A Study of IXAZOMIB in Adult Patients With Lymphoma: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Study of IXAZOMIB in Adult Patients With Lymphoma (NCT00893464), a na phase 1 study. The primary outcome is Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs).

2. Clinical Question

The registry describes an open-label, multicenter, phase 1 study in adult patients with lymphoma and identifies ixazomib as a second-generation proteasome inhibitor. Its brief summary says this study would be the first to administer ixazomib to patients with lymphoma. The record does not describe a randomized comparison, masking, or an untreated group.

The recorded adverse-event counts are separated by dose cohort. Those counts can describe what was recorded among participants at each dose, but they do not establish that differences between cohorts were caused by dose. Cohort sizes differ, and the record does not report a planned statistical comparison across dose levels. The primary question is the occurrence of adverse events in the safety population, rather than whether ixazomib improves lymphoma outcomes.

Pharmacokinetic secondary outcomes include plasma concentration, exposure over time, elimination half-life, accumulation, urinary excretion, renal clearance, and maximum observed effect. Numerical results for those outcomes are not reported in the registry record. The record also does not report a tumor-response outcome or an efficacy analysis.

3. Trial Design

This was an open-label, multicenter, phase 1, dose-escalation study of ixazomib in adults with lymphoma. The registry lists the study as completed, with enrollment of 31. The recorded start is 2009-08 and primary completion is 2014-10. The listed intervention is ixazomib, and the study model is single group.

Allocation is recorded as not applicable, and masking as none. Accordingly, the dose cohorts are not randomized arms and are not a like-for-like control comparison. They represent dose levels within a dose-escalation study. The registry record does not provide the escalation rules, dose-limiting toxicity definition, stopping rules, cohort assignment process, or the rationale used to select dose levels. Those details are not reported in the registry record.

The primary outcome is a participant count for treatment-emergent adverse events and serious adverse events, with a timeframe from baseline up to 30 days after the last dose. The safety population is defined as all participants who received at least 1 dose of ixazomib. The record lists 15 outcome measures overall, including pharmacokinetic measures among the secondary outcomes, but numerical results for those measures are not reported in the registry record.

The registry lists no analyses. A formal statistical analysis plan, sample-size justification, interim analyses, and procedures for deciding escalation or the final dose are not reported in the registry record. Although the enrollment is recorded, it should not be treated as evidence of a particular statistical power or as proof that a prespecified target was met.

4. Participant Flow and Accounting

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

Before assignment: Participants with historical diagnosis of lymphoma, for whom at least 2 previous chemotherapeutic regimens failed and no curative option existed enrolled in 1 of 8 treatment groups based on ixazomib's dose: 0.125 milligram per square meter (mg/m\^2), 0.25 mg/m\^2, 0.5 mg/m\^2, 1 mg/m\^2, 1.4 mg/m\^2, 1.76 mg/m\^2, 2.34 mg/m\^2, 3.11 mg/m\^2.

Only the first 6 of 8 groups are shown.

Overall Study

Reasons for not completing this period:

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

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: Safety population included all participants who received at least 1 dose of ixazomib.

Only the first 6 of 9 groups are shown.

6. Primary Endpoint

The registry lists the primary outcome as Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs), measured over Baseline up to 30 days after last dose of study drug.

The primary endpoint is the number of participants reporting one or more treatment-emergent adverse events and serious adverse events. Its timeframe runs from baseline up to 30 days after the last dose of study drug. A treatment-emergent adverse event is defined in the record as an adverse event whose onset occurs after receiving study drug. An adverse event does not have to be judged related to the drug; it may be an unfavorable sign, symptom, or disease temporally associated with drug use.

The record defines a serious adverse event by outcomes or clinical importance, including death, initial or prolonged inpatient hospitalization, a life-threatening experience, persistent or significant disability, congenital anomaly, or another medically important event. Thus, the endpoint is a safety measure that includes both events classified as serious and other treatment-emergent events. It counts participants, rather than measuring event duration, severity on a continuous scale, or the total number of event episodes.

This endpoint is used in a phase 1 study to describe adverse events observed during exposure and the stated follow-up period. It does not, by itself, establish whether an event was caused by ixazomib. Nor does a count without a concurrent control group estimate the excess risk attributable to treatment. The registry record does not report a primary efficacy endpoint.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

Methods should be interpreted in light of the study's single-group, open-label, dose-escalation design. The record presents adverse events by dose cohort, but it does not report a statistical analysis plan or inferential analysis. The explanation below distinguishes the descriptive data from general statistical principles.

What does a participant count represent?

The primary outcome counts participants reporting one or more treatment-emergent adverse events and serious adverse events. For a binary outcome, each participant is classified according to whether the event definition was met during the stated observation period. A count is meaningful alongside its denominator: the numerator records participants with the event, and the denominator records participants at risk in that cohort. The registry lists both for the serious and other adverse-event records.

A participant count is not the same as an event count. A participant may experience more than one event, but the primary endpoint is worded as the number of participants reporting one or more events. The record's event-term listing does not provide enough information to reconstruct participant-level overlap among different terms. It also does not supply event-level timing or duration for each listed adverse event.

