Idasanutlin, 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 Idasanutlin, Ixazomib Citrate, and Dexamethasone in Treating Patients With Relapsed Multiple Myeloma (NCT02633059), a na phase 1, phase 2 study. The primary outcome is The Number of Participants Who Experienced Dose Limiting Toxicities. Maximum Tolerated Dose (MTD) of Ixazomib Citrate and Idasanutlin in Combination With Dexamethasone (Phase I).

2. Clinical Question

The trial also lists Phase I and Phase II adverse-event outcomes, as well as Phase II overall survival, progression-free survival, complete response, and partial response. These outcomes address safety and clinical activity, but the registry record does not report their results. The study therefore raises a dose-finding question first, rather than a randomized estimate of the combination’s effect relative to another treatment. The scope of the available record is the trial design and the adverse-event counts described in the safety information; it does not establish comparative benefit.

3. Trial Design

This is a completed Phase 1 / 2 clinical trial sponsored by Mayo Clinic. The registry records a start date of 2015-12-30 and a primary completion date of 2021-01-31, with enrollment of 33. Its title and conditions identify relapsed multiple myeloma with chromosome 17p loss. The registry classifies the design as sequential, allocation as not applicable, and masking as none. It does not describe a randomized control group, and explicitly cautions that the arms are not a like-for-like control comparison.

The treatment arm combines ixazomib citrate, idasanutlin, and dexamethasone. Ixazomib citrate and idasanutlin are given orally on specified days within 28-day cycles; dexamethasone is also scheduled within those cycles, with its duration described as 12 courses at the treating physician’s discretion. Treatment with ixazomib citrate and idasanutlin is described as continuing in the absence of disease progression or unacceptable toxicity. Details of dose assignment beyond the dose-level labels, the sequence in which participants entered dose levels, and rules for moving between levels are not reported in the registry record.

The Phase I primary endpoint is dose-limiting toxicity over 28 days and the maximum tolerated dose. Phase II outcomes include adverse events, overall survival, progression-free survival, and response measures. The registry lists 11 outcome measures, but the specific analysis populations and statistical analysis plan are not reported in the registry record. Enrollment describes the overall trial record; it should not be read as a group-specific count or as the number assessed for any particular outcome. The listed treatment arms include Phase 1 Dose Level 0, Phase 1 Dose Level 1, Phase 1 Dose Level 2, and Phase 2 Dose Level 1.

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.

6. Primary Endpoint

The registry lists the primary outcome as The Number of Participants Who Experienced Dose Limiting Toxicities. Maximum Tolerated Dose (MTD) of Ixazomib Citrate and Idasanutlin in Combination With Dexamethasone (Phase I), measured over 28 days.

The primary Phase I endpoint counts participants who experienced dose-limiting toxicities during the 28-day timeframe. Toxicities are graded according to National Cancer Institute Common Terminology Criteria for Adverse Events version 4.03. The registry defines a dose-limiting toxicity threshold as toxicity in at least one-third of patients, specified as at least 2 of a maximum of 6 new patients at a dose level. The maximum tolerated dose is defined as the dose level below the lowest dose that induces toxicity at that threshold.

This endpoint is used in early dose-finding because treatment-related toxicities can help distinguish dose levels that are tolerable under the study’s definition. It is not itself a measure of tumor response, survival, or comparative effectiveness. Its interpretation depends on the stated toxicity grading rules, the assessment window, and the number of participants evaluated at each dose level. The registry names this endpoint and its definition, but does not report the number of participants experiencing dose-limiting toxicity or the maximum tolerated dose identified.

More generally, a dose-limiting toxicity rule is a decision criterion for dose selection within a trial; it does not establish that a selected dose is optimal for every patient or setting. The registry’s definition sets the rule for this study, while the actual conclusion requires the observed endpoint results and details of the dose-level decisions. Those results and decision details are not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The statistical information needs to be read in light of the trial’s early-phase, sequential design. The record identifies dose levels, a toxicity-based primary endpoint, and later-phase outcomes, but does not report the full protocol or statistical analysis plan. General statistical explanations below describe how these methods are commonly interpreted; they do not imply that a particular unreported procedure was used in this trial.

