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 Melphalan and Bortezomib Prior to Autologous Stem Cell Transplant in Treating Patients With Multiple Myeloma (NCT02353572), a na phase 1, phase 2 study. The primary outcome is Maximally Tolerable Dose (MTD) of Both Melphalan and Bortezomib as Combination.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT02353572 |
| Phase | Phase 1, Phase 2 |
| Condition | Plasma Cell Myeloma, Plasmacytosis, Recurrent Plasma Cell Myeloma |
| Allocation | Not applicable (single group) |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 3 |
| Arms in the primary outcome | n/a |
| Lead sponsor | University of Colorado, Denver |
| Results posted | Yes |
2. Clinical Question
Population
Patients with multiple myeloma were the intended population. The registry also lists plasma cell myeloma, plasmacytosis, recurrent plasma cell myeloma, and smoldering plasma cell myeloma among the conditions. Enrollment was 3.
Intervention
The study evaluated melphalan and bortezomib before autologous transplant. The listed regimen also included dexamethasone. The described schedule gives melphalan IV continuously on days -5 to -2, bortezomib IV on days -4 and -1, and dexamethasone IV on day -1 before the second bortezomib dose. The transplant description is incomplete in the registry record.
Comparator
No separate comparator group is recorded. This is a single-group study, not a randomized comparison, so the record does not support a treatment-versus-control estimate.
Primary question
The primary question was the maximally tolerable dose of melphalan and bortezomib in combination, assessed in the context of dose-limiting toxicity and mortality or toxicity within 100 days. The registry states that the study was terminated and its endpoints were not reached.
In broad terms, the trial sought to examine dose and safety for a chemotherapy combination given before autologous transplant. The registry summary describes the rationale as using bortezomib with melphalan before transplant, while the primary endpoint focuses on tolerability rather than a comparative estimate of benefit. The record does not report an efficacy result or a completed dose-finding result.
The listed conditions include several plasma-cell disorders, but the registry’s description of the study population centers on patients with multiple myeloma. The record does not provide enough information to characterize participants’ disease history, prior treatment, eligibility details, or baseline health. Those characteristics are not reported in the registry record.
Because there is no comparator group, the central question is not whether the regimen outperformed another treatment. It is whether the study identified a dose meeting its stated tolerability definition. The record says that the endpoints were not reached, so it does not answer that question.
3. Trial Design
NCT02353572 is registered as a phase I-II study sponsored by University of Colorado, Denver. The registry classifies it as a single-group study with no masking and allocation listed as NA. Enrollment is recorded as 3. The study status is terminated. The recorded start is 2009-11, and primary completion is 2011-09.
The study was designed around melphalan and bortezomib administered before autologous transplant. Dexamethasone is also listed as an intervention. The arm description gives a schedule for the drug administrations, but its transplant description ends mid-sentence. Further treatment or transplant details beyond that text are not reported in the registry record.
The single-group structure matters when reading the results. There is no control arm to serve as a like-for-like comparator, and the record does not describe random assignment. The study therefore cannot provide a randomized between-group contrast. Its stated primary endpoint instead concerns the maximally tolerable combination dose under specified toxicity criteria.
The registry describes the study as phase I-II, but does not report a completed endpoint result. It explicitly states that the study was terminated and study endpoints were not reached. The record lists one outcome measure and no analyses. It does not report why the trial was terminated, whether enrollment stopped before the planned target, or whether any dose-level decisions were made.
Study dates and status provide context, but do not establish how much follow-up participants received or which assessments were completed. Those details are not reported in the registry record. Likewise, the planned enrollment target, any sample-size justification, and any protocol amendments are not reported. These omissions limit reconstruction of the trial’s operational conduct from the registry entry alone.
4. Participant Flow and Accounting
The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.
Before assignment: Within 35 days of planned therapy, patients were evaluated for eligibility by standard tests: paraprotein assessment, bone marrow biopsy and aspiration, MRI scan, PET/CT scan, echocardiography and pulmonary function test. Patients who were not be able to pursue the tandem autotransplant were eligible for one autotransplant.
