A Multicenter, Open-label, Phase 1b Study of Carfilzomib, Cyclophosphamide and Dexamethasone in Newly Diagnosed Multiple Myeloma Subjects: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Multicenter, Open-label, Phase 1b Study of Carfilzomib, Cyclophosphamide and Dexamethasone in Newly Diagnosed Multiple Myeloma Subjects (NCT01980589), a na phase 1 study. The primary outcome is Number of Participants With Dose-limiting Toxicities (DLTs).

2. Clinical Question

3. Trial Design

This was a completed, multicenter, open-label, Phase 1b study sponsored by Amgen. The registry lists the start as 2013-08 and primary completion as 2016-03. It enrolled 22 participants and used a single-group model. Allocation is marked NA, and masking is recorded as none. There was no separate randomized control arm, so the dose groups should be understood as groups receiving different carfilzomib doses, not as randomized treatment-versus-control comparisons.

The intervention combined carfilzomib, cyclophosphamide, and dexamethasone. The treatment description allows up to eight 28-day cycles, with treatment ending earlier for progressive disease, unacceptable toxicity, withdrawal of consent, or death. The primary objective focused on the maximum tolerated dose of twice-weekly carfilzomib in this combination. The primary endpoint timeframe was the first 28-day treatment cycle.

The registry lists three carfilzomib dose groups: 36 mg/m², 45 mg/m², and 56 mg/m². Their recorded group sizes are 3, 3, and 16 participants, respectively. The record does not report the procedure or timing used to assign participants to these dose groups, nor does it describe any dose-escalation rules. Those details should not be inferred from the dose levels or group sizes alone.

The primary measure was the number of participants with DLTs, rather than a continuous response measure. The secondary outcomes listed were overall response rate, time to response, and number of participants with adverse events. The record identifies four outcome measures in total, but it reports no analyses. Its completed status does not itself establish that numerical findings for each outcome are available 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: Eligible participants were enrolled into sequential dose-escalation cohorts consisting of 3 to 6 participants to establish the maximum tolerated dose (MTD) of carfilzomib when given in combination with cyclophosphamide and dexamethasone. Additional participants were enrolled in an expansion cohort at the established MTD to collect safety data.

Overall Study

Analysis population for the primary outcome, as defined in the registry: The Safety population is defined as all enrolled participants who received any study treatment.

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 Number of Participants With Dose-limiting Toxicities (DLTs), measured over First cycle treatment over 28-days.

The primary endpoint counts participants who experienced a dose-limiting toxicity during the first treatment cycle, which lasted 28 days. The registry describes DLTs as carfilzomib-related adverse events meeting specified toxicity criteria. These include nonhematologic toxicity of grade 3 or higher, certain serious kidney injury, specified severe or persistent blood-count abnormalities, febrile neutropenia, and thrombocytopenia associated with bleeding. The detailed criteria include duration and laboratory thresholds; the actual number of participants meeting them is not reported in the registry record.

The endpoint is used to support dose selection in an early-phase study. The stated maximum tolerated dose is the highest carfilzomib dose at which fewer than 33% of participants experience a treatment-related DLT during the first cycle. This definition makes the event count at each dose important: the endpoint is not simply an overall toxicity total across all dose groups. The registry record does not report the dose-specific DLT counts or identify a resulting maximum tolerated dose, so the stated definition cannot be applied to determine the study’s dose-selection result.

A participant count gives the number of people meeting the endpoint, not necessarily the number of separate events. More than one qualifying event in a participant would not, by itself, mean more than one participant had the endpoint. The registry describes the primary result as a number of participants, but that numerical result is not reported in the record. No estimate of uncertainty around the primary result is reported either.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The design determines what statistical interpretation is available. This study is recorded as single group, with no masking and no allocation to a control group. Its dose groups can be described separately, but they are not randomized treatment arms for estimating a comparative treatment effect. The record does not report the process by which participants entered the dose groups. Without a reported assignment procedure, differences among groups cannot be cleanly separated from differences in who entered each group or when they entered it.

What does a participant count represent?

