Bortezomib, Doxorubicin Hydrochloride Liposome, and Dexamethasone Followed by Thalidomide and Dexamethasone With or Without Bortezomib in Treating Patients With Multiple Myeloma: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Bortezomib, Doxorubicin Hydrochloride Liposome, and Dexamethasone Followed by Thalidomide and Dexamethasone With or Without Bortezomib in Treating Patients With Multiple Myeloma (NCT00458705), a na phase 2 study. The primary outcome is Disease Response.

2. Clinical Question

The trial asks whether this treatment approach can be evaluated for disease response and side effects in the stated multiple myeloma population. Its design is important to the interpretation: it is a single-group phase II study, not a randomized comparison of BDD followed by one sequence against BDD followed by another. Although the treatment description includes two possible post-BDD sequences, the registry record does not report how participants were assigned to or received those sequences. It therefore does not establish a like-for-like comparison between them.

The registry lists an enrollment of 45 participants. That number describes enrollment, not the number necessarily assessed for the primary outcome at the end of therapy. The analysis population and the number with evaluable disease-response measurements are not reported in the registry record. The central clinical outcome is also not reported there, so the record cannot answer how many participants had a response.

3. Trial Design

This was a phase II study sponsored by Memorial Sloan Kettering Cancer Center and registered as NCT00458705. The study status is completed. The registry lists a start in 2006-11 and primary completion in 2011-04. Enrollment was 45. The population was described as patients with symptomatic untreated high-risk or primary resistant multiple myeloma.

The registered model is single group, allocation is NA, and masking is none. These features mean the record does not describe a randomized, masked comparison between treatment strategies. The trial title and arm description present sequential treatment: bortezomib, pegylated liposomal doxorubicin, and dexamethasone, followed by thalidomide and dexamethasone, with or without bortezomib in the later combination. The arm description states that treatment begins with three cycles of BDD. It does not give the full treatment schedule or explain how the later sequence was selected.

The distinction between a treatment sequence and a comparator matters. A record can describe alternative treatment components without documenting a randomized allocation or an analysis comparing them. Here, the registry specifically identifies a single-group model and notes that this is not a randomized comparison. The available record does not show whether the later treatment choices were determined by a protocol rule, clinician decision, participant characteristics, or another process; that information is not reported in the registry record.

The registry's purpose statement says the phase II trial studied side effects and how well the sequence worked. The only registered primary outcome measure is disease response. The record lists no analyses. It does not report a statistical analysis plan, analysis populations, sample-size justification, interim analyses, or criteria for choosing or changing the post-BDD treatment sequence. The sample-size planning illustrations associated with the posted results are not the trial's own design justification and should not be interpreted as a record of the study's planned enrollment or an observed measure of power.

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

Reasons for not completing this period:

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.

6. Primary Endpoint

The registry lists the primary outcome as Disease Response, measured over 2 years.

The primary outcome is disease response, recorded in participants, with a timeframe of 2 years. The registry describes assessment of myeloma response using standard electrophoretic and immunofixation tests of blood and urine for monoclonal protein, together with bone marrow aspirate and biopsy. These assessments were to be performed at enrollment and at the conclusion of therapy.

In general, measuring a disease response with laboratory and tissue assessments can provide evidence about changes in disease status during treatment. Blood and urine testing for monoclonal protein and bone marrow evaluation examine different aspects of myeloma, so they contribute distinct information to an assessment. That is a general explanation of the measurement approach, not a claim about the response observed in this study.

The registry names the outcome as disease response but does not provide the response categories, thresholds, adjudication process, or a detailed rule for combining test results. Those details are not reported in the registry record. Nor does the record provide the number of participants assessed, the number responding, or a statistical estimate of response. The endpoint description therefore identifies what was intended to be measured and when, but does not establish the study's observed disease-response result.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry identifies this as a phase II study with a single-group model. Allocation is listed as NA and masking as none. These labels describe design features; they do not provide an analysis method. The record reports zero analyses, so no statistical model, test, or estimate for the primary outcome is available in the registry record.

