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, Pegylated Liposomal Doxorubicin Hydrochloride, and Dexamethasone in Treating Patients With Relapsed or Refractory Multiple Myeloma (NCT01246063), a non-randomized phase 1, phase 2 study. The primary outcome is Maximum Tolerated Dose (MTD) of Carfilzomib and Pegylated Liposomal Doxorubicin (Phase I - Part 1)..
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT01246063 |
| Phase | Phase 1, Phase 2 |
| Condition | Multiple Myeloma |
| Allocation | Non-Randomized |
| Design model | Sequential |
| Masking | None (open label) |
| Enrollment | 40 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Washington University School of Medicine |
| Results posted | Yes |
2. Clinical Question
Population
The study concerned patients with relapsed or refractory multiple myeloma. The registry reports enrollment of 40 participants across the trial, but does not give the number evaluable for every outcome. For the primary endpoint, it specifies that only participants enrolled in Phase I - Part 1 were evaluable.
Intervention
The treatment program combined carfilzomib and pegylated liposomal doxorubicin (PLD). Dexamethasone was added in Phase I - Part 2 and Phase 2. The Phase I - Part 1 dose levels used carfilzomib schedules described as 20/27, 20/36, 20/45, and 20/56 mg/m^2, with PLD at 30 mg/m^2. Later cohorts are described with carfilzomib at 56 mg/m^2, PLD at 30 mg/m^2, and dexamethasone 20 mg.
Comparator
There was no randomized control group. The trial was non-randomized and sequential, so dose levels and later cohorts are not like-for-like treatment comparisons. Differences between these groups could reflect their place in the study, patient composition, treatment schedules, or other factors that are not described in the registry record.
Primary question
The primary endpoint asked what maximum tolerated dose of carfilzomib with PLD could be established in Phase I - Part 1. The registry defines the maximum tolerated dose by dose-limiting toxicities (DLTs) during Cycle 1: if a DLT was observed, the next lower dose level would be the MTD. The registry states that the MTD was not reached and characterizes the posted data as the recommended dosage for further studies, but the specific primary endpoint value is not reported in the registry record.
3. Trial Design
This was a Phase I/II study conducted at Washington University School of Medicine. It is marked completed, with a reported enrollment of 40. The registry lists a start date of 2012-05-14 and a primary completion date of 2017-12-28. The study addressed multiple myeloma, specifically relapsed or refractory disease.
The design was non-randomized, unmasked, and sequential. In Phase I - Part 1, participants were assigned across carfilzomib dose levels with PLD. The listed carfilzomib schedules were 20/27, 20/36, 20/45, and 20/56 mg/m^2, while PLD was described at 30 mg/m^2. The primary dose-finding endpoint applied only to participants in this part.
Phase I - Part 2 added dexamethasone to carfilzomib and PLD. The Phase 2 cohort also used this three-drug combination. The later cohorts are described with carfilzomib at 56 mg/m^2, PLD at 30 mg/m^2, and dexamethasone 20 mg, with treatment schedules changing by cycle as recorded. The study aim was to determine the MTD, then establish the safety and efficacy of the combination. Those aims do not make the sequential groups randomized comparisons: the registry explicitly notes that the arms are not like-for-like controls.
The registry lists median overall survival, progression-free survival time in Phase 2 only, and median duration of overall response as secondary outcomes. Numerical results for those outcomes are not reported in the registry record. It lists 8 outcome measures and no posted analysis records. Details of the protocol for assigning participants among sequential cohorts, beyond the dose descriptions and MTD definition, 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.
Overall Study
| Stage | Phase I - Part 1 Dose Level 0 (Carfilzomib 20/27 mg/m^2) | Phase I - Part 1 Dose Level 1 (Carfilzomib 20/36 mg/m^2) | Phase I - Part 1 Dose Level 2 (Carfilzomib 20/45 mg/m^2) | Phase I - Part 1 Dose Level 3 (Carfilzomib 20/56 mg/^2) | Phase I -Part 2 Cohort 0 (Carfilzomib 56 mg/m^2+Dexamethasone) | Phase 2 (Carfilzomib 56 mg/m^2+ Dexamethasone) |
|---|---|---|---|---|---|---|
| STARTED | 3 | 4 | 4 | 5 | 7 | 17 |
| COMPLETED | 3 | 4 | 4 | 5 | 7 | 17 |
| NOT COMPLETED | 0 | 0 | 0 | 0 | 0 | 0 |
Analysis population for the primary outcome, as defined in the registry: Participants enrolled in the Phase I - Part 1 portion of this study were the only evaluable participants for this outcome measure.
