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 Combination High Dose Melphalan and Autologous Peripheral Blood Stem Cell (PBSC) Transplant With Bortezomib for Multiple Myeloma: A Dose and Schedule Finding Study (NCT00793650), a randomized phase 1, phase 2 study. The primary outcome is Safety and Engraftment.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT00793650 |
| Phase | Phase 1, Phase 2 |
| Condition | Cancer, Multiple Myeloma |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | None (open label) |
| Enrollment | 39 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Emory University |
| Results posted | Yes |
2. Clinical Question
Population
The study concerned patients with multiple myeloma receiving high-dose melphalan and autologous peripheral blood stem cell transplantation. The registry record describes the primary population as “As per the protocol.” Further eligibility criteria and the characteristics of enrolled participants are not reported in the registry record. Enrollment was 39.
Intervention
One randomized group received a single escalating dose of bortezomib 24 hours before melphalan; the other received a single escalating dose 24 hours after melphalan. Both descriptions list doses of 1.0, 1.3, or 1.6 mg/m2. The transplant used the patient’s own peripheral blood stem cells.
Comparator
The comparison was between the timing schedules: bortezomib before melphalan versus bortezomib after melphalan. The record describes randomized allocation and a parallel design, with no masking. It does not describe a group receiving neither bortezomib nor transplantation, so this is not presented as a comparison with no bortezomib.
Primary question
The stated primary outcome is “Safety and Engraftment,” with a timeframe of Day 30 after transplant. The record identifies a median and full range in days but gives no numerical result or explicit operational definition of engraftment. The study’s broad question was whether the schedules could be evaluated for safety and engraftment in this transplant setting; the registry record does not report a comparative estimate answering that question.
3. Trial Design
This was a randomized, parallel-group Phase 1 and Phase 2 study sponsored by Emory University. Enrollment was 39. The registry record lists the study status as terminated, with a start date of 2005-05 and primary completion of 2009-10. The reason for termination is not reported in the registry record.
The two groups differed in the timing of a single bortezomib dose relative to melphalan. The “Bortezomib before Melphalan” description places the dose 24 hours before melphalan; the “Bortezomib after Melphalan” description places it 24 hours after. Both descriptions list escalating doses of 1.0, 1.3, or 1.6 mg/m2. Both groups were in the setting of high-dose melphalan and autologous peripheral blood stem cell transplantation. The registry record does not describe a separate untreated or transplant-only comparison group.
Randomization is reported, but the method used to generate the allocation sequence, concealment before assignment, and any stratification factors are not reported in the registry record. Masking is listed as none. The record therefore describes an unmasked randomized comparison of timing schedules, but does not provide details needed to assess all aspects of the allocation process or conduct of the study.
The stated primary outcome is safety and engraftment at Day 30 after transplant. A secondary outcome is response rate using EBMT criteria at Day +100 after transplant. The record identifies two outcome measures, but does not give a numerical response-rate result. It also does not provide a numerical primary endpoint result. The protocol, full eligibility criteria, treatment discontinuation rules, and details of follow-up are not reported in the registry record.
The enrollment figure describes the study overall; the registry record lists 19 participants at risk for serious adverse events in the before-melphalan group and 20 in the after-melphalan group. These safety denominators should not automatically be treated as the denominator for every outcome, since outcome-specific analysis populations 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 | Bortezomib Before HD Melphalan | Bortezomib After HD melphalanAll |
|---|---|---|
| STARTED | 19 | 20 |
| COMPLETED | 19 | 20 |
| NOT COMPLETED | 0 | 0 |
Analysis population for the primary outcome, as defined in the registry: As per the protocol
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 | Bortezomib Before HD Melphalan | Bortezomib After HD melphalanAll | Total |
|---|---|---|---|---|
| Participants analysed | 19 | 20 | 39 | |
| Age, Categorical: <=18 years | Participants | 0 | 0 | 0 |
| Age, Categorical: Between 18 and 65 years | Participants | 14 | 14 | 28 |
| Age, Categorical: >=65 years | Participants | 5 | 6 | 11 |
| Age Continuous | years | 58.32 (SD 7.92) | 58.75 (SD 8.05) | 58.54 (SD 7.88) |
| Sex: Female, Male: Female | Participants | 9 | 7 | 16 |
| Sex: Female, Male: Male | Participants | 10 | 13 | 23 |
| Region of Enrollment: United States | participants | 19 | 20 | 39 |
6. Primary Endpoint
The registry lists the primary outcome as Safety and Engraftment, measured over Day 30 after transplant.
| Element | Registry entry |
|---|---|
| Result type | Median |
| Measure of spread | Full Range |
| Unit | days |
| Endpoint classification | Time-to-Event Analysis |
The primary outcome is titled “Safety and Engraftment.” The registry record assigns it a timeframe of Day 30 after transplant and describes the measure as a median in days with a full range. It does not report the median, the range, or the precise event or threshold used to define engraftment. Consequently, the endpoint’s label and summary format are available, but the numerical result and some operational details are not reported in the registry record.