What does a single-group design allow?

In general, a single-group design can describe outcomes among participants receiving a treatment approach. If a defined outcome and its results are reported, readers can examine the observed frequency or pattern in that group. A single-group study does not, by itself, provide the counterfactual outcome: what would have happened to comparable participants under a different treatment or no treatment. A randomized control group can support a more direct treatment comparison because randomization aims to balance other influences between groups. This study is not registered as such a comparison.

The treatment description includes a shared initial sequence of BDD and two possible later sequences. The record does not say how the choice between those later options was made, and it provides no group-specific outcome analysis. Consequently, there is no basis in the registry record for treating the options as randomized arms or for estimating a comparative effect between them. Any interpretation of their relative outcomes would require information not reported in the registry record.

How should the primary outcome be understood?

The primary outcome is disease response, measured using blood and urine electrophoretic and immunofixation tests for monoclonal protein and bone marrow aspirate and biopsy. Assessments are described at enrollment and at the conclusion of therapy, with a timeframe of 2 years. In general, a response outcome requires an operational definition: the tests or measurements that qualify, the thresholds for each response category, and the rules for handling incomplete or discordant assessments. Those detailed criteria are not reported in the registry record. The registry also does not report the observed response counts or an estimate of response.

In general, binary outcomes count whether participants meet a defined condition or do not. This record identifies the outcome type as participants with an event, expressed as counts, but does not report the primary endpoint results. Without the response definition and observed counts, readers cannot check how participants were classified, calculate an uncertainty interval, or evaluate whether exclusions or missing measurements might affect the result.

What do the planning illustrations mean?

The sample-size assumptions describe planning illustrations computed from an observed effect, rather than the trial's own design. They specify a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation; the effect to detect is described as a stated fraction of the observed effect. These are assumptions for an illustration, not evidence that this trial enrolled randomized arms, used those assumptions in its protocol, or achieved a particular probability of detecting an effect. The registry does not report the trial's sample-size justification. Planning illustrations are not observed power and should not be used to describe how informative this completed study was.

In general, sample-size calculations depend on the outcome, the effect considered important to detect, variability or event frequency, the chosen significance level, and the intended power. Changing assumptions changes the planning result. For binary outcomes, planning also depends on the event probability in the groups being compared. For time-to-event outcomes, the number of events can be central to the calculation. These general principles do not fill in the missing design justification for this study. The planning assumptions described with the posted results do not match the registry's single-group design as a description of the trial itself, because the illustration specifies equal allocation between two arms.

Why does over-dispersion matter in general?

For count outcomes, a simple model may assume that the variability is determined by the mean. Over-dispersion means that actual variability is greater than that assumption allows. If it is ignored, standard errors can be too small and uncertainty can appear narrower than warranted. A model that accounts for over-dispersion may give more realistic uncertainty. This is a general statistical point; the registry does not report an over-dispersion analysis, and the primary outcome is recorded as a participant response rather than a reported count model.

What uncertainty information is missing?

The registry does not report an estimate or confidence interval for disease response, a p-value, or a statistical model. In general, a confidence interval gives a range of values compatible with the data under the specified method and communicates estimation uncertainty. It is not a guarantee that the true value lies in that range. A p-value is interpreted relative to a null hypothesis and the model assumptions; it does not measure the size or clinical importance of an effect. Neither quantity can be discussed for the primary outcome when no result or analysis is reported.

The record also does not report a prespecified analysis population, how missing measurements were handled, whether any outcomes were adjusted for other variables, or whether analyses were planned at interim time points. These omissions mean the registry record cannot establish which participants contributed to a primary outcome analysis or how its uncertainty would have been calculated. They should be treated as unavailable information rather than assumptions about the conduct of the study.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists one primary outcome measure, disease response, and zero analyses. It does not report a statistical analysis plan, analysis populations, interim analyses, or the handling of missing outcome measurements. It also does not report whether secondary outcomes were analyzed or whether any adjustment for multiple testing was planned. These items are not reported in the registry record.

