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 + High Dose Melphalan as Preparative Regimen for Autologous Hematopoietic Stem Cell Transplantation (NCT01690143), a na phase 1, phase 2 study. The primary outcome is Maximum Tolerated Dose (MTD) of Carfilzomib Plus Melphalan as Conditioning for Autologous Hematopoietic Cell Transplantation in Patients With Relapsed Multiple Myeloma(MM) [Phase I Portion of Study].
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT01690143 |
| Phase | Phase 1, Phase 2 |
| Condition | Multiple Myeloma |
| Allocation | Not applicable (single group) |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 45 |
| Arms in the primary outcome | n/a |
| Lead sponsor | University of Alabama at Birmingham |
| Results posted | Yes |
2. Clinical Question
Population
The study concerned patients with relapsed multiple myeloma who were candidates for autologous hematopoietic stem cell transplantation. The primary Phase 1 outcome population is described more narrowly as patients who underwent transplantation during Phase 1. The record does not give further demographic or clinical characteristics for that population.
Intervention
The conditioning regimen combined carfilzomib with high-dose melphalan before transplantation. The study had a Phase 1 dose-escalation portion intended to examine carfilzomib safety and identify a dose that could be combined with melphalan. The record says participants received different dose levels, but detailed dose-escalation rules are not reported in the registry record.
Comparator
There was no separate comparison group: the registry describes a single-group study, with allocation listed as not applicable and masking as none. The record therefore does not describe a randomized comparison of the combined regimen against melphalan alone or another conditioning approach. Outcomes must be understood as observations from the study group, not as differences between assigned treatment groups.
Primary question
The primary Phase 1 question was what maximum tolerated dose of carfilzomib could be safely combined with high-dose melphalan as conditioning before autologous transplantation in eligible patients with relapsed multiple myeloma. This is principally a dose and tolerability question. The numerical maximum tolerated dose and the analysis supporting it are not reported in the registry record.
3. Trial Design
This completed study is registered as Phase 1 and Phase 2, and its official title describes it as Phase 1/2A. It enrolled 45 participants. The registry dates the study start to 2012-05 and primary completion to 2017-11-01. The listed condition is multiple myeloma, and the record identifies the study as a single-group design.
The intervention combined carfilzomib and high-dose melphalan as conditioning therapy before autologous hematopoietic stem cell transplantation. In this procedure, as described in the registry summary, a patient's stem cells are collected before high-dose chemotherapy and returned afterward. The Phase 1 portion used dose escalation to examine carfilzomib safety and determine a dose for combination with melphalan. The summary notes that participants received different dose levels and that the first three participants were to receive the starting dose. Further escalation procedures and decision rules are not reported in the registry record.
There was no randomized allocation and no masking. With one study group, the design can describe outcomes observed under the regimen but does not directly estimate a treatment contrast against a concurrent control group. The primary outcome was the maximum tolerated dose of carfilzomib plus melphalan in patients who underwent transplantation during Phase 1, with a timeframe of up to 4 1/2 months. The record does not provide the numerical outcome or a reported analysis. It also does not give enough detail to characterize the Phase 2 analysis or its results.
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 | Carfilzomib + High Dose Melphalan |
|---|---|
| STARTED | 45 |
| COMPLETED | 44 |
| NOT COMPLETED | 1 |
Reasons for not completing this period:
| Reason | Carfilzomib + High Dose Melphalan |
|---|---|
| Withdrawal by Subject | 1 |
Analysis population for the primary outcome, as defined in the registry: Patients who underwent transplantation during phase 1
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: Patients with relapsed multiple myeloma, candidates for autologous hematopoietic cell transplantation
| Characteristic | Unit | Carfilzomib + High Dose Melphalan |
|---|---|---|
| Participants analysed | 45 | |
| Age, Continuous | years | 58 (41 to 69) |
| Sex: Female, Male: Female | Participants | 25 |
| Sex: Female, Male: Male | Participants | 20 |
| Race/Ethnicity, Customized: Non-Hispanic Whites | Participants | 26 |
| Race/Ethnicity, Customized: Non-Hispanic Blacks | Participants | 18 |
| Race/Ethnicity, Customized: Other | Participants | 1 |
6. Primary Endpoint
The registry lists the primary outcome as Maximum Tolerated Dose (MTD) of Carfilzomib Plus Melphalan as Conditioning for Autologous Hematopoietic Cell Transplantation in Patients With Relapsed Multiple Myeloma(MM) [Phase I Portion of Study], measured over Up to 4 1/2 months.
| Element | Registry entry |
|---|---|
| Result type | Number |
| Measure of spread | not applicable |
| Unit | mg/m2 |
| Endpoint classification | not reduced to a single comparison |
The primary endpoint concerns the maximum tolerated dose of carfilzomib when combined with high-dose melphalan as conditioning before autologous hematopoietic cell transplantation. It is expressed in mg/m2 and applies to patients with relapsed multiple myeloma who underwent transplantation during Phase 1. The stated timeframe is up to 4 1/2 months.
