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 Carfilzomib and Lenalidomide With Dexamethasone Combination in Newly Diagnosed, Previously Untreated Multiple Myeloma (NCT01029054), a na phase 1, phase 2 study. The primary outcome is The Maximum Tolerated Dose (MTD) of Carfilzomib.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT01029054 |
| Phase | Phase 1, Phase 2 |
| Condition | Multiple Myeloma |
| Allocation | Not applicable (single group) |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 53 |
| Arms in the primary outcome | n/a |
| Lead sponsor | University of Michigan Rogel Cancer Center |
| Results posted | Yes |
2. Clinical Question
Population
Participants had newly diagnosed, previously untreated multiple myeloma requiring systemic chemotherapy. The registry record lists 53 enrolled participants; 35 entered the Phase I portion. The record does not give further eligibility details or describe the characteristics of the enrolled participants.
Intervention
The intervention was carfilzomib in combination with lenalidomide and dexamethasone. In Phase I, the combination was given through escalating carfilzomib dosage levels to determine the maximum tolerated dose. In Phase II, carfilzomib was to be given at the dose established in Phase I.
Comparator
There was no separate comparator group. The study is registered as single-group, with no allocation and no masking. Its results therefore describe outcomes in participants receiving the combination; they do not directly compare the combination with another treatment or with a control group.
Primary question
The primary outcome was the maximum tolerated dose of carfilzomib when combined with lenalidomide and dexamethasone, with a stated timeframe of 6 months. The registry record does not report the dose value or an analysis result. It also lists the percentage of patients alive without progression as a secondary outcome, without a reported result.
Statistically, this is a dose-finding question rather than a randomized treatment-comparison question. The Phase I portion was intended to identify a carfilzomib dose level for the combination; the Phase II portion was planned to use the dose established in Phase I. The record describes this sequence but does not give the dose levels, the criteria used to select a maximum tolerated dose, or the number of participants who entered Phase II.
The clinical question is framed for people with newly diagnosed multiple myeloma who had not previously received treatment and required systemic chemotherapy. The record does not report detailed eligibility criteria, how participants were selected, or participant characteristics that would show how closely the enrolled group represents other people with the condition. Those details matter when considering the relevance of findings beyond the trial participants.
Because there is no comparator, the study cannot estimate a between-group treatment effect from its design. Descriptive outcomes can characterize what was recorded during treatment, but they do not by themselves establish how the combination compares with an alternative. The registry record does not report an estimate for the primary dose outcome, so even a descriptive result for the main question cannot be assessed from this record.
3. Trial Design
This was a multicenter, open-label, single-arm Phase 1b/2 study, registered as Phase 1 and Phase 2. The sponsor was University of Michigan Rogel Cancer Center. The record lists the study as completed, with a start date of 2009-09 and primary completion in 2011-12. These dates describe the recorded study timeline; they do not establish when individual participants began or finished treatment.
In the Phase I portion, carfilzomib was combined with lenalidomide and dexamethasone across escalating carfilzomib dose levels to determine the maximum tolerated dose. The Phase II portion was planned to use the maximum tolerated dose established in Phase I. The primary outcome is the maximum tolerated dose of carfilzomib, with a timeframe of 6 months. The registry record says 35 of the 53 enrolled participants entered Phase I, but does not report how many entered Phase II or how participants were assigned between the portions.
Open-label means that masking was not used. Single-arm and no allocation indicate that the design did not assign participants to separate treatment groups. The intervention is the three-drug combination; the registry lists it twice in its intervention entries, while the arm description identifies one combination arm. There is no like-for-like control arm described in the record.
The registry lists three outcome measures and no analyses. The secondary outcome named in the record is the percentage of patients alive without progression. The record does not provide results for that outcome, or for the other listed measures. It also does not report the protocol, a statistical analysis plan, a sample-size justification, interim analyses, or details of how dose escalation and dose selection were carried out.