Overall Study
| Stage | Melphalan, Bortezomib, Autologous Transplant |
|---|---|
| STARTED | 3 |
| COMPLETED | 0 |
| NOT COMPLETED | 3 |
Reasons for not completing this period:
| Reason | Melphalan, Bortezomib, Autologous Transplant |
|---|---|
| Withdrawal by Subject | 1 |
| Study terminated | 2 |
Analysis population for the primary outcome, as defined in the registry: The study was terminated, study endpoints were not reached.
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: Based on the annual number of referrals made to the Myeloma and Amyloidosis Program, expected accrual to this study was about 20 patients per year.
| Characteristic | Unit | Melphalan, Bortezomib, Autologous Transplant |
|---|---|---|
| Participants analysed | 3 | |
| Age, Categorical: <=18 years | Participants | 0 |
| Age, Categorical: Between 18 and 65 years | Participants | 2 |
| Age, Categorical: >=65 years | Participants | 1 |
| Age, Continuous | Years | 62.3 (SD 5.0) |
| Sex: Female, Male: Female | Participants | 1 |
| Sex: Female, Male: Male | Participants | 2 |
| Race (NIH/OMB): American Indian or Alaska Native | Participants | 0 |
| Race (NIH/OMB): Asian | Participants | 0 |
| Race (NIH/OMB): Native Hawaiian or Other Pacific Islander | Participants | 0 |
| Race (NIH/OMB): Black or African American | Participants | 2 |
| Race (NIH/OMB): White | Participants | 1 |
| Race (NIH/OMB): More than one race | Participants | 0 |
| Race (NIH/OMB): Unknown or Not Reported | Participants | 0 |
| Region of Enrollment: United States | participants | 3 |
6. Primary Endpoint
The registry lists the primary outcome as Maximally Tolerable Dose (MTD) of Both Melphalan and Bortezomib as Combination, measured over 100 days.
| Element | Registry entry |
|---|---|
| Result type | N/A |
| Measure of spread | not applicable |
| Unit | not stated |
| Endpoint classification | not reduced to a single comparison |
The primary outcome is titled “Maximally Tolerable Dose (MTD) of Both Melphalan and Bortezomib as Combination.” Its timeframe is 100 days. The registry defines MTD as one dose below the dose at which 33% of patients within a cohort experienced dose-limiting toxicity. It specifies unacceptable toxicities, including intractable veno-occlusive disorder, new onset of renal failure requiring dialysis, acute heart failure of New York Heart Association class III/IV, interstitial pneumonia requiring ventilator management for longer than 3 days, or grade 4 neuropathy.
The endpoint also treats a 100-day mortality/toxicity rate of 3% or more as unacceptable. The stated evidence criterion is an observed 100-day mortality/toxicity rate whose lower one-sided 90% confidence bound exceeds 3%. In general, a confidence bound expresses uncertainty around an estimate; using a lower bound asks whether the data are compatible with a rate above the specified threshold even after accounting for statistical uncertainty.
A dose-finding endpoint is used to guide tolerability decisions, rather than to compare treatment effects against a control. Here, however, the registry says the study endpoints were not reached. It does not report a dose identified as the MTD, an observed endpoint estimate, or a confidence bound. The stated criteria describe the intended measure and decision rule, not a result established by this record.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The key interpretive fact is that the registry marks the study as terminated and states that study endpoints were not reached. Although the record lists an enrollment of 3 and describes a primary MTD endpoint, it does not report a completed estimate of the maximally tolerable dose. No dose-level outcome or endpoint analysis is recorded. The study therefore does not answer its stated dose-finding question in the posted results.
The primary outcome is not a simple count of any adverse event. It is framed around dose-limiting toxicities within cohorts, with specified severe events, and a separate 100-day mortality/toxicity threshold. The registry’s decision criterion calls for the lower one-sided 90% confidence bound on the observed rate to exceed 3%. Without a reported rate, bound, or endpoint result, that criterion cannot be evaluated from the record.