In general, an engraftment endpoint describes recovery of blood-cell production after a stem cell transplant. The timing of this recovery can be relevant to describing the course after transplantation. A median is a measure of the middle of an observed distribution: it is less affected by unusually long or short observations than an arithmetic mean can be. A full range gives the lowest and highest observed values, but does not show how observations are distributed between those extremes. These are general statistical explanations, not additional details about the study’s endpoint definition.
The record also describes stem-cell collection and transplant graft characteristics. Cells were collected using either chemo-mobilization (27 of 39, 69%) or growth factor mobilization (12 of 39, 31%). Patients received an average of 9.0 × 10^6/kg CD34+ cells, with a range of 2.3-65. These details characterize the transplant context; they are not a substitute for the missing numerical safety and engraftment outcome. The registry record does not report a comparison of engraftment between the timing groups.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record establishes that this was a randomized study comparing the timing of bortezomib around melphalan in patients undergoing autologous peripheral blood stem cell transplantation for multiple myeloma. It reports two schedule groups, escalating dose levels, and a primary outcome labeled safety and engraftment. It does not report a numerical result for that primary outcome, an effect estimate comparing the groups, or a statistical test for the comparison.
That distinction matters: the existence of a randomized design does not by itself tell readers what the observed difference was, how uncertain it was, or whether any difference was compatible with chance variation. Without a reported group-specific endpoint result or a comparative estimate with uncertainty, the registry record cannot support a quantitative conclusion about how the schedules differed in engraftment or safety. The record’s secondary outcome is response rate using EBMT criteria at Day +100 after transplant, but a response result is not reported in the registry record either.
For serious adverse events, the listed groups have 4 affected participants among 19 at risk in the “Bortezomib Before HD Melphalan” group and 2 among 20 in the “Bortezomib After HD melphalanAll” group. These are descriptive counts. The registry record does not provide an adjusted comparative estimate, confidence interval, or statistical test for these figures. They should not be interpreted as proof that one timing schedule is safer. Nor do these group counts establish the kinds of events experienced by each participant or their timing, duration, severity beyond the serious-event classification, or relationship to treatment; those details are not reported in the registry record.
The record also lists other adverse events affecting 19 of 19 and 18 of 20 participants in the respective groups. These are broad counts, not measures of event frequency per person over time. The registry record does not give the event-level detail needed to determine whether participants had one event or multiple events, how events were defined, or how these counts relate to treatment exposure.
The listed serious adverse event terms include “Expired” at 15.8%, “Hemorrhage/Bleeding-Hemorrhage” at 5.3%, and “Acute pulmonary embolus” at 5.0%. The registry record does not assign these terms to particular timing groups in the information reported, nor does it provide their event counts alongside these percentages. The “Expired” term cannot be translated into a group-specific death count from the record. Death counts are not reported in the registry record.
The study is listed as terminated, but the reason is not reported in the registry record. The status alone does not show whether the study ended because of safety, enrollment, administrative, or other considerations. Overall, the posted information describes the design, treatment schedules, some safety counts, and transplant context; it does not provide enough comparative outcome information to estimate the effect of timing or its precision.
9. Statistical Methods Explained
The registry record identifies randomization, a parallel-group model, no masking, and Phase 1 and Phase 2. Those labels describe broad features of the design, not the full statistical plan. The sequence-generation method, allocation concealment, any stratification, planned comparisons, and analysis populations are not reported in the registry record. The material available therefore supports a description of the design but not a reconstruction of the analysis methods.
What does randomization contribute?
In general, randomization assigns participants to study groups using a chance-based process. Its purpose is to reduce systematic differences between groups at the point of assignment, including differences that may not have been measured. Randomization does not guarantee that groups will be identical, especially in a small study, and it does not remove the need to describe outcomes and uncertainty. Here, randomization is reported, but its implementation details are not reported in the registry record.
The parallel design means the record frames the groups as separate schedule assignments rather than as repeated treatment periods for each participant. The two schedules place the same described single escalating bortezomib dose on opposite sides of melphalan. Masking is listed as none. In general, lack of masking can matter when outcomes involve judgment or reporting, although objective measures may be less directly affected. The record does not give sufficient outcome-definition detail to assess the practical influence of masking for each measure.
