Study of High Dose Carfilzomib in Multiple Myeloma Patients Who Have Progressed On Standard Dose Carfilzomib: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Study of High Dose Carfilzomib in Multiple Myeloma Patients Who Have Progressed On Standard Dose Carfilzomib (NCT01775553), a na phase 2 study. The primary outcome is Safety and Efficacy of High Dose Carfilzomib.

2. Clinical Question

The question is clinically focused on a specific treatment history: participants had already progressed on standard-dose carfilzomib. That makes the study different from a trial asking whether carfilzomib should be used initially or comparing it with another treatment. The registry also lists progression-free survival, overall response rate, duration of response to high-dose carfilzomib, and markers of ER stress as secondary outcomes. Numerical results for those outcomes are not reported in the registry record.

Because every participant received carfilzomib and there was no separate control group, the study can describe what happened in this cohort but cannot, by itself, establish how outcomes would have differed under another treatment or no treatment. The registry record does not report a specific efficacy estimate for the primary outcome beyond its description as a count of participants with adverse events. It also does not report criteria defining high dose, the standard-dose schedule, or the eligibility details beyond the disease and progression context.

3. Trial Design

This is a completed phase II, single-group study of carfilzomib in relapsed or refractory multiple myeloma after progression on standard-dose carfilzomib. Enrollment was 13 participants. The arm description states that all participants receive carfilzomib, and the record lists no allocation method or masking. In practical terms, this is an open-label, single-group design rather than a randomized comparison.

The study began in 2013-09, had primary completion in 2016-05, and is listed as completed. Its stated purpose includes assessing safety and activity with higher doses after standard dosing has become ineffective. The brief description also mentions laboratory investigation of resistance to carfilzomib and whether it can be overcome. The registry record does not report enough detail to characterize that laboratory work as a clinical endpoint or to explain its methods.

The primary outcome is titled “Safety and Efficacy of High Dose Carfilzomib,” but its description specifies the number of participants with adverse events, with a timeframe of up to 4 years. The record lists progression-free survival, overall response rate, duration of response, and markers of ER stress as secondary outcomes. Numerical results for these named secondary outcomes are not reported in the registry record.

With a single group, observed outcomes can be described in the enrolled cohort, but there is no concurrent control group to separate treatment-associated changes from the underlying course of disease, prior treatment history, or other influences. The absence of masking can also matter for outcomes that depend on clinical assessment or reporting. The registry record does not report a detailed protocol, recruitment flow, dose schedule, planned analysis methods, or the criteria used to assess response.

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

Reasons for not completing this period:

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 Safety and Efficacy of High Dose Carfilzomib, measured over up to 4 years.

The primary endpoint is described as the number of participants with adverse events during a timeframe of up to 4 years. It is a count-based measure: it asks how many participants experienced an event, rather than how many events occurred in total or how severe each event was. The registry labels the primary outcome “Safety and Efficacy,” but the operational description specifically names adverse events. It does not give a separate primary efficacy measure in that description.

Counting participants with adverse events is a straightforward way to summarize how many people in a treated group experienced an event during the stated observation period. This is useful for describing safety in the cohort, but a participant count alone does not show the number of recurrent events, their duration, their timing, or their relationship to treatment. Nor does it provide a comparison with an untreated or differently treated group.

The record does not report definitions for adverse events, severity grading, attribution rules, or how participants lost to follow-up were handled. It also does not report a time-to-event estimate for the primary measure. These details affect how the count should be interpreted, especially because follow-up is described as extending up to 4 years rather than as a single fixed observation time for every participant.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

General: Clinical trial methods determine what question an estimate answers, how uncertainty is represented, and which assumptions are needed for interpretation. For this study, the registry identifies a phase II single-group design and describes a participant count for adverse events. It does not report the detailed analysis plan, so the statistical methods used beyond the posted summaries are not reported in the registry record.

What does a single-group design tell us?

In a single-group study, outcomes are observed among participants receiving the study intervention. The resulting descriptions can characterize that cohort, but they do not directly estimate a contrast between interventions. A comparison with an external or historical group would require additional data and assumptions; no such comparison is described in the registry record. This is why the reported adverse-event counts should be read as observations in the carfilzomib group rather than as evidence of a difference from another treatment.

Random allocation, when used, helps make treatment groups comparable in expectation by assigning participants through chance. This study lists allocation as not applicable and describes a single group. Masking is listed as none. General: without masking, expectations or knowledge of treatment can influence some clinical assessments or reports, although the extent of any such influence in this study is not reported.

How should counts and percentages be read?

A participant count is a summary of how many people met an event definition during the specified observation period. It is not the same as an event count: one participant may experience repeated events, but the participant-level measure counts that person once if the endpoint is defined that way. The registry describes the primary measure as the number of participants with adverse events. Its separate serious and other adverse-event entries give participants at risk and participants affected. The record does not describe event recurrence, exposure time, or detailed event definitions.