Without a comparator, the study design is suited to describing the dose-finding experience and outcomes recorded in the treated group, not estimating a randomized contrast. Its two phases have different stated roles: Phase I was to establish the dose, and Phase II was to use that dose. The record does not provide enough detail to reconstruct how those aims were implemented or whether the planned sequence was completed as described.
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.
Phase I
| Stage | Dose Escalation Cohort 1 | Dose Escalation Cohort 2 | Dose Escalation Cohort 3 |
|---|---|---|---|
| STARTED | 4 | 13 | 18 |
| COMPLETED | 4 | 13 | 18 |
| NOT COMPLETED | 0 | 0 | 0 |
Phase II
| Stage | Dose Escalation Cohort 1 | Dose Escalation Cohort 2 | Dose Escalation Cohort 3 |
|---|---|---|---|
| STARTED | 0 | 0 | 18 |
| COMPLETED | 0 | 0 | 18 |
| NOT COMPLETED | 0 | 0 | 0 |
Analysis population for the primary outcome, as defined in the registry: Of the 53 patients enrolled, 35 were entered into the Phase I portion of the study.
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.
| Characteristic | Unit | Carfilzomib, Lenalidomide w/Dexamethasone |
|---|---|---|
| Participants analysed | 53 | |
| Age, Continuous | years | 59 (35 to 81) |
| Gender: Female | Participants | 14 |
| Gender: Male | Participants | 39 |
6. Primary Endpoint
The registry lists the primary outcome as The Maximum Tolerated Dose (MTD) of Carfilzomib, measured over 6 Months.
| Element | Registry entry |
|---|---|
| Result type | Number |
| Measure of spread | not applicable |
| Unit | mg/m^2 |
| Endpoint classification | not reduced to a single comparison |
The primary outcome is the maximum tolerated dose of carfilzomib when combined with lenalidomide and dexamethasone. It is expressed as a dose in mg/m^2, and the timeframe stated in the registry record is 6 months. The record describes the outcome as a number, but does not report the dose value, a measure of uncertainty, or a result from an analysis.
In general, a maximum tolerated dose is used in dose-finding research to identify a dose level judged tolerable under the study’s rules for a particular treatment combination. Identifying a dose in combination matters because tolerability of a drug may depend on the other drugs given with it. The registry describes escalating carfilzomib doses with lenalidomide and dexamethasone in Phase I, followed by planned use of the established dose in Phase II. The particular rules used to judge tolerability are not reported in the registry record.
This endpoint answers a different kind of question from an outcome such as survival or disease progression. It focuses on dose selection and tolerability in the study context; it is not, by itself, a comparison of treatment benefit against another option. The record lists the percentage of patients alive without progression as a secondary outcome, but does not report its result. Without the primary dose result, the registry record does not show what maximum tolerated dose was identified.
The population description states that 35 of the 53 enrolled participants entered Phase I. It does not say whether all of those participants contributed to the primary outcome or how missing or unevaluable dose-finding observations were handled. Those analysis details, along with the endpoint result, are not reported in the registry record.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record identifies the study as a single-arm investigation of carfilzomib with lenalidomide and dexamethasone in newly diagnosed, previously untreated multiple myeloma. Its primary question was dose finding: determine the maximum tolerated dose of carfilzomib in the combination. Although the record describes the Phase I escalation and planned Phase II dose, it does not report the selected dose. There is therefore no primary outcome estimate in the record to interpret for magnitude or precision.
The registry lists 53 participants as enrolled and says 35 entered Phase I. Those numbers describe enrollment and the stated Phase I population, not the number included in every outcome analysis. The number entering Phase II and the analysis population for each outcome are not reported in the registry record. The record also lists three outcome measures but no analyses. A measure being registered does not establish that a result was observed, analyzed, or reported.
