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 Phase 1b/2, Multicenter, Open-label Study of Oprozomib and Dexamethasone in Patients With Relapsed and/or Refractory Multiple Myeloma (NCT01832727), a non-randomized phase 1, phase 2 study. The primary outcome is Participants With Dose-Limiting Toxicities (DLT).
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT01832727 |
| Phase | Phase 1, Phase 2 |
| Condition | Multiple Myeloma |
| Allocation | Non-Randomized |
| Design model | Parallel |
| Masking | None (open label) |
| Enrollment | 65 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Amgen |
| Results posted | Yes |
2. Clinical Question
Population
Patients with relapsed and/or refractory multiple myeloma. The registry lists multiple myeloma as the condition and records enrollment of 65.
Intervention
Oral oprozomib in combination with dexamethasone. Phase 1b examined several dose levels and schedules; the Phase 2 cohort used the 300 mg 2/7 schedule with dexamethasone.
Comparator
There was no randomized control group. Participants entered non-randomized dose and schedule cohorts, so those cohorts are not like-for-like treatment comparisons.
Primary question
In Phase 1b, the study aimed to identify a maximum tolerated dose and recommended Phase 2 dose and to assess safety and tolerability. In Phase 2, the stated objective was to estimate overall response rate and assess safety and tolerability. The listed primary outcome measures participants with dose-limiting toxicities.
The clinical question therefore combines dose finding with an early estimate of antitumour activity. Dose finding asks whether toxicities judged related to oprozomib occur during a prespecified assessment period at the dose under study. The registry defines the assessment period differently for continuous and step-up dosing. The Phase 2 objective shifts toward estimating overall response rate, while continuing to evaluate safety.
These objectives are descriptive and exploratory in the context of a non-randomized, open-label study. The registry record does not describe a concurrent control arm, and the listed cohorts differ by dose, schedule, or study phase. Consequently, a contrast between cohorts would not isolate the effect of dose or schedule from other potential differences. The record does not report a formal comparative clinical question or an adjusted analysis for such contrasts.
3. Trial Design
This was a multicenter, open-label, non-randomized, parallel study in Phase 1b and Phase 2. The registry lists enrollment of 65 and status as terminated. The recorded start date is 2013-07-02 and the primary completion date is 2019-06-25. The reason for termination is not reported in the registry record.
Phase 1b investigated oprozomib dose and schedule alongside dexamethasone. The listed cohorts included 180 mg and 210 mg on the 5/14 schedule, a 150/180 mg step-up 5/14 schedule, and dose levels from 210 mg through 330 mg on the 2/7 schedule. The Phase 2 cohort used oprozomib 300 mg on the 2/7 schedule with dexamethasone. The registry states that the Cohort Safety Review Committee determined 300 mg on the 2/7 schedule to be the recommended Phase 2 dose.
For the 5/14 schedule, oprozomib was given on days 1, 2, 3, 4, and 5 of a 14-day cycle, with dexamethasone on days 1, 2, 8, and 9. For the described 2/7 schedules, both drugs were given on days 1, 2, 8, and 9 of a 14-day cycle. The 150/180 mg cohort began at 150 mg and stepped up to 180 mg starting in cycle 2. These schedule details describe the listed regimens; they do not establish that participants in different cohorts were comparable.
Allocation was non-randomized and masking was none. The record does not report a randomization procedure, blinding, a control treatment, or a statistical adjustment intended to make cohort comparisons causal. The planned enrollment is not reported separately from the registry enrollment of 65. Further details of site-specific enrollment and the number assessed in each 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.
Before assignment: Eighty-one subjects were screened; sixteen were not enrolled due to entry criteria violations.
Only the first 6 of 9 groups are shown.
