Panobinostat (LBH589): Acute Graft Versus Host Disease (aGVHD) Prevention: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Panobinostat (LBH589): Acute Graft Versus Host Disease (aGVHD) Prevention (NCT02588339), a na phase 2 study. The primary outcome is Number of Participants Stratified by Acute Graft Versus Host Disease GVHD Stage.

2. Clinical Question

3. Trial Design

This was a phase II study sponsored by H. Lee Moffitt Cancer Center and Research Institute. The registry lists enrollment of 42, a single-group model, no masking, and allocation as not applicable. Its status is completed. The study began on 2016-03-04, and primary completion was recorded as 2018-12-07.

Participants received standard-of-care chemotherapy before an allogeneic hematopoietic cell transplant. For GVHD prevention, the intervention was panobinostat, sirolimus, and tacrolimus. Because the study had one group and no concurrent control, its design can describe outcomes in participants treated with this regimen, but it cannot by itself make a like-for-like comparison with another prevention strategy. The endpoint record's incidence target and acceptability threshold provide context, but they do not constitute a control arm.

The primary outcome is described as the number of participants stratified by acute GVHD stage, with the endpoint description specifying cumulative incidence of grades II-IV by day 100. Other listed outcomes cover chronic GVHD stage, stable engraftment, relapse, non-relapse mortality, overall survival, and relapse-free survival. The registry lists seven outcome measures, but the posted information contains no outcome-analysis results. Details such as the statistical analysis plan, eligibility criteria, and any planned interim analyses 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:

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 Number of Participants Stratified by Acute Graft Versus Host Disease GVHD Stage, measured over 100 days post transplant.

The primary endpoint concerns acute GVHD grades II-IV after transplant. The registry describes the measure as cumulative incidence by day 100 and titles it as a count of participants stratified by acute GVHD stage. It also states that GVHD severity stage and grading would be assessed weekly from transplant through day 90 +/- 14, using a standard scoring system. The overall acute GVHD grade would combine the site-specific assessments, including skin, liver, and gut involvement.

In general, a cumulative-incidence endpoint describes how often an event has occurred by a specified time, while accounting for the possibility that another event can prevent the event of interest from occurring or being observed. That distinction can matter in transplant studies, where outcomes such as relapse or death may affect the chance of observing GVHD. The registry record does not report the specific estimator or handling of competing events used for the primary analysis, so the stated endpoint description should not be taken as evidence of a particular statistical method.

The endpoint is used to summarize acute GVHD burden over a defined period after transplant. Investigators described 23% as the target incidence and an incidence of 43% or greater as not acceptable. Those are protocol benchmarks, not observed results. The primary-endpoint result itself is not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

Statistical methods translate the clinical question into a definition of what is counted, how outcomes are summarized, and how uncertainty is assessed. Here, the registry identifies cumulative incidence of acute GVHD grades II-IV by day 100 as the primary endpoint. It does not report the statistical analysis plan or the numerical primary result. The explanations below distinguish general statistical concepts from methods that can actually be confirmed in the record.

What does cumulative incidence describe?

In general, cumulative incidence is the probability of experiencing an event of interest by a specified time. It differs from a simple proportion when follow-up time varies or when another event can prevent the event of interest from occurring. In a transplant setting, death or relapse may be relevant competing events for GVHD. The registry's endpoint description uses the term cumulative incidence, but the specific estimator and competing-event procedures are not reported in the registry record.

The stated endpoint focuses on acute GVHD grades II-IV. The record says severity would be evaluated using a standard scoring system, with site-specific stages and a composite overall grade. Assessment was described as weekly from transplant through day 90 +/- 14, while the primary endpoint's stated timeframe is day 100 post transplant. These details describe the intended measurement framework; they do not reveal how incomplete assessments or different observation times were handled in analysis.

How should the benchmarks be read?

The endpoint description states that investigators used 23% incidence as a target and regarded an incidence of 43% or greater as not acceptable. In general, a target is a reference point for interpreting a treatment group's observed estimate; it is not the same thing as a randomized control group's result. The registry does not report the observed estimate or the inferential procedure used to compare it with either benchmark. It also does not report whether the thresholds were tied to a formal hypothesis test or a decision rule.

A confidence interval, in general, expresses the uncertainty around an estimated quantity under a specified statistical procedure. A narrow interval indicates greater precision than a wide interval, but neither one alone establishes causality. No primary-endpoint confidence interval is reported in the registry information. Without an estimate and interval, readers cannot judge how precisely the actual incidence was measured or whether uncertainty would span one of the stated benchmarks.

What does the single-group design allow?

