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 Study of Oral Ixazomib in Adult Participants With Relapsed or Refractory Light Chain Amyloidosis (NCT01318902), a non-randomized phase 1 study. The primary outcome is Number of Participants With at Least One Treatment Emergent Adverse Event (TEAE) and Serious Adverse Event (SAE).
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT01318902 |
| Phase | Phase 1 |
| Condition | Light-Chain Amyloidosis |
| Allocation | Non-Randomized |
| Design model | Parallel |
| Masking | None (open label) |
| Enrollment | 27 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Millennium Pharmaceuticals, Inc. |
| Results posted | Yes |
2. Clinical Question
Population
Adults with previously treated systemic relapsed or refractory light-chain (AL) amyloidosis who required further treatment. The safety population was defined as participants who received at least one dose of ixazomib.
Intervention
Oral ixazomib, studied in dose-escalation cohorts at 4.0 mg and 5.5 mg and in dose-expansion cohorts at 4.0 mg. The expansion cohorts distinguished participants who were PI naive from those who were PI exposed. Dexamethasone could be added in the dose-escalation regimen when there was no hematologic response.
Comparator
There was no randomized control group. Cohorts were non-randomized and differed by dose, study phase, or prior proteasome-inhibitor exposure, so they should not be treated as equivalent groups in a controlled comparison.
Primary question
How many participants experienced at least one treatment-emergent adverse event (TEAE) and how many experienced a serious adverse event (SAE) during the specified safety follow-up? The study’s stated aim also included determining safety and the maximum tolerated dose or recommended phase 2 dose; whether either dose was established is not reported in the registry record.
This is a safety-focused question in a phase 1 study, rather than a randomized test of ixazomib against another treatment. The primary endpoint counts participants with events, not the total number of event occurrences, and the registry defines the safety population as participants who received at least one dose. The reported cohorts describe different treatment settings and prior-treatment categories. Any differences in their counts can reflect those design and population differences as well as chance; they cannot isolate a treatment effect. The record also lists investigator-assessed best organ response and pharmacokinetic and pharmacodynamic outcomes among secondary outcomes. Numerical results for those outcomes are not reported in the registry record.
3. Trial Design
This was an open-label, non-randomized, parallel-group phase 1 study of oral ixazomib in adults with relapsed or refractory light-chain amyloidosis. The registry lists enrollment of 27 and a completed status. The study began on 2011-04-27, and primary completion was recorded as 2018-11-13. The sponsor was Millennium Pharmaceuticals, Inc.
The study included dose-escalation and dose-expansion cohorts. The escalation cohorts used ixazomib 4.0 mg or 5.5 mg. The expansion cohorts used 4.0 mg and distinguished participants who were PI naive from those who were PI exposed. In the dose-escalation descriptions, dexamethasone could be added when there was no hematologic response. The available regimen descriptions are incomplete, so details beyond the text recorded in the registry are not reported in the registry record.
The study was unmasked: participants and investigators were not assigned under a blinded comparison. Allocation was non-randomized, and there was no like-for-like control arm. Dose, cohort stage, and prior PI exposure therefore define different groups rather than randomized treatment assignments. This matters when interpreting between-cohort differences: they are descriptive and cannot establish that one dose or subgroup caused a different outcome.
The registry describes the primary outcome as the number of participants with at least one TEAE and SAE, measured from first study-drug dose through 30 days after the last dose or until subsequent antineoplastic therapy, with follow-up stated as up to approximately 13 months. It also lists pharmacokinetic, pharmacodynamic, and investigator-assessed organ-response outcomes. The registry record does not report a statistical analysis plan, a dose-selection conclusion, or numerical results for those secondary outcomes.
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 previously treated systemic light chain (AL) amyloidosis were enrolled in 2 dose escalation cohorts and were treated with ixazomib 4.0 or 5.5 mg. Participants with relapsed or refractory amyloidosis were enrolled in 2 dose expansion cohorts and treated with ixazomib 4.0 mg in proteosome inhibitor (PI) Naive and PI Exposed groups.