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.
Only the first 6 of 7 groups are shown.
| Characteristic | Unit | Phase I - Part 1 Dose Level 0 (Carfilzomib 20/27 mg/m^2) | Phase I - Part 1 Dose Level 1 (Carfilzomib 20/36 mg/m^2) | Phase I - Part 1 Dose Level 2 (Carfilzomib 20/45 mg/m^2) | Phase I - Part 1 Dose Level 3 (Carfilzomib 20/56 mg/^2) | Phase I-Part 2 Cohort 0 (Carfilzomib 56 mg/m^2+Dexamethasone) | Phase 2 (Carfilzomib 56 mg/m^2+ Dexamethasone) |
|---|---|---|---|---|---|---|---|
| Participants analysed | 3 | 4 | 4 | 5 | 7 | 17 | |
| Age, Continuous | years | 65 (62 to 66) | 66.5 (53 to 71) | 72 (55 to 79) | 57 (54 to 69) | 63 (27 to 67) | 65 (46 to 70) |
| Sex: Female, Male: Female | Participants | 2 | 2 | 2 | 5 | 5 | 7 |
| Sex: Female, Male: Male | Participants | 1 | 2 | 2 | 0 | 2 | 10 |
| Ethnicity (NIH/OMB): Hispanic or Latino | Participants | 0 | 0 | 0 | 0 | 0 | 0 |
| Ethnicity (NIH/OMB): Not Hispanic or Latino | Participants | 1 | 4 | 4 | 4 | 7 | 17 |
| Ethnicity (NIH/OMB): Unknown or Not Reported | Participants | 2 | 0 | 0 | 1 | 0 | 0 |
| Race (NIH/OMB): American Indian or Alaska Native | Participants | 0 | 0 | 0 | 0 | 0 | 0 |
| Race (NIH/OMB): Asian | Participants | 0 | 0 | 0 | 0 | 0 | 0 |
| Race (NIH/OMB): Native Hawaiian or Other Pacific Islander | Participants | 0 | 0 | 0 | 0 | 0 | 0 |
| Race (NIH/OMB): Black or African American | Participants | 1 | 1 | 1 | 1 | 0 | 5 |
| Race (NIH/OMB): White | Participants | 2 | 3 | 3 | 4 | 7 | 11 |
| Race (NIH/OMB): More than one race | Participants | 0 | 0 | 0 | 0 | 0 | 0 |
| Race (NIH/OMB): Unknown or Not Reported | Participants | 0 | 0 | 0 | 0 | 0 | 1 |
| Region of Enrollment: United States | Participants | 3 | 4 | 4 | 5 | 7 | 17 |
6. Primary Endpoint
The registry lists the primary outcome as Maximum Tolerated Dose (MTD) of Carfilzomib and Pegylated Liposomal Doxorubicin (Phase I - Part 1)., measured over 28 days (completion of first cycle of all Phase I - Part 1 patients).
| 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 endpoint was the maximum tolerated dose of carfilzomib and pegylated liposomal doxorubicin in Phase I - Part 1. Its unit is mg/m^2, and its stated timeframe is 28 days, corresponding to completion of the first cycle for all Phase I - Part 1 participants. The registry says that only participants in this portion were evaluable for this endpoint.
In general, a dose-finding endpoint such as MTD is used in early-phase research to identify a dose level for further study while monitoring for dose-limiting toxicity. The registry's definition ties the decision to DLTs observed during Cycle 1: if a DLT was observed, the next lower dose level would be the MTD. The record does not provide further details about DLT criteria or how individual toxicities were adjudicated.