Why are the dose cohorts not a controlled comparison?

Randomization is a method for making treatment groups comparable, on average, with respect to measured and unmeasured characteristics. This record has no randomized allocation and no control group. Its dose cohorts are therefore not equivalent to randomized treatment arms. Differences in their adverse-event counts cannot be attributed to dose alone from these data.

In general, dose-escalation studies organize exposure across dose levels to examine safety and guide decisions about further study. Statistical methods can be used for escalation, but the record does not state which method or decision rules were used. The escalation protocol, dose-limiting toxicity criteria, and any model relating dose to toxicity are not reported in the registry record.

How should uncertainty be understood?

A proportion estimates the frequency of an event in the population represented by the participants, while a confidence interval describes the range of values compatible with the data under a specified statistical method. General statistical explanation: smaller denominators ordinarily produce less precise estimates than larger denominators when the observed proportions are similar. This is especially relevant when some cohorts contain few participants. Confidence intervals for the adverse-event counts are not reported in the registry record, so the posted counts do not quantify their sampling uncertainty.

Over-dispersion is a general issue when observed variability exceeds what a chosen probability model expects. It can arise when participants differ in underlying risk or when events cluster. If a model assumes more uniform risk than is present, standard errors may be too small and intervals too narrow. The registry does not report a model for these data, so there is no basis to say whether over-dispersion was assessed or how it would affect a formal analysis.

What does the record say about planning calculations?

The planning illustration uses a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. Its stated effect is a fraction of the observed effect. For time-to-event outcomes, the stated planning quantity is total events; for other outcomes, it is participants per arm. These are planning assumptions, not features of the trial's design: the study itself is recorded as single group and not randomized. The registry record does not report the trial's own sample-size justification. Any planning estimates based on an observed effect are illustrations and should not be interpreted as observed power or as proof that the study was adequately sized.

What analyses were reported?

The registry record lists no analyses. It does not report p-values, confidence intervals, adjusted estimates, a dose-response model, or a statistical comparison of cohorts. General statistical practice would distinguish descriptive summaries from inferential tests and would specify the analysis population, missing-data handling, and multiplicity approach in advance. Those elements are not reported in the registry record, so the adverse-event counts should be interpreted descriptively rather than as results of a documented confirmatory analysis.

The listed secondary outcomes concern ixazomib pharmacokinetics and observed effect, including concentration, exposure, half-life, accumulation, urinary excretion, renal clearance, and maximum observed effect. Their names indicate what was measured, but numerical results and analysis methods are not reported in the registry record. No additional conclusions about these outcomes can be drawn from their titles alone.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists 15 outcome measures, while the primary outcome concerns treatment-emergent adverse events and serious adverse events. Several secondary outcomes describe pharmacokinetic properties, including concentration, exposure, elimination half-life, accumulation, urinary excretion, renal clearance, and maximum observed effect. When multiple outcomes are examined, the chance of at least one apparently unusual result can increase. General statistical practice may address this through prespecified outcome hierarchies or multiplicity adjustments, but whether any such strategy was planned or used is not reported in the registry record.

The registry lists no analyses. It does not report how missing outcome data were handled, whether participants who discontinued were followed for safety, or whether the analysis included all eligible observations for each outcome. The primary safety population is defined as participants who received at least 1 dose of ixazomib. That definition identifies who is included in the stated safety population, but it does not describe how missing event information or incomplete follow-up was treated.

The primary outcome's observation window runs from baseline up to 30 days after the last dose. The record does not explain whether follow-up was complete for every participant or how time outside that window was handled. It also does not report whether any outcomes were changed, omitted, or added after study initiation. Therefore, the extent to which the posted outcome list matches the original analysis plan is not reported in the registry record.

These omissions do not alter the recorded counts, but they limit assessment of how complete and prespecified the analysis was. The results should be read as registry-reported descriptive safety information, without assuming an undocumented missing-data or multiplicity procedure.

11. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: pyrexia (25.0%), blood creatinine increased (25.0%), septic shock (20.0%), mantle cell lymphoma (20.0%), renal failure acute (20.0%).

The serious adverse-event counts are recorded by dose cohort, with both affected participants and participants at risk listed. The serious-event figures are 0 of 1 for each of the cohorts at 0.125 mg/m^2, 0.25 mg/m^2, 0.5 mg/m^2, and 1.0 mg/m^2; 2 of 4 at 1.4 mg/m^2; 1 of 7 at 1.76 mg/m^2; 4 of 10 at 2.34 mg/m^2; and 3 of 5 at 3.11 mg/m^2. Each figure describes only the corresponding cohort in this study.

The record separately lists other adverse events, with 1 of 1, 1 of 1, 1 of 1, and 1 of 1 in the first four dose cohorts; 4 of 4 at 1.4 mg/m^2; 7 of 7 at 1.76 mg/m^2; 10 of 10 at 2.34 mg/m^2; and 5 of 5 at 3.11 mg/m^2. These separate listings should not be added together to infer a unique participant count; the registry record does not describe overlap between categories.

