Study of Panobinostat in Combination With Bortezomib and Dexamethasone in Japanese Patients With Relapsed/Refractory Multiple Myeloma: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Study of Panobinostat in Combination With Bortezomib and Dexamethasone in Japanese Patients With Relapsed/Refractory Multiple Myeloma (NCT02290431), a na phase 2 study. The primary outcome is Percentage of Participants With Near Complete Response (nCR)/ Complete Response (CR) Rate.

2. Clinical Question

Statistically, the study asks how often this response category was observed among participants receiving the combination, as defined by the registry’s outcome description. It does not directly answer how that response rate compares with another treatment or with outcomes under a control condition. The design is open label, and the primary outcome is based on investigator assessment. Those features matter when interpreting an observed response proportion: the result would describe the recorded responses in the study group, rather than an effect estimated from a randomized between-group comparison.

3. Trial Design

The registry describes a Phase II, multicenter, single-arm, open-label study of panobinostat with bortezomib and dexamethasone in Japanese patients with relapsed or refractory multiple myeloma. The record lists Novartis Pharmaceuticals as the sponsor, enrollment of 31, and a completed status. The recorded study start is 2014-12-16 and the primary completion date is 2017-12-29.

There was one treatment group: LBH589, or panobinostat, with bortezomib and dexamethasone. The arm description states that participants received the combination on a 2 weeks on/1 week off schedule. Masking is recorded as none, so the study is open label. Allocation is NA, consistent with the registry’s single-group model; no randomized allocation or concurrent control group is listed.

The primary outcome was the percentage of participants with near complete response or complete response after 24 weeks (8 cycles; cycle = 21 days). The registry defines the response as the participant’s best overall response, assessed by the investigator using modified European Society for Bone and Marrow Transplantation criteria. The outcome population is the Full Analysis Set, defined as all subjects who took at least one dose of any study treatment component.

The registry also lists secondary outcomes involving progression-free survival, overall response rate, overall survival, minimal response rate, time to response, time to progression or relapse, duration of response, and quality of life measured with the FACT/GOG-Ntx total score. The record lists 16 outcome measures and one analysis, but additional details about the analysis are not reported in the registry record. The total number screened, treatment exposure, follow-up completeness, and reasons for discontinuation 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

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Full Analysis Set (FAS): The Full analysis set (FAS) comprised of all subjects who took at least one dose of any study treatment component.

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: The Full analysis set (FAS) comprised of all subjects who took at least one dose of any study treatment component.

6. Primary Endpoint

The registry lists the primary outcome as Percentage of Participants With Near Complete Response (nCR)/ Complete Response (CR) Rate, measured over after 24 weeks (8 cycles; cycle = 21 days).

The primary endpoint is the percentage of participants whose best overall response was near complete response or complete response after 24 weeks (8 cycles; cycle = 21 days). Response was defined using modified EBMT criteria and assessed by the investigator. The specified analysis population is the Full Analysis Set, comprising subjects who took at least one dose of any study treatment component.

A response proportion is a binary-outcome summary: each participant is classified according to whether the defined response occurred, and the percentage describes the share meeting that criterion. Such an endpoint can express how frequently a response category was recorded during treatment. It is different from a time-to-event endpoint, which describes the time until an event, and from a comparative treatment effect, which requires a contrast between treatment conditions.

Near complete response and complete response are combined in this primary outcome. The registry’s endpoint description therefore focuses on the proportion reaching either category as their best overall response, rather than reporting the two categories separately. The timeframe and response definition specify what counts and when it is assessed, helping readers understand the intended interpretation of the measure.

The registry lists a 90% confidence interval as the endpoint’s dispersion measure, but the numerical response percentage and interval are not reported in the registry record. Without those values, the observed response frequency and its statistical precision cannot be described. The primary endpoint may be relevant to characterizing response in the enrolled group, but the single-group design does not by itself provide a comparison with another treatment or control condition.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary outcome is a binary response proportion. For each participant in the Full Analysis Set, the endpoint definition distinguishes whether the best overall response met the combined near complete response or complete response criterion. The resulting percentage would summarize the frequency of that classification in the study group. The registry states that the outcome uses investigator assessment according to modified EBMT criteria after 24 weeks (8 cycles; cycle = 21 days). It does not report the numerical estimate.