The registry states that the MTD was not reached. It also says that the posted data represent the recommended dosage for further studies. However, a numeric primary endpoint result is not reported in the registry record. The dose schedules for the later study parts are described, but those descriptions should not be substituted for a separately reported MTD value.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The main statistical message is that the registry describes a sequential dose-finding study, not a randomized treatment comparison. Its primary endpoint was the MTD of carfilzomib with PLD in Phase I - Part 1, assessed over 28 days. The registry states that the MTD was not reached. It does not report the numeric endpoint value, the count of DLTs at each dose level, or the uncertainty around the dose-finding result. Consequently, the registry record alone does not show how precisely the MTD was estimated or which specific evidence supported the statement that it was not reached.
The Phase I - Part 1 dose levels are recorded as carfilzomib schedules of 20/27, 20/36, 20/45, and 20/56 mg/m^2, with PLD at 30 mg/m^2. Later parts incorporated dexamethasone, and the Phase 2 schedule is described with carfilzomib at 56 mg/m^2, PLD at 30 mg/m^2, and dexamethasone 20 mg. These are sequential study groups, not randomized arms. Their outcomes cannot be interpreted as an unbiased comparison of dose levels or of adding dexamethasone: allocation was not randomized, and the registry does not report a control group or an adjusted comparative analysis.
The posted safety information reports, for each cohort, the number at risk and number affected for serious and other adverse events, along with deaths. These are descriptive counts. They do not establish that the regimen caused every event, and differences among cohorts should not be read as treatment effects. The cohort sizes are limited, and the record does not provide confidence intervals for these safety counts. The serious-event term percentages also lack term-specific denominators in the registry record, which limits interpretation of their precision and comparability.
The registry lists secondary outcomes for overall survival, progression-free survival in Phase 2, and duration of overall response, but numerical results are not reported in the registry record. Thus the record supports an account of the study question, schedules, and selected safety counts, but it does not provide enough outcome detail to quantify efficacy or to make precise comparative claims. The study's stated purpose of assessing efficacy and safety is not itself evidence of the magnitude or certainty of an outcome.
Any sample-size illustrations associated with an observed effect are planning calculations under stated assumptions, not observed power. The registry record does not provide the trial's own sample-size justification, and such illustrations should not be confused with the observed enrollment or with a randomized comparison. No recalculated treatment contrast is appropriate from the information recorded because the design is non-randomized and the posted primary result is not numeric.
9. Statistical Methods Explained
The study combines dose finding in Phase I with further evaluation in Phase 2. The registry identifies its allocation as non-randomized, its masking as none, and its model as sequential. These features determine what the results can support. The study can describe events observed in its cohorts, but its structure does not create a randomized comparison between dose groups or between treatment combinations.
What does sequential allocation mean?
In general, a sequential design evaluates groups or dose levels in an ordered study process rather than assigning participants randomly among concurrent treatment arms. For dose finding, this can help investigators examine tolerability as dose levels change. However, comparisons across sequential cohorts may be influenced by cohort composition, study timing, changes in treatment schedules, or other differences. The registry does not report enough detail to assess these possibilities or the exact rules used to assign participants to each cohort.
The record lists Phase I - Part 1 carfilzomib schedules of 20/27, 20/36, 20/45, and 20/56 mg/m^2, with PLD at 30 mg/m^2. It then describes a Phase I - Part 2 cohort and a Phase 2 cohort using carfilzomib at 56 mg/m^2, PLD at 30 mg/m^2, and dexamethasone 20 mg. These schedules are descriptive treatment information. They do not, by themselves, show which schedule had a better benefit-risk balance or establish a causal difference between cohorts.
How should the MTD endpoint be understood?
The primary endpoint concerns a dose level, expressed in mg/m^2, and its timeframe is 28 days, defined as completion of the first cycle for Phase I - Part 1 participants. In general, an MTD endpoint is used in early-phase studies to guide selection of a dose for further research by considering dose-limiting toxicities. The registry defines the MTD as the maximum tolerated dose level tested unless DLTs are observed during Cycle 1; if DLTs are observed, it says the next lower dose level would be the MTD.