The enrollment figure is small in absolute terms, but it should not be turned into an estimate of precision or a formal power statement. The record provides no completed analysis and no sample-size justification. No observed effect is reported for the primary endpoint. A sample-size calculation or a hypothetical planning illustration cannot substitute for the endpoint data, and it would not establish what the study observed.
The single-group design also limits what the record can establish. It has no recorded comparator, and allocation is listed as NA. Any observations in this study would not provide a randomized contrast with another regimen or usual care. The stated research aim concerns dose and tolerability in the treatment setting described, not a comparative treatment effect.
The safety entry records 3 at risk for serious adverse events and 0 affected, and 3 at risk for other adverse events and 0 affected. These figures describe what is entered in the registry’s adverse-event summary. The death count is not reported. These safety entries should not be read as a completed assessment of the primary endpoint: the registry separately says the endpoints were not reached, and it does not provide event-level detail or follow-up completeness.
In general, zero recorded events in a small study do not demonstrate that an event cannot occur or precisely determine its frequency. The registry does not provide enough information to assess how complete adverse-event ascertainment was, whether all participants completed the 100-day timeframe, or how toxicity was evaluated for the dose-finding endpoint. The posted results therefore support a narrow conclusion: the record documents enrollment and adverse-event summary counts, but does not report an endpoint-based dose conclusion.
9. Statistical Methods Explained
What does the endpoint’s dose rule mean?
The MTD definition uses a dose-limiting toxicity threshold within a cohort. In general, dose-finding studies use observed tolerability at tested dose levels to inform which dose is acceptable for further study. The registry’s definition places the MTD one dose below the dose at which 33% of patients within a cohort experienced dose-limiting toxicity. The record does not report the cohort structure, tested dose levels, or the number of participants assigned to any cohort. It also does not report whether dose escalation or another dose-selection procedure was used.
The named toxicity criteria make the endpoint clinically specific: the registry identifies particular serious events that count as unacceptable. The endpoint description also includes a 100-day mortality/toxicity threshold. These criteria are a prespecified definition in the registry record, not evidence that an event occurred or that a dose met the rule. The study’s termination and uncompleted endpoints mean the record does not establish which dose, if any, satisfied the definition.
Why use a confidence bound?
The endpoint description does not rely only on the observed mortality/toxicity rate. It states that evidence would be an observed 100-day rate whose lower one-sided 90% confidence bound exceeds 3%. In general, a confidence interval or bound conveys uncertainty in an estimate: it distinguishes the observed rate from the range of values still reasonably compatible with the data under the method’s assumptions. A lower one-sided bound focuses on whether the data support a rate above a threshold. Requiring the bound to exceed the threshold is more demanding than comparing the observed rate alone with that threshold.
No observed rate or confidence bound is reported for this endpoint. Thus, the registry supplies a decision rule but not the numerical result needed to apply it. The confidence level and threshold do not by themselves indicate the event frequency or the study’s conclusion.
What can be inferred from a single-group design?
In general, a single-group study describes outcomes among participants receiving the study regimen. Without a separate comparator group, it cannot estimate a randomized difference between the regimen and another treatment. This design can be relevant to early dose and tolerability questions, but interpretation depends on the outcome data and how the dose-selection process was carried out. The registry identifies a single group and does not report a comparative analysis.
Allocation is recorded as NA and masking as none. Those classifications do not supply details about enrollment procedures, assessment methods, or the handling of subjective judgments. Such details are not reported in the registry record. The endpoint is a dose-finding measure, but the registry entry does not give enough information to reconstruct the statistical procedure for selecting a dose.
What do the adverse-event counts represent?
In general, an at-risk count is the number of participants represented in an adverse-event category, and an affected count records participants with a qualifying event in that category. The record lists 3 at risk and 0 affected for serious adverse events, and 3 at risk and 0 affected for other adverse events. These are descriptive registry counts. They do not provide event-level timing, duration, severity distribution beyond the category, or a confidence interval. The death count is not reported.