The primary outcome is a count of participants with at least one qualifying DLT during the first 28-day cycle. A participant-level count answers how many participants met the endpoint; it is not automatically a count of all toxicity episodes. The registry defines the safety population as all enrolled participants who received any study treatment. It does not report a separate safety-population total. The enrollment figure is 22, while the listed dose-group counts are 3, 3, and 16.

The endpoint’s definition combines clinical event categories with severity, laboratory, and duration criteria. Such a composite definition can support a practical dose-selection rule, but its interpretation depends on applying the criteria consistently. The registry record describes the criteria but does not report adjudication procedures, participant-level event details, or the number satisfying each criterion. It also does not report whether any participants were excluded from the primary endpoint analysis.

How is the maximum tolerated dose defined?

The registry states that the maximum tolerated dose is the highest carfilzomib dose at which fewer than 33% of participants experience a treatment-related DLT during the first cycle. This is a decision rule, not a reported study finding. Applying it requires the number of evaluable participants and the number with qualifying DLTs at each dose. Those outcome counts are not reported in the registry record. The record also does not describe additional dose-selection rules, such as how uncertainty or incomplete first-cycle follow-up would be handled.

In general, proportions based on very small groups can be imprecise: an individual participant’s outcome represents a substantial part of the group’s observed experience. That matters when reading the groups with 3 participants each. It does not mean an unreported estimate can be reconstructed, and no uncertainty interval for these dose groups is reported in the registry record. The group with 16 participants is larger than the other listed groups, but group size alone does not remove the design limitations or establish a comparative effect.

What would comparative testing require?

In general, a comparative test evaluates a defined contrast between groups under stated assumptions. A confidence interval expresses uncertainty around an estimate of that contrast or another parameter. The registry record reports no comparative analysis, estimate, confidence interval, or p-value. Since this is a single-group study without a control arm, a comparison between the listed doses would also require care: the groups are not described as randomized, and the record supplies no adjustment strategy.

General statistical methods can also be affected by over-dispersion, which occurs when variation is greater than a model assumes. A model that ignores that extra variation can understate uncertainty. This is a general consideration for count outcomes, not a reported finding or method in this study. The registry does not report the statistical model used for outcome analyses; it lists zero analyses, so no specific model or variance assumption can be attributed to the study.

How should planning calculations be read?

Planning illustrations are not observed power and do not add evidence about the trial’s outcomes. The stated planning assumptions use a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation; the effect to detect is a stated fraction of the observed effect. For time-to-event calculations, the stated method counts total events using Schoenfeld’s approach; other planning outputs are expressed as participants per arm. These are generic calculation assumptions, not a description of the study’s single-group design. The registry record does not report a trial-specific sample-size justification or provide numerical planning results within the outcome information summarized in this record.

For a single-group dose-finding study, planning values based on equal allocation between two arms should not be mistaken for the actual enrollment design. Nor should a sample-size illustration be read as evidence that an observed effect was detected with a particular probability. The registry does not report an observed-effect estimate for the primary endpoint, so no such planning illustration can establish the precision of the DLT findings.

What can the secondary outcomes contribute?

Overall response rate is a proportion-type outcome, while time to response concerns the timing of an event. In general, time-to-event methods account for differing follow-up and participants whose event time is not observed during follow-up. The registry record names time to response but does not report its analysis method, follow-up handling, or results. It also names adverse events as a secondary outcome without reporting a full outcome analysis. The serious adverse event counts are descriptive safety information and do not substitute for an analysis of the listed efficacy outcomes or the primary DLT endpoint.

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("Carfilzomib 36 mg/m²", "Carfilzomib 45 mg/m²", "Carfilzomib 56 mg/m²")
n      <- c(3, 3, 16)
events <- c(0, 0, 0)
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  Carfilzomib 36 mg/m²  3  0  0.0  0.0  70.8  0.0  56.1  0.6  60.2
ARM  Carfilzomib 45 mg/m²  3  0  0.0  0.0  70.8  0.0  56.1  0.6  60.2
ARM  Carfilzomib 56 mg/m²  16  0  0.0  0.0  20.6  0.0  19.4  0.1  19.5

11. Multiplicity, Missing Data and Analysis Populations

The registry lists one primary outcome and three secondary outcomes: number of participants with DLTs, overall response rate, time to response, and number of participants with adverse events. It does not report a multiplicity plan, such as whether or how the interpretation of multiple secondary outcomes would be adjusted. Without such a plan, the record does not establish a formal family of hypotheses or a controlled overall error rate. No p-values are reported, so there is no multiplicity adjustment to interpret from the posted results.