The record states that the MTD was not reached and that the posted data are the recommended dosage for further studies. It does not report the numeric endpoint value, the number of DLTs by dose level, or the criteria used to define a DLT. Without those details, readers cannot independently reconstruct the dose-finding decision or evaluate its precision. The dose schedule recorded for Phase 2 should not be treated as a substitute for missing primary endpoint reporting.
What do the safety counts measure?
For each listed cohort, the registry gives numbers at risk and affected for serious adverse events and other adverse events, and it reports deaths. These are counts within the cohort rather than a randomized contrast. In general, counts describe how many participants were recorded with events, while rates or comparative estimates require a clearly defined denominator, follow-up period, and event definition. Even when a denominator is listed for a cohort, the registry does not provide adjusted comparisons or uncertainty estimates for these safety figures.
The serious adverse event terms are accompanied by percentages, including Sepsis at 75.0%, Pain at 33.3%, Acute rental failure at 33.3%, Pneumonitis at 28.6%, Aortic valve disease at 25.0%, and Diverticulitis at 25.0%. Their term-specific denominators are not reported in the registry record. These percentages therefore should be read as posted descriptive figures, not as comparative risks or precise estimates for a broader population. The term “Acute rental failure” is reproduced as recorded.
What can a confidence interval and a planning calculation tell us?
In general, a confidence interval expresses the statistical uncertainty around an estimate under a specified analysis. It can help distinguish a relatively precise estimate from one compatible with a wide range of values. The registry record does not report confidence intervals for the primary endpoint or the posted adverse-event counts, so their precision cannot be assessed from these results.
The sample-size assumptions describe planning illustrations based on an observed effect, with a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. For time-to-event outcomes, the stated illustrations concern total events using the Schoenfeld method; for other outcomes they concern participants per arm. These are planning assumptions, not the trial's own design justification, and not observed power. The record does not report a trial-specific sample-size justification. In addition, the study is non-randomized, so an illustration framed around two equal arms should not be mistaken for an analysis of randomized treatment groups.
The registry lists 8 outcome measures and no posted analysis records. No statistical analysis plan, handling of multiplicity, missing-data method, interim analysis plan, or adjusted model is reported in the registry record. Those methods should not be inferred from the design label or from the stated study aims.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists 8 outcome measures, including the primary MTD endpoint and secondary outcomes for median overall survival, progression-free survival time in Phase 2 only, and median duration of overall response. It reports no posted analysis records. A complete statistical analysis plan, including any prespecified hierarchy among outcomes or adjustment for multiple testing, is not reported in the registry record.
In general, examining multiple outcomes can increase the chance of findings that appear notable by chance, particularly when many tests are interpreted together. Methods such as a prespecified testing hierarchy or multiplicity adjustment can address that issue, but the registry does not state whether either was planned or used. No multiplicity procedure should be assumed.
Missing-data handling, censoring rules for time-to-event outcomes, and the analysis populations for secondary outcomes are not reported in the registry record. The primary endpoint population is specified as participants enrolled in Phase I - Part 1, and the registry states that only those participants were evaluable for that endpoint. It does not give outcome-specific participant counts for the secondary endpoints or explain how incomplete follow-up was handled.
These omissions limit interpretation of the completeness and robustness of the posted outcome record. They do not establish that data were missing or that analyses were inappropriate; they mean that the registry record does not document how such issues were addressed.