The summary counts should be interpreted within their documented scope. The registry does not report whether the adverse-event follow-up covered the full 100-day endpoint window for everyone, or whether the categories capture all events relevant to the MTD definition. General statistical caution is warranted: a zero count in a limited set of observations is not proof that the underlying risk is zero.
What is known about statistical planning?
The record does not report a statistical analysis plan, a sample-size justification, interim analyses, or an analysis population. It records no analyses. Those details prevent assessment of planned operating characteristics, data-handling rules, or whether any analytic decisions were made after enrollment. The record also contains a generic description of sample-size planning assumptions: two-sided significance level 0.05, equal allocation between two arms, and a normal approximation, with planning based on a stated fraction of an observed effect. Those assumptions do not match the registered single-group design as a comparative analysis, and no observed effect or completed endpoint result is reported. They should not be treated as the trial’s own design or as observed power.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists one primary outcome measure and no analyses. It does not report multiple testing adjustments, a hierarchy of endpoints, or a multiplicity plan. Because the study endpoints were not reached, the record offers no completed set of inferential results from which to assess multiplicity in practice. The absence of a reported plan does not show whether one existed elsewhere; it means the registry record does not report it.
Missing-data procedures are not reported in the registry record. There is no description of how incomplete follow-up, unavailable toxicity assessments, or missing endpoint information would be handled. The record does not state whether all enrolled participants completed the 100-day observation period. This matters because the primary endpoint’s stated timeframe is 100 days, and a rate estimate depends on knowing which participants were observed and how outcomes were ascertained.
Analysis populations are also not reported. The record does not define an intention-to-treat, per-protocol, or safety population, nor does it identify which participants contributed to any endpoint analysis. The adverse-event summary lists at-risk counts, but those counts alone do not define an analysis set or establish complete follow-up.
Without an analysis plan, missing-data rules, or reported endpoint results, it is not possible to evaluate whether the intended analysis was carried out as planned. The registry’s statement that endpoints were not reached is the clearest account of outcome status. No inferential conclusion about MTD can be recovered from the information recorded.
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 |
|---|---|---|---|
| Melphalan, Bortezomib, Autologous Transplant | 0 | 3 | 0.0% |
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 |
|---|---|
| Melphalan, Bortezomib, Autologous Transplant | 0 of 3 |
The registry’s adverse-event summary lists the Melphalan, Bortezomib, Autologous Transplant group with 3 at risk for serious adverse events and 0 affected. For other adverse events, it also lists 3 at risk and 0 affected. No top serious adverse-event terms are listed. The death count is not reported.
These are registry summary counts, not a detailed safety analysis. They do not describe individual events, onset, duration, severity beyond the serious or other category, or the methods used to collect events. The record does not report whether all participants were followed through the primary endpoint’s 100-day timeframe. It also does not state how the adverse-event summary relates to the dose-limiting toxicity definition.
In general, zero recorded events does not prove that the true risk is zero. That caution is especially important when the recorded at-risk group is small and when follow-up completeness is not described. The serious and other adverse-event counts can be reported as entered, but they do not establish that the study met its safety endpoint. The registry states that study endpoints were not reached.
12. What the Result Does, and Does Not, Mean
The record establishes that a phase I-II, single-group study of melphalan and bortezomib before autologous transplant was registered, that enrollment was 3, and that the study was terminated. It also records a primary endpoint centered on the maximally tolerable combination dose and specifies toxicity criteria and a 100-day mortality/toxicity rule. These are details about the study’s purpose and registry record.
The record does not establish the MTD. It explicitly says that study endpoints were not reached, and it reports no primary outcome analysis. There is no dose-level result, observed 100-day mortality/toxicity rate, or lower confidence bound with which to apply the stated criterion. The recorded adverse-event counts are descriptive and do not replace the missing endpoint result.
The study also does not establish a comparative effect. It has no separate comparator group, is classified as single-group, and has allocation listed as NA. Therefore, the registry does not provide a randomized comparison with another treatment. The treatment rationale described in the registry summary is not itself evidence of a treatment effect.