A single-group study can summarize outcomes observed among participants receiving the regimen. Without a concurrent comparison group, it cannot separate the regimen's association with outcomes from other influences on those outcomes. That includes differences in participant characteristics, transplant care, and follow-up. General statistical adjustment may address measured differences in some settings, but no adjusted analysis or comparison group is reported. The record lists no masking, and no allocation between treatment groups applies to this single-group design.

The study's enrollment is listed as 42, while the safety summary lists 39 participants at risk. These values are not enough to identify the analysis set for the primary outcome. In general, the analysis population could be defined by enrollment, treatment received, or availability of outcome assessment, but the registry does not report the primary analysis population or explain the denominator used for that endpoint.

What do the planning illustrations represent?

The sample-size section contains planning illustrations based on the observed effect, with a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. The stated effect to detect is a fraction of the observed effect. These are planning illustrations, not the design of this single-group trial: the trial had no two-arm allocation. They should not be interpreted as observed power, nor as evidence that the trial was designed around those assumptions. The registry record does not report the trial's own sample-size justification.

In general, sample-size planning asks how much information would be needed to detect a chosen effect under a specified model and assumptions. It depends on the outcome, variability, significance level, allocation, and the effect regarded as meaningful. A planning calculation using an observed effect is conditional on that effect estimate and the assumptions used; it cannot replace a prespecified design justification. The posted illustrations should therefore be read as hypothetical planning aids rather than results from the study.

The registry lists seven outcome measures and zero analyses in the posted results information. That absence limits what can be evaluated statistically: the record does not show the analysis methods, uncertainty estimates, adjusted comparisons, or sensitivity analyses for the outcomes. It is not possible to infer any of these from the endpoint definitions alone.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists seven outcome measures, including acute and chronic GVHD measures, engraftment, relapse, non-relapse mortality, overall survival, and relapse-free survival. When a study evaluates multiple outcomes, multiplicity can arise because many estimates or tests create multiple opportunities for apparently notable findings. In general, a prespecified hierarchy, adjustment procedure, or clear distinction between primary and exploratory outcomes can help readers understand how results should be interpreted.

The available record identifies a primary endpoint and lists secondary outcomes, but it does not report a multiplicity strategy, a testing hierarchy, or an analysis plan. It is therefore not possible to tell whether any multiplicity adjustment was planned or applied. No outcome analyses are posted here, so readers cannot evaluate how the investigators handled multiple comparisons in practice.

Missing-data methods and analysis populations are also not reported in the registry record. The primary endpoint involves assessments over time after transplant, but the record does not describe how missed visits, incomplete grading, withdrawal, or death were handled in the primary analysis. It does not identify whether the analysis used all enrolled participants, participants who received treatment, or a different group. The enrollment count and the safety summary's at-risk count do not establish the primary endpoint denominator.

In general, missing observations can affect an estimate when participants with incomplete follow-up differ from those with complete follow-up. The size and direction of any effect depend on the amount and pattern of missingness, as well as the assumptions and methods used. Because the registry does not describe missingness or its handling, these potential effects cannot be assessed from the posted information. A complete analysis report would be needed to evaluate these issues and the role of competing events.

11. 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 0% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: rash maculo-papular (12.8%), enterocolitis (7.7%), confusion (5.1%), lung infection (5.1%), sepsis (5.1%).

The safety summary lists the Panobinostat (PANO) Therapy group with 39 participants at risk for serious adverse events and 12 affected. It lists 39 participants at risk for other adverse events and 32 affected, and records 2 deaths. These are descriptive counts from the registry. They should be read in their stated categories; the record does not establish that the events were caused by the study drugs.

The listed serious adverse-event terms include Rash maculo-papular at 12.8%, Enterocolitis at 7.7%, Confusion at 5.1%, Lung infection at 5.1%, Sepsis at 5.1%, and Nausea at 5.1%. These entries identify terms and associated percentages, but the information does not specify their time window, event duration, recurrence, or how the percentages were calculated. Participants may have experienced more than one event, and the record does not provide enough detail to determine overlap among terms.

The counts do not provide a comparison with another regimen or background rate. The cause and timing of the deaths, the safety follow-up period, and the relationship between the enrolled group and the at-risk denominator are not reported in the registry record. Accordingly, the posted figures describe recorded safety events but do not, by themselves, establish comparative safety or causation.

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

This study's registry entry describes an investigation of panobinostat with sirolimus and tacrolimus for prevention of acute GVHD after allogeneic hematopoietic cell transplant. It states the primary outcome, the time point, and the investigators' incidence benchmarks. It also reports selected adverse-event counts. Those details explain what the study set out to evaluate and what safety information was posted.