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 |
|---|---|---|---|
| Phase I - Part 1 Dose Level 0 (Carfilzomib 20/27 mg/m^2) | 2 | 3 | 66.7% |
| Phase I - Part 1 Dose Level 1 (Carfilzomib 20/36 mg/m^2) | 3 | 4 | 75.0% |
| Phase I - Part 1 Dose Level 2 (Carfilzomib 20/45 mg/m^2) | 4 | 4 | 100.0% |
| Phase I - Part 1 Dose Level 3 (Carfilzomib 20/56 mg/^2) | 3 | 5 | 60.0% |
| Phase I -Part 2 Cohort 0 (Carfilzomib 56 mg/m^2+Dexamethasone) | 2 | 7 | 28.6% |
| Phase 2 (Carfilzomib 56 mg/m^2+ Dexamethasone) | 10 | 17 | 58.8% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Phase I - Part 1 Dose Level 0 (Carfilzomib 20/27 mg/m^2) | 0 of 3 |
| Phase I - Part 1 Dose Level 1 (Carfilzomib 20/36 mg/m^2) | 0 of 4 |
| Phase I - Part 1 Dose Level 2 (Carfilzomib 20/45 mg/m^2) | 2 of 4 |
| Phase I - Part 1 Dose Level 3 (Carfilzomib 20/56 mg/^2) | 0 of 5 |
| Phase I -Part 2 Cohort 0 (Carfilzomib 56 mg/m^2+Dexamethasone) | 0 of 7 |
| Phase 2 (Carfilzomib 56 mg/m^2+ Dexamethasone) | 1 of 17 |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 0% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Phase I - Part 1 Dose Level 0 (Carfilzomib 20/27 mg/m^2) | 3 of 3 |
| Phase I - Part 1 Dose Level 1 (Carfilzomib 20/36 mg/m^2) | 4 of 4 |
| Phase I - Part 1 Dose Level 2 (Carfilzomib 20/45 mg/m^2) | 4 of 4 |
| Phase I - Part 1 Dose Level 3 (Carfilzomib 20/56 mg/^2) | 5 of 5 |
| Phase I -Part 2 Cohort 0 (Carfilzomib 56 mg/m^2+Dexamethasone) | 7 of 7 |
| Phase 2 (Carfilzomib 56 mg/m^2+ Dexamethasone) | 17 of 17 |
Most frequent serious adverse event terms
| Event term | Organ system | Phase I - Part 1 Dose Level 0 (Carfilzomib 20/27 mg/m^2) | Phase I - Part 1 Dose Level 1 (Carfilzomib 20/36 mg/m^2) | Phase I - Part 1 Dose Level 2 (Carfilzomib 20/45 mg/m^2) | Phase I - Part 1 Dose Level 3 (Carfilzomib 20/56 mg/^2) | Phase I -Part 2 Cohort 0 (Carfilzomib 56 mg/m^2+Dexamethasone) | Phase 2 (Carfilzomib 56 mg/m^2+ Dexamethasone) |
|---|---|---|---|---|---|---|---|
| Upper respiratory infection | Infections and infestations | 0 of 3 | 0 of 4 | 1 of 4 | 0 of 5 | 1 of 7 | 4 of 17 |
| Sepsis | Infections and infestations | 0 of 3 | 0 of 4 | 3 of 4 | 0 of 5 | 1 of 7 | 1 of 17 |
| Pneumonitis | Respiratory, thoracic and mediastinal disorders | 0 of 3 | 0 of 4 | 1 of 4 | 1 of 5 | 2 of 7 | 0 of 17 |
| Fever | General disorders | 0 of 3 | 0 of 4 | 0 of 4 | 1 of 5 | 1 of 7 | 1 of 17 |
| Urinary tract infection | Infections and infestations | 0 of 3 | 0 of 4 | 0 of 4 | 0 of 5 | 0 of 7 | 2 of 17 |
| Dehydration | Metabolism and nutrition disorders | 0 of 3 | 0 of 4 | 1 of 4 | 0 of 5 | 0 of 7 | 1 of 17 |
| Thrombotic thrombocytopenic purpura | Blood and lymphatic system disorders | 0 of 3 | 0 of 4 | 0 of 4 | 0 of 5 | 1 of 7 | 0 of 17 |
| Aortic valve disease | Cardiac disorders | 0 of 3 | 0 of 4 | 1 of 4 | 0 of 5 | 0 of 7 | 0 of 17 |
| Supraventricular tachycardia | Cardiac disorders | 0 of 3 | 0 of 4 | 0 of 4 | 0 of 5 | 0 of 7 | 1 of 17 |
| Diarrhea | Gastrointestinal disorders | 0 of 3 | 0 of 4 | 0 of 4 | 0 of 5 | 0 of 7 | 1 of 17 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Phase I - Part 1 Dose Level 0 (Carfilzomib 20/27 mg/m^2) | Phase I - Part 1 Dose Level 1 (Carfilzomib 20/36 mg/m^2) | Phase I - Part 1 Dose Level 2 (Carfilzomib 20/45 mg/m^2) | Phase I - Part 1 Dose Level 3 (Carfilzomib 20/56 mg/^2) | Phase I -Part 2 Cohort 0 (Carfilzomib 56 mg/m^2+Dexamethasone) | Phase 2 (Carfilzomib 56 mg/m^2+ Dexamethasone) |