Percentages provide a relative description of a count, but they need a denominator and consistent event definitions for comparison. The registry reports 7.7% for each of three serious adverse-event terms. It does not state in the posted results whether participants could appear in more than one term or provide term-specific counts alongside those percentages. No further arithmetic or aggregation is warranted from the listed entries alone.

General: event rates can also account for differing follow-up time, for example by relating events to person-time at risk. Such a rate can be informative when participants have different observation durations. The registry does not report person-time or an incidence-rate analysis, and the primary timeframe is stated as up to 4 years. Therefore, the available counts should not be treated as if every participant had an identical follow-up period.

What do uncertainty measures add?

General: a point estimate is a single summary derived from the observed data. A confidence interval communicates statistical uncertainty around an estimate under a particular method and assumptions. A hypothesis test evaluates data against a specified null hypothesis, but a p-value does not measure the probability that a treatment works or the size of a treatment effect. The registry record does not report confidence intervals, p-values, or a hypothesis test for the adverse-event counts.

General: small cohorts tend to yield imprecise estimates, particularly for outcomes that occur infrequently. A zero count in a cohort does not prove that the underlying risk is zero; it means no events of that category were recorded in the observed group under the study’s reporting and follow-up. The record reports 0 deaths, but does not give an uncertainty interval or detail the death ascertainment process.

Why does over-dispersion matter?

General: some count models assume that variation in event counts follows a specified distribution. Over-dispersion occurs when the observed variability is greater than the model expects. If it is ignored, standard errors may be too small and uncertainty may be understated. This concept may matter for repeated event counts or heterogeneous event processes, but the registry describes a participant count for the primary outcome, not a repeated-event model. It does not report a count-model analysis, dispersion estimate, or model diagnostics.

What can planning illustrations show?

General: sample-size calculations illustrate how many participants might be needed to detect a chosen effect under stated assumptions. Such illustrations depend on inputs such as the effect size, significance level, allocation, and analysis method. They are not observed trial results and do not establish the study’s actual power. The registry does not report a sample-size justification or the assumptions used to plan enrollment. Any planning illustration associated with these results is therefore not evidence of the original design rationale and should not be mistaken for observed power.

The record also does not report a prespecified statistical analysis plan, interim analyses, adjustment for multiple comparisons, missing-data methods, or analysis populations. These omissions prevent a full assessment of whether the posted summaries correspond to prespecified analyses or how all enrolled participants were handled in each outcome analysis.

10. Multiplicity, Missing Data and Analysis Populations

The registry record names multiple secondary outcomes: progression-free survival, overall response rate, duration of response to high-dose carfilzomib, and markers of ER stress. It also describes a primary outcome focused on adverse events. Numerical results for the named secondary outcomes are not reported in the registry record, and the record does not explain which outcomes were tested together or which were considered confirmatory.

General: multiplicity arises when several outcomes, time points, subgroups, or statistical tests are examined. With more opportunities to find an apparently notable result, the chance of at least one false-positive finding can increase. Statistical plans may address this by prioritizing outcomes or adjusting inference. The registry record does not report a multiplicity strategy, hierarchy of outcomes, or planned adjustment; none should be assumed.

Missing-data handling and analysis populations are also not reported in the registry record. It does not describe how participants who stopped treatment, missed assessments, or had incomplete follow-up were included in each outcome analysis. Nor does it specify whether analyses used all enrolled participants, only participants who received treatment, or another defined group. These details matter because outcome counts and time-to-event summaries can depend on who is observed and how incomplete observations are handled.

The number of outcome measures is listed as 5, while the record names four secondary outcomes. The registry does not clarify the remaining measure or provide analysis details for the named outcomes. No interim analyses are reported in the registry record. The absence of this information is not proof that no such procedures existed; it means they cannot be characterized from the registry entry.

11. 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: acute pulmonary embolism (7.7%), pneumonia (7.7%), leg pain (7.7%).

The registry lists 13 participants at risk for serious adverse events and 3 affected. It reports 13 at risk and 13 affected for other adverse events, and 0 deaths. These entries describe participants in the carfilzomib group; there is no separate control group for comparison.

The serious adverse-event terms listed are Acute Pulmonary Embolism, Pneumonia, and Leg pain, each reported as 7.7%. The record does not give a breakdown of the number of participants for each term or explain whether the same participant may be represented under more than one term. The percentages should be retained as reported and not added together.

General: serious adverse events are a distinct reporting category from the broader set of adverse events, and seriousness should not be confused with severity. The registry record does not provide its event definitions, grading system, treatment attribution, timing, or details about recurrent events. A count of participants affected also does not show how long an event lasted or whether it resolved. With follow-up described as up to 4 years, the record does not establish that every participant was observed for the same length of time.

These figures are descriptive safety information from a small, uncontrolled cohort. They cannot establish that the intervention caused or prevented an event, and they do not quantify a comparative safety difference. The listed counts also do not provide uncertainty intervals.

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

The posted results describe a completed phase II study of high-dose carfilzomib in 13 participants with relapsed or refractory multiple myeloma who had progressed on standard-dose carfilzomib. The safety entries report 3 participants affected by serious adverse events, 13 affected by other adverse events, and 0 deaths. Three serious adverse-event terms are listed, each with a reported percentage of 7.7%.

