Phase 2 Study of Carfilzomib in Relapsed Multiple Myeloma: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Phase 2 Study of Carfilzomib in Relapsed Multiple Myeloma (NCT00530816), a na phase 2 study. The primary outcome is Best Overall Response Rate (ORR) in the Response Evaluable Subset Population.

2. Clinical Question

3. Trial Design

This was a phase 2, open-label, single-group study of carfilzomib in patients with relapsed or refractory multiple myeloma. The record lists enrollment of 164, allocation as not applicable, and masking as none. The study status is completed. The recorded start was 2007-09 and primary completion was 2013-01.

The intervention description specifies intravenous carfilzomib on Days 1, 2, 8, 9, 15, and 16 of 28-day treatment cycles, with a maximum of 12 cycles. The initial dose was 20 mg/m². Starting with Amendment 3, participants who tolerated all doses in Cycle 1 could receive 27 mg/m² in subsequent cycles. The adverse-event record separately identifies Part 1 at 20 mg/m², Part 2 at 20 mg/m², and Part 2 at 20/27 mg/m². These are not randomized comparator groups; a causal comparison between them is not supported by the design.

The primary endpoint was best overall response rate in the Response Evaluable Subset Population. Disease response was assessed on Day 15 of Cycle 1, on Day 1 of Cycles 2 through 12, and at the end of the study, 30 days after the last dose. The recorded median treatment duration was 100 days for Part 1 and 170 days for Part 2 participants. The registry lists clinical benefit rate, duration of response, time to progression, progression-free survival, and overall survival as secondary outcomes.

The registry record does not report a randomized allocation, a masking procedure, or a concurrent control arm. The sample-size justification, detailed statistical analysis plan, and rationale for the enrollment target 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: Two groups of patients with MM were initially studied: bortezomib-treated (Part 1) and bortezomib-naïve (Part 2). Following Amendment 2, only bortezomib-naïve patients were enrolled. With Amendment 3, a new cohort of "stepped up" dosing was added to the trial. Study results were analyzed in 2 parts, based on previous bortezomib treatment.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: The Response Evaluable Subset population consists of all treated patients with measurable disease at Baseline as assessed by M-protein or by quantitative serum Ig for certain patients with IgA myeloma, and with a baseline and at least 1 post-baseline disease assessment. Patients whose disease was only measurable by SFLC were excluded.

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 patients enrolled on study and who received at least 1 dose of carfilzomib.

6. Primary Endpoint

The registry lists the primary outcome as Best Overall Response Rate (ORR) in the Response Evaluable Subset Population, measured over Disease response was assessed on Day 15 of Cycle 1, Day 1 of Cycles 2 through 12, and at End of Study, 30 days after last dose. Median duration of treatment was 100 days for Part 1 and 170 days for Part 2 participants..

Best overall response rate is the percentage of participants in the Response Evaluable Subset Population whose best recorded response met one of the specified response categories: stringent complete response, complete response, very good partial response, or partial response. Response was determined by an Independent Review Committee using International Uniform Response Criteria for Multiple Myeloma, with qualifying responses documented by consecutive assessments before new therapy began.

The categories distinguish levels of disease response using laboratory, imaging, and bone-marrow findings. For example, the definitions incorporate M-protein measurements and, for some categories, findings on soft tissue plasmacytomas or bone marrow. The registry record describes stringent complete response as meeting complete-response criteria with additional findings involving the free light chain ratio and clonal cells. It defines complete response using serum and urine immunofixation, plasmacytoma status, and bone-marrow plasma-cell findings. Very good partial response and partial response are defined through specified changes in serum or urine M-protein.

A response proportion is used to describe how often a prespecified response category was achieved in the population being assessed. It is not, by itself, a comparison with what would have happened without treatment. The estimate and its 95% confidence interval are not reported in the registry record, so the observed response frequency and its precision cannot be assessed from the posted results.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does the endpoint estimate?

Best overall response rate is a proportion: the numerator is the number of evaluable participants whose best response met one of the qualifying categories, and the denominator is the response-evaluable population. The registry record describes that population as treated participants with measurable disease at baseline and at least one post-baseline assessment, in addition to a baseline assessment. The actual numerator and denominator are not reported in the registry record, so the rate cannot be reconstructed.