In general, a maximum tolerated dose endpoint is used in early dose-finding research to identify a dose boundary based on observed tolerability under a study's rules. It is not the same as an endpoint measuring whether a treatment improves survival, disease control, or another comparative outcome. Interpretation depends on the dose levels tested, the toxicity definitions, the observation window, and the decision rules used to escalate or stop. Those protocol details are not reported in the registry record.
The registry lists the endpoint and its measurement unit, but does not report a numerical maximum tolerated dose, participant-level dose outcomes, or an estimate of uncertainty. Consequently, the record does not establish which dose was selected or how precisely it was determined. The endpoint's purpose can be described, but its result cannot be reconstructed from the reported information.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The study is best read as an early-phase, single-group investigation of a conditioning regimen, with a Phase 1 primary question focused on dose and tolerability. Its design differs from a randomized trial intended to compare outcomes between treatment groups. There was no separate control group, allocation was listed as not applicable, and masking was none. Observed outcomes in the study group therefore cannot, on their own, isolate the effect of adding carfilzomib to melphalan.
The registry reports enrollment of 45 participants and describes the primary endpoint population as patients who underwent transplantation during Phase 1. Those figures should not be treated as interchangeable: the record does not report how many of the 45 enrolled participants belonged to the primary endpoint population or contributed to its analysis. The maximum tolerated dose result itself is not reported in the registry record. No numerical dose estimate, uncertainty interval, or analysis result is listed, and the record lists no analyses.
Safety information is descriptive. Among 44 patients undergoing transplantation who were at risk for serious adverse events, 1 was affected; among 44 at risk for other adverse events, 25 were affected. The registry records 0 deaths. Heart failure and renal failure are each listed among the leading serious adverse-event terms at 2.3%. These counts and percentages describe the recorded events in this study group. Without further information about event definitions, observation periods, severity grading, and follow-up, they do not provide a complete account of safety or a comparison with another regimen.
General statistical point: a confidence interval, when reported, conveys uncertainty around an estimate and helps distinguish a precise estimate from one compatible with a wider range of values. No interval for the primary dose outcome is reported in the registry record, so the precision of that outcome cannot be assessed from the record. A missing interval is not evidence that the estimate was precise or imprecise; it means that the record does not give that information.
Any sample-size calculations associated with the posted results should be treated as planning illustrations, not as the study's original design or as evidence of observed power. The assumptions described for those illustrations include a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. Those assumptions do not match the registered single-group design. They therefore should not be used to characterize the actual enrollment or infer what the study could detect.
9. Statistical Methods Explained
Design and estimand. The registered design is single-group, with no randomized allocation and no masking. In general, a single-group study estimates or describes outcomes within the treated cohort. A randomized comparison instead estimates a contrast between groups assigned to different strategies. Because this study has no listed control group, its data cannot directly estimate the difference between carfilzomib plus melphalan and melphalan alone. This distinction is important even when a study reports event counts or a dose outcome: a within-group description is not a controlled treatment effect.
The primary endpoint is a dose-finding quantity, not a conventional continuous or time-to-event efficacy measure. The registry describes the target as the maximum tolerated dose of carfilzomib that can be safely combined with high-dose melphalan before transplantation. In general, dose-finding methods use observed tolerability at tested doses to guide decisions about doses to explore next. The choice of method and the operating rules determine how the endpoint is interpreted. The registry summary mentions dose escalation and different dose levels, but the detailed algorithm, dose levels, toxicity criteria, and escalation or stopping rules are not reported in the registry record.
Population and denominator. The overall enrollment is 45, while the primary endpoint population is described as patients who underwent transplantation during Phase 1. These definitions refer to different stages of participation. In general, the number enrolled, the number receiving an intervention, and the number contributing to a particular endpoint can differ. The registry does not report the size of the primary endpoint population or explain any difference between enrollment and the reported safety denominator. For adverse events, the registry gives 44 patients at risk for serious events and 44 at risk for other events. Those denominators should be retained when reading the event counts, rather than replaced by the total enrollment.
Counts and proportions. The safety record reports affected participants and participants at risk. A count gives the number of participants with a recorded event; a proportion expresses that count relative to the at-risk population. The posted serious-event information gives 1 affected among 44 at risk, while the other-event information gives 25 affected among 44 at risk. The record also lists the percentage for each of the leading serious-event terms. These measures describe the observed study group. They do not show how event risk would compare under another treatment, and they do not by themselves convey the duration over which participants were monitored.