Overall Study
| Stage | Cohort 180 mg 5/14 Schedule (Phase 1b) | Cohort 210 mg 5/14 Schedule (Phase 1b) | Cohort 150/180 mg 5/14 Schedule (Phase 1b) | Cohort 210 mg 2/7 Schedule (Phase 1b) | Cohort 240 mg 2/7 Schedule (Phase 1b) | Cohort 270 mg 2/7 Schedule (Phase 1b) |
|---|---|---|---|---|---|---|
| STARTED | 9 | 7 | 3 | 4 | 4 | 6 |
| COMPLETED | 0 | 0 | 0 | 0 | 0 | 0 |
| NOT COMPLETED | 9 | 7 | 3 | 4 | 4 | 6 |
Reasons for not completing this period:
| Reason | Cohort 180 mg 5/14 Schedule (Phase 1b) | Cohort 210 mg 5/14 Schedule (Phase 1b) | Cohort 150/180 mg 5/14 Schedule (Phase 1b) | Cohort 210 mg 2/7 Schedule (Phase 1b) | Cohort 240 mg 2/7 Schedule (Phase 1b) | Cohort 270 mg 2/7 Schedule (Phase 1b) |
|---|---|---|---|---|---|---|
| Adverse Event | 4 | 6 | 1 | 0 | 1 | 1 |
| Disease progression | 3 | 0 | 2 | 1 | 3 | 3 |
| Lost to Follow-up | 0 | 0 | 0 | 1 | 0 | 0 |
| Physician Decision | 1 | 0 | 0 | 1 | 0 | 1 |
| Withdrawal by Subject | 1 | 1 | 0 | 1 | 0 | 1 |
| Study terminated by sponsor | 0 | 0 | 0 | 0 | 0 | 0 |
Analysis population for the primary outcome, as defined in the registry: Safety population
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: all subjects who receive at least 1 dose of study treatment
Only the first 6 of 10 groups are shown.
| Characteristic | Unit | Cohort 180 mg 5/14 Schedule (Phase 1b) | Cohort 210 mg 5/14 Schedule (Phase 1b) | Cohort 150/180 mg 5/14 Schedule (Phase 1b) | Cohort 210 mg 2/7 Schedule (Phase 1b) | Cohort 240 mg 2/7 Schedule (Phase 1b) | Cohort 270 mg 2/7 Schedule (Phase 1b) |
|---|---|---|---|---|---|---|---|
| Participants analysed | 9 | 7 | 3 | 4 | 4 | 6 | |
| Age, Customized: <65 years | Participants | 5 | 4 | 2 | 1 | 4 | 2 |
| Age, Customized: 65 - <75 years | Participants | 2 | 3 | 0 | 2 | 0 | 3 |
| Age, Customized: >=75 years | Participants | 2 | 0 | 1 | 1 | 0 | 1 |
| Sex: Female, Male: Female | Participants | 3 | 4 | 1 | 2 | 1 | 2 |
| Sex: Female, Male: Male | Participants | 6 | 3 | 2 | 2 | 3 | 4 |
| Ethnicity (NIH/OMB): Hispanic or Latino | Participants | 0 | 0 | 0 | 0 | 1 | 0 |
| Ethnicity (NIH/OMB): Not Hispanic or Latino | Participants | 9 | 7 | 3 | 4 | 2 | 6 |
| Ethnicity (NIH/OMB): Unknown or Not Reported | Participants | 0 | 0 | 0 | 0 | 1 | 0 |
| Race (NIH/OMB): American Indian or Alaska Native | Participants | 0 | 0 | 0 | 0 | 0 | 0 |
| Race (NIH/OMB): Asian | Participants | 1 | 0 | 0 | 0 | 0 | 0 |
| Race (NIH/OMB): Native Hawaiian or Other Pacific Islander | Participants | 0 | 0 | 0 | 0 | 0 | 0 |
| Race (NIH/OMB): Black or African American | Participants | 0 | 0 | 1 | 1 | 1 | 2 |
| Race (NIH/OMB): White | Participants | 8 | 7 | 2 | 3 | 2 | 4 |
| Race (NIH/OMB): More than one race | Participants | 0 | 0 | 0 | 0 | 0 | 0 |
| Race (NIH/OMB): Unknown or Not Reported | Participants | 0 | 0 | 0 | 0 | 1 | 0 |
6. Primary Endpoint
The registry lists the primary outcome as Participants With Dose-Limiting Toxicities (DLT), measured over Day 1 to Day 14 (Cycle 1) for continous dosing and Day 15 to Day 28 (Cycle 2) for step-up dosing.
| Element | Registry entry |
|---|---|
| Result type | Count Of Participants |
| Measure of spread | not applicable |
| Unit | Participants |
| Endpoint classification | Binary Endpoint |
The listed primary endpoint is the count of participants with dose-limiting toxicities, assessed in the safety population. A dose-limiting toxicity, or DLT, was a toxicity graded under Common Terminology Criteria for Adverse Events version 4.03 and judged by the investigator to be related to oprozomib. The endpoint focuses on toxicities during the period at the dose being studied: Cycle 1 for continuous dosing or Cycle 2 for step-up dosing. The stated timeframe is Day 1 to Day 14 for continuous dosing and Day 15 to Day 28 for step-up dosing.