The secondary outcome is the percentage of patients alive without progression. No value, timeframe, uncertainty estimate, or analysis result for that outcome appears in the record. Consequently, the registry record does not support a quantitative interpretation of this secondary endpoint. It also does not report a comparison with another treatment, and the design has no separate comparator group. Any outcomes in the treated group would be descriptive rather than a randomized estimate of a difference between treatments.
The safety entries report 23 participants affected by serious events among 53 at risk, and 53 affected by other events among 53 at risk. The registry also lists serious-event terms and percentages, including pneumonia at 7.5% and urinary tract infection at 5.7%. These entries describe recorded events in this study group. They do not provide a comparative safety estimate, and the record does not give event-level timing, duration, severity beyond the serious classification, or participant-level detail for each listed term.
In general, a confidence interval describes the uncertainty around an estimated quantity under the assumptions of the analysis. No confidence interval is reported for the primary or secondary outcomes in this record, so their statistical precision cannot be evaluated. Similarly, no p-values or inferential analyses are reported. This is not evidence that an effect is absent; it means that the record does not provide the analyses needed to assess an estimate statistically.
Any planning illustrations based on an observed effect should not be mistaken for observed trial findings or for the original design justification. The record does not state that such planning assumptions were used to design the trial. In particular, a hypothetical two-arm calculation does not turn this single-arm study into a controlled comparison. The sponsor’s own analysis would take precedence if a discrepancy were identified, but the record reports no analysis results to compare.
9. Statistical Methods Explained
Statistical interpretation starts with the question the design can answer. This study is registered as single-group, without allocation and without masking. It therefore has no randomized control group. In general, random allocation helps make treatment groups comparable in expectation, while a concurrent control group supports direct estimation of a between-group contrast. Those design features are absent. Outcomes in the combination group can be described, but a difference attributable to treatment cannot be estimated by comparing randomized groups because there is no second group.
What does a dose-finding outcome represent?
The primary endpoint is the maximum tolerated dose of carfilzomib with lenalidomide and dexamethasone. The record describes escalating carfilzomib doses in Phase I, then planned use of the established dose in Phase II. In general, dose-finding studies use prespecified rules to decide whether observed tolerability supports increasing, maintaining, or selecting a dose. The precise rules, dose levels, and criteria for declaring a maximum tolerated dose are not reported in the registry record. Without those details, a reader cannot reproduce the dose decision or assess how the endpoint was operationalized.
The stated timeframe for the primary endpoint is 6 months. That timeframe does not describe the length of follow-up for every participant or establish when endpoint assessments occurred. The record gives no more detailed assessment schedule. It also does not report the primary endpoint value or a measure of its uncertainty. Thus the dose-finding aim is clear at a broad level, but its reported quantitative result cannot be evaluated from this record.
What can the enrollment figures tell a reader?
The registry lists 53 enrolled participants and states that 35 entered Phase I. Enrollment is not automatically the same as the analysis population. Some participants might not contribute to a particular outcome for reasons such as not receiving the relevant assessment, but whether that occurred in this study is not reported in the registry record. The number who entered Phase II, the number assessed for each outcome, and the approach to missing observations are also not reported. These distinctions matter because the population analyzed can affect how an outcome is interpreted.
In general, an analysis population should be defined in relation to the question and the participants’ course through the trial. A dose-finding analysis may use participants with dose-limiting safety assessments, while a disease-outcome analysis may require a defined follow-up period. Those are general examples, not descriptions of this study’s analysis choices. The registry record does not specify the populations used for any outcome, and it lists no analyses.
How should uncertainty be considered?
A point estimate gives a single value for an outcome; a confidence interval gives a range of values compatible with the data and analysis assumptions at a stated confidence level. In general, wider intervals indicate less precision, while narrower intervals indicate greater precision. The record does not report an estimate or confidence interval for the maximum tolerated dose or the secondary outcome, so statistical precision cannot be assessed. The absence of an interval should not be read as evidence of precision or certainty.