General statistical point: event counts can be informative but may be unstable when based on a small number of observations. A confidence interval around a proportion, if available, would describe the uncertainty associated with that estimate. No such interval is reported for the safety proportions in the registry record. The absence of an interval means precision cannot be evaluated from the record; it does not justify assuming a particular degree of uncertainty.
Dispersion and event patterns. The primary outcome is listed as a number with a unit of mg/m2, and no dispersion measure is reported. For a dose endpoint, a single summary value would not necessarily show how many participants received each dose or what toxicities occurred at each dose. In general, dose-level distributions and toxicity summaries help readers understand how a dose-finding conclusion was reached. Those details are not reported in the registry record. The adverse-event terms identify heart failure and renal failure as leading serious terms, each with a listed percentage, but do not provide further event-level detail.
Comparisons and sample-size illustrations. The registry has no like-for-like control comparison. General planning calculations that assume equal allocation between two arms address a hypothetical comparative design, not this single-group study. The assumptions described for such planning illustrations include a two-sided significance level of 0.05 and a normal approximation. Such calculations are design aids under stated assumptions; they are not a retrospective measure of the study's power and do not supply missing treatment-group comparisons. A planning illustration cannot turn a single-group observation into a randomized effect estimate.
Uncertainty and interpretation. Statistical uncertainty concerns the range of values compatible with the observations under a specified model. It is distinct from clinical uncertainty about how well a regimen performs in other settings. For the primary dose outcome, the record provides no numerical estimate or interval, so neither the selected value nor its statistical precision can be evaluated. For safety, counts are reported, but there is no comparative estimate or uncertainty interval. The registry also lists no analyses. In general, a result should be interpreted together with its analysis method, population definition, missing-data handling, and uncertainty; much of that information is not reported in the registry record.
10. Multiplicity, Missing Data and Analysis Populations
The registry record does not report a multiplicity strategy. Multiplicity arises in general when several hypotheses or endpoints are tested and the chance of at least one false-positive result can increase across tests. It is not possible to determine from the record whether confirmatory testing was planned, whether any adjustment was used, or how multiple outcomes were prioritized beyond the listed primary endpoint.
Missing-data methods and the amount of missing endpoint data are not reported in the registry record. The record does not explain whether participants who did not undergo transplantation were excluded from the primary endpoint population, how incomplete follow-up was handled, or whether any sensitivity analyses were conducted. These details matter because the endpoint population is described as patients who underwent transplantation during Phase 1, while total enrollment is also reported. The relationship between those populations is not specified.
The analysis populations and analysis procedures are not described in detail, and the registry lists no analyses. The record therefore does not identify an intention-to-treat population, a safety population definition beyond the stated at-risk counts, or a method for handling participants with incomplete observations. These omissions do not establish that such procedures were absent from the study; they mean they are not reported in the registry record. The numerical primary endpoint result and its uncertainty are also not reported, limiting assessment of the dose-finding conclusion.
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 |
|---|---|---|---|
| Patients Undergoing Transplantation | 1 | 44 | 2.3% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Patients Undergoing Transplantation | 0 of 44 |
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 |
|---|---|
| Patients Undergoing Transplantation | 25 of 44 |
Most frequent serious adverse event terms
| Event term | Organ system | Patients Undergoing Transplantation |
|---|---|---|
| heart failure | Cardiac disorders | 1 of 44 |
| renal failure | Renal and urinary disorders | 1 of 44 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Patients Undergoing Transplantation |
|---|---|---|
| Infection | Infections and infestations | 17 of 44 |
| diarrhea | Gastrointestinal disorders | 5 of 44 |
| hypertension | Cardiac disorders | 4 of 44 |
| rash | Immune system disorders | 3 of 44 |
| hyperkalemia | Endocrine disorders | 3 of 44 |
Serious events with the highest arm-level rate: heart failure (2.3%), renal failure (2.3%).
The registry reports safety information for patients undergoing transplantation. For serious adverse events, 44 patients were at risk and 1 was affected. For other adverse events, 44 were at risk and 25 were affected. The record lists 0 deaths. Heart failure and renal failure are each among the leading serious adverse-event terms, with 2.3% listed for each.
These figures are descriptive counts and percentages from the study group, not estimates of how the regimen compares with another treatment. The at-risk denominator is important: the counts should be read in relation to the 44 patients recorded as at risk for each category. The record does not report event timing, duration of follow-up, severity grading, recurrent-event counts, or detail on how events were attributed. It also does not provide uncertainty intervals around the event estimates.