The primary outcome result is not reported in the registry record. Therefore, readers cannot determine from this information whether the observed cumulative incidence was near the stated target of 23%, below or above the stated 43% acceptability threshold, or estimated with useful precision. No confidence interval or primary-endpoint analysis is posted. The endpoint definition and benchmarks are not substitutes for an observed result.

Even if a numerical outcome estimate were available, the single-group design would limit comparative interpretation. Without a concurrent control, the study could describe outcomes in its treatment group but could not establish how those outcomes differed from what would have occurred under another approach. The registry does not report an adjusted comparison or an analysis that resolves this limitation.

The safety entries likewise do not show whether events were treatment-related or how the observed counts compare with another group. Details on event timing, follow-up, and the analysis population are not reported. The listed serious-event terms and percentages should therefore be treated as descriptive registry information, not as evidence of causal effects.

The most defensible reading is narrow: the record documents a completed phase II, single-group study and its endpoint framework, along with selected safety data, but does not post the primary efficacy result or outcome analyses. It does not support a conclusion about treatment benefit, lack of benefit, or comparative safety.

13. Why This Trial Matters Statistically

This trial raises several important statistical issues in a clinically consequential setting. First, it uses a time-defined incidence endpoint after transplant. A cumulative-incidence measure can be more informative than a simple event count when follow-up and competing events matter. The endpoint description identifies a day-100 timeframe, but the registry does not report the estimator or the way competing events were handled. That gap prevents readers from checking whether the analysis method matched the clinical question.

Second, the record distinguishes an intended target from an acceptability threshold. Those benchmarks can make an estimate easier to interpret when paired with the observed result and its uncertainty. Here, the estimate and interval are not reported, so the benchmarks remain context rather than evidence of how the regimen performed.

Third, the single-group design is central to interpretation. It may characterize outcomes in the treated group, but cannot provide a direct randomized comparison. This matters when outcomes in transplant populations may reflect factors beyond the prevention regimen. Readers should not treat a historical or stated benchmark as though it were a concurrent control.

Finally, the available registry information illustrates why endpoint definitions alone are not enough for a statistical appraisal. Analysis methods, missing-data handling, analysis populations, and results are needed to assess precision and robustness. The safety summary adds descriptive information, but without comparable data and event context it cannot establish relative safety or causation. In this record, key outcome analyses are absent, which sharply limits what can be concluded statistically.

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 this trial page is that the registry record does not report the primary-endpoint result or any outcome analyses. The endpoint's cumulative-incidence definition, day-100 timeframe, and benchmarks are described, but no observed estimate or uncertainty interval is available. The listed secondary outcomes likewise lack posted analyses.

The study was single-group, with no masking and no concurrent control. This prevents a direct like-for-like comparison and limits causal interpretation. The record does not report details of the statistical analysis plan, including the estimator for cumulative incidence, handling of competing events, or any planned adjustment for participant characteristics.

The registry lists enrollment of 42, while its safety summary identifies 39 participants at risk. The record does not explain this difference or identify the denominator and analysis population for the primary endpoint. It also does not report how missing assessments, withdrawal, or incomplete follow-up were handled. These omissions make it difficult to assess potential selection or missing-data effects.

The endpoint description says GVHD would be graded weekly from transplant through day 90 +/- 14 and that pathological confirmation would follow usual clinical practice rather than being required by the protocol. This leaves details of diagnostic ascertainment and completeness of assessment unreported. In addition, the safety summary lacks information about event timing, follow-up duration, attribution, and the cause of deaths. These limitations constrain interpretation of both effectiveness and safety information in the posted record.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Panobinostat (LBH589): Acute Graft Versus Host Disease (aGVHD) Prevention — NCT02588339.
• Registry record last updated 2021-07-21; status last verified 2021-07.
• Results first posted 2020-01-03.
• 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

The registry record describes NCT02588339, a completed phase II study titled Panobinostat (LBH589): Acute Graft Versus Host Disease (aGVHD) Prevention. H. Lee Moffitt Cancer Center and Research Institute sponsored the study. It lists enrollment of 42, a single-group design, no masking, and allocation as not applicable. The study began on 2016-03-04, with primary completion on 2018-12-07.

Participants received panobinostat, sirolimus, and tacrolimus for GVHD prevention after standard-of-care chemotherapy and allogeneic hematopoietic cell transplant. The primary endpoint was cumulative incidence of acute GVHD grades II-IV by day 100, with 23% stated as the target and an incidence of 43% or greater described as not acceptable. The primary result and outcome analyses are not reported in the registry record. Selected safety counts and serious-event terms are posted, but the registry does not provide comparative safety results or enough detail to establish causation.