reported estimate also means the endpoint’s observed result cannot be interpreted from the registry record. The record names response percentage as primary; it does not provide a separate primary endpoint result or analysis output.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary outcome is a binary response summarized as a proportion. The registry definition counts a success when an evaluable participant has a partial response or better as the objective status on two consecutive evaluations. The planned proportion is the number of successes divided by the total number of evaluable patients. This describes the frequency of participants meeting the stated criterion; it is not a comparison between treatment groups.

In general, a confidence interval expresses uncertainty around an estimate. For a response proportion, the interval gives a range of values compatible with the observed data under the method’s assumptions. A wider interval indicates less precision, while a narrower interval indicates more precision. The registry record specifies the Duffy and Santner approach for calculating confidence intervals for the true success proportion. It does not report the estimate or interval, so the precision of the planned primary result cannot be assessed from the record.

The denominator is important. The definition refers to evaluable patients, not automatically to everyone enrolled. In general, the rules for defining evaluability and handling participants without sufficient assessments can affect both the numerator and denominator. Neither those rules nor the number evaluable are reported in the registry record. No missing-data approach is reported either. Consequently, the reported enrollment of 13 should not be substituted for the endpoint denominator without additional information.

The study is described as single-group, with allocation listed as NA and masking as NONE. In general, a single-group design can describe outcomes observed among those receiving an intervention, but it cannot by itself control for differences that might arise from participant selection, disease course, other care, or measurement. A randomized comparator helps estimate a treatment contrast by creating groups intended to be comparable; that kind of comparison is not part of this registry design. The response proportion, even if reported, would remain a within-group descriptive estimate.

The primary endpoint timeframe is up to 9 months. In general, a defined assessment window helps make clear when outcomes are intended to be measured. Interpretation also depends on how assessments were scheduled and what happened when a participant was not assessed during that window. The registry record gives the endpoint timeframe and confirmation requirement, but does not report a detailed assessment schedule or missing-assessment rules.

The registry record lists 9 outcome measures and zero analyses. Those entries do not provide outcome estimates or test results. The absence of a listed analysis is not evidence that no statistical work occurred; it means results of analyses are not reported in the registry record. No p-value, treatment-effect estimate, or hypothesis-testing result for the primary endpoint is reported.

The record also includes sample-size assumptions for planning illustrations: two-sided significance level 0.05, equal allocation between two arms, and a normal approximation, with the effect to detect specified as a fraction of an observed effect. These are described as planning illustrations computed from the observed effect, not as the trial’s own design. They do not alter the single-group design described for this study, and their assumptions do not establish that the trial enrolled an adequate sample for its primary objective. A planning sample size is not observed power, and it cannot substitute for a reported outcome estimate. The record does not report the trial’s own sample-size justification.

In general, small samples tend to yield less precise estimates, particularly for binary outcomes when the number of observed responses is limited. That is a statistical consideration, not a claim about the unreported response result in this study. The record’s enrollment count alone cannot establish the response frequency or the width of its confidence interval. It also does not reveal whether the planned Duffy and Santner interval was calculated for the enrolled group.

Over-dispersion is a general issue in some statistical models when variability exceeds what a model assumes. It can lead to uncertainty estimates that are too small if not accounted for. The registry record does not describe an over-dispersion model or indicate that over-dispersion was relevant to the primary binary proportion analysis. The specified primary method is the Duffy and Santner confidence interval; additional modeling details are not reported in the registry record.

10. Exact Estimates for Each Arm

No two-arm comparison is shown for this trial, but each arm's result can still be summarized with exact interval estimates computed from the posted counts. The Clopper-Pearson interval is exact and conservative; the Wilson interval is a common closer-to-nominal alternative; the Bayesian credible interval uses a uniform Beta(1, 1) prior. For small groups the three can differ noticeably.