Overall Study
| Stage | Dose Escalation Cohort: Ixazomib 4.0 mg | Dose Escalation Cohort: Ixazomib 5.5 mg | Dose Expansion Cohort: Ixazomib 4.0 mg (PI Naive) | Dose Expansion Cohort: Ixazomib 4.0 mg (PI Exposed) |
|---|---|---|---|---|
| STARTED | 6 | 5 | 5 | 11 |
| COMPLETED | 5 | 2 | 3 | 5 |
| NOT COMPLETED | 1 | 3 | 2 | 6 |
Reasons for not completing this period:
| Reason | Dose Escalation Cohort: Ixazomib 4.0 mg | Dose Escalation Cohort: Ixazomib 5.5 mg | Dose Expansion Cohort: Ixazomib 4.0 mg (PI Naive) | Dose Expansion Cohort: Ixazomib 4.0 mg (PI Exposed) |
|---|---|---|---|---|
| Symptomatic Deterioration | 0 | 1 | 1 | 2 |
| Withdrawal by Patient | 0 | 1 | 0 | 3 |
| Unsatisfactory Therapeutic Response | 1 | 0 | 0 | 1 |
| Adverse Event | 0 | 1 | 0 | 0 |
| Terminated by Sponsor | 0 | 0 | 1 | 0 |
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.
| Characteristic | Unit | Dose Escalation Cohort: Ixazomib 4.0 mg | Dose Escalation Cohort: Ixazomib 5.5 mg | Dose Expansion Cohort: Ixazomib 4.0 mg (PI Naive) | Dose Expansion Cohort: Ixazomib 4.0 mg (PI Exposed) | Total |
|---|---|---|---|---|---|---|
| Participants analysed | 6 | 5 | 5 | 11 | 27 | |
| Age, Continuous | years | 63.3 (SD 6.15) | 69.0 (SD 8.51) | 65.8 (SD 6.26) | 66.7 (SD 8.49) | 66.2 (SD 7.46) |
| Sex: Female, Male: Female | Participants | 2 | 4 | 2 | 5 | 13 |
| Sex: Female, Male: Male | Participants | 4 | 1 | 3 | 6 | 14 |
| Ethnicity (NIH/OMB): Hispanic or Latino | Participants | 0 | 0 | 0 | 1 | 1 |
| Ethnicity (NIH/OMB): Not Hispanic or Latino | Participants | 5 | 4 | 5 | 8 | 22 |
| Ethnicity (NIH/OMB): Unknown or Not Reported | Participants | 1 | 1 | 0 | 2 | 4 |
| Race/Ethnicity, Customized: White | Participants | 5 | 5 | 3 | 10 | 23 |
| Race/Ethnicity, Customized: Asian | Participants | 0 | 0 | 1 | 0 | 1 |
| Race/Ethnicity, Customized: Black or African American | Participants | 0 | 0 | 1 | 0 | 1 |
| Race/Ethnicity, Customized: Not Reported | Participants | 0 | 0 | 0 | 1 | 1 |
| Race/Ethnicity, Customized: Other | Participants | 1 | 0 | 0 | 0 | 1 |
| Height | cm | 173.26 (SD 7.504) | 159.17 (SD 11.043) | 173.56 (SD 20.728) | 167.35 (SD 9.056) | 168.30 (SD 12.436) |
| Weight | kg | 76.78 (SD 5.464) | 64.03 (SD 12.664) | 85.83 (SD 40.280) | 70.96 (SD 11.402) | 73.73 (SD 19.536) |
6. Primary Endpoint
The registry lists the primary outcome as Number of Participants With at Least One Treatment Emergent Adverse Event (TEAE) and Serious Adverse Event (SAE), measured over From the first dose of study drug plus 30 days after last dose of study drug or until the initiation of subsequent antineoplastic therapy (Up to approximately 13 months).
| Element | Registry entry |
|---|---|
| Result type | Count Of Participants |
| Measure of spread | not applicable |
| Unit | Participants |
| Endpoint classification | Binary Endpoint |
The primary endpoint concerns participants who experienced at least one TEAE and participants who experienced an SAE. An adverse event is an untoward medical occurrence during use of an investigational medicinal drug; the event need not be caused by treatment. The record defines an SAE by seriousness criteria that include death, a life-threatening event, inpatient hospitalization or its prolongation, persistent or significant disability, congenital anomaly or birth defect, and other medically important events that could require intervention. A TEAE is an adverse event occurring after the first study-drug dose and through 30 days after the last dose, or until subsequent antineoplastic therapy begins.
Counting participants with an event is useful in an early-phase safety study because it describes how many people in the safety population had at least one event meeting the specified definition. It is distinct from counting every event: one participant may have multiple events, while a participant-level count records that person once for the relevant category. The record states that the safety population included participants who received at least one dose of ixazomib.