The record reports zero analyses. It does not report missing-data methods, imputation, censoring rules for time to response, or how participants with incomplete first-cycle assessment were handled. These details are not reported in the registry record and should not be inferred from the endpoint definition or treatment schedule. The record also does not report the number of participants with missing outcome data.

The safety population is defined as all enrolled participants who received any study treatment. The record does not give its total size separately or identify the population used for each secondary outcome. It therefore does not establish whether all enrolled participants were included in each outcome analysis. The enrollment figure of 22 is not by itself evidence that 22 participants contributed data to every endpoint.

These omissions matter because the analysis population and missing-data approach affect how outcome counts and estimates should be interpreted. For example, a count based only on participants with an observed assessment could differ in meaning from one based on all treated participants under an explicit missing-data rule. The registry record does not indicate which approach was used for the primary endpoint or secondary outcomes.

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: coronary artery occlusion (33.3%), acute kidney injury (12.5%), pyrexia (6.2%), sepsis (6.2%), urinary tract infection (6.2%).

The serious adverse event listing reports participant counts by carfilzomib dose group. At 36 mg/m², 0 of 3 participants are listed as affected; at 45 mg/m², 1 of 3; and at 56 mg/m², 5 of 16. These are descriptive group figures. Because the study has no randomized control arm and the groups differ in size, they do not establish a causal dose comparison.

The listing also reports participants with other adverse events: 3 of 3 at 36 mg/m², 3 of 3 at 45 mg/m², and 16 of 16 at 56 mg/m². Serious adverse events and other adverse events are separate reporting categories. Neither set of counts should be treated as the primary DLT outcome: the DLT endpoint has its own carfilzomib-related criteria and is limited to the first 28-day cycle.

The registry lists serious event terms with percentages: coronary artery occlusion, 33.3%; acute kidney injury, 12.5%; pyrexia, 6.2%; sepsis, 6.2%; urinary tract infection, 6.2%; and dehydration, 6.2%. The denominator and dose-group distribution for these percentages are not reported in the registry record. The death figures are not reported in the record. These safety summaries describe reported events; they do not by themselves establish whether an event was caused by treatment or how its timing related to treatment.

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

The record establishes the study’s objective, treatment combination, dose groups, primary DLT definition, and selected safety counts. It also documents that the study is completed. It does not report the primary endpoint counts or state which carfilzomib dose, if any, met the maximum tolerated dose criterion. Therefore, the registry entry alone does not establish the study’s dose-finding result.

The serious adverse event counts and adverse-event participant counts describe safety reporting by dose group. They are not a randomized comparison and are not the same as the primary endpoint. The record’s serious event terms and percentages add descriptive information, but their denominator and dose-group distribution are not stated. They cannot be used to reconstruct missing DLT results.

The registry lists overall response rate and time to response as secondary outcomes, but does not report their results. It therefore does not support a numerical interpretation of response frequency or timing. The lack of reported estimates, confidence intervals, and analyses also means that the precision of any response findings cannot be assessed from this record.

In general, a single-group study can describe what happened among its participants under the recorded treatment, but without a control group it cannot establish how those outcomes compare with another treatment or with no treatment. Open-label status also means masking is not part of this design. These design features do not invalidate descriptive reporting, but they constrain comparative interpretations. No conclusion about treatment benefit or lack of benefit follows from the information reported in the registry.

Finally, the enrollment of 22 should not be confused with the number contributing to every endpoint. The registry defines the safety population but does not report its separate total, outcome-specific analysis populations, or missing-data handling. Those limitations leave important details about the completeness and precision of outcome reporting unresolved.

14. Why This Trial Matters Statistically

This trial is statistically notable for the distinction between a dose-selection question and a treatment-effect comparison. Its stated primary objective was to identify a maximum tolerated dose using a first-cycle DLT rule. That is different from asking whether the combination improves an outcome relative to a control treatment. The single-group design and the absence of randomization mean that the listed dose groups do not serve as randomized controls.