In general, a trial’s purpose and its results are distinct. A protocol may be designed to answer a question, but an uncompleted endpoint cannot answer it. Similarly, a small set of recorded safety counts cannot support a definitive risk estimate without further information about follow-up, event ascertainment, and analysis methods. The registry does not report those details.
The careful interpretation is limited: the study record describes an intended dose and tolerability investigation, records enrollment and adverse-event summary counts, and reports termination before the endpoints were reached. It does not support a conclusion about an acceptable dose, comparative efficacy, or the absence of clinically important toxicity.
13. Why This Trial Matters Statistically
This trial is statistically informative in part because it illustrates the difference between a registered endpoint and a reported result. The record gives a precise MTD definition and a specific 100-day mortality/toxicity decision rule. Yet it also states that the study endpoints were not reached. The presence of a detailed endpoint definition should not be mistaken for evidence that the endpoint was evaluated successfully.
The single-group design makes the distinction between dose-finding and comparative effectiveness especially important. A dose-finding question can be framed around toxicity within cohorts, while a comparative question requires a comparator and an appropriate contrast. This record describes the former but does not provide a completed dose decision or a randomized comparison.
The small enrollment and absent analysis results also highlight why raw counts need context. The adverse-event summary records zero affected for its serious and other categories, but the record does not document complete follow-up, analysis populations, or endpoint analyses. In general, counts without sufficient detail do not convey the uncertainty or completeness of safety assessment.
Finally, the entry illustrates why statistical planning assumptions should be distinguished from the actual design and results. Generic assumptions about equal allocation between two arms do not describe the registered single-group structure. Nor can planning calculations stand in for observed outcomes. A transparent registry interpretation separates the intended question, the recorded design, and what the posted results actually establish.
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 is that the registry says the study was terminated and the endpoints were not reached. The primary endpoint therefore has no reported result, and the reason for termination is not reported in the registry record. The record does not show whether dose levels were completed or whether any dose-selection decision was made.
Enrollment was 3, and the registry does not report a planned enrollment target or a sample-size justification. The record also does not provide cohort sizes, tested dose levels, or the number exposed at each dose. Without these details, the dose-finding process cannot be reconstructed.
The design is single-group, with allocation listed as NA and no comparator arm recorded. This prevents a randomized between-group comparison. Masking is listed as none, while details about outcome assessment and toxicity adjudication are not reported in the registry record.
Important analysis details are absent: no statistical analysis plan, interim analyses, missing-data procedures, or analysis populations are reported. The registry lists no analyses. It does not report whether participants completed the 100-day endpoint timeframe, or provide an observed mortality/toxicity rate or confidence bound.
The adverse-event summary provides aggregate counts but no event-level descriptions; the death count is not reported. The transplant description is incomplete in the arm text. These limitations restrict interpretation to the study’s recorded purpose, status, enrollment, and summary adverse-event counts rather than a conclusion about dose or safety.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Melphalan and Bortezomib Prior to Autologous Stem Cell Transplant in Treating Patients With Multiple Myeloma — NCT02353572.
- Registry record last updated 2015-03-09; status last verified 2015-01.
- Results first posted 2015-03-09.
- 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
NCT02353572 is a phase I-II, single-group study sponsored by University of Colorado, Denver, evaluating melphalan and bortezomib before autologous transplant for patients with multiple myeloma. Dexamethasone is also listed. Enrollment is recorded as 3; study status is terminated. The recorded start is 2009-11 and primary completion is 2011-09.
The primary outcome is the maximally tolerable dose of melphalan and bortezomib in combination, with a 100-day timeframe and specified toxicity criteria. The registry states that study endpoints were not reached and lists no analyses. It does not report a completed MTD result, an endpoint estimate, or a comparator-based result.
The adverse-event summary records 0 affected for serious adverse events and 0 affected for other adverse events, with 3 at risk in each category. The death count is not reported. No separate comparator group is recorded.