The registry describes DLTs as hematologic or nonhematologic and gives examples, including qualifying severe nonhematologic events, prolonged fatigue, severe neutropenia, febrile neutropenia, and severe thrombocytopenia. Some examples depend on duration or clinical qualifications, so the endpoint is not simply a count of every adverse event. The investigator’s attribution to oprozomib is part of the definition.
In general, a DLT endpoint is used in dose-finding work because it summarizes important treatment-limiting toxicity within a defined assessment window. It can inform selection of a dose for further study, but it does not by itself describe the full safety profile over all treatment cycles or establish comparative safety. The registry record lists the endpoint definition but does not report the observed DLT count or a dose-finding analysis.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The posted registry information describes the study design, objectives, endpoint definition, and cohort-specific adverse-event summaries. It does not report the primary endpoint result: no observed count of participants with dose-limiting toxicities is listed. Although Phase 2 aimed to estimate overall response rate, an overall response rate result is not reported in the registry record. The record lists no analyses. Therefore, the page can explain what the study sought to assess, but cannot summarize a posted estimate of DLT frequency or response.
The safety summary reports serious adverse events by cohort. For example, the 180 mg 5/14 cohort lists 4 affected participants among 9 at risk, while the Phase 2 300 mg 2/7 cohort lists 9 among 18. Other adverse events are also shown by cohort in the posted figures. These are descriptive counts, not randomized comparisons. The cohort sizes and regimens differ, and participants were not randomly allocated. Any apparent variation between rows should therefore be read as a description of the registry’s cohorts, not as evidence that one dose or schedule caused more or fewer events than another.
The record also lists deaths by cohort: one in the 210 mg 5/14 cohort and one in the 240 mg 2/7 cohort, with zero listed in the other cohorts. These counts do not establish the cause of death or its relationship to study treatment. Cause and attribution are not reported in the registry record. Likewise, the listed serious-event terms and percentages are descriptive; the record does not give enough information to interpret them as comparative risks or to infer an event’s treatment relationship.
The study’s objectives and its available posted results must be kept distinct. Stating that Phase 1b sought an MTD and RP2D or that Phase 2 sought an ORR does not mean those outcomes are reported. The registry identifies the recommended Phase 2 dose as 300 mg on the 2/7 schedule, but does not provide the committee’s supporting DLT results or its decision process. An outcome’s definition is not an outcome estimate.
Because the design was open-label and non-randomized, the record does not support an unbiased treatment-effect comparison against a control. No control group is listed. The safety summaries can still convey which counts were recorded in the cohorts, but they do not account for differences in exposure, patient characteristics, or follow-up. Those details and any statistical adjustment are not reported in the registry record. Interpretation should therefore remain descriptive and limited to the information posted.
9. Statistical Methods Explained
The registry record gives a defined primary endpoint and several study objectives, but it does not report the statistical analysis methods used to produce inferential estimates. The explanations below distinguish the endpoint’s stated definition from general statistical principles. No specific model, confidence interval method, hypothesis test, or missing-data procedure is reported in the registry record.
What does a participant count represent?
The primary outcome is a count of participants with at least one DLT under the registry definition. In general, a binary participant-level endpoint classifies each person as having or not having the event during a specified assessment window. A count is the number classified as having the event; interpretation ordinarily requires a clearly defined population and denominator. Here, the registry names the safety population and specifies the timing and criteria, but does not post the DLT count or the number evaluated for this endpoint in each cohort.
A count should not be confused with the number of individual adverse-event episodes. A participant can experience more than one toxicity, while the endpoint title concerns participants with DLTs. The detailed criteria also matter: the registry requires investigator judgment that the toxicity was related to oprozomib and describes particular severity, duration, or clinical conditions. A general adverse-event listing is not interchangeable with the DLT endpoint.
Why define an assessment window?