What does the dose-limiting toxicity endpoint measure?

The endpoint is a count of participants with a dose-limiting toxicity within 28 days. A count is a direct description of how many participants met the defined event criterion. Its interpretation depends on who was eligible for the toxicity assessment and whether each participant had complete observation during the window. The registry defines the toxicity grading system as NCI CTCAE version 4.03 and sets the dose-level threshold for defining the maximum tolerated dose. It does not report the observed primary endpoint count or the way participants were handled if they did not complete the assessment window.

In general, dose-finding rules use observed toxicities to guide decisions about dose levels. Such rules are not the same as a comparison of treatment groups and do not, on their own, estimate a causal treatment effect. The record calls the design sequential, but the details of dose escalation, dose assignment, and decision-making are not reported in the registry record. It would therefore be inappropriate to infer the precise dose-selection algorithm from the design label alone.

How should adverse-event counts be read?

For each listed group, the record gives a count at risk and a count affected for serious and other adverse events, as well as a death count. These figures are descriptive. A serious adverse-event count does not indicate whether every event was judged treatment-related, and the listed information does not establish causality. Event terms can describe different events experienced by the same participant; without a stated rule for deduplication, counts or percentages across terms should not be combined. The registry gives several term-specific percentages but does not report uncertainty intervals for those percentages.

In general, adverse-event comparisons across groups can be difficult when groups differ in phase, dose, follow-up, or participant characteristics. A larger count in one group is not automatically evidence of a higher underlying risk, particularly when there is no randomized control and when the number and duration of observations may differ. The record provides no follow-up details for these safety summaries beyond the primary endpoint’s 28-day window, so those counts should not be assumed to cover identical exposure periods.

What would uncertainty estimates add?

In general, a confidence interval expresses the range of estimates that are reasonably compatible with the observed data under a statistical model. For a proportion, it can show how imprecise an estimate may be when the number of observations is limited. A p-value, when used appropriately, measures the compatibility of data with a specified null model; it does not measure the size or clinical importance of an effect. Neither confidence intervals nor p-values for these outcomes are reported in the registry record. Without them, the precision of the posted safety counts cannot be assessed through those summaries.

Small early-phase dose groups often yield imprecise estimates. That is a general feature of sparse event data, not a claim about an unreported estimate from this trial. A single event can have substantial influence when observations are few. General methods for binary outcomes may use likelihood-based or exact approaches when counts are sparse; the registry record does not identify which, if any, were used for analysis.

What do the planning illustrations mean?

The sample-size assumptions describe planning illustrations computed from an observed effect, not the trial’s own design. They specify a two-sided significance level of 0.05, equal allocation between two arms, a normal approximation, and an effect to detect stated as a fraction of the observed effect. For time-to-event settings, the illustration concerns the total number of events using the Schoenfeld approach; other illustrations are expressed as participants per arm. These assumptions are not evidence that the trial was randomized or that it planned an equal-allocation comparison. The registry record does not report a sample-size justification for the trial. Such illustrations are planning aids, never observed power, and their numerical outputs are not reported in the registry record.

Overall survival and progression-free survival are time-to-event outcomes, while complete response, partial response, and adverse events are event or count outcomes. In general, time-to-event analysis accounts for the timing of events and may account for incomplete follow-up through censoring, whereas simple counts do not convey when an event occurred. The registry lists these outcomes but does not report their estimates, censoring rules, analysis methods, or follow-up distributions. No specific model or adjustment should be attributed to the study without that information.