What does a median with a full range describe?
In general, a median is the central observed value after measurements are ordered. It can be useful when a distribution is skewed or includes values far from the center. A full range reports the extremes and conveys the span of observed measurements, but it does not describe concentration, variability around the median, or uncertainty in the median. The registry record says the primary measure is a median in days with a full range at Day 30 after transplant, but the actual median and range are not reported in the registry record. No between-group median comparison or interval estimate is reported.
There is a distinction between describing a distribution and estimating a treatment contrast. A group-specific median describes the observed timing within that group; it does not alone quantify how the groups differ. A comparative analysis would need to specify the contrast and its uncertainty, as well as how censoring or participants without the event were handled if applicable. Those methods are not reported in the registry record, and the endpoint’s operational definition is not reported there either.
How should event counts and percentages be read?
In general, an adverse-event count is a descriptive tally, while a percentage expresses that tally relative to a stated denominator. Interpretation depends on the event definition, observation period, participant population, and whether participants can contribute more than one event. The registry record reports serious adverse event affected counts and numbers at risk for each group. It also lists selected event terms with percentages. It does not provide all event-level counts, the denominators used for each listed percentage, or a detailed account of event collection and coding. The listed percentages should therefore be read as reported terms, not reinterpreted as comparable group-specific risks.
Confidence intervals are used in general to communicate the precision of an estimate: they show a range of values compatible with the data under the stated statistical model and procedure. A narrower interval usually indicates greater precision, while a wider interval indicates greater uncertainty. The registry record does not report a confidence interval for the primary endpoint or the adverse-event group comparison, so the precision of those contrasts cannot be assessed from the reported information.
What can the planning illustration say?
The registry record describes a planning illustration based on a fraction of the observed effect, with a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. It states that time-to-event calculations use the total number of events, while other calculations use participants per arm. These are planning assumptions, not observed outcomes and not the number enrolled in this study. No numerical planning results are reported in the registry record used for this analysis, and the illustration should not be read as observed power.
In general, sample-size planning asks how much information a future study would need to detect a specified effect under stated assumptions. Its output depends on the outcome, effect size, variability or event rate, allocation, significance threshold, and power target. A planning calculation does not demonstrate that the current study had a particular probability of detecting an effect after its results are known. The observed effect used in a planning illustration may also be imprecise, especially when estimated from a small study. The registry record does not report a protocol-based sample-size justification or enough numerical results to assess the planning illustration’s inputs independently.
What is not available about the analysis?
The registry record lists zero analyses and does not provide a statistical analysis plan, the method for handling missing outcomes, any adjustment for multiple comparisons, or a description of analysis populations. It does not report whether results were analyzed according to randomized assignment, treatment received, or another population definition. These omissions limit assessment of how outcomes were selected and analyzed. They do not establish that particular methods were or were not used outside the information in the registry record.
In general, a transparent statistical report identifies outcome definitions, analysis populations, estimands or contrasts, missing-data procedures, and the methods used to quantify uncertainty. Without these elements and the numerical results, readers cannot reproduce a comparison or assess whether the reported analysis followed a prespecified plan. The registry record does not provide enough information to do so for this study.
10. Multiplicity, Missing Data and Analysis Populations
The registry record identifies a primary outcome of safety and engraftment and a secondary outcome of response rate using EBMT criteria at Day +100 after transplant. It does not provide a complete statistical analysis plan, a hierarchy of tests, or a description of how multiple outcomes or comparisons were handled. Any multiplicity adjustment, or a decision not to adjust, is not reported in the registry record.
Multiplicity is a general concern when several outcomes, time points, dose levels, or group comparisons are examined. Repeated testing can increase the chance of finding an apparently unusual result even when there is no underlying difference. A prespecified hierarchy or adjustment can address some of this concern, but the registry record does not state whether such an approach was used. The primary outcome is described at Day 30 after transplant, while the secondary response outcome is specified at Day +100; the record does not give numerical results for either outcome.
Missing-data methods and outcome-specific analysis populations are not reported in the registry record. The enrollment figure is 39, while serious adverse event denominators are reported separately by group as 19 and 20. Those figures do not establish how many participants contributed data to each endpoint or how unavailable outcomes were handled. The record also does not state whether every randomized participant was included in each analysis, how withdrawals were treated, or whether any imputation was used.
