Bortezomib and Vorinostat in Treating Patients With Multiple Myeloma Who Have Undergone Autologous Stem Cell Transplant: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Bortezomib and Vorinostat in Treating Patients With Multiple Myeloma Who Have Undergone Autologous Stem Cell Transplant (NCT00839956), a na phase 2 study. The primary outcome is Toxicity as Assessed by National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v3.0.

2. Clinical Question

The study also listed time to disease progression among patients who progressed, survival for all patients, and median follow-up survival for all patients as secondary outcomes. The registry record does not report numerical results for those outcomes. Its stated primary question concerns toxicity; it does not establish whether the regimen improves survival or delays progression compared with another approach.

3. Trial Design

This was a completed phase II study sponsored by Fred Hutchinson Cancer Center. The registry lists an enrollment of 31 and a single-group model. Allocation is recorded as not applicable, and masking is listed as none. These design features mean the study describes treatment in one group rather than comparing randomized groups.

Participants received bortezomib and vorinostat after autologous stem cell transplant. Bortezomib was administered IV on days 2 and 5, while vorinostat was taken by mouth once daily on days 1-14. Courses repeated every 28 days for 12 courses unless disease progression or unacceptable toxicity occurred. The registry record does not report additional details about adherence, dose changes, or treatment actually received.

The registry lists the study start as 2009-02, primary completion as 2012-08, and status as completed. The primary outcome covered the first three months of therapy and evaluated toxicity using NCI CTCAE version 3.0. Its description focused stopping rules on withdrawal due to significant toxicity, defined in the entry as grade IV, non-hematological, non-metabolic, nonperipheral neuropathy.

Four outcome measures are listed, including the primary toxicity outcome and secondary progression and survival outcomes. The registry record does not report a statistical analysis plan, analysis population definitions, or the methods used to analyze the secondary outcomes. No analysis records are listed. These omissions limit what can be concluded about how the investigators intended to estimate treatment effects or handle uncertainty.

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:

Analysis population for the primary outcome, as defined in the registry: No patients met stopping rules for significant toxicity in the first three months of therapy.

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 Toxicity as Assessed by National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v3.0, measured over The first three months of therapy.

The primary endpoint counts participants in relation to toxicity assessed using NCI CTCAE version 3.0. Its stated observation period is the first three months of therapy. The endpoint description emphasizes stopping rules for unacceptable toxicity, specifically rules based on withdrawal due to significant toxicity of the listed grades and types. The registry reports that no patients met those stopping rules during that period.

A toxicity endpoint is used to describe whether treatment-related safety concerns reach a prespecified operational threshold during a defined period. Such a threshold can guide decisions about continuing a study, but it is not a complete account of every adverse event. A participant may experience an adverse event without meeting a stopping rule. Thus, the reported stopping-rule finding should not be interpreted as evidence that no toxicity or other adverse events occurred.

General statistical context: a participant-count endpoint records whether people meet a specified criterion, rather than measuring the severity or duration of every event. To interpret a count fully, readers need the criterion, observation window, and population included in the assessment. The registry states the criterion and time period, but does not report a separate numerical primary-endpoint count or additional details about the analyzed population. The finding is therefore best read narrowly as a report about the study’s stated stopping rules in the first three months.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does a single-group design tell us?

The study’s single-group model means the registry describes outcomes in a treatment group without a concurrent control group. In general, a control group helps distinguish the outcome observed under treatment from what might have happened under another care strategy. Without that comparison, a result is descriptive rather than a randomized estimate of the difference between strategies. The registry also lists allocation as not applicable and masking as none. It does not report a statistical plan that would add a different form of comparison.

The regimen was repeated on a schedule, but the registry entry alone does not establish how consistently it was received, how often doses changed, or whether all participants completed treatment. Those details are not reported in the registry record. They matter when interpreting outcomes because the recorded group-level results may not describe exposure identically for every participant.

How should a participant-count outcome be read?

The primary endpoint is framed around participants meeting a toxicity stopping rule during a defined time window. A count answers how many people met that rule; it does not state how many total events occurred, how severe every event was, or how long an event lasted. The registry reports that no patients met the stopping rules for significant toxicity in the first three months, but does not report a separate numerical count for all toxicity events under the primary endpoint.

General statistical context: when a binary outcome is expressed as a proportion, the numerator is the number meeting the criterion and the denominator is the number assessed. A confidence interval describes uncertainty around an estimate, rather than guaranteeing that the true value lies within a particular range. The registry record does not report a confidence interval for the primary endpoint. The adverse-event entries do give their own at-risk denominators, which should be read separately rather than assumed to be interchangeable.

What do the analysis details establish?

The registry lists four outcome measures and no analysis records. It does not report hypothesis tests, confidence intervals, adjustment methods, covariate models, or a detailed statistical analysis plan. It is therefore not possible from the registry record to determine whether any unreported analysis was adjusted, how the secondary outcomes were analyzed, or what analysis population was used for each outcome. The absence of analysis records is not evidence that no analyses were conducted; it means the registry does not provide those results in its analysis entries.