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 1: Dose Level 0", "Phase 1: Dose Level 1", "Phase 1: Dose Level 2", "Phase 2: Dose Level 1")
n      <- c(4, 7, 4, 18)
events <- c(0, 0, 2, 1)
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 1: Dose Level 0  4  0  0.0  0.0  60.2  0.0  49.0  0.5  52.2
ARM  Phase 1: Dose Level 1  7  0  0.0  0.0  41.0  0.0  35.4  0.3  36.9
ARM  Phase 1: Dose Level 2  4  2  50.0  6.8  93.2  15.0  85.0  14.7  85.3
ARM  Phase 2: Dose Level 1  18  1  5.6  0.1  27.3  1.0  25.8  1.3  26.0

11. Multiplicity, Missing Data and Analysis Populations

The registry lists 11 outcome measures, including Phase I and Phase II adverse-event outcomes, Phase II overall survival and progression-free survival, and Phase II complete and partial response rates. These outcomes address different questions and can involve multiple statistical tests or summaries. When many outcomes are examined, the chance of at least one apparently notable result can increase. General approaches to multiplicity include prespecifying a primary hypothesis, controlling an overall error rate, or treating secondary outcomes as exploratory. The registry record does not report a multiplicity strategy or statistical analysis plan, so it is not possible to determine whether any adjustment or hierarchy was used.

The registry record includes no analysis entries. This does not establish that no analysis was performed; it means the analysis details are not reported in the record. Results, uncertainty estimates, and any prespecified versus exploratory distinctions are not reported for the primary endpoint or the listed Phase II outcomes.

Information about missing observations and analysis populations is also not reported in the registry record. The record does not specify how participants with incomplete follow-up, unevaluable toxicity assessments, treatment discontinuation, or missing response assessments were handled. It does not identify whether analyses used all enrolled participants, treated participants, or a narrower evaluable population. These distinctions matter because an outcome count can change depending on who is included and how missing status is handled.

For time-to-event outcomes, censoring rules and the definition of an event influence interpretation; these details are not reported in the registry record. For response outcomes, assessment timing and criteria are not provided. Without such information, the reader cannot assess potential bias from missingness, compare analyses across outcomes, or reproduce the reported analysis. These are reporting gaps, not evidence that a particular method was or was not used.

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: pain (14.3%), white blood cell decreased (14.3%), hypercalcemia (14.3%), peripheral sensory neuropathy (14.3%), platelet count decreased (11.8%).

The registry reports serious adverse events by phase and dose level. It lists 0 affected among 4 at risk for Phase 1 Dose Level 0, 3 among 7 for Phase 1 Dose Level 1, 0 among 4 for Phase 1 Dose Level 2, and 6 among 17 for Phase 2 Dose Level 1. The death counts for these same groups are 0, 0, 0, and 2. These figures are counts within the listed groups; they are not a comparison against an untreated or randomized control group.

The registry also lists term-level percentages for serious adverse events. Pain, White blood cell decreased, Hypercalcemia, and Peripheral sensory neuropathy are each listed at 14.3%; Platelet count decreased and “Neoplasms benign, mal, uncpec - Oth spec” are each listed at 11.8%. The record does not state whether the same participant could contribute to more than one term. Therefore, the percentages should be read separately, not summed into an overall percentage.

Serious adverse events are not equivalent to all adverse events, and the term list does not describe severity grading, duration, timing, or attribution for each event. The record gives no basis for deciding whether an event was caused by treatment. Counts can describe the safety experience recorded in each group, but interpretation is limited by the absence of a control comparison and by unreported details about follow-up and analysis populations.

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

The record establishes that a completed Phase 1 / 2 trial examined idasanutlin with ixazomib citrate and dexamethasone in relapsed multiple myeloma with chromosome 17p loss. It identifies a Phase I toxicity-based primary endpoint and lists later outcomes spanning safety, survival, and response. Its safety information includes serious adverse-event counts by dose level and phase, deaths, and selected event terms with percentages.

Those details do not establish the primary endpoint result. The registry does not report how many participants experienced dose-limiting toxicity under the 28-day definition or which dose was identified as the maximum tolerated dose. Nor does it report the results for overall survival, progression-free survival, complete response, or partial response. The listed adverse-event information is not a substitute for those results.

The design also limits causal interpretation. The registry does not identify a randomized comparator and specifically notes that the arms are not a like-for-like control comparison. Observed differences between dose-level groups therefore cannot be interpreted as treatment effects. The safety counts do not show what would have happened to comparable participants under a different treatment or no treatment.