What a confidence interval communicates

In general, a confidence interval expresses uncertainty around an estimate. For a response proportion, it gives a range of values compatible with the observed data under the interval’s statistical assumptions. A narrower interval generally indicates greater precision, while a wider interval indicates more uncertainty. The registry specifies a 90% confidence interval for the primary endpoint, but neither its limits nor the response percentage are reported in the registry record. The interval’s calculation method is also not reported in the registry record, so it is not possible to assess which specific method was used.

What the single-group structure means

In general, a single-group study can describe outcomes among participants receiving a treatment regimen, but it does not estimate a randomized difference between that regimen and a concurrent comparison group. The record identifies this study as single group, with allocation recorded as NA, and lists no comparator arm. Therefore, a contrast between treatment groups is not part of the stated design. General statistical comparisons with external benchmarks would require information and assumptions not reported in the registry record.

Analysis population and response assessment

The primary outcome population is the Full Analysis Set. The registry defines it as all subjects who took at least one dose of any study treatment component. This makes treatment exposure part of the stated population definition. The record does not separately give the size of the Full Analysis Set, nor does it describe how participants with unavailable or unevaluable response assessments were handled. The assessment is identified as investigator-based, but methods for independent review, resolving disagreements, or maintaining consistency across sites are not reported in the registry record.

Interpreting the timeframe

The primary endpoint is tied to assessment after 24 weeks (8 cycles; cycle = 21 days), and it uses best overall response. In general, a best-response endpoint summarizes the best qualifying category recorded over the defined assessment period, rather than only the status at a single assessment visit. The registry’s wording specifies the best overall response and the assessment timeframe; detailed visit schedules, response confirmation rules, and handling of assessments outside the timeframe are not reported in the registry record.

Other outcome types

The secondary outcomes include percentages and time-to-event measures. In general, a time-to-event analysis accounts for both whether an event occurs and when it occurs; participants without a recorded event by the end of observation may contribute follow-up time under the analysis method. The registry lists progression-free survival, overall survival, time to response, time to progression or relapse, and duration of response, but does not report their numerical results or analysis details in the record. The specific time origins, event definitions, censoring rules, and estimation methods are not reported in the registry record.

For binary outcomes, over-dispersion is a general concern when the variability in observed outcomes exceeds what a model assumes. When present, an overly simple model may understate uncertainty. The registry information available does not identify a model for the response proportion or provide enough details to determine whether over-dispersion was assessed. No specific modeling approach should therefore be attributed to this study from the endpoint description alone.

The registry identifies a 90% confidence interval for the primary measure, but does not state a hypothesis test, a null value, an adjustment method, or the complete statistical analysis plan. It lists one analysis, yet the analysis specification and numerical result are not reported in the registry record. Accordingly, the statistical methods that can be described with confidence are the endpoint’s binary proportion format, its investigator-based definition, its stated analysis population, and its specified interval level—not a particular calculation procedure or inferential conclusion.

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("LBH589 + Bortezomib + Dexamethasone")
n      <- c(31)
events <- c(15)
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  LBH589 + Bortezomib + Dexamethasone  31  15  48.4  30.2  66.9  32.0  65.2  31.9  65.3

11. Multiplicity, Missing Data and Analysis Populations

The record lists 16 outcome measures and one analysis. It names secondary outcomes covering progression-free survival, overall response rate, overall survival, minimal response rate, time to response, time to progression or relapse, duration of response, and quality of life measured by the FACT/GOG-Ntx total score. These measures represent several kinds of outcomes, but the number of listed outcome measures does not reveal which were included in a formal testing family or how they were prioritized.