General statistical context: time-to-event outcomes account for both when an event occurs and how long a participant is observed. Participants without an event by the end of observation may be censored, meaning their later event time is unknown. The listed secondary outcomes include time to disease progression and survival, but the registry record does not report event counts, follow-up summaries, survival estimates, or methods for handling censoring. No time-to-event result can therefore be reconstructed from the listed outcome names alone.

How should planning calculations be distinguished from observed results?

The registry’s stated sample-size assumptions describe planning illustrations based on an observed effect, not the trial’s own design. They specify a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation, with the effect to detect expressed as a stated fraction of the observed effect. The description distinguishes total event counts for time-to-event calculations from participants per arm for other calculations. These assumptions do not make this single-group trial a two-arm comparison and should not be treated as its enrollment rationale.

General statistical context: a sample-size calculation asks how many observations a hypothetical study might need under chosen assumptions. Its result depends on the assumed effect, variability or event rate, significance level, power target, allocation, and analysis method. Such a calculation is a planning illustration, not evidence that the completed study had a particular probability of detecting an effect. The registry does not report the trial’s own sample-size justification or a power analysis. No numerical sample-size result or power value is reported in the registry record.

Over-dispersion is a general issue when observed variability exceeds what a statistical model assumes; ignoring it can make uncertainty appear too small. The registry record does not report a model for the primary endpoint or evidence about over-dispersion, so this issue cannot be assessed for the trial’s analyses. More broadly, an estimate is only as interpretable as its outcome definition, denominator, follow-up, and analysis choices. The record provides some endpoint and safety definitions, but leaves several of those analysis details unreported.

10. Exact Estimates for Each Arm

No two-arm comparison is shown for this trial, but each arm's result can still be summarized with exact interval estimates computed from the posted counts. The Clopper-Pearson interval is exact and conservative; the Wilson interval is a common closer-to-nominal alternative; the Bayesian credible interval uses a uniform Beta(1, 1) prior. For small groups the three can differ noticeably.

R code and output

arm    <- c("Arm I (Bortezomib and Vorinostat)")
n      <- c(31)
events <- c(0)
for (i in seq_along(n)) {
  ci <- binom.test(events[i], n[i])$conf.int          # Clopper-Pearson exact interval
  cr <- qbeta(c(0.025, 0.975), 1 + events[i], 1 + n[i] - events[i])   # Bayesian, uniform Beta(1,1) prior
  wi <- (function(x, n) { p <- x / n; z <- qnorm(0.975); d <- 1 + z^2 / n
    c((p + z^2 / (2 * n) - z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d, (p + z^2 / (2 * n) + z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d) })(events[i], n[i])
  cat(sprintf("ARM|%s|%d|%d|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f\n", arm[i], n[i], events[i], 100 * events[i] / n[i],
              100 * ci[1], 100 * ci[2], 100 * wi[1], 100 * wi[2], 100 * cr[1], 100 * cr[2]))
}

ARM  Arm I (Bortezomib and Vorinostat)  31  0  0.0  0.0  11.2  0.0  11.0  0.1  10.9

11. Multiplicity, Missing Data and Analysis Populations

The registry lists a primary toxicity outcome and secondary outcomes covering disease progression and survival. Considering several outcomes creates a general multiplicity issue: the more questions examined, the greater the chance that a seemingly notable result may arise by chance when many statistical tests are conducted. Whether and how that concern should be addressed depends on the planned analyses and the purpose of each outcome. A multiplicity strategy is not reported in the registry record, and no analysis records are listed.

The record does not report p-values, confidence intervals, or statistical tests for the outcomes. It is therefore not possible to determine whether any adjustment for multiple testing was used, or whether the listed secondary outcomes were analyzed in a prespecified way. Their presence in the registry does not establish that a particular result was observed.

Missing-data handling is also not reported in the registry record. The safety entries list 31 at risk for serious adverse events and 30 at risk for other adverse events, but the reason for the different denominators is not stated. The registry does not describe how incomplete follow-up, missing outcome assessments, or withdrawals were handled in analyses.

The analysis populations are not reported in the registry record. For example, the entry does not state whether outcome summaries included everyone enrolled, only participants who began treatment, or another defined group. These definitions affect the denominator and interpretation of an estimate. Without them, readers should not assume that enrollment and the population assessed for every outcome are identical.

12. Safety Results

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

Deaths

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: influenza a infection (3.2%), elevated creatinine kinase levels (3.2%), anaphylactic reaction (3.2%).

For Arm I, the registry reports 3 participants with serious adverse events among 31 at risk. It reports 21 participants with other adverse events among 30 at risk, and 0 deaths. These are separate entries with separate denominators; the reason that the at-risk count differs is not reported in the registry record. The counts should not be combined or treated as interchangeable measures.

The leading serious adverse-event terms listed are Influenza A Infection, Elevated Creatinine Kinase Levels, and Anaphylactic reaction. Each term is recorded as 3.2%. The registry does not provide additional detail in this entry about event timing, severity beyond the serious classification, recurrence, or attribution to treatment. The term-specific percentages should not be read as an overall serious-event percentage or added together to create one.