As a general statistical explanation, a proportion summarizes the frequency of an event in a defined population. Its interpretation depends on clear rules for the event and for who enters the denominator. Here, response categories and assessment timing are described, but the posted record does not provide the numerical result or the analysis population size.

What does a confidence interval contribute?

The endpoint specifies a 95% confidence interval. As a general concept, a confidence interval represents uncertainty around an estimated quantity under the statistical method used. It helps distinguish a relatively precise estimate from one with substantial uncertainty. It does not remove design limitations, such as the lack of a concurrent comparator, and it is not a range that guarantees where an individual participant's outcome will fall. Because neither the estimate nor its interval is reported in the registry record, the uncertainty around the primary response rate cannot be evaluated.

How should the response assessments be understood?

The record states that assessments occurred at scheduled points during treatment and at the end of the study, 30 days after the last dose. The Independent Review Committee assessed responses according to International Uniform Response Criteria for Multiple Myeloma. A best-response endpoint uses the best qualifying response recorded over the assessment period, rather than treating each assessment as a separate participant-level outcome. The record says qualifying responses were documented by consecutive assessments made before new therapy began. The detailed handling of participants who stopped treatment early or lacked later assessments is not reported in the registry record.

The response categories are based on clinical and laboratory criteria. The definitions refer to serum and urine M-protein, immunofixation or electrophoresis findings, soft tissue plasmacytomas, bone-marrow plasma cells, and, for stringent complete response, free light chain and clonal-cell findings. Such criteria make the endpoint more operational than an unstructured judgment, but they do not show how consistently assessments were available or how missing assessments were handled.

What can a single-group study estimate?

In a single-group study, an observed response proportion can describe the participants who meet the analysis definition. Without a concurrent comparison group, the study cannot directly estimate the difference between carfilzomib and an alternative. General considerations such as natural disease course, participant selection, and changes in care over time can affect outcomes in an uncontrolled study. This is a design limitation, not a claim about what occurred in these participants.

Open-label describes the absence of masking in the registry record. The use of an Independent Review Committee is stated for response assessment, but further details of the committee process and its masking status are not reported in the registry record. It would therefore be inappropriate to assume additional safeguards or procedures.

What do the planning assumptions mean?

The registry record does not report the trial's sample-size justification or full statistical plan. The stated sample-size assumptions for planning illustrations are a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation, with the effect to detect expressed as a fraction of the observed effect. These are assumptions for a planning illustration, not evidence that the original single-group study used that design. Any planning sample sizes are illustrations and must not be interpreted as observed power or as a feature of the completed trial.

General statistical planning often examines how a proposed sample size relates to a target effect and uncertainty assumptions. Such planning does not change what was observed, and it cannot replace the study's missing endpoint estimate. Over-dispersion is a general concern when count outcomes vary more than a model assumes; it is not identified as an issue for this binary response endpoint in the registry record. The specific methods used for the primary analysis, including any adjustment or model, are not reported in the registry record.

10. Exact Estimates for Each Arm

No two-arm comparison is shown for this trial, but each arm's result can still be summarized with exact interval estimates computed from the posted counts. The Clopper-Pearson interval is exact and conservative; the Wilson interval is a common closer-to-nominal alternative; the Bayesian credible interval uses a uniform Beta(1, 1) prior. For small groups the three can differ noticeably.

R code and output

arm    <- c("Part 1: Carfilzomib 20 mg/m²", "Part 2: Carfilzomib 20 mg/m²", "Part 2: Carfilzomib 20/27 mg/m²")
n      <- c(31, 53, 66)
events <- c(5, 21, 35)
for (i in seq_along(n)) {
  ci <- binom.test(events[i], n[i])$conf.int          # Clopper-Pearson exact interval
  cr <- qbeta(c(0.025, 0.975), 1 + events[i], 1 + n[i] - events[i])   # Bayesian, uniform Beta(1,1) prior
  wi <- (function(x, n) { p <- x / n; z <- qnorm(0.975); d <- 1 + z^2 / n
    c((p + z^2 / (2 * n) - z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d, (p + z^2 / (2 * n) + z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d) })(events[i], n[i])
  cat(sprintf("ARM|%s|%d|%d|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f\n", arm[i], n[i], events[i], 100 * events[i] / n[i],
              100 * ci[1], 100 * ci[2], 100 * wi[1], 100 * wi[2], 100 * cr[1], 100 * cr[2]))
}