The follow-up window defines which events are eligible for this endpoint; it does not by itself establish that ixazomib caused an event. The registry supplies counts by cohort for serious and other adverse events, but it does not report a causal assessment or an adjusted comparison. The endpoint is therefore best read as a description of observed safety experience within these cohorts. A maximum tolerated dose or recommended phase 2 dose was part of the study aim, but the result of that assessment is not reported in the registry record.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The posted safety counts describe four non-randomized cohorts. In the 4.0 mg dose-escalation cohort, 3 of 6 participants were recorded with a serious adverse event and 6 of 6 with another adverse event. In the 5.5 mg dose-escalation cohort, the corresponding counts were 5 of 5 and 5 of 5. In the 4.0 mg PI-naive expansion cohort, they were 5 of 5 and 5 of 5; in the 4.0 mg PI-exposed expansion cohort, they were 5 of 11 and 10 of 11. These are descriptive counts, not randomized estimates of differences between doses or prior-treatment groups.
The cohorts are small, and the denominators differ. Consequently, a count in one cohort should not be compared with a count in another as though participants had been randomly assigned to otherwise identical groups. Prior treatment, cohort stage, dose, and other participant characteristics can differ. The record does not report adjusted estimates or a formal comparison across these cohorts.
The registry separately lists deaths: 0 in the 4.0 mg dose-escalation cohort, 0 in the 5.5 mg dose-escalation cohort, 1 in the PI-naive expansion cohort, and 0 in the PI-exposed expansion cohort. These are recorded death counts, not an attribution of cause or treatment relationship. Such attribution is not reported in the registry record.
The listed serious-event terms include atrial fibrillation at 40.0%, cardiac failure congestive at 20.0%, pleural effusion at 20.0%, abdominal pain at 20.0%, angina pectoris at 20.0%, and basal cell carcinoma at 20.0%. The record does not specify the denominator or further analysis context for these term percentages in the available information, so they should not be interpreted as comparative risks.
No inferential analysis results are listed: the registry reports 0 analyses. There are no reported confidence intervals, p-values, or model-based estimates with which to quantify uncertainty beyond the small cohort denominators. The figures characterize observed events in this study; they do not establish comparative safety or treatment effect.
9. Statistical Methods Explained
In general, a participant-level adverse-event endpoint counts whether each person experienced at least one event in a defined category and observation period. It does not count the total number of event occurrences. A person who has several events may still contribute once to the count of participants with at least one event in that category. This distinction matters because participant counts describe the breadth of exposure to an event category, while event counts describe its total recorded occurrences.
What does the denominator represent?
The registry defines the safety population as all participants who received at least one dose of ixazomib. The adverse-event figures are presented with cohort-specific numbers at risk and numbers affected. A cohort denominator is essential to interpret a count: the same affected-participant count can convey different levels of observed frequency when denominators differ. The figures should therefore be read with their own cohort denominators, rather than compared by raw counts alone. The record does not state whether any participant-level endpoint data were missing or how missing observations were handled.
Why distinguish serious from other adverse events?
The registry uses a specific seriousness definition. Seriousness refers to the consequences or clinical importance of an event under the stated criteria; it is not a judgment that the event was caused by the study drug. TEAE is a timing classification: it identifies events occurring after treatment begins and within the defined follow-up window. An event can meet the timing definition without being treatment-related. The record does not provide a causal assessment for the reported events, so the categories should not be read as evidence of causation.
What does uncertainty mean for these counts?
In general, a confidence interval expresses the range of values compatible with data under a statistical model and its assumptions. For participant-level event proportions, uncertainty is influenced by the number of participants observed and the number with events. Small cohort sizes generally allow less precise estimates than larger cohorts. The registry record does not report confidence intervals or other uncertainty intervals for these adverse-event counts. No interval should be inferred from the counts alone in a narrative interpretation.
Likewise, a p-value from a valid comparison would address how compatible data are with a specified null model; it would not measure the probability that a treatment works or that a result is true. The registry lists 0 analyses, and it does not report a randomized comparison or inferential test for these cohort counts. Thus, there is no reported p-value to interpret. A visual or descriptive difference among the cohorts is not, by itself, evidence of a statistically established difference.
Why does over-dispersion matter in general?