|---|---|---|---|---|---|---|---|
| Lymphocyte count decreased | Investigations | 3 of 3 | 1 of 4 | 3 of 4 | 4 of 5 | 7 of 7 | 17 of 17 |
| Platelet count decreased | Investigations | 2 of 3 | 1 of 4 | 3 of 4 | 5 of 5 | 7 of 7 | 17 of 17 |
| Anemia | Blood and lymphatic system disorders | 0 of 3 | 3 of 4 | 4 of 4 | 4 of 5 | 6 of 7 | 14 of 17 |
| White blood cell decreased | Investigations | 1 of 3 | 2 of 4 | 3 of 4 | 3 of 5 | 5 of 7 | 17 of 17 |
| Fatigue | General disorders | 3 of 3 | 2 of 4 | 3 of 4 | 5 of 5 | 5 of 7 | 10 of 17 |
| Aspartate aminotransferase increased | Investigations | 2 of 3 | 1 of 4 | 3 of 4 | 3 of 5 | 4 of 7 | 14 of 17 |
| Neutrophil count decreased | Investigations | 1 of 3 | 2 of 4 | 1 of 4 | 4 of 5 | 6 of 7 | 12 of 17 |
| Hypocalcemia | Metabolism and nutrition disorders | 3 of 3 | 3 of 4 | 4 of 4 | 5 of 5 | 5 of 7 | 6 of 17 |
| Nausea | Gastrointestinal disorders | 3 of 3 | 1 of 4 | 3 of 4 | 4 of 5 | 4 of 7 | 9 of 17 |
| Creatinine increased | Investigations | 3 of 3 | 2 of 4 | 3 of 4 | 3 of 5 | 5 of 7 | 8 of 17 |
Serious events with the highest arm-level rate: sepsis (75.0%), pain (33.3%), acute rental failure (33.3%), pneumonitis (28.6%), aortic valve disease (25.0%).
The registry reports serious adverse event and other adverse event counts separately for the listed study cohorts, along with deaths. For example, the Phase 2 cohort lists 17 at risk for serious adverse events and 10 affected; it lists 17 at risk for other adverse events and 17 affected, with 1 death. These are descriptive cohort counts, not estimates from a randomized comparison. The registry also reports deaths in the Dose Level 2 cohort, with 2 deaths; the other listed cohorts report 0 deaths.
The serious-event terms with the largest posted percentages include Sepsis at 75.0%, Pain at 33.3%, Acute rental failure at 33.3%, Pneumonitis at 28.6%, Aortic valve disease at 25.0%, and Diverticulitis at 25.0%. The registry record does not report the denominator for each term-specific percentage. These figures therefore should not be interpreted as comparable risks across cohorts or as precise estimates for other patients.
In general, adverse-event counts describe what was recorded during study follow-up; they do not by themselves establish causation. The registry does not report enough detail about event definitions, follow-up duration by cohort, or attribution to treatment to support broader causal conclusions.
12. What the Result Does, and Does Not, Mean
The record documents a non-randomized, sequential Phase I/II study of carfilzomib and PLD, with dexamethasone incorporated in later study parts, among patients with relapsed or refractory multiple myeloma. Its primary question was dose finding in Phase I - Part 1. The registry reports that the MTD was not reached and says the posted data represent the recommended dosage for further studies.
That statement should be kept distinct from a fully reported numeric MTD result. The specific primary endpoint value is not reported in the registry record, nor are the DLT counts by dose level or uncertainty estimates. The dose schedules in the later cohorts describe what was administered; they do not independently establish the endpoint result or prove a particular dose is optimal.