In general, missingness can affect interpretation when the probability of an outcome being unavailable is related to a participant’s condition or treatment experience. Complete-case analysis, imputation, and sensitivity analyses rely on different assumptions, so a report should make the chosen approach explicit. Since these methods and the reasons for any missing outcomes are not reported in the registry record, their potential influence cannot be assessed. The record’s omission does not establish that missing data occurred; it means the information needed to evaluate their handling is not reported.
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 |
|---|---|---|---|
| Bortezomib Before HD Melphalan | 4 | 19 | 21.1% |
| Bortezomib After HD melphalanAll | 2 | 20 | 10.0% |
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 |
|---|---|
| Bortezomib Before HD Melphalan | 19 of 19 |
| Bortezomib After HD melphalanAll | 18 of 20 |
Most frequent serious adverse event terms
| Event term | Organ system | Bortezomib Before HD Melphalan | Bortezomib After HD melphalanAll |
|---|---|---|---|
| Expired | General disorders | 3 of 19 | 1 of 20 |
| Acute pulmonary embolus | General disorders | 0 of 19 | 1 of 20 |
| Hemorrhage/Bleeding-Hemorrhage | General disorders | 1 of 19 | 0 of 20 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Bortezomib Before HD Melphalan | Bortezomib After HD melphalanAll |
|---|---|---|---|
| Nausea | Gastrointestinal disorders | 19 of 19 | 18 of 20 |
| Muscositis | Gastrointestinal disorders | 18 of 19 | 16 of 20 |
| Diarrhea | Gastrointestinal disorders | 16 of 19 | 18 of 20 |
| Febrile Neutropenia | Blood and lymphatic system disorders | 11 of 19 | 13 of 20 |
| Vomiting | Gastrointestinal disorders | 11 of 19 | 11 of 20 |
| Renal toxicities | Renal and urinary disorders | 4 of 19 | 7 of 20 |
| Liver Toxicities | Hepatobiliary disorders | 5 of 19 | 4 of 20 |
| Rash | Skin and subcutaneous tissue disorders | 2 of 19 | 5 of 20 |
| Pulmonary toxicities | Respiratory, thoracic and mediastinal disorders | 2 of 19 | 5 of 20 |
| Hypotension | Cardiac disorders | 4 of 19 | 2 of 20 |
Serious events with the highest arm-level rate: expired (15.8%), hemorrhage/bleeding-hemorrhage (5.3%), acute pulmonary embolus (5.0%).
The serious adverse event summary reports 4 affected participants among 19 at risk in the group labeled “Bortezomib Before HD Melphalan” and 2 among 20 in the group labeled “Bortezomib After HD melphalanAll.” These are counts of participants, not necessarily counts of all events. The registry record does not report a comparative statistical analysis, confidence interval, or detailed event timing for these group summaries.
The record also reports other adverse events affecting 19 of 19 and 18 of 20 participants in the respective groups. It does not provide enough event-level information to tell whether an affected participant experienced one event or several, or whether the categories differ in observation time or ascertainment. These counts should therefore be treated as descriptive rather than as a complete account of event burden.
Among the listed serious adverse event terms are “Expired” at 15.8%, “Hemorrhage/Bleeding-Hemorrhage” at 5.3%, and “Acute pulmonary embolus” at 5.0%. The registry record does not identify the group attribution or denominators for these term percentages in the reported information. It gives no death counts; the “Expired” term should not be converted into a group-specific count. Event definitions, relatedness assessments, and the reason for termination are not reported in the registry record. These summaries do not by themselves establish a safety difference between schedules.
12. What the Result Does, and Does Not, Mean
The record describes a randomized comparison of bortezomib timing in a transplant setting for multiple myeloma. Its practical statistical contribution is the documentation of the study question, the two timing schedules, the reported enrollment, and selected safety and transplant details. It also records that the study was terminated. These registry entries help characterize what was studied, but they are not equivalent to a complete report of comparative outcomes.
The primary outcome is named safety and engraftment and is associated with a median in days, full range, and Day 30 after transplant. Yet the numerical primary result, the endpoint definition, and a between-group estimate are not reported in the registry record. The secondary response-rate outcome at Day +100 is identified, but its result is also not reported in the registry record. Without estimates and uncertainty measures, readers cannot determine the size or precision of a difference between schedules from this information.
The adverse-event counts are useful descriptive information, but they do not prove that the schedules have equivalent or different safety profiles. A lack of a reported statistical test is not evidence that the groups were the same; conversely, a difference in raw counts would not by itself establish a treatment effect. Interpretation requires event definitions, relevant denominators, follow-up information, and an analysis suited to the outcome. Much of that information is not reported in the registry record.