R code and output

arm    <- c("Treatment (Ixazomib Citrate, Pembrolizumab, and De")
n      <- c(13)
events <- c(0)
for (i in seq_along(n)) {
  ci <- binom.test(events[i], n[i])$conf.int          # Clopper-Pearson exact interval
  cr <- qbeta(c(0.025, 0.975), 1 + events[i], 1 + n[i] - events[i])   # Bayesian, uniform Beta(1,1) prior
  wi <- (function(x, n) { p <- x / n; z <- qnorm(0.975); d <- 1 + z^2 / n
    c((p + z^2 / (2 * n) - z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d, (p + z^2 / (2 * n) + z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d) })(events[i], n[i])
  cat(sprintf("ARM|%s|%d|%d|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f\n", arm[i], n[i], events[i], 100 * events[i] / n[i],
              100 * ci[1], 100 * ci[2], 100 * wi[1], 100 * wi[2], 100 * cr[1], 100 * cr[2]))
}

ARM  Treatment (Ixazomib Citrate, Pembrolizumab, and De  13  0  0.0  0.0  24.7  0.0  22.8  0.2  23.2

11. Multiplicity, Missing Data and Analysis Populations

The registry lists several secondary outcomes in addition to overall response percentage: at least very good partial response, complete response, survival time, progression-free survival, and incidence of adverse events. It lists 9 outcome measures in total. When multiple outcomes are examined, the chance of finding an apparently notable result can depend on how many comparisons are made and whether a multiplicity strategy is prespecified. In general, a plan may distinguish a primary outcome from secondary or exploratory outcomes and may specify whether statistical error rates are adjusted across tests.

No multiplicity approach, hierarchy among secondary endpoints, or adjustment procedure is reported in the registry record. The record lists zero analyses and does not report hypothesis tests or outcome estimates, so there is no basis for assessing how multiplicity was handled in the reported analyses. This absence should not be interpreted as evidence that no adjustment was used; the approach is not reported in the registry record.

Missing-data methods and analysis populations are also not reported. The primary outcome is defined among evaluable patients, but the registry does not state how evaluability was determined, how participants without adequate response assessments were treated, or whether any imputation or sensitivity analysis was planned. The number evaluable is not reported. Thus, enrollment of 13 does not establish the endpoint denominator.

The registry record also does not identify an intention-to-treat population, a per-protocol population, or another named analysis set. It does not report how participants who stopped treatment, missed assessments, or had incomplete follow-up were included in the analyses. These omissions limit assessment of the primary proportion and secondary outcomes, because analysis populations and missing-data handling can affect the results and their interpretation.

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: gastrointestinal disorders - oth spec (7.7%).

The treatment group lists 13 participants at risk for serious adverse events and 1 affected by a serious adverse event. For other adverse events, the group lists 13 at risk and 12 affected. The record also lists 6 deaths. These are group-level counts as recorded; they do not, by themselves, establish that an event or death was caused by the study treatment. The registry record does not report event-level timing, duration, individual clinical details, or the relationship of each event to treatment.

The listed serious event term with the highest reported frequency is “Gastrointestinal disorders - Oth spec” at 7.7%. The record does not provide further detail in that term beyond the wording and percentage. Serious adverse events and other adverse events are presented as separate categories, but the registry record does not explain whether participants could be counted in both categories. The counts therefore should not be added or treated as mutually exclusive. The death count is also not accompanied by a stated cause or attribution in the record. These figures describe reported safety information; they do not alone establish the overall safety profile or a causal risk.

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

The registry record establishes that a Phase 2, single-group study evaluated pembrolizumab with ixazomib citrate and dexamethasone in relapsed multiple myeloma. It records 13 enrolled participants and defines overall response as partial response or better on two consecutive evaluations, within up to 9 months. It also describes the intended proportion and confidence-interval method. These details clarify what the primary endpoint was designed to measure.

The record does not report the primary response count, response percentage, confidence interval, or number of evaluable participants. Therefore, it does not allow a reader to determine how many participants met the endpoint, how large the estimated response proportion was, or how precise that estimate might have been. The existence of a defined endpoint is not itself evidence of a particular result.

The single-group design also sets limits on what an outcome could establish. A response proportion within the treated group would be descriptive and would not directly compare the combination with another regimen. It would not isolate the contribution of any single component of the combination or establish what would have happened to comparable participants under a different treatment. The registry record does not report a randomized control comparison.