In general, a dose-finding endpoint is tied to a period in which toxicity is assessed at the dose under study. The registry specifies Cycle 1 for continuous dosing and Cycle 2 for step-up dosing, corresponding to Day 1 to Day 14 and Day 15 to Day 28, respectively. These windows are not identical calendar periods across the two dosing approaches. A comparison across schedules would need to account for this distinction and for the fact that the cohorts were not randomized. The record does not describe an analysis addressing those issues.
General statistical practice treats the endpoint definition, window, and denominator as parts of the estimand: the precise quantity an analysis is intended to describe. If the endpoint is a participant count, an accompanying proportion can help relate the count to the number evaluated, but no DLT proportion is posted. A confidence interval, in general, would express the statistical uncertainty around an estimate; it would not remove bias from non-random allocation or correct differences between cohorts. No confidence interval for the primary endpoint is reported in the registry record.
What do the cohort summaries support?
The adverse-event figures display participants at risk and participants affected for serious and other adverse events, along with deaths. These are descriptive safety summaries. In general, a count within one cohort describes the events recorded for that group; comparing counts across groups without considering denominators can be misleading. Even where denominators are displayed, different doses, schedules, follow-up, and participant characteristics may affect the numbers. The study’s non-randomized allocation means the cohort summaries are not like-for-like control comparisons.
The registry’s listed serious-event terms include influenza, meningitis aseptic, oesophagitis, pneumonia, sepsis, and urinary tract infection, each with a posted percentage. Those terms should be read as the registry presents them. The record does not explain the percentage denominator or provide a comparative analysis for these terms. General statistical interpretation cannot fill in an unstated denominator or establish treatment attribution.
How should planning illustrations be read?
Any sample-size section on the page is a planning illustration computed from the observed effect, not the trial’s own design. The stated assumptions are a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation; the effect to detect is the stated fraction of the observed effect. For time-to-event examples, the stated convention is total events; other examples are participants per arm. Read a row as a hypothetical planning scenario, such as planning for 75% of the observed effect, and report a target as participants per arm for 80% power where applicable.
These hypothetical calculations are not the number enrolled, an account of the original design, or observed power. The registry identifies this study as non-randomized and says its arms are not a like-for-like control comparison, so equal allocation between two arms is an illustration rather than a description of the trial. The record does not report the study’s own sample-size justification. It also does not report a statistical plan showing that the stated planning assumptions were used in the trial.
What is unavailable for independent assessment?
The record lists no analyses, and it does not provide a model specification, a prespecified hypothesis-testing strategy, an inferential method for the Phase 2 response objective, or a confidence-interval method. It also does not state whether any interim analyses occurred. These omissions limit assessment of precision and the handling of multiple outcomes. The methods above explain general concepts only; they should not be mistaken for procedures documented for this study.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists multiple objectives and outcomes. Phase 1b focused on dose finding and safety, while Phase 2 aimed to estimate overall response rate and evaluate safety and tolerability. The listed secondary outcomes include pharmacokinetic measures for oprozomib tablet and extended-release formulations and a Phase 2 clinical benefit response assessed by the investigator. The record lists 16 outcome measures, but does not report how testing or interpretation across outcomes was managed.
Multiplicity is the general statistical issue that arises when several outcomes, time points, or comparisons are examined: the chance of at least one apparently notable result can increase when many analyses are considered. A prespecified testing hierarchy or adjustment can address some multiplicity concerns, but neither an approach nor a hierarchy is reported in the registry record. No inferential analyses are listed, so there are no posted tests from which to assess multiplicity in practice.
Missing-data methods are also not reported in the registry record. The endpoint description identifies the safety population, but the record does not explain how participants with incomplete DLT assessment were handled, how missing response assessments were treated, or whether any imputation was used. It does not report endpoint-specific analysis populations or participant flow through each analysis. The registry enrollment of 65 should not be assumed to be the denominator for every outcome.
These absences matter because the interpretation of an estimate depends on who was included, how incomplete observations were handled, and which outcomes were emphasized. Without those details or posted efficacy results, the record does not allow readers to reconstruct the analysis or evaluate whether missingness or multiple analyses influenced conclusions.