In general, multiplicity arises when several hypotheses or outcomes are tested and the chance of at least one false-positive finding can increase across tests. Statistical plans may address this through a prespecified hierarchy, adjustment procedure, or clearly labeled exploratory analyses. That general concern cannot be assessed for this study from the registry entry: no analysis results or multiplicity strategy are reported. The absence of a described adjustment should not be interpreted as proof that none was used outside the registry record.

Missing outcome data can also affect interpretation. In general, participants without an endpoint measurement may differ from those with measurements, and the analysis approach determines how such data contribute to the estimate. The registry describes assessments at enrollment and at the conclusion of therapy, but does not report how many participants completed those assessments or how missing results were handled. Enrollment of 45 is not necessarily the denominator for every endpoint analysis.

The record does not define an intention-to-treat, per-protocol, or safety population for disease response. Nor does it describe exclusions, withdrawals, or the treatment of participants who did not complete therapy. Those details are not reported in the registry record, so the analysis population and potential effects of missingness cannot be evaluated.

11. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: thrombosis/thrombus/embolism (13.3%), renal and urinary disorders -other, specify, renal failure (11.1%), dyspnea (6.7%), hyperglycemia (6.7%), pneumonia (6.7%).

The registry lists one combination therapy group, with 45 participants at risk for serious adverse events and 22 participants affected. It also lists 45 at risk for other adverse events and 23 affected. The record does not report deaths in the provided serious adverse event group field as a numeric value; a blank death entry should not be read as a count of zero.

The listed serious adverse event terms and percentages are thrombosis/thrombus/embolism, 13.3%; renal and urinary disorders -other, specify, Renal failure, 11.1%; dyspnea, 6.7%; hyperglycemia, 6.7%; pneumonia, 6.7%; and infection, 6.7%. These are registry-listed categories and percentages. The record does not provide further detail on timing, duration, event severity beyond the serious-event classification, attribution to treatment, or whether a participant experienced more than one listed event.

In general, adverse event counts describe events observed in a study and do not establish that treatment caused them. The figures should be read as safety reporting for the registered group, not as a comparison against another treatment or an untreated group. The registry does not report an overall comparative safety analysis, and this single-group design cannot provide a randomized safety contrast.

12. What the Result Does, and Does Not, Mean

The registry record establishes that this was a completed phase II, single-group study enrolling 45 participants with symptomatic untreated high-risk or primary resistant multiple myeloma. It describes treatment beginning with BDD and continuing with thalidomide and dexamethasone, with or without bortezomib. It identifies disease response as the primary outcome and describes blood, urine, and bone marrow assessments. These are details about the registered design and intended measurement.

The record does not report the disease-response result. It therefore does not show how many participants responded, provide an estimated response frequency, or quantify uncertainty around an estimate. It also does not report a statistical analysis of the primary outcome. A description of what was intended to be measured cannot substitute for the observed outcome.

The safety entries give counts of participants affected and a list of serious adverse event categories with percentages. They do not provide the context needed for a comparative assessment, such as a control group, event attribution, or detailed participant-level information. The reported safety information can be described, but it cannot establish from this record alone whether an event was caused by treatment.

In general, a single-group study can document experience among participants receiving the treatment approach, but it cannot isolate the effect of treatment from other explanations as a randomized comparison can. The registry does not describe random allocation, and it explicitly notes that the study is not a randomized comparison. The two post-BDD options should therefore not be interpreted as having been compared on equal terms.

The record also does not report the detailed response criteria, analysis population, missing-data approach, confidence intervals, p-values, or statistical model. Those gaps limit assessment of both the outcome definition and the precision of any result. The study's completion status does not itself supply missing findings. The appropriate interpretation is that the registry documents a trial design and selected safety information, while the primary disease-response result and its statistical interpretation are not reported in the registry record.