The listed safety counts are likewise descriptive. Counts of serious adverse events, other adverse events, and deaths cannot alone show that the treatment caused those events. The record does not provide the timing, attribution, or detailed event histories needed to interpret causation. Secondary outcomes are named, but their results are not reported in the registry record.

Accordingly, the record is informative about the study’s design, regimen, outcome definitions, and selected safety counts, but it is insufficient for a conclusion about the observed primary response or comparative treatment effect. The missing numerical outcome information should not be replaced by assumptions based on the study title, summary, sample size, or planned endpoint.

14. Why This Trial Matters Statistically

This study illustrates why an endpoint definition and an endpoint result are different kinds of information. The registry record describes the response criterion, the assessment window, and a confidence-interval method. Those details tell readers what the investigators intended to quantify and how uncertainty was intended to be represented. Without the resulting count, proportion, and interval, however, the planned statistical summary cannot answer how often the endpoint was met or how precise an estimate was.

The distinction between enrolled and evaluable participants is another important statistical issue. Enrollment is reported as 13, while the primary definition uses evaluable patients. Without the evaluable denominator and the rules used to determine evaluability, the analysis population cannot be reconstructed. This matters especially for a proportion, because both the count of successes and the denominator determine the estimate.

The single-group design also clarifies the scope of inference. A within-group response percentage can describe observed outcomes, but it does not provide a controlled comparison. Readers should distinguish a descriptive outcome from evidence of a difference between treatments. The design information prevents a comparative claim from being inferred where no comparator is described.

Finally, the record separates the existence of safety counts from causal interpretation. Serious events, other events, and deaths are reported, but the record does not provide details sufficient to attribute them to treatment. This is a useful reminder that numerical counts need context about definitions, timing, attribution, follow-up, and analysis populations. The statistical value of a registry entry depends not only on the stated methods, but also on whether outcome results and their uncertainty are reported.

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 consequential limitation for interpretation is that the primary outcome result is not reported in the registry record. No response count, percentage, confidence interval, or evaluable denominator is given. The analysis population and missing-data handling are also not reported, which prevents assessment of how incomplete assessments or departures from treatment may have affected the endpoint.

The design is single-group, with no randomized comparator described. This limits the study’s ability to estimate a comparative treatment effect. Any within-group outcome would not, on its own, distinguish the effects of the three-drug combination from disease course, participant characteristics, or other influences. The registry record does not report blinding; masking is listed as NONE.

Other limitations of the available record include the absence of reported results for the listed secondary outcomes and the absence of analysis details, despite 9 outcome measures being listed. A multiplicity plan, sample-size justification for the trial’s own design, interim-analysis details, and detailed statistical plan are not reported in the registry record. The planning assumptions described for sample-size illustrations are not the trial’s own design and do not resolve those omissions.

The safety information is limited to group counts and a listed serious-event term. The record does not report detailed event narratives, timing, treatment attribution, or whether categories overlap. It also does not give a cause for the 6 deaths. These limitations preclude causal safety conclusions from the counts alone. The regimen description’s cycle wording is incomplete at its end, further limiting the detail available about the planned treatment course.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Pembrolizumab, Ixazomib Citrate, and Dexamethasone in Treating Patients With Relapsed Multiple Myeloma — NCT03506360.
• Registry record last updated 2024-01-09; status last verified 2024-01.
• Results first posted 2022-11-14.
• 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 2, single-group study sponsored by Mayo Clinic, with enrollment of 13 participants and the combination of pembrolizumab, ixazomib citrate, and dexamethasone for relapsed multiple myeloma. The recorded start date is 2018-06-19, and primary completion is dated 2019-11-14.

The primary endpoint is overall response percentage, defined as partial response or better on two consecutive evaluations within up to 9 months. The record describes a Duffy and Santner confidence-interval method, but does not report the endpoint estimate, interval, or evaluable denominator. Secondary outcomes are listed without reported numerical results.

Safety counts include 1 participant affected by a serious adverse event, 12 affected by other adverse events, and 6 deaths, with 13 participants at risk in each adverse-event category. The record does not establish event causation. Overall, it provides design and endpoint details but not the primary response result.