For event counts, a simple statistical model may assume that variability follows a particular relationship to the average count. Over-dispersion occurs when observed variation exceeds that assumption. If ignored, standard errors can be too small and intervals or tests can appear more precise than warranted. This is a general consideration for analyses of event counts; the registry record does not report an over-dispersion assessment or a count model. The primary endpoint is the number of participants with events, not a reported model of recurrent event totals.
How should planning calculations be understood?
General sample-size illustrations are planning exercises, not descriptions of the trial’s observed evidence and not measures of observed power. The planning assumptions described for the calculations use a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation, with the target effect expressed as a fraction of the observed effect. Those assumptions do not turn this non-randomized, multi-cohort study into an equal-allocation trial. They should not be treated as the study’s original design rationale or as a basis for inferring that the study could detect a particular effect. The registry does not report its own sample-size justification.
In general, an analysis plan would specify outcome definitions, analysis populations, model choices, uncertainty measures, and how multiple outcomes are handled. Those details are not reported in the registry record. The statistical interpretation must therefore remain descriptive and close to the stated endpoint definitions and posted counts.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists 23 outcome measures, including the primary safety endpoint, pharmacokinetic and pharmacodynamic measures, and investigator-assessed best organ response. It records 0 analyses. A plan for controlling multiplicity across outcomes, defining a hierarchy of tests, or distinguishing confirmatory from exploratory analyses is not reported in the registry record. Because numerical secondary-outcome results and inferential tests are also not reported, the record does not support conclusions based on multiple endpoint comparisons.
The primary outcome’s stated population is the safety population: participants who received at least one dose of ixazomib. That is an explicit analysis-population definition for the safety endpoint. A separate efficacy population, an intention-to-treat population, and rules for handling participants who discontinue or have incomplete measurements are not reported in the registry record.
The endpoint has a defined follow-up period, extending from the first dose through 30 days after the last dose or until initiation of subsequent antineoplastic therapy, with the timeframe described as up to approximately 13 months. The registry does not explain how observation time was handled when participants had different follow-up durations, whether event status was complete for every participant, or how missing event information was treated. No imputation method, censoring approach, or sensitivity analysis is reported. These omissions limit assessment of how complete and comparable the safety observation was across cohorts.
In general, multiplicity can increase the chance of apparently notable findings when many outcomes are examined, while missing data can affect estimates if completeness differs across participants or outcomes. These are general concerns; the registry record does not report procedures addressing them. The descriptive safety counts remain interpretable as posted, but the absent analysis and missing-data details constrain stronger statistical claims.
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 |
|---|---|---|---|
| Dose Escalation Cohort: Ixazomib 4.0 mg | 3 | 6 | 50.0% |
| Dose Escalation Cohort: Ixazomib 5.5 mg | 5 | 5 | 100.0% |
| Dose Expansion Cohort: Ixazomib 4.0 mg (PI Naive) | 5 | 5 | 100.0% |
| Dose Expansion Cohort: Ixazomib 4.0 mg (PI Exposed) | 5 | 11 | 45.5% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Dose Escalation Cohort: Ixazomib 4.0 mg | 0 of 6 |
| Dose Escalation Cohort: Ixazomib 5.5 mg | 0 of 5 |
| Dose Expansion Cohort: Ixazomib 4.0 mg (PI Naive) | 1 of 5 |
| Dose Expansion Cohort: Ixazomib 4.0 mg (PI Exposed) | 0 of 11 |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 5% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Dose Escalation Cohort: Ixazomib 4.0 mg | 6 of 6 |
| Dose Escalation Cohort: Ixazomib 5.5 mg | 5 of 5 |
| Dose Expansion Cohort: Ixazomib 4.0 mg (PI Naive) | 5 of 5 |
| Dose Expansion Cohort: Ixazomib 4.0 mg (PI Exposed) | 10 of 11 |