The serious and other adverse-event categories should be kept distinct as the registry presents them. The reported term percentages do not, by themselves, provide a full account of the number, course, or clinical context of events. Accordingly, the safety figures describe what the record lists, while leaving important details about ascertainment and follow-up not reported in the registry record.
12. What the Result Does, and Does Not, Mean
The registry describes a Phase 1/2 study of carfilzomib plus high-dose melphalan before autologous transplantation in relapsed multiple myeloma. Its primary Phase 1 outcome asks about the maximum tolerated dose of carfilzomib in that combination. This makes the central statistical question one of dose selection and tolerability, rather than a direct test of comparative efficacy.
The record establishes the study design, enrollment, outcome definition, and selected safety counts. It does not report the numerical maximum tolerated dose or an analysis of that endpoint. Without the endpoint result and its supporting dose-level data, the registry record cannot show which dose was identified or how uncertain that conclusion was. It also does not report a comparative treatment effect, because no separate control group is listed.
The adverse-event counts and percentages summarize events recorded among patients undergoing transplantation. They are useful descriptions of the study group, but they do not establish the relative safety of the regimen compared with another approach. The record does not give enough detail about event definitions, timing, grading, or follow-up to interpret the counts beyond their stated scope.
General statistical point: a study's design determines the questions its results can answer. A single-group dose-finding study can inform understanding of observed tolerability and dose selection when its methods and results are reported. It cannot by itself separate treatment effects from other influences in the way a suitable controlled comparison can. Here, the primary numerical outcome and details needed to evaluate its analysis are not reported in the registry record. The appropriate reading is therefore limited to the registered purpose and the reported descriptive safety information, without inferring a dose result or a comparative benefit.
13. Why This Trial Matters Statistically
This trial is statistically distinctive because its registered primary question is about finding a tolerable dose of carfilzomib within a conditioning regimen, rather than estimating a treatment effect against a concurrent control group. The dose-escalation purpose makes the tested dose levels, toxicity definitions, and decision rules central to interpreting the outcome. The registry summary identifies the general purpose but does not report those details or the numerical dose result.
The design also illustrates why enrollment and endpoint populations should not be assumed to be the same. The record reports 45 enrolled participants, while the primary endpoint is defined for patients who underwent transplantation during Phase 1 and safety denominators are 44. Keeping these populations distinct is necessary for correctly interpreting counts and understanding which participants contributed to each outcome.
Finally, the record highlights the limits of descriptive safety data without a comparator or uncertainty estimates. Counts can communicate what was recorded in a study group, but they do not establish how the event experience would differ under another regimen. The trial's statistical contribution cannot be fully assessed from the registry record because the main dose-finding result, its analysis, and several methods details are not reported there.
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 interpretation is that the registry record does not report the numerical maximum tolerated dose, despite listing it as the primary Phase 1 endpoint. It also does not provide dose-level outcomes or an uncertainty estimate. Without these, readers cannot evaluate the reported dose-finding conclusion or its precision.
The single-group design has no randomized control group, so it does not support a direct comparison with melphalan alone or another conditioning regimen. The record lists allocation as not applicable and masking as none. Any differences from outcomes in other populations or studies would not constitute a controlled comparison within this trial.
The registry gives overall enrollment of 45, but does not report the number contributing to the primary endpoint. The safety denominators are 44 for both serious and other adverse events, and the record does not explain their relationship to enrollment or the primary endpoint population. Detailed eligibility characteristics, dose levels, toxicity rules, missing-data handling, follow-up for safety events, and analysis procedures are not reported in the registry record. The record also lists no analyses. These gaps limit assessment of the endpoint, safety ascertainment, and the generalizability of the observations.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Carfilzomib + High Dose Melphalan as Preparative Regimen for Autologous Hematopoietic Stem Cell Transplantation — NCT01690143.
- Registry record last updated 2018-08-07; status last verified 2018-07.
- Results first posted 2018-07-10.
- 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
The registry describes a completed Phase 1/2 single-group study of carfilzomib plus high-dose melphalan as conditioning before autologous hematopoietic stem cell transplantation for relapsed multiple myeloma. Enrollment was 45; the study start was 2012-05, and primary completion was 2017-11-01. The Phase 1 primary outcome was the maximum tolerated dose of carfilzomib in combination with melphalan, among patients who underwent transplantation during Phase 1, over a timeframe of up to 4 1/2 months.
The primary numerical outcome and its analysis are not reported in the registry record. Safety information lists 1 serious adverse event among 44 at risk, 25 other adverse events among 44 at risk, 0 deaths, and heart failure and renal failure at 2.3% each among the leading serious-event terms. The record does not describe a randomized comparator, masking, or detailed analysis methods.