The record also contains cohort-level safety counts and lists secondary outcomes related to survival and response. Those entries do not support a causal comparison among regimens because treatment allocation was not randomized and the cohorts were sequential. Numerical results for the listed secondary outcomes are not reported in the registry record. Therefore, the record does not allow readers to quantify comparative efficacy or the precision of an efficacy estimate.
In general, a trial's stated aim and its design are not equivalent to evidence for a treatment effect. Interpretation depends on reported outcome values, denominators, uncertainty, and analysis methods. Here, the posted information supports a description of the dose-finding question, schedules, design, and selected safety counts. It does not establish that a treatment works or does not work, and it does not justify medical advice.
13. Why This Trial Matters Statistically
This trial illustrates why design labels matter when interpreting clinical results. A sequential, non-randomized study can be useful for early dose exploration, but its cohorts are not interchangeable control groups. The listed dose levels and later treatment combinations document the study's progression; they do not create a like-for-like comparison from which to attribute outcome differences to a dose or to dexamethasone.
The primary endpoint also makes clear that dose-finding conclusions depend on more than a dose schedule. The registry defines the MTD using DLTs during Cycle 1 and reports that the MTD was not reached. Yet the numeric endpoint result and dose-level DLT counts are not reported in the registry record. This gap highlights the distinction between a conclusion stated in a record and the supporting detail needed to assess its precision independently.
Safety counts need similar care. Counts and percentages are informative descriptions of recorded events, but without fully reported denominators, follow-up, and comparative analysis, they should not be treated as estimates of treatment effects. The study's non-randomized design and the limited detail about event definitions further constrain interpretation.
Finally, the registry lists survival and response outcomes without numerical results or posted analysis records. That makes the record a useful example of how trial registration and outcome reporting can describe intent and structure while still leaving important questions about estimates, uncertainty, missing data, and multiplicity unanswered. Statistical interpretation depends on both the design and the level of detail available for the results.
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 the primary result is that the registry states the MTD was not reached but does not report a numeric MTD value, dose-limiting toxicity counts by dose level, or confidence intervals. The endpoint applies only to Phase I - Part 1 participants, and the record does not report their evaluable count separately.
The non-randomized, sequential design does not support a like-for-like comparison between cohorts. Phase I - Part 1 tested several carfilzomib dose schedules with PLD, while later parts added dexamethasone. Differences in observed safety or outcomes cannot be attributed to a specific treatment difference from these cohort descriptions alone.
The registry lists secondary survival and response outcomes but does not report their numerical results. It also does not report a statistical analysis plan, analysis populations for those outcomes, handling of missing data or censoring, multiplicity procedures, or interim analyses. These methods are not reported in the registry record and should not be inferred.
Safety reporting is descriptive, and term-specific denominators for the posted serious adverse event percentages are not reported. The record also does not give the event attribution or enough follow-up detail to support a broader comparison. These limitations constrain interpretation of the registry record; they do not establish that unreported analyses or procedures were absent from the study itself.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Carfilzomib, Pegylated Liposomal Doxorubicin Hydrochloride, and Dexamethasone in Treating Patients With Relapsed or Refractory Multiple Myeloma — NCT01246063.
- Registry record last updated 2019-04-08; status last verified 2019-04.
- Results first posted 2019-04-08.
- 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
NCT01246063 is a completed Phase I/II, non-randomized, unmasked, sequential trial sponsored by Washington University School of Medicine. It enrolled 40 participants with multiple myeloma and studied carfilzomib with PLD, with dexamethasone included in later parts. The registry lists a start date of 2012-05-14 and a primary completion date of 2017-12-28.
The primary endpoint was the MTD of carfilzomib and PLD in Phase I - Part 1 over 28 days. The registry states that the MTD was not reached, but the numeric endpoint result is not reported in the registry record. Cohort-level adverse event counts and deaths are posted. Numerical results for the listed secondary survival and response outcomes, and the statistical analysis methods for those outcomes, are not reported in the registry record.