The record does not report p-values, hypothesis tests, or a statistical analysis plan. It is therefore not possible to determine what inferential procedures were planned or performed. The registry’s listing of three outcome measures does not indicate which analyses were conducted, whether analyses were adjusted, or how outcome timing was handled. Those details are not reported in the registry record.
What do the planning illustrations mean?
In general, a sample-size calculation translates assumptions about an effect, variability, significance level, and power into a planning target. The record describes planning illustrations using a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. The illustrations are based on fractions of an observed effect. For time-to-event outcomes, the stated convention is to express the total number of events; for other outcomes, it is participants per arm.
These assumptions describe hypothetical planning calculations, not the trial’s own design. The trial is single-arm, and the illustrations assume two arms with equal allocation. They therefore do not describe the enrollment structure of this study or establish that the trial had the stated power. The record gives no sample-size justification for the actual trial and does not report an observed-effect estimate that could be used to judge the illustrations. Planning values are not observed power, and they do not show whether an outcome was statistically significant.
In general, over-dispersion occurs when observed variability exceeds what a statistical model assumes. If present and not accounted for, it can make uncertainty estimates too small. The registry record does not identify a statistical model for the trial outcomes or report evidence about over-dispersion; this general concept cannot be used to infer what happened in this study.
Because the record contains no outcome analyses, recalculated estimates are not available to compare with sponsor analyses. If a discrepancy between a sponsor analysis and a simple recalculation were present, the sponsor’s own analysis would take precedence. No such comparison can be made from the registry record. Interpretation is therefore limited to the registered design, stated outcome definitions, enrollment information, and recorded safety entries.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists three outcome measures, identifies the maximum tolerated dose of carfilzomib as the primary outcome, and names the percentage of patients alive without progression as a secondary outcome. It does not report results for these outcomes or describe analyses. The identity and analysis of the remaining listed measure are not detailed in the record. A statistical analysis plan, including any hierarchy or adjustment for multiple outcomes, is not reported in the registry record.
In general, when several outcomes are tested, the chance of a false-positive finding can increase if each is evaluated separately without an appropriate strategy. Some studies address this by designating a primary outcome, setting an order for testing, or adjusting inference. The registry identifies a primary outcome, but that alone does not reveal whether multiplicity procedures were planned or used. No such procedure should be assumed.
The record does not describe missing-data definitions, the extent of missingness, imputation, censoring rules, or sensitivity analyses. It does not specify an analysis population for the primary endpoint, the secondary outcome, or the safety summaries. The enrollment information says that 35 of 53 participants entered Phase I, but does not say which participants contributed to each analysis or how the remaining participants were treated in analyses.
In general, missingness can affect interpretation when participants with unavailable measurements differ from those with observed measurements. The direction and size of any such effect depend on the reasons for missing data and the analysis approach. Since those details are not reported in the registry record, the impact of missing observations cannot be assessed. No conclusion about the handling of missing data or multiplicity can be drawn from the listed outcomes alone.