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 |
|---|---|---|---|
| Cohort 180 mg 5/14 Schedule (Phase 1b) | 4 | 9 | 44.4% |
| Cohort 210 mg 5/14 Schedule (Phase 1b) | 2 | 7 | 28.6% |
| Cohort 150/180 mg 5/14 Schedule (Phase 1b) | 2 | 3 | 66.7% |
| Cohort 210 mg 2/7 Schedule (Phase 1b) | 2 | 4 | 50.0% |
| Cohort 240 mg 2/7 Schedule (Phase 1b) | 1 | 4 | 25.0% |
| Cohort 270 mg 2/7 Schedule (Phase 1b) | 1 | 6 | 16.7% |
| Cohort 300 mg 2/7 Schedule (Phase 1b) | 3 | 8 | 37.5% |
| Cohort 330 mg 2/7 Schedule (Phase 1b) | 0 | 6 | 0.0% |
| Phase 2 300 mg 2/7 Schedule | 9 | 18 | 50.0% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Cohort 180 mg 5/14 Schedule (Phase 1b) | 0 of 9 |
| Cohort 210 mg 5/14 Schedule (Phase 1b) | 1 of 7 |
| Cohort 150/180 mg 5/14 Schedule (Phase 1b) | 0 of 3 |
| Cohort 210 mg 2/7 Schedule (Phase 1b) | 0 of 4 |
| Cohort 240 mg 2/7 Schedule (Phase 1b) | 1 of 4 |
| Cohort 270 mg 2/7 Schedule (Phase 1b) | 0 of 6 |
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 |
|---|---|
| Cohort 180 mg 5/14 Schedule (Phase 1b) | 9 of 9 |
| Cohort 210 mg 5/14 Schedule (Phase 1b) | 7 of 7 |
| Cohort 150/180 mg 5/14 Schedule (Phase 1b) | 3 of 3 |
| Cohort 210 mg 2/7 Schedule (Phase 1b) | 4 of 4 |
| Cohort 240 mg 2/7 Schedule (Phase 1b) | 4 of 4 |
| Cohort 270 mg 2/7 Schedule (Phase 1b) | 6 of 6 |
Most frequent serious adverse event terms
| Event term | Organ system | Cohort 180 mg 5/14 Schedule (Phase 1b) | Cohort 210 mg 5/14 Schedule (Phase 1b) | Cohort 150/180 mg 5/14 Schedule (Phase 1b) | Cohort 210 mg 2/7 Schedule (Phase 1b) | Cohort 240 mg 2/7 Schedule (Phase 1b) | Cohort 270 mg 2/7 Schedule (Phase 1b) |
|---|---|---|---|---|---|---|---|
| Pneumonia | Infections and infestations | 1 of 9 | 1 of 7 | 0 of 3 | 1 of 4 | 0 of 4 | 0 of 6 |
| Sepsis | Infections and infestations | 0 of 9 | 1 of 7 | 0 of 3 | 0 of 4 | 1 of 4 | 0 of 6 |
| Acute kidney injury | Renal and urinary disorders | 1 of 9 | 0 of 7 | 0 of 3 | 1 of 4 | 0 of 4 | 0 of 6 |
| Thrombocytopenia | Blood and lymphatic system disorders | 0 of 9 | 1 of 7 | 0 of 3 | 0 of 4 | 0 of 4 | 0 of 6 |
| Gastrointestinal haemorrhage | Gastrointestinal disorders | 1 of 9 | 0 of 7 | 0 of 3 | 0 of 4 | 0 of 4 | 0 of 6 |
| Nausea | Gastrointestinal disorders | 1 of 9 | 0 of 7 | 0 of 3 | 0 of 4 | 0 of 4 | 0 of 6 |
| Oesophagitis | Gastrointestinal disorders | 0 of 9 | 0 of 7 | 0 of 3 | 1 of 4 | 0 of 4 | 0 of 6 |
| Non-cardiac chest pain | General disorders | 1 of 9 | 0 of 7 | 0 of 3 | 0 of 4 | 0 of 4 | 0 of 6 |
| Clostridium difficile infection | Infections and infestations | 1 of 9 | 0 of 7 | 0 of 3 | 0 of 4 | 0 of 4 | 0 of 6 |
| Influenza | Infections and infestations | 0 of 9 | 0 of 7 | 1 of 3 | 0 of 4 | 0 of 4 | 0 of 6 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Cohort 180 mg 5/14 Schedule (Phase 1b) | Cohort 210 mg 5/14 Schedule (Phase 1b) | Cohort 150/180 mg 5/14 Schedule (Phase 1b) | Cohort 210 mg 2/7 Schedule (Phase 1b) | Cohort 240 mg 2/7 Schedule (Phase 1b) | Cohort 270 mg 2/7 Schedule (Phase 1b) |
|---|---|---|---|---|---|---|---|
| Nausea | Gastrointestinal disorders | 8 of 9 | 7 of 7 | 3 of 3 | 4 of 4 | 3 of 4 | 5 of 6 |
| Diarrhoea | Gastrointestinal disorders | 8 of 9 | 6 of 7 | 2 of 3 | 4 of 4 | 3 of 4 | 6 of 6 |
| Vomiting | Gastrointestinal disorders | 6 of 9 | 5 of 7 | 3 of 3 | 4 of 4 | 3 of 4 | 2 of 6 |
| Fatigue | General disorders | 6 of 9 | 4 of 7 | 2 of 3 | 2 of 4 | 2 of 4 | 4 of 6 |
| Decreased appetite | Metabolism and nutrition disorders | 5 of 9 | 1 of 7 | 2 of 3 | 0 of 4 | 3 of 4 | 0 of 6 |