General statistical context: adverse-event counts describe what was recorded under the study’s collection and classification procedures. A participant can potentially experience more than one event, so counts of participants and counts of event terms do not necessarily represent the same quantity. The record does not specify whether participants appear under more than one listed term. These safety figures complement, but do not replace, the primary finding about whether stopping rules were met.

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

The primary safety finding is limited and specific: no patients met the study’s stopping rules for significant toxicity in the first three months of therapy. It describes the result of applying the stated stopping criteria during that window. It does not establish that no toxicity occurred, that all adverse events were mild, or that participants had no safety concerns after the primary observation period.

The adverse-event entries add descriptive information, including serious adverse events, other adverse events, and deaths. They are not a controlled comparison and do not establish that the regimen caused or prevented a particular event. The registry does not report further information needed to interpret event attribution, timing, or the difference in at-risk denominators.

The study’s single-group design also limits conclusions about disease outcomes. Although progression and survival are listed as secondary outcomes, their numerical results are not reported in the registry record. The study entry therefore does not establish a comparative effect on progression or survival. A treatment effect would require an appropriate comparison and outcome results, neither of which can be inferred from the listed outcome names.

General statistical context: absence of a reported threshold event is not equivalent to proof that the true risk is zero. Estimates from a study are subject to uncertainty, and an unreported confidence interval cannot be inferred from a count alone. The registry record does not report a primary-endpoint confidence interval or a statistical test. The most defensible interpretation is therefore descriptive: the registry reports that the specified stopping rules were not met in the first three months, alongside the separately listed adverse-event counts.

14. Why This Trial Matters Statistically

This trial illustrates why the question an endpoint answers should be kept distinct from broader questions about safety and efficacy. Its primary endpoint focused on whether participants met toxicity stopping rules within the first three months. That operational question is not the same as asking whether any adverse event occurred, and it is not a measure of disease control or survival.

The record also illustrates the limits of interpreting a single-group study. Without a control group, the observations describe outcomes in the treated group but do not provide a randomized estimate of what would have happened under a different strategy. This distinction matters particularly when the study lists progression and survival outcomes but does not report their numerical results.

Denominators are another important part of statistical reading. The safety entries use different at-risk counts for serious and other adverse events. Because the record does not explain that difference, readers should preserve the denominators as reported and avoid treating the entries as directly interchangeable. The term-specific serious-event percentages are also not an overall event rate.

Finally, the registry’s planning assumptions are separate from the design actually used. A hypothetical calculation based on a two-arm allocation does not change the study’s single-group structure, nor does it establish that the trial was designed with that calculation. Distinguishing observed findings, analysis details, and planning illustrations helps prevent a descriptive safety result from being overstated as a comparative or definitive conclusion.

15. 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 single-group design has no concurrent comparator, so the study cannot provide a randomized estimate of how outcomes differ from another treatment strategy. Allocation is listed as not applicable, and masking is listed as none. The record does not report other design features that would support a causal comparison.

The primary endpoint is narrowly defined by a stopping rule during the first three months. The registry states that no patients met the rule, but does not provide a separate numerical primary-endpoint count or confidence interval. That result cannot describe all toxicity, all adverse events, or safety beyond the stated period.

Important analysis details are absent. The statistical analysis plan, analysis populations, missing-data methods, and methods for the secondary outcomes are not reported in the registry record. The record also does not provide numerical results for progression or survival. The adverse-event entry lists different at-risk denominators for serious and other events without explaining why.

The registry lists an enrollment of 31, but does not report further detail about treatment adherence, dose modifications, or the completeness of follow-up. These omissions constrain interpretation of exposure and outcome ascertainment. The sample-size assumptions are described as planning illustrations rather than the trial’s own design rationale; the trial’s own sample-size justification is not reported in the registry record.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Bortezomib and Vorinostat in Treating Patients With Multiple Myeloma Who Have Undergone Autologous Stem Cell Transplant — NCT00839956.
• Registry record last updated 2017-05-09; status last verified 2017-04.
• Results first posted 2017-03-29.
• 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.

19. Record Summary

This completed phase II study evaluated bortezomib and vorinostat as maintenance therapy after autologous stem cell transplant for multiple myeloma. It used a single-group design, with enrollment listed as 31. Treatment consisted of bortezomib IV on days 2 and 5 and vorinostat by mouth once daily on days 1-14, repeated every 28 days for 12 courses unless progression or unacceptable toxicity occurred.

The primary outcome assessed toxicity using NCI CTCAE version 3.0 during the first three months. The registry reports that no patients met stopping rules for significant toxicity in that period. Safety entries list 3 participants with serious adverse events among 31 at risk, 21 with other adverse events among 30 at risk, and 0 deaths. Numerical results for the listed progression and survival outcomes are not reported in the registry record. The record does not report a statistical analysis plan, analysis populations, or missing-data methods.