ARM  Part 1: Carfilzomib 20 mg/m²  31  5  16.1  5.5  33.7  7.1  32.6  7.2  32.8
ARM  Part 2: Carfilzomib 20 mg/m²  53  21  39.6  26.5  54.0  27.6  53.1  27.6  53.1
ARM  Part 2: Carfilzomib 20/27 mg/m²  66  35  53.0  40.3  65.4  41.2  64.6  41.1  64.6

11. Multiplicity, Missing Data and Analysis Populations

The registry lists best overall response rate as the primary outcome and lists clinical benefit rate, duration of response, time to progression, progression-free survival, and overall survival as secondary outcomes. The record also gives a count of seven outcome measures and zero analyses. It does not explain how those registry entries relate to a prespecified testing hierarchy, or whether inferential tests were performed for the outcomes.

When several outcomes are assessed, the chance of at least one apparently notable finding can increase if each is tested separately without an appropriate strategy. This is a general statistical issue. The registry record does not report a multiplicity adjustment, a hierarchy among secondary outcomes, or an analysis plan for controlling multiple testing. No conclusion about whether such procedures were used outside the registry record can be drawn.

The primary endpoint population was narrower than all enrolled participants: it required treatment, measurable disease at baseline, and baseline plus at least one post-baseline assessment. The number meeting those criteria is not reported in the registry record. The full endpoint-population description is incomplete in the record, and the handling of missing response assessments, withdrawals, or participants who began new therapy is not reported beyond the stated response documentation rule.

Missing outcome information can affect both the denominator and interpretation of a response proportion. As a general matter, exclusions or unavailable assessments may make an evaluable-population result differ from a result based on all enrolled participants. The registry record does not report imputation, sensitivity analyses, or another method for addressing missing primary endpoint data. It is therefore not possible to assess whether missingness was likely to alter the result.

12. 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: pneumonia (10.2%), pyrexia (5.7%), hypercalcaemia (5.7%), renal failure acute (4.3%), cardiac failure congestive (3.4%).

The serious adverse-event record gives group-specific numbers at risk and numbers affected. In Part 1 at 20 mg/m², 35 participants were at risk and 12 were recorded as affected. In Part 2 at 20 mg/m², 59 were at risk and 18 were affected. In Part 2 at 20/27 mg/m², 70 were at risk and 27 were affected. These are counts within the recorded groups, not comparative estimates against a control arm.

The listed serious-event terms include pneumonia at 10.2%, pyrexia at 5.7%, hypercalcaemia at 5.7%, acute renal failure at 4.3%, congestive cardiac failure at 3.4%, and tumour lysis syndrome at 3.4%. The denominator and method used for these term percentages are not reported in the registry record, so they should be read as the registry's listed percentages rather than recalculated or compared with an assumed population.

The other adverse-event fields record all participants in each group as affected, but the registry information does not clarify the event definition underlying that field. Deaths are listed as null for each group; deaths are therefore not reported in the registry record, rather than documented as absent. Serious-event counts do not establish that an event was caused by treatment, and the single-group design does not provide a controlled comparison of safety risks.

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

The record establishes that a phase 2, open-label, single-group study evaluated carfilzomib in relapsed or refractory multiple myeloma. It defines best overall response rate as the primary endpoint, describes the response categories and assessment schedule, and reports selected group-specific serious adverse-event counts. These design and measurement details help define what the study set out to assess.

The primary response estimate and its 95% confidence interval are not reported in the registry record. Without them, readers cannot determine the recorded response frequency or how precisely it was estimated. The enrollment count of 164 is not a substitute for the endpoint denominator, because the response-evaluable population had additional eligibility requirements. That denominator is not reported in the registry record.

The single-group design also limits what the study can establish. An uncontrolled response proportion, even if available, would describe outcomes in the study population rather than quantify a comparative effect against another treatment. The dose groups listed for adverse events are not randomized control groups and should not be interpreted as a direct dose comparison. No statement that treatment works or does not work follows from the available registry entries.