| Constipation | Gastrointestinal disorders | 2 of 9 | 2 of 7 | 1 of 3 | 2 of 4 | 1 of 4 | 1 of 6 |
| Hypertension | Vascular disorders | 3 of 9 | 1 of 7 | 1 of 3 | 1 of 4 | 1 of 4 | 2 of 6 |
| Anaemia | Blood and lymphatic system disorders | 3 of 9 | 2 of 7 | 1 of 3 | 1 of 4 | 1 of 4 | 0 of 6 |
| Thrombocytopenia | Blood and lymphatic system disorders | 1 of 9 | 2 of 7 | 1 of 3 | 1 of 4 | 1 of 4 | 2 of 6 |
| Dyspepsia | Gastrointestinal disorders | 3 of 9 | 1 of 7 | 0 of 3 | 0 of 4 | 2 of 4 | 1 of 6 |
Serious events with the highest arm-level rate: influenza (33.3%), meningitis aseptic (33.3%), oesophagitis (25.0%), pneumonia (25.0%), sepsis (25.0%).
The safety figures are organized by dose and schedule cohort. For each cohort, they show participants at risk and participants affected by serious adverse events, other adverse events, and deaths. Read each affected-participant count with its cohort’s at-risk count; do not treat the count as a rate across the whole study. The figures are descriptive summaries, and the cohorts were not randomized.
For instance, the Phase 2 300 mg 2/7 cohort lists 9 participants with serious adverse events among 18 at risk. The 180 mg 5/14 cohort lists 4 among 9. These examples illustrate how to read the posted columns, not a valid comparative safety contrast. Differences in cohort size, regimen, exposure, and follow-up may affect the counts, and the record does not provide an adjusted comparison.
Deaths are listed separately: one in the 210 mg 5/14 cohort and one in the 240 mg 2/7 cohort. The table does not establish whether a death was caused by treatment. The record does not report cause or treatment attribution for those deaths. Serious-event terms are also listed with percentages, but the percentage denominator is not reported in the registry record. Avoid treating these percentages as directly comparable risks without that information.
In general, safety counts describe what was recorded, not necessarily the causal effect of treatment. They also do not replace the primary DLT endpoint, which has its own criteria and assessment window.
12. What the Result Does, and Does Not, Mean
This record documents a non-randomized Phase 1b/2 investigation of oprozomib with dexamethasone, including several Phase 1b dose and schedule cohorts and a Phase 2 cohort at the recommended Phase 2 dose stated in the registry. It defines a DLT endpoint and posts cohort-level adverse-event summaries. Those details allow readers to understand the study’s structure and the kinds of safety information recorded.
The record does not report the primary DLT result or an overall response rate result. It therefore does not permit a conclusion about the observed frequency of DLTs or the size and precision of a Phase 2 response estimate. The stated Phase 2 objective is not evidence that a response result was achieved or reported. Likewise, a committee’s selection of a recommended Phase 2 dose is a recorded design decision, not a substitute for the supporting outcome data, which are not reported in the registry record.
The study cannot be read as a randomized comparison of oprozomib and dexamethasone against another treatment. Allocation was non-randomized, masking was none, and no control group is listed. Cohort differences in safety counts do not isolate the effect of dose or schedule. The record also does not report statistical adjustments, outcome precision estimates, or missing-data methods that might further inform interpretation.