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 |
|---|---|---|---|
| Carfilzomib, Lenalidomide w/Dexamethasone | 23 | 53 | 43.4% |
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 |
|---|---|
| Carfilzomib, Lenalidomide w/Dexamethasone | 53 of 53 |
Most frequent serious adverse event terms
| Event term | Organ system | Carfilzomib, Lenalidomide w/Dexamethasone |
|---|---|---|
| Pneumonia | Infections and infestations | 4 of 53 |
| Urinary Tract Infection | Infections and infestations | 3 of 53 |
| Acute Renal Failure | Renal and urinary disorders | 2 of 53 |
| Dyspnea | Respiratory, thoracic and mediastinal disorders | 2 of 53 |
| Hyperglycemia | Metabolism and nutrition disorders | 2 of 53 |
| Anemia | Blood and lymphatic system disorders | 2 of 53 |
| Acute Mental Status Change | Nervous system disorders | 1 of 53 |
| Appendicitis | Infections and infestations | 1 of 53 |
| Atrial Fibrillation | Cardiac disorders | 1 of 53 |
| Clostridium Difficile | Infections and infestations | 1 of 53 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Carfilzomib, Lenalidomide w/Dexamethasone |
|---|---|---|
| Hyperglycemia | Metabolism and nutrition disorders | 38 of 53 |
| Thrombocytopenia | Blood and lymphatic system disorders | 36 of 53 |
| Anemia | Blood and lymphatic system disorders | 32 of 53 |
| Edema | General disorders | 25 of 53 |
| Hypophosphatemia | Metabolism and nutrition disorders | 24 of 53 |
| Fatigue | General disorders | 20 of 53 |
| Muscle Cramping | Musculoskeletal and connective tissue disorders | 17 of 53 |
| Neutropenia | Blood and lymphatic system disorders | 16 of 53 |
| Rash | Skin and subcutaneous tissue disorders | 15 of 53 |
| Elevated Liver Function Test | Investigations | 15 of 53 |
Serious events with the highest arm-level rate: pneumonia (7.5%), urinary tract infection (5.7%), acute renal failure (3.8%), dyspnea (3.8%), hyperglycemia (3.8%).
The safety entries list 53 participants at risk for serious events, with 23 recorded as affected, and 53 at risk for other events, with 53 recorded as affected. These are counts in the registry’s safety summary. They do not describe how many events each participant experienced, when events occurred, or how long they lasted. The record does not report deaths in the corresponding field.
The listed serious-event terms include pneumonia at 7.5%, urinary tract infection at 5.7%, and acute renal failure, dyspnea, hyperglycemia, and anemia at 3.8% each. These percentages are reported as registry entries; they should be read as event summaries for this study group, not as comparisons against another treatment. The record does not state whether participants could contribute to more than one listed term or provide the event counts underlying each percentage.
In general, serious adverse events are a category of events defined by regulatory criteria; “serious” is not interchangeable with “severe.” The record supplies serious-event summaries but does not provide enough detail to characterize severity for each event or assess timing and attribution. Since the study has no comparator group, these figures do not quantify a relative safety difference. The registry record also does not report a complete narrative of safety monitoring or the analysis population used for each entry.
12. What the Result Does, and Does Not, Mean
The record describes a Phase 1b/2, open-label, single-arm study of carfilzomib with lenalidomide and dexamethasone for newly diagnosed, previously untreated multiple myeloma. It states that Phase I used escalating carfilzomib doses to determine the maximum tolerated dose and that Phase II was planned to use the dose established in Phase I. It also records 53 enrolled participants, of whom 35 entered Phase I.
Those design details do not establish the primary result. The registry record does not report the maximum tolerated dose, an uncertainty estimate, or an analysis of the primary endpoint. It does not report a result for the secondary outcome, the percentage of patients alive without progression. The listed safety entries describe affected participants and serious-event terms, but do not provide a controlled comparison or the detail needed to assess event timing, duration, or attribution.
In general, a single-arm study can describe observations among participants receiving a treatment combination, but cannot separate treatment effects from other explanations using a randomized comparison. Changes in outcomes over time, if reported, could reflect multiple influences; the registry record does not provide such outcome estimates. There is no control group in this design with which to estimate what would have happened under another treatment.
The record also does not establish why the enrollment target was chosen, how missing observations were handled, or whether planned analyses were completed. The statistical planning illustrations described for a hypothetical two-arm calculation are not evidence that this study was designed or powered as a two-arm trial. They are planning illustrations, not observed power or findings.
Accordingly, the registry record supports a description of the study’s intended dose-finding sequence, enrollment, and recorded safety summaries. It does not support a quantitative conclusion about the selected dose, the secondary disease outcome, or comparative benefit and harm. This distinction is important: an unreported result is not a result showing no effect, and a single-arm record is not a controlled estimate of treatment differences.