The named secondary outcomes indicate broader areas of interest, but their numerical results and analysis details are not reported in the registry record. Likewise, serious adverse-event counts and term percentages are descriptive safety information; they do not alone establish causation or comparative risk. The record does not report deaths in the group data, which should not be read as evidence that no deaths occurred.

Overall, the registry record makes the study question, intervention, endpoint definition, and some safety reporting visible, while leaving key outcome estimates and analysis details unavailable. Interpretation should remain bounded by those omissions and by the absence of a concurrent comparator.

14. Why This Trial Matters Statistically

This study illustrates why a clearly defined endpoint is only one part of statistical interpretation. The registry record specifies best overall response rate, names the qualifying response categories, identifies an Independent Review Committee, and describes when disease assessments took place. Those details explain what the intended response measure represents and which participants were eligible for its analysis.

At the same time, the primary numerical result and confidence interval are not reported in the registry record. Without the estimate, readers cannot assess the magnitude of the observed response proportion; without its interval, they cannot assess its statistical precision. The distinction between having a detailed endpoint definition and having a reportable endpoint result is important when interpreting trial records.

The single-group design is another central statistical feature. It can describe outcomes in the treated study population, but does not supply a randomized, concurrent comparison for estimating a treatment contrast. The listed dose groups do not change that point: the registry record identifies them in safety data, but does not establish them as like-for-like control groups.

The endpoint population also matters. It is defined through measurable baseline disease and available baseline and post-baseline assessments, rather than simply by enrollment. Since its size and the handling of missing assessments are not reported in the registry record, the relationship between the enrolled population and the analyzed population cannot be fully evaluated.

Finally, the study record names multiple secondary outcomes without providing their results or a multiplicity strategy. This highlights the difference between registering outcomes and reporting their estimates and analysis. Careful reading separates what the design and endpoint definitions establish from what requires numerical results that are not reported.

15. Limitations

• The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
• Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.

The primary endpoint estimate and 95% confidence interval are not reported in the registry record. The response-evaluable population size and the number of participants meeting its criteria are also not reported, so the endpoint cannot be reconstructed from the enrollment figure.

The single-group, open-label design has no concurrent control arm. The recorded dose groups should not be treated as randomized comparisons. The registry record does not report the sample-size justification, detailed statistical plan, or a basis for causal comparison. The planning assumptions listed for sample-size illustrations do not establish the design or analysis used in the completed study.

The record does not report how missing primary endpoint assessments were handled, whether sensitivity analyses were conducted, or how participants with incomplete follow-up were treated. Although response assessments were scheduled during treatment and at study end, the number of assessments available and the extent of missingness are not reported.

Several secondary outcomes are named, but their numerical results and analysis details are not reported in the registry record. A multiplicity strategy is not reported. For safety, the listed serious adverse-event counts are descriptive, the denominator for the listed event-term percentages is not reported, and deaths are not reported in the group data. These limitations restrict assessment of outcome precision, missing-data effects, multiplicity, and comparative safety.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Phase 2 Study of Carfilzomib in Relapsed Multiple Myeloma — NCT00530816.
• Registry record last updated 2017-05-02; status last verified 2017-04.
• Results first posted 2015-12-03.
• Data retrieved from ClinicalTrials.gov on 2026-11-09.
• Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.

19. Record Summary

NCT00530816 is a completed phase 2, open-label, single-group study of carfilzomib in patients with relapsed or refractory multiple myeloma. Enrollment was 164. The recorded start was 2007-09 and primary completion was 2013-01. The intervention description specifies intravenous treatment in 28-day cycles for a maximum of 12 cycles, with a possible dose escalation under the stated amendment.

The primary outcome was best overall response rate in a response-evaluable subset, assessed using defined response criteria and an Independent Review Committee. Clinical benefit rate, duration of response, time to progression, progression-free survival, and overall survival were listed as secondary outcomes. The primary estimate and 95% confidence interval are not reported in the registry record. The registry also lists serious adverse-event counts by dose group and selected serious-event terms. No concurrent control group is recorded.