Multiplicity arises in general when multiple outcomes or hypotheses are examined: the chance of at least one apparently notable result can increase as the number of statistical tests grows. Whether and how this concern was handled in this study is not reported in the registry record. A multiplicity adjustment, testing hierarchy, or distinction between confirmatory and exploratory analyses is not reported in the registry record. The listed number of analyses alone does not establish that only one statistical question was considered.

Missing-data handling is likewise not reported in the registry record. The Full Analysis Set is defined as subjects who took at least one dose of any study treatment component, but this definition does not explain how missing response assessments, withdrawals, or unevaluable outcomes were classified. The record does not report imputation methods, sensitivity analyses, or the amount and pattern of missing outcome data.

The record also does not describe whether all enrolled participants were included in each secondary outcome analysis or specify analysis populations for those outcomes. These omissions limit assessment of how incomplete follow-up and multiple endpoints might affect interpretation. They should not be filled in by assuming a conventional approach: the endpoint definitions do not disclose the analysis plan.

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: pneumonia (12.9%), thrombocytopenia (6.5%), fatigue (6.5%), platelet count decreased (6.5%), coagulopathy (3.2%).

The safety figures describe a single treatment group, LBH589 with bortezomib and dexamethasone. The serious adverse event grouping lists 31 participants at risk and 14 affected. The other adverse event grouping lists 31 at risk and 31 affected. The registry also reports zero deaths for this group. These counts describe the posted safety record; they are not a comparison between treatment groups.

The most frequently listed serious adverse event terms are pneumonia at 12.9%, and thrombocytopenia, fatigue, and platelet count decreased at 6.5% each. Coagulopathy and cataract are each listed at 3.2%. These percentages are reproduced as recorded. The record does not provide event-level detail, severity grades, timing, duration, or information about whether an individual experienced more than one listed event.

In general, an at-risk count identifies the participants used as the denominator for a safety summary, while an affected count records participants with the specified event grouping. Participants may contribute to more than one event term, so term-specific counts should not be added to estimate a total number of affected participants. The registry’s aggregate figures do not establish whether an event was caused by treatment. They also do not offer a direct comparison with another regimen. The reported zero deaths applies to the listed group and should be read as a registry count, not as evidence about risks outside the study’s observed participants or follow-up.

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

The registry record establishes that a completed Phase II, open-label, single-group study evaluated panobinostat with bortezomib and dexamethasone in Japanese patients with relapsed or refractory multiple myeloma. It defines a primary response endpoint based on near complete response or complete response, assessed by the investigator using modified EBMT criteria. The endpoint is specified for after 24 weeks (8 cycles; cycle = 21 days), with the Full Analysis Set defined as subjects who received at least one dose of any study treatment component.

Those details describe what the study was designed to measure, but the numerical primary response result and its 90% confidence interval are not reported in the registry record. Therefore, the available information does not show the observed response percentage or how precisely it was estimated. The listed secondary outcomes also do not include numerical results in the information.

The study design further limits the conclusions that can be drawn. A single group has no concurrent control condition, and the record identifies no randomized comparison. The study can characterize outcomes recorded among its participants, but the design does not estimate a between-treatment difference. Open-label conduct and investigator assessment are also features readers should keep in view when considering how the endpoint was obtained.

The safety record reports serious adverse event and other adverse event groupings, along with selected serious event terms and a death count. These are descriptive counts for the listed study group. They do not provide comparative safety estimates, and the registry information does not establish that any event was caused by the treatment combination.

In general, a trial result should be interpreted in light of its endpoint definition, analysis population, precision, and design. For this study, the endpoint definition and some safety counts are available, while the primary efficacy estimate, interval limits, missing-data procedures, and detailed analysis plan are not reported in the registry record. That distinction separates what the record documents from conclusions it cannot support.