13. Why This Trial Matters Statistically
This trial is statistically notable because its primary question is about dose selection rather than a direct comparison of treatments. The Phase I portion was intended to explore escalating carfilzomib doses with lenalidomide and dexamethasone, while the Phase II portion was planned to use the dose established in Phase I. Recognizing that structure helps distinguish what the study set out to do from what a randomized comparative trial would address.
The registry record also illustrates why endpoint labels and outcome results must be read separately. It identifies the maximum tolerated dose as the primary outcome and gives a timeframe of 6 months, but does not report the dose value or an analysis. It names the percentage of patients alive without progression as a secondary outcome but does not report that result. A registered outcome defines an intended measurement; it is not itself evidence that a numerical finding is available.
The single-arm design makes the limits of interpretation especially important. Descriptive safety summaries can show what was recorded among participants, but there is no control group for a like-for-like comparison. This prevents estimating a randomized difference in safety or disease outcomes. The design information therefore sets a boundary on claims that can be supported, independent of whether the treatment combination was of interest to researchers.
Finally, the record lists enrollment and a Phase I population but does not report analysis populations, missing-data methods, or the statistical plan. These are not minor technicalities: they determine which observations contribute to estimates and how uncertainty is assessed. Since the record also lists no analyses, the appropriate statistical reading is cautious and descriptive. The study’s aims and structure are documented more clearly than its quantitative outcomes.
14. Limitations
- The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
- Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.
The principal limitation for interpreting this registry record is the absence of reported outcome analyses. Although the maximum tolerated dose is identified as the primary endpoint, its value is not reported. The record also does not report results for the secondary outcome or the other listed outcome measure. Without those results, the intended dose-finding question cannot be answered quantitatively from the registry record.
The single-arm design has no comparator group. It can describe outcomes recorded among participants receiving the combination but cannot provide a randomized contrast with another treatment. Open-label conduct also means masking was not used; the record does not describe outcome-assessment procedures or safeguards against potential measurement influences.
The population details are limited. The record identifies 53 enrolled participants and states that 35 entered Phase I, but does not report the number in Phase II or the analysis population for each outcome. Detailed eligibility criteria and participant characteristics are not reported in the registry record. That limits assessment of who was represented and how broadly the findings might apply.
The record does not report the dose levels, the criteria for declaring the maximum tolerated dose, the statistical analysis plan, sample-size justification, interim analyses, or missing-data methods. It also does not provide confidence intervals or other measures of precision. These omissions prevent assessment of how dose selection was implemented, how uncertainty was handled, and whether the planned analyses match the reported outcomes.
The safety summaries give affected-participant counts and selected serious-event percentages, but do not supply event-level details or a comparison group. The record does not report deaths in the safety field. These limits mean that the safety entries can be described, but should not be interpreted as a comprehensive comparative assessment.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Carfilzomib and Lenalidomide With Dexamethasone Combination in Newly Diagnosed, Previously Untreated Multiple Myeloma — NCT01029054.
- Registry record last updated 2017-01-30; status last verified 2016-12.
- Results first posted 2014-11-20.
- 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
NCT01029054 is a completed, multicenter, open-label, single-arm Phase 1b/2 study of carfilzomib, lenalidomide and dexamethasone in newly diagnosed, previously untreated multiple myeloma. The sponsor was University of Michigan Rogel Cancer Center. The registry lists 53 participants as enrolled and states that 35 entered Phase I.
The primary outcome was the maximum tolerated dose of carfilzomib in the combination, with a stated timeframe of 6 months. Phase I was intended to use escalating carfilzomib doses; Phase II was planned to use the dose established in Phase I. The registry record does not report the selected dose or an analysis result. It lists the percentage of patients alive without progression as a secondary outcome, without a reported result.
The safety summary records 23 affected participants among 53 at risk for serious events and 53 among 53 for other events. No analyses are listed. The record does not report a comparator, statistical analysis plan, missing-data methods, or analysis populations beyond the stated Phase I enrollment information.