In general, early-phase dose-finding trials can provide information about tolerability and guide further study. They are not, by design alone, definitive tests of comparative benefit. Here, the registry’s endpoint definition gives a framework for dose selection, but without the endpoint results and analysis details the selection outcome cannot be evaluated. The proper conclusion is limited to what is recorded: trial design, outcome definitions, and descriptive safety counts. Claims about efficacy, comparative safety, or a preferred dose are not supported by the registry information reported.

14. Why This Trial Matters Statistically

This trial is statistically informative as an example of how early-phase and later-phase questions can sit within a single sequential study. Its Phase I primary endpoint is framed around dose-limiting toxicity and the maximum tolerated dose, while its Phase II outcomes include adverse events, survival, and response. These endpoints are related to different scientific questions and should not be treated as interchangeable evidence.

The record also illustrates why design labels and group summaries need careful interpretation. The study is classified as sequential, with allocation not applicable and no masking. The registry warns that the arms are not a like-for-like control comparison. The dose-level groups can describe observations at those levels, but the data structure does not support a direct randomized estimate of the combination’s effect compared with a control treatment.

The toxicity threshold is explicitly defined, making clear the decision rule that the primary outcome was intended to inform. At the same time, the absence of the observed primary result prevents assessment of how that rule was applied or what dose was selected. This distinction between a defined endpoint and a reported endpoint result is important: a clear definition improves interpretability, but it cannot replace the underlying observations.

The safety counts further show why sparse descriptive data should be read with restraint. Term-level adverse-event percentages are not necessarily independent, and group counts do not establish causation. Uncertainty estimates, analysis populations, missing-data methods, multiplicity handling, and detailed follow-up are not reported. These omissions limit reproducibility and precision assessment. The registry record is therefore useful for understanding the study’s structure and stated questions, while leaving key inferential conclusions unavailable.

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 registry record leaves several trial-specific details unclear. Although it identifies a sequential model and dose-level groups, it does not report how participants were assigned to levels, how dose escalation or de-escalation was governed, or the rules used to select the maximum tolerated dose. The dose-limiting toxicity definition is stated, but the observed number of such toxicities and the resulting dose conclusion are not reported.

The record does not provide participant characteristics beyond relapsed multiple myeloma and chromosome 17p loss. Eligibility criteria, prior treatment history, baseline disease status, and other characteristics that could help assess the enrolled population are not reported. The enrollment count is not broken down across groups in the general trial description, and group-specific outcome denominators beyond the adverse-event at-risk counts are not given.

The safety information is limited to grouped counts and selected serious adverse-event terms. Timing, duration, severity grades, attribution, and exposure-adjusted summaries are not reported. Because the listed groups differ by phase and dose level and there is no randomized control, safety counts cannot support causal comparisons. The record does not clarify overlap between term-specific events.

Outcome analysis details are also absent. Statistical models, confidence intervals, analysis populations, missing-data handling, censoring rules, response criteria, and multiplicity procedures are not reported in the registry record. Although the study is marked completed, the primary endpoint and the listed Phase II outcome results are not reported. These limitations constrain the interpretation to the design description and the specific descriptive safety information available.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Idasanutlin, Ixazomib Citrate, and Dexamethasone in Treating Patients With Relapsed Multiple Myeloma — NCT02633059.
• Registry record last updated 2024-09-19; status last verified 2024-08.
• Results first posted 2022-12-02.
• 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 describes a completed sequential Phase 1 / 2 study sponsored by Mayo Clinic, with enrollment of 33. It examines idasanutlin, ixazomib citrate, and dexamethasone in relapsed multiple myeloma with chromosome 17p loss. The Phase I primary endpoint is the count of participants with dose-limiting toxicity during 28 days, used to define the maximum tolerated dose under a stated toxicity threshold.

The record lists Phase I and Phase II adverse-event outcomes and Phase II survival and response outcomes. It provides serious adverse-event counts by phase and dose level, selected term-level percentages, and death counts. It does not report the primary endpoint result, Phase II outcome results, analysis methods, missing-data procedures, or analysis populations. The registry notes that this is not a randomized comparison and that the arms are not a like-for-like control comparison.