13. Why This Trial Matters Statistically

This study illustrates why design labels and outcome reporting need to be read together. The title and treatment description include multiple drugs and alternative later sequences, but the registered model is single group and allocation is NA. Without a randomized comparator and a documented assignment process, the treatment options cannot be treated as a head-to-head experiment. The design determines which questions an analysis could answer, regardless of how many treatment components are named.

It also illustrates the difference between an endpoint description and an endpoint result. The registry gives a clear general account of how disease response was intended to be assessed: tests of blood and urine for monoclonal protein and bone marrow evaluation, at enrollment and at conclusion of therapy. Yet it does not report the response criteria in detail or the observed response. Readers need both a defined measurement and its results to evaluate an endpoint statistically.

The listed adverse event information provides another useful distinction. Counts of affected participants and percentages of serious adverse event categories are descriptive safety information. In a single-group record, they do not provide a randomized comparison of safety, and the listed categories do not establish causation. Understanding the denominator, event definition, and analysis context is essential when reading such figures.

Finally, planning illustrations are conceptually different from the study's design justification and from observed results. The stated illustration assumptions include equal allocation between two arms, while the registered trial is single group. Keeping those contexts separate prevents planning calculations from being mistaken for actual enrollment decisions, observed power, or evidence of comparative effects. The registry entry shows how a record can convey meaningful design and measurement details while leaving key outcome and analysis information unavailable.

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 limitation for interpreting efficacy is that the registry record does not report the disease-response result. It names the endpoint and assessment approach, but provides no response count, estimate, confidence interval, p-value, or analysis. The response criteria and detailed rules for classifying participants are also not reported in the registry record.

The single-group model and absence of random allocation mean there is no registered control group for a like-for-like treatment comparison. Although the treatment description includes alternative post-BDD sequences, the registry does not report how participants entered those sequences or provide outcomes by sequence. Comparative effects between the sequences cannot be determined from this record.

The record lists enrollment of 45, but the number included in a disease-response analysis and the number completing endpoint assessments are not reported. The handling of missing data, withdrawals, exclusions, and analysis populations is not reported in the registry record. This prevents assessment of whether the enrollment total corresponds to the endpoint denominator.

Safety interpretation is also limited. Serious and other adverse event counts and selected serious-event percentages are listed, but the registry does not report event timing, duration, attribution, detailed severity, or whether listed events overlapped within participants. The death entry is not populated with a numeric value, so it cannot be interpreted as a reported zero.

Finally, the registry does not report the trial's sample-size justification, statistical analysis plan, interim analyses, or multiplicity approach. Planning illustrations use assumptions for an equal-allocation two-arm calculation and are not a substitute for those trial-specific details. These limitations concern what can be established from the registry record; they do not demonstrate that unreported procedures or analyses were absent from the study itself.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Bortezomib, Doxorubicin Hydrochloride Liposome, and Dexamethasone Followed by Thalidomide and Dexamethasone With or Without Bortezomib in Treating Patients With Multiple Myeloma — NCT00458705.
• Registry record last updated 2016-01-22; status last verified 2015-12.
• Results first posted 2016-01-22.
• 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.

18. Record Summary

NCT00458705 is a completed phase II study sponsored by Memorial Sloan Kettering Cancer Center. It enrolled 45 participants and registered a single-group, unmasked design with allocation listed as NA. The population was patients with symptomatic untreated high-risk or primary resistant multiple myeloma.

The treatment description begins with bortezomib, pegylated liposomal doxorubicin, and dexamethasone, followed by thalidomide and dexamethasone, with or without bortezomib. Disease response is the primary outcome, with blood, urine, and bone marrow assessments described over a timeframe of 2 years. The record lists serious and other adverse event counts and selected serious-event categories.

The disease-response result, detailed statistical analysis, analysis population, missing-data handling, and sample-size justification are not reported in the registry record. Because the study is single group, its registered information does not constitute a randomized comparison between the alternative treatment sequences.