14. Why This Trial Matters Statistically

This study is statistically notable for the way its design and endpoint shape the interpretation. The registry describes a single-group Phase II study, not a randomized comparison. Its primary outcome is a response proportion, defined as the percentage with near complete response or complete response as the best overall response after 24 weeks (8 cycles; cycle = 21 days). This makes the intended estimand a description of response frequency in the defined study population, rather than a difference between treatment strategies.

The population definition is also explicit: the Full Analysis Set includes subjects who took at least one dose of any study treatment component. That definition is important because the population used for an estimate determines what group the estimate describes. The registry does not report the size of that analysis set separately, how missing assessments were handled, or the primary estimate itself. Consequently, readers can identify the target of the analysis but cannot evaluate its observed value or precision from the registry record.

The stated 90% confidence interval would ordinarily help communicate uncertainty around a response proportion. Its limits are not reported, so precision cannot be judged. This matters because a proportion alone, even if available, would not communicate how much uncertainty surrounds it. A single-group result also cannot address what would have happened under a different treatment condition without additional assumptions or a suitable comparator.

The record’s mix of response, survival, time-to-event, and quality-of-life outcomes illustrates why a statistical analysis plan matters. Multiple outcomes can answer different questions, and their interpretation depends on prespecified definitions, analysis populations, missing-data rules, and any approach to multiplicity. Those details are not reported in the registry record. The statistical importance of this trial therefore lies not in an efficacy conclusion unavailable from the record, but in recognizing the boundary between descriptive evidence and comparative inference.

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 most direct limitation for interpreting this record is that the primary response percentage and its 90% confidence interval are not reported in the registry record. The outcome definition is available, but without the numerical estimate there is no basis for describing the observed response frequency or its precision. Numerical results for the listed secondary outcomes are likewise not reported in the registry information.

The study is single group, with allocation recorded as NA and no concurrent comparator listed. Its design cannot provide a randomized between-group treatment contrast. The open-label conduct and investigator assessment of the primary outcome are additional features that may matter when evaluating response ascertainment. Details of any independent review or assessment procedures are not reported in the registry record.

The registry reports enrollment of 31, but does not separately report the Full Analysis Set size. It defines that set by receipt of at least one dose of any study treatment component. The number with evaluable primary outcome data, missing-data handling, withdrawals, and reasons for discontinuation are not reported in the registry record. These omissions limit appraisal of how the analysis population and incomplete assessments may relate to the endpoint.

The enrolled population is described as Japanese patients with relapsed or refractory multiple myeloma. The record does not establish how well findings would apply to populations beyond those described, and the absent primary result prevents even a numerical description of the study’s response experience. Finally, safety summaries are group-level counts without reported event timing, severity grading, or comparative rates. These constraints call for a descriptive reading of the record, not a comparative or causal conclusion.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Study of Panobinostat in Combination With Bortezomib and Dexamethasone in Japanese Patients With Relapsed/Refractory Multiple Myeloma — NCT02290431.
• Registry record last updated 2019-11-18; status last verified 2019-10.
• Results first posted 2019-11-18.
• 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.

19. Record Summary

NCT02290431 is a completed Phase II, multicenter, open-label, single-group study sponsored by Novartis Pharmaceuticals. It enrolled 31 Japanese patients with relapsed or refractory multiple myeloma and evaluated panobinostat, also called LBH589, with bortezomib and dexamethasone on a 2 weeks on/1 week off schedule.

The primary outcome was the percentage with near complete response or complete response as best overall response after 24 weeks (8 cycles; cycle = 21 days), assessed by the investigator using modified EBMT criteria. The defined population was the Full Analysis Set, consisting of subjects who took at least one dose of any study treatment component. A 90% confidence interval was specified, but the response percentage and interval limits are not reported in the registry record.

The registry lists secondary response, survival, time-to-event, and quality-of-life outcomes. Safety summaries list 14 affected participants in the serious adverse event grouping, 31 in the other adverse event grouping, and zero deaths. The study has no listed comparator, and its record does not report detailed statistical analysis or missing-data procedures.