The primary endpoint is a participant count tied to clinical toxicity criteria, while the dose decision uses a threshold involving the proportion of participants with treatment-related DLTs. The registry record reports the rule but not the dose-specific event counts needed to apply it. This illustrates a general statistical point: a clearly defined endpoint and decision rule are not substitutes for a reported estimate and its uncertainty.

Group size is also central to interpretation. The dose groups contain 3, 3, and 16 participants. In general, observations from very small groups yield limited precision, so a descriptive result from one or two participants can substantially shape the apparent pattern. The registry does not report uncertainty intervals for the DLT outcome, and the absence of those results prevents a full assessment of how stable the dose-specific findings might be.

Safety reporting and efficacy reporting have different roles. The serious adverse event counts and listed terms provide descriptive safety information, while response rate and time to response are named as secondary outcomes without numerical results. Reading these as separate evidence streams helps avoid treating all adverse event counts as DLTs or interpreting safety descriptions as comparative efficacy evidence.

The record therefore demonstrates why statistical interpretation depends on more than an endpoint name or a completed-study status. Design, population definition, event counts, analysis methods, and uncertainty all matter. Here, several of those numerical and methodological details are not reported in the registry record, limiting what can be concluded from the posted information.

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 limitation for interpreting this specific study record is the absence of the primary DLT result. Although the registry defines the first-cycle endpoint and the maximum tolerated dose rule, it does not report the number of participants with DLTs by dose or the resulting dose decision. The study’s principal question therefore cannot be answered from the posted registry information alone.

The groups were not randomized control arms, and the registry does not describe the dose assignment procedure. Their sizes are unequal: 3 participants at 36 mg/m², 3 at 45 mg/m², and 16 at 56 mg/m². Such groups support descriptive reporting but do not establish a causal dose-response relationship. The registry also does not report comparative estimates or adjustment methods.

The record identifies a safety population but does not give its total separately from enrollment, nor does it specify the analysis population for each outcome. Missing-data handling, endpoint-specific denominators, and the treatment of incomplete first-cycle follow-up are not reported. The listed serious adverse event percentages lack a stated denominator and dose-group breakdown in the registry record. Death figures are not reported.

Results for the named secondary outcomes—overall response rate and time to response—are not reported in the registry record. No statistical analyses are listed, and there are no reported confidence intervals or p-values. Multiplicity procedures, sample-size justification, and details of the statistical plan are also not reported. These gaps prevent assessment of the precision, completeness, and inferential status of the outcomes.

The treatment description allows up to eight 28-day cycles, but the primary toxicity endpoint is restricted to the first cycle. The registry entry does not give additional follow-up information that would allow a broader assessment of later outcomes. These limitations concern the information available in the record and do not establish what may have been reported elsewhere.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: A Multicenter, Open-label, Phase 1b Study of Carfilzomib, Cyclophosphamide and Dexamethasone in Newly Diagnosed Multiple Myeloma Subjects — NCT01980589.
• Registry record last updated 2017-05-30; status last verified 2017-04.
• Results first posted 2016-10-31.
• 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

NCT01980589 is a completed, multicenter, open-label, Phase 1b, single-group study sponsored by Amgen in newly diagnosed multiple myeloma. The registry reports an enrollment of 22 and treatment with carfilzomib, cyclophosphamide, and dexamethasone for up to eight 28-day cycles, subject to the stated stopping conditions.

The primary outcome was the number of participants with DLTs during the first 28-day cycle. The registry’s maximum tolerated dose definition depends on the proportion with treatment-related DLTs at a dose. Three carfilzomib dose groups are listed: 36 mg/m², 45 mg/m², and 56 mg/m². The primary DLT counts and resulting dose decision are not reported in the registry record.

Secondary outcomes were overall response rate, time to response, and adverse events. The record includes serious adverse event counts by dose group and a list of serious event terms, but reports zero analyses. Outcome estimates, uncertainty intervals, missing-data methods, multiplicity procedures, and a trial-specific sample-size justification are not reported in the registry record.