Most frequent serious adverse event terms
| Event term | Organ system | Dose Escalation Cohort: Ixazomib 4.0 mg | Dose Escalation Cohort: Ixazomib 5.5 mg | Dose Expansion Cohort: Ixazomib 4.0 mg (PI Naive) | Dose Expansion Cohort: Ixazomib 4.0 mg (PI Exposed) |
|---|---|---|---|---|---|
| Atrial fibrillation | Cardiac disorders | 0 of 6 | 2 of 5 | 0 of 5 | 0 of 11 |
| Cardiac failure congestive | Cardiac disorders | 1 of 6 | 0 of 5 | 1 of 5 | 0 of 11 |
| Pleural effusion | Respiratory, thoracic and mediastinal disorders | 1 of 6 | 1 of 5 | 0 of 5 | 0 of 11 |
| Abdominal pain | Gastrointestinal disorders | 0 of 6 | 1 of 5 | 0 of 5 | 0 of 11 |
| Acute kidney injury | Renal and urinary disorders | 0 of 6 | 0 of 5 | 0 of 5 | 1 of 11 |
| Angina pectoris | Cardiac disorders | 0 of 6 | 1 of 5 | 0 of 5 | 0 of 11 |
| Basal cell carcinoma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | 0 of 6 | 0 of 5 | 1 of 5 | 0 of 11 |
| Cardiac arrest | Cardiac disorders | 0 of 6 | 1 of 5 | 0 of 5 | 0 of 11 |
| Cardiac failure | Cardiac disorders | 0 of 6 | 0 of 5 | 0 of 5 | 1 of 11 |
| Cholecystitis | Hepatobiliary disorders | 0 of 6 | 1 of 5 | 0 of 5 | 0 of 11 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Dose Escalation Cohort: Ixazomib 4.0 mg | Dose Escalation Cohort: Ixazomib 5.5 mg | Dose Expansion Cohort: Ixazomib 4.0 mg (PI Naive) | Dose Expansion Cohort: Ixazomib 4.0 mg (PI Exposed) |
|---|---|---|---|---|---|
| Nausea | Gastrointestinal disorders | 4 of 6 | 4 of 5 | 3 of 5 | 4 of 11 |
| Diarrhoea | Gastrointestinal disorders | 3 of 6 | 3 of 5 | 3 of 5 | 5 of 11 |
| Fatigue | General disorders | 2 of 6 | 3 of 5 | 3 of 5 | 6 of 11 |
| Constipation | Gastrointestinal disorders | 1 of 6 | 3 of 5 | 2 of 5 | 2 of 11 |
| Decreased appetite | Metabolism and nutrition disorders | 2 of 6 | 2 of 5 | 1 of 5 | 3 of 11 |
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | 1 of 6 | 2 of 5 | 3 of 5 | 2 of 11 |
| Pyrexia | General disorders | 1 of 6 | 1 of 5 | 1 of 5 | 5 of 11 |
| Oedema peripheral | General disorders | 3 of 6 | 0 of 5 | 2 of 5 | 2 of 11 |
| Upper respiratory tract infection | Infections and infestations | 2 of 6 | 0 of 5 | 3 of 5 | 2 of 11 |
| Asthenia | General disorders | 0 of 6 | 1 of 5 | 0 of 5 | 5 of 11 |
Serious events with the highest arm-level rate: atrial fibrillation (40.0%), cardiac failure congestive (20.0%), pleural effusion (20.0%), abdominal pain (20.0%), angina pectoris (20.0%).
The cohort figures report participants affected, alongside the number at risk, for serious and other adverse events. For example, the 4.0 mg dose-escalation cohort lists 3 of 6 participants with a serious event and 6 of 6 with another adverse event; the PI-exposed expansion cohort lists 5 of 11 and 10 of 11, respectively. The other two cohorts each list all participants at risk as affected for both categories. These are participant counts, not counts of individual event episodes.
Serious adverse events are defined by consequences such as death, life-threatening events, hospitalization, significant disability, congenital anomaly or birth defect, or other medically important events. The separate death counts are 0, 0, 1, and 0 across the four cohorts in the order described in the registry. The record does not state that the death was caused by ixazomib or identify its cause.
The listed serious-event terms and percentages are descriptive. The available record does not state their denominator or provide a comparative analysis. Also, an adverse event is not necessarily caused by treatment. These counts should be read as the safety experience recorded within this study, not as a causal estimate or a comparison against an untreated group.
12. What the Result Does, and Does Not, Mean
The posted results describe adverse-event experience among participants in a small, open-label phase 1 study with non-randomized dose-escalation and dose-expansion cohorts. The counts show that serious and other adverse events were recorded in each cohort. They also show that the cohort denominators were not the same. This is useful descriptive information about the participants observed under the study’s treatment regimens and follow-up definition.
These data do not establish that ixazomib caused any particular event. The registry’s adverse-event definition explicitly does not require a causal relationship, and no event-attribution results are reported. The listed death count is not accompanied by a cause or treatment relationship. Nor do these data establish that one dose or subgroup is safer than another: the cohorts were not randomized, and they differ by dose, cohort stage, and prior PI exposure.