The enrollment of 39 also does not, by itself, show whether the study was adequately sized for a particular comparison. The registry record describes a planning illustration, but it does not report a protocol-based sample-size justification or the numerical output needed to evaluate it. In general, precision depends on the amount and distribution of outcome information, not enrollment alone.
Accordingly, the posted record supports a careful account of the design and the reported descriptive data, not a conclusion that one timing schedule is superior, safer, or equivalent. It also does not establish why the study was terminated. Those questions require information not reported in the registry record.
13. Why This Trial Matters Statistically
This trial is statistically notable as a randomized comparison of treatment timing within a complex transplant regimen. The intervention contrast is not simply receipt versus non-receipt of bortezomib: the two described groups received the drug on different sides of melphalan, with the same listed escalating dose levels. That makes the intended comparison specifically about schedule, in the setting of high-dose melphalan and autologous peripheral blood stem cell transplantation.
Its Phase 1 and Phase 2 designation and dose-escalating descriptions put safety and schedule-finding in the foreground. For dose- and schedule-finding research, clear reporting of dose-level assignment, safety definitions, dose-limiting events if applicable, and the basis for selecting a schedule is important. The registry record does not report whether dose escalation followed a formal rule, how dose levels were assigned within each timing group, or any schedule-selection conclusion. Those details should not be inferred from the existence of escalating dose descriptions.
The study also illustrates why design labels and outcome numbers need to be interpreted together. Randomization is reported, but key details of allocation and analysis are not. Safety counts are present, but comparative uncertainty and outcome-specific analysis populations are not. The primary outcome is identified, but its numerical result is absent. These gaps limit what can be learned from the registry record even though it contains information about transplant cell collection, graft dose, and selected adverse events.
In general, clinical statistics is not only about whether a result is statistically significant. It is also about defining the question, quantifying the contrast, communicating uncertainty, and making the analysis reproducible. Here, no comparative primary endpoint estimate or precision measure is reported. The record therefore serves more as a partial account of study design and selected observations than as a complete statistical report of the randomized comparison.
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 primary outcome lacks its numerical median and full range, and the registry record does not define the engraftment event operationally. It therefore does not allow readers to verify what was measured or compare the reported timing between randomized groups. The record also does not report a group-specific response-rate result for the EBMT-based assessment at Day +100 after transplant.
The exact allocation method, concealment procedures, stratification, eligibility criteria, and detailed analysis populations are not reported in the registry record. The record lists no analyses and does not give a statistical analysis plan, uncertainty intervals, or comparative tests. Missing-data procedures, outcome ascertainment methods, and any multiplicity strategy are also not reported. These limitations prevent assessment of the analysis process and the precision of any treatment contrast.
The serious adverse event summary supplies affected counts and at-risk counts by group, but not detailed event-level data or an adjusted comparison. The record’s selected serious event terms have percentages without corresponding group attribution or denominators in the reported information. Death counts and the reasons for study termination are not reported in the registry record. Consequently, neither the meaning of those term percentages nor the circumstances surrounding termination can be established from the posted information.
The study enrolled 39, but enrollment alone cannot establish the adequacy of the information available for the outcomes. The registry record describes a planning illustration rather than a protocol-based justification, and numerical planning outputs are not reported in the information used. It also does not state how the dose escalation was governed or how the timing comparison was intended to guide a final schedule. These are trial-specific gaps; they should not be filled by assumptions about typical study practice.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Combination High Dose Melphalan and Autologous Peripheral Blood Stem Cell (PBSC) Transplant With Bortezomib for Multiple Myeloma: A Dose and Schedule Finding Study — NCT00793650.
- Registry record last updated 2012-08-30; status last verified 2012-08.
- Results first posted 2012-06-18.
- 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
NCT00793650 is a randomized, unmasked, parallel Phase 1 and Phase 2 study sponsored by Emory University, with enrollment of 39 and status listed as terminated. It compared a single escalating bortezomib dose given 24 hours before melphalan with a single escalating dose given 24 hours after melphalan, in the setting of high-dose melphalan and autologous peripheral blood stem cell transplantation for multiple myeloma.
The primary outcome is labeled safety and engraftment, with a median in days and full range at Day 30 after transplant. A secondary outcome is response rate using EBMT criteria at Day +100 after transplant. Numerical results for these outcomes, a comparative statistical analysis, and the reason for termination are not reported in the registry record. The record includes descriptive serious and other adverse-event counts and transplant cell-collection information, but the available details do not establish a comparative treatment effect.