The listed serious-event terms and percentages are descriptive term-level information. They do not show causality, establish comparative risk, or indicate whether the same participant contributed to multiple terms. As the study lacks a randomized control group and cohort sizes differ, the figures cannot isolate an effect of dose or treatment. The registry record does not report confidence intervals or inferential safety comparisons.

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

The registry record documents a completed, open-label, phase 1 dose-escalation study of ixazomib in adults with lymphoma, with adverse-event counts reported across dose cohorts. The serious and other adverse-event listings describe what was recorded in those cohorts. The safety population is defined as those who received at least 1 dose, and the primary observation window extends from baseline up to 30 days after the last dose.

These data do not establish that ixazomib caused a particular event. The adverse-event definition explicitly does not require a causal relationship to treatment. Nor do the data show that one dose level is safer or more hazardous than another: the cohorts are not randomized comparators, their sizes differ, and the registry does not report an inferential dose comparison. The numbers are descriptive observations, not estimates of a treatment effect against a control group.

The registry record also does not report tumor-response results, a primary efficacy outcome, or numerical results for the listed pharmacokinetic secondary outcomes. Therefore the safety counts cannot be used to conclude whether the treatment improves lymphoma outcomes or to make a broader benefit-risk assessment. Such conclusions would require evidence beyond these registry entries.

General statistical interpretation: any estimate from a small cohort has uncertainty, and observed differences may arise from chance or from differences among the participants rather than the dose itself. The record does not provide confidence intervals or a formal statistical model to quantify that uncertainty. The most defensible reading is limited to the recorded event counts and the definitions and follow-up period stated in the registry.

13. Why This Trial Matters Statistically

This study is statistically informative as an example of how phase 1 safety data differ from results of a randomized comparative trial. The registry describes an open-label, single-group, dose-escalation design. Its adverse-event counts are organized by dose cohort, but the cohorts are not randomized arms with a control group. That distinction determines what can and cannot be inferred: the record can describe events observed during the study, but it cannot isolate a treatment effect through a controlled comparison.

The endpoint also illustrates the importance of definitions and denominators. The primary outcome counts participants with one or more treatment-emergent adverse events and serious adverse events, and the registry defines both the event concepts and the observation window. Reporting the number affected alongside the number at risk allows the reader to understand the cohort-specific counts. At the same time, sparse cohort denominators make estimates imprecise, and no confidence intervals are reported in the registry record.

Finally, the record lists a range of pharmacokinetic outcomes but provides no numerical results or analyses for them. A list of planned or named outcomes is not itself evidence about their results. The absence of a reported analysis plan, multiplicity procedure, and missing-data approach further limits assessment of the analytic process. The study is therefore a useful case for separating descriptive safety reporting from causal comparisons and for recognizing when registry information is insufficient to assess uncertainty or efficacy.

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 principal limitation for interpretation is the design: this was an open-label, single-group dose-escalation study without randomized allocation or a control group. Dose cohorts should not be treated as directly comparable arms. Any differences in recorded adverse events could reflect chance, cohort composition, or other factors; the record does not report an adjusted comparison or a dose-response analysis.

Cohort sizes are small and uneven, which limits the precision of cohort-specific event proportions. The registry reports counts but no confidence intervals for these adverse-event data. It also does not report the criteria used for dose escalation, the definition of dose-limiting toxicity, stopping rules, or the rationale for the selected dose levels.

The registry record lists no analyses and does not report a formal statistical analysis plan, a sample-size justification, multiplicity procedures, missing-data methods, or completeness of follow-up. Although it defines the safety population and follow-up window, it does not explain how incomplete observations were handled. The record does not report whether outcome definitions or analyses changed during the study.

The primary outcome is safety-focused, and numerical results for the listed pharmacokinetic outcomes are not reported in the registry record. A tumor-response endpoint or efficacy analysis is also not reported. Consequently, these registry entries cannot support conclusions about antitumor benefit, comparative safety, or causal attribution of individual events.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: A Study of IXAZOMIB in Adult Patients With Lymphoma — NCT00893464.
• Registry record last updated 2015-11-11; status last verified 2015-10.
• Results first posted 2015-11-11.
• 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.

18. Record Summary

The registry identifies NCT00893464 as a completed, open-label, multicenter, phase 1 dose-escalation study of ixazomib in adults with lymphoma. Enrollment is recorded as 31. The recorded start is 2009-08, and primary completion is 2014-10. The study is listed as single group, with allocation not applicable and no masking.

The primary outcome counts participants reporting one or more treatment-emergent adverse events and serious adverse events from baseline up to 30 days after the last dose. The safety population includes participants who received at least 1 dose. Adverse-event counts are recorded by dose cohort. The registry lists 15 outcome measures and no analyses. Numerical results for the listed pharmacokinetic secondary outcomes, a statistical analysis plan, and missing-data procedures are not reported in the registry record.