These results do not provide numerical estimates for progression-free survival, overall response rate, or duration of response, despite those outcomes being listed as secondary measures. Nor does the primary outcome description provide a separate efficacy estimate: it identifies adverse-event counts as the measure. The record therefore does not permit a quantitative assessment of the study’s efficacy outcomes from the posted entries.

The results also do not establish how the observed outcomes compare with another treatment. All participants received carfilzomib, and the registry lists no control group. Without a comparator, changes cannot be separated from the course of disease, prior treatment, or other influences. The single-group design can describe observations in this cohort, but it cannot establish a treatment contrast.

General: absence of a reported event or estimate is different from evidence that the event or outcome did not occur. The record reports 0 deaths, but it does not provide uncertainty around that count. Likewise, efficacy results that are not reported cannot be interpreted as either favorable or unfavorable. The registry entry does not report the detailed analysis plan, missing-data handling, or outcome definitions needed for a fuller appraisal.

The appropriate reading is therefore narrow: these are descriptive safety counts for a small cohort in a specific treatment-history setting. They do not establish causal effects, comparative benefit or harm, or the precision of efficacy estimates. The registry record does not supply the detail required to draw broader statistical conclusions.

13. Why This Trial Matters Statistically

This trial addresses a focused statistical problem: describing outcomes after progression on standard-dose carfilzomib when all participants receive higher-dose carfilzomib. The treatment history defines a specialized cohort, so the observed counts apply to that cohort and should not automatically be generalized to people with different disease or treatment histories.

The single-group design illustrates the distinction between describing outcomes and estimating a treatment effect. A cohort can contribute useful descriptive information about events recorded during treatment, but without a concurrent comparator it cannot quantify what would have happened under another strategy. This limitation is particularly important when the question uses terms such as safety and efficacy together: the registry’s primary measure is an adverse-event count, while the named efficacy outcomes lack numerical results in the registry record.

The record also illustrates why outcome definitions and analysis details matter. A participant-level count, an event-level count, and a time-adjusted rate answer different questions. The registry reports participants affected but does not describe recurrence, exposure time, or detailed event definitions. Similarly, follow-up of up to 4 years does not show whether observation time was the same for each participant.

Finally, small-cohort estimates need to be read with attention to uncertainty. The posted entries contain counts and selected percentages, but no confidence intervals or formal testing results. Those omissions limit assessment of precision and statistical compatibility with other possible event rates. The analysis is most useful as a bounded description of the registry’s reported cohort and as a reminder that design, endpoint definition, follow-up, and reporting completeness all shape what a trial can answer.

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 main design limitation is the absence of a comparator. All participants received carfilzomib, so the study cannot estimate a relative effect against another treatment or distinguish treatment effects from other influences. The lack of masking may also affect outcomes that involve clinical judgment or participant reporting; the registry does not describe how those outcomes were assessed.

Enrollment was 13 participants, which limits the amount of information available for describing event patterns, particularly for uncommon outcomes or subgroup comparisons. The record provides no confidence intervals for the reported counts, so their statistical precision cannot be evaluated from the posted results. The 0 deaths entry is a cohort observation, not evidence that the underlying risk is zero.

The primary outcome title refers to safety and efficacy, but its description specifies the number of participants with adverse events. That leaves the primary efficacy question unclear. Although progression-free survival, overall response rate, duration of response, and markers of ER stress are listed as secondary outcomes, their numerical results are not reported in the registry record.

Important operational details are also absent: the specific dose schedule, adverse-event definitions and grading, response-assessment criteria, follow-up completeness, missing-data methods, and analysis populations are not reported in the registry record. The record does not report a sample-size justification, a prespecified statistical analysis plan, or a multiplicity strategy. It also does not explain whether the serious adverse-event terms can overlap across participants. These gaps constrain interpretation of both the counts and the study’s intended efficacy assessment.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Study of High Dose Carfilzomib in Multiple Myeloma Patients Who Have Progressed On Standard Dose Carfilzomib — NCT01775553.
• Registry record last updated 2017-06-21; status last verified 2017-05.
• Results first posted 2017-06-21.
• 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

NCT01775553 is a completed phase II, single-group study of high-dose carfilzomib in relapsed or refractory multiple myeloma after progression on standard-dose carfilzomib. The registry reports enrollment of 13 participants, no masking, and no separate comparator group. The study began in 2013-09 and had primary completion in 2016-05.

The primary outcome is described as the number of participants with adverse events over up to 4 years. The registry reports 3 participants affected by serious adverse events, 13 affected by other adverse events, and 0 deaths. Acute Pulmonary Embolism, Pneumonia, and Leg pain are each listed at 7.7% among the serious adverse-event terms.

Progression-free survival, overall response rate, duration of response, and markers of ER stress are listed as secondary outcomes, but numerical results for them are not reported in the registry record. The registry record does not report a detailed statistical analysis plan, sample-size justification, missing-data methods, or analysis populations.