In general, confidence intervals help show how precisely an estimate is determined by the data, while study design and analysis assumptions affect whether an estimate answers a causal question. No primary endpoint confidence interval or inferential result is posted. These general concepts cannot supply the missing estimates or resolve design limitations.
The sound reading is therefore bounded: the registry describes an early-phase dose-finding and response-estimation study and posts selected safety counts, but its available information is insufficient to quantify the primary endpoint, assess response precision, or compare regimens causally. This is a limitation of what is reported in the registry record, not a claim about unposted study documents or results.
13. Why This Trial Matters Statistically
This trial is statistically instructive because its objectives span two related but distinct tasks. Phase 1b investigated dose and schedule, with the aim of identifying a maximum tolerated dose and recommended Phase 2 dose. Phase 2 aimed to estimate overall response rate. Dose-finding outcomes and response outcomes answer different questions and require distinct definitions, assessment populations, and analysis plans. The registry presents these objectives, but does not post the primary DLT result or a response estimate.
The study also illustrates why design labels matter. Non-randomized allocation means cohorts should not be treated as interchangeable groups in a controlled comparison. Different doses and schedules were studied, and the registry identifies no randomized comparator. A visual difference between cohort summaries may be useful descriptively, but it does not by itself identify a treatment effect.
Another useful lesson is that endpoint definitions carry analytical meaning. DLT status depends on investigator attribution, severity criteria, and a defined treatment period. For step-up dosing, the registry places assessment in Cycle 2; for continuous dosing, it places assessment in Cycle 1. A simple event count without its definition and window would lose information needed to interpret it.
Finally, transparent reporting is essential for evaluating statistical precision and reproducibility. The record gives cohort safety counts and names the safety population for the primary outcome, but does not list analyses, DLT results, inferential methods, missing-data handling, or the study’s sample-size justification. Readers can describe what the registry reports while recognizing that objectives and endpoint definitions alone are not outcome findings.
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 central limitation is that the registry record does not report the primary endpoint result, despite defining participants with DLTs as the primary outcome. It also does not report the Phase 2 overall response rate result. The record lists no analyses, so readers cannot evaluate estimates, confidence intervals, tests, or the precision of the principal outcomes.
The study was non-randomized and open-label, with no listed control group. This limits causal interpretation of differences among dose and schedule cohorts. The registry explicitly notes that the arms are not a like-for-like control comparison. It does not report statistical adjustment that would address baseline differences or other confounding, nor does it supply enough information to assess cohort comparability.
The safety material is also limited in scope. Cohort-level counts are available, but the record does not report exposure-adjusted summaries, detailed event timing, or the relationship of each event to study treatment. The denominator underlying the percentages shown for listed serious-event terms is not reported in the registry record. Death counts are posted, but cause and treatment attribution are not.
Other relevant information is absent: the reason for termination, the study’s sample-size justification, interim analyses, statistical analysis plan, missing-data methods, and outcome-specific analysis populations are not reported in the registry record. The primary outcome identifies the safety population, but that does not establish the population used for every other outcome. These reporting gaps constrain interpretation; they should not be filled by assumptions about the protocol or unposted analyses.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Phase 1b/2, Multicenter, Open-label Study of Oprozomib and Dexamethasone in Patients With Relapsed and/or Refractory Multiple Myeloma — NCT01832727.
- Registry record last updated 2020-07-13; status last verified 2020-06.
- Results first posted 2020-07-13.
- 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
The registry describes a multicenter, open-label, non-randomized Phase 1b/2 study of oprozomib with dexamethasone in patients with relapsed and/or refractory multiple myeloma. Enrollment is listed as 65, status as terminated, and the study includes dose and schedule cohorts in Phase 1b and a 300 mg 2/7 cohort in Phase 2. The Phase 1b objectives were dose finding and safety; the Phase 2 objectives were response estimation and safety.
The primary outcome is participants with DLTs in the safety population, with assessment timing specified for continuous and step-up dosing. The registry posts cohort safety counts, but does not report the DLT result, the overall response rate result, or analyses. Allocation was non-randomized, so the cohorts do not form a like-for-like control comparison. The reason for termination and several important analysis details are not reported in the registry record.