The study’s stated aim included determining a maximum tolerated dose or recommended phase 2 dose. The registry record does not report the dose-selection result, so the cohort counts alone cannot supply that conclusion. The record also lists organ-response, pharmacokinetic, and pharmacodynamic outcomes, but their numerical findings are not reported in the registry record. The posted safety results therefore do not establish a treatment benefit or lack of benefit.
In general, precise conclusions require attention to denominators, follow-up, uncertainty, and the design that generated the data. Here, the registry lists 0 analyses and does not report confidence intervals, p-values, adjusted comparisons, or a detailed missing-data plan. This means the strongest supported reading is descriptive: the figures state how many participants in each listed cohort were recorded with the specified event categories. They should not be extended to other populations or used as a controlled estimate of comparative risk.
13. Why This Trial Matters Statistically
This study illustrates why early-phase safety data need to be read in the context of design. A dose-escalation and dose-expansion study can describe events observed under different regimens and in different participant groups. However, non-randomized cohorts do not balance participant characteristics by design, and there is no like-for-like randomized control comparison. Apparent differences between cohort counts may reflect several factors and cannot be attributed to dose or prior PI exposure from these data alone.
It also demonstrates the importance of distinguishing participant counts from event counts and of preserving the endpoint’s time window. The primary outcome counts participants with at least one TEAE and SAE, while the definitions specify when events qualify for inclusion. Seriousness and treatment-emergent timing answer different questions; neither alone establishes causation.
Finally, the registry record distinguishes a stated study aim from a reported analysis. Although the study aimed to assess safety and determine a maximum tolerated dose or recommended phase 2 dose, the dose-selection result and inferential analyses are not reported. That distinction prevents descriptive counts from being mistaken for a formal dose decision, a comparative safety estimate, or evidence about organ response. The record is statistically informative about how the endpoint is defined and how events were counted, while leaving important inferential and analytic details unresolved.
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 is the non-randomized design. There is no control group that can serve as a like-for-like comparison, and cohort assignment is associated with dose, escalation or expansion stage, and prior PI exposure. Therefore, between-cohort differences are descriptive and cannot establish the effect of dose or prior treatment. Open-label conduct also means the study was not blinded, though the registry does not provide information about how awareness of treatment may have affected event assessment.
The cohort sizes are small, with denominators of 6, 5, 5, and 11 in the adverse-event records. Such counts provide limited precision, and no confidence intervals or other uncertainty estimates are reported. The registry also lists 0 analyses, so there are no reported adjusted comparisons or inferential tests to supplement the descriptive data.
The event definitions clarify timing and seriousness, but the record does not report causal attribution for the events or the cause and treatment relationship of the recorded death. The percentages for listed serious-event terms lack a stated denominator in the available record. Follow-up is described as up to approximately 13 months, but participant-level follow-up completeness and handling of missing event data are not reported.
The study aimed to determine a maximum tolerated dose or recommended phase 2 dose, but that conclusion is not reported in the registry record. Numerical results for listed secondary outcomes, including organ response and pharmacokinetic or pharmacodynamic measures, are also not reported. These limitations restrict interpretation to the posted safety counts and definitions.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Study of Oral Ixazomib in Adult Participants With Relapsed or Refractory Light Chain Amyloidosis — NCT01318902.
- Registry record last updated 2020-04-01; status last verified 2020-03.
- Results first posted 2020-04-01.
- 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.
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18. Record Summary
NCT01318902 is a completed, open-label, non-randomized phase 1 study of oral ixazomib in adults with relapsed or refractory light-chain amyloidosis. The registry lists enrollment of 27 and four dose-escalation or dose-expansion cohorts. Dexamethasone could be added in the dose-escalation regimen when there was no hematologic response.
The primary outcome counts participants with at least one TEAE and SAE in a safety population defined by receipt of at least one ixazomib dose. Cohort-level counts for serious and other adverse events and separate death counts are posted. The registry also lists pharmacokinetic, pharmacodynamic, and organ-response outcomes, but their numerical results are not reported in the registry record.
There is no randomized comparator, and the registry records 0 analyses. The results support a descriptive account of safety events in the listed cohorts, not a controlled estimate of comparative risk or a reported dose-selection conclusion.