Belinostat in Relapsed or Refractory Peripheral T-Cell Lymphoma: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Belinostat in Relapsed or Refractory Peripheral T-Cell Lymphoma (NCT00865969), a na phase 2 study. The primary outcome is Objective Response Rate.

2. Clinical Question

The study was intended to assess efficacy and safety in participants whose disease had returned or had not responded after prior systemic therapy. The central efficacy question is about the proportion meeting a defined response criterion, rather than a comparison of response rates between treatment groups. Complete response meant disappearance of all evidence of disease; partial response meant regression of measurable disease with no new sites.

The registry record identifies 129 participants as the enrollment total. That total should not automatically be treated as the denominator for the primary endpoint: the stated efficacy population has its own criteria, and the posted record does not give the number analyzed for the response endpoint. It also does not report the response percentage or confidence interval. As a result, the clinical question can be described from the endpoint definition, but the primary result cannot be quantified from the registry information recorded.

3. Trial Design

This was a phase 2, multicenter, open-label trial of belinostat in participants with relapsed or refractory PTCL. The registry record describes the study model as single group, lists allocation as NA, and indicates no masking. Enrollment was 129, and the study status is completed. The recorded study start date is 2008-12-15 and the primary completion date is 2013-11-05.

All participants in the treatment group received belinostat. The regimen was 1000 mg/m^2 as a 30 minute intravenous infusion on Days 1-5 of every 3-week cycle. Treatment was to continue until disease progression or unmanageable treatment-related toxicities. The registry record does not describe a control arm, random assignment, or masking of treatment assignment. These design features mean the record presents a single-group assessment, not a randomized treatment comparison.

The primary outcome was objective response rate, measured as the percentage of participants with complete or partial response under International Working Group criteria. The endpoint description states that response was assessed using clinical and radiological criteria and that the primary analysis was based on the Independent Review Committee assessment. The stated timeframe was 24 months. Other listed outcomes included time to response, duration of response, time to progression, progression-free survival, overall survival, and serious treatment-emergent adverse events.

The registry record identifies an efficacy analysis population of participants who received at least one dose and had a confirmed PTCL diagnosis. It does not report how many participants met these criteria or how many were included in the primary endpoint analysis. Further details about recruitment, eligibility criteria beyond the stated disease and prior-treatment description, follow-up procedures, and analysis methods are not reported in the registry record. The design can therefore be characterized from its listed structure and intervention, while several operational details remain unavailable.

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: Participants with relapsed or refractory T-Cell lymphoma who signed the informed consent form and met all Inclusion/Exclusion criteria were enrolled in the study.

Overall Study

Analysis population for the primary outcome, as defined in the registry: Efficacy Analysis Dataset included participants who received at least 1 dose of belinostat and had a confirmed peripheral T-cell lymphoma (PTCL) diagnosis.

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: Full Analysis Set included all participants who were received at least 1 dose of belinostat.

6. Primary Endpoint

The registry lists the primary outcome as Objective Response Rate, measured over 24 months.

The primary endpoint, objective response rate, is the percentage of participants whose disease met criteria for complete response or partial response. A complete response required disappearance of all evidence of disease. A partial response required regression of measurable disease without new sites. Response assessment used clinical and radiological criteria, and the prespecified primary endpoint assessment was based on the Independent Review Committee.

As a binary outcome, each participant is classified as having met the response definition or not having met it for the analysis. The resulting percentage describes the share of the analyzed population classified as responders. It is useful because it expresses the frequency of a defined response in a way that can be interpreted at the participant level. It does not, by itself, describe how long a response lasted, how quickly it occurred, or what happened after response; the registry lists separate outcomes for time to response, duration of response, and survival-related measures.

The endpoint timeframe is 24 months. The registry record does not report the observed response percentage, the number of responders, the analyzed denominator, or the 95% confidence interval. Without those results, the endpoint definition is clear, but the response estimate and its precision cannot be interpreted from this record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry record gives the endpoint definition and identifies the Independent Review Committee assessment as the basis for the primary endpoint analysis. It does not describe the statistical procedure used to estimate the response rate, calculate its confidence interval, or address incomplete response assessments. The explanations below describe general statistical concepts that help interpret a binary response endpoint; they do not assert that a particular method was used in this trial unless the registry record states it.

What does a response percentage represent?

For a binary endpoint, each participant is classified according to whether the defined event occurred. Here, the event is an objective response: a complete response or partial response under International Working Group criteria. The response percentage represents the share of participants in the analysis population classified as responders. The population definition matters: the record specifies participants who received at least one dose and had a confirmed PTCL diagnosis, but does not report how many participants met those conditions for the endpoint analysis.

A percentage is a point estimate, meaning it gives one value as an estimate of the response frequency in the analyzed group. It does not show all the uncertainty associated with that estimate. The registry record does not post the point estimate, responder count, or denominator, so the primary response frequency cannot be reconstructed or evaluated from the record.

How should a confidence interval be understood?

In general, a confidence interval describes uncertainty around an estimated quantity under a specified statistical procedure. For a response percentage, it gives a range of values compatible with the observed data and method, rather than a second observed result. A narrower interval indicates a more precise estimate; a wider interval indicates less precision. The primary endpoint description specifies a 95% confidence interval, but the interval itself is not reported in the registry record. Its width, limits, and relation to the response estimate therefore cannot be assessed.

A confidence interval is not a guarantee that the true value lies within its limits, and it does not resolve limitations in study design or endpoint ascertainment. In particular, an interval around a single-group response estimate would describe uncertainty in that group’s response frequency; it would not create a comparison with an unobserved control group.

What does the single-group design permit?

In general, a single-group study can describe outcomes among the participants treated, subject to the endpoint definition and analysis population. Without a concurrent comparator, it does not estimate a randomized between-group contrast. Differences from outcomes in other settings cannot be interpreted as a trial-based treatment contrast unless a suitable comparative design and analysis are available. The registry record lists this study as single group and provides no comparator arm.

Allocation is listed as NA and masking as none. Those labels describe the recorded design; they do not establish details about how response assessors carried out their work. The record says the primary assessment was based on an Independent Review Committee, but does not report whether committee members were masked or provide procedures for adjudication. Such details are not reported in the registry record.

Why do the response criteria matter?

A statistical estimate is only as interpretable as the outcome it summarizes. The record defines response using clinical and radiological criteria under International Working Group criteria. Complete response means disappearance of all evidence of disease. Partial response means regression of measurable disease with no new sites. A participant who does not meet either definition is not counted as having the specified response for this endpoint, although the registry record does not detail how unevaluable cases were classified.

The primary endpoint is a proportion at the stated 24-month timeframe. It is distinct from time-to-event outcomes such as duration of response, time to progression, progression-free survival, and overall survival, which the record lists separately. A response proportion does not by itself provide information about the timing or persistence of responses.

What can be said about planning calculations?

General sample-size calculations use assumptions about the target effect, statistical error rate, allocation, and analysis method. Any planning illustration based on an observed effect is a hypothetical design calculation, not observed power and not evidence that the trial had a particular probability of detecting its result. The registry record does not report a trial-specific sample-size justification or the assumptions used in the original design. It also does not report a comparative effect for this single-group study in the information recorded. Consequently, a design rationale cannot be inferred from the enrollment total.

The record describes an enrollment of 129, but that count alone does not establish the precision of the primary endpoint. Precision depends on the number analyzed and the observed response frequency, neither of which is reported for the endpoint. It would be inappropriate to treat enrollment as the response denominator without confirmation from the analysis results.

The registry record lists zero posted analyses. This means the registry entry does not provide analysis results in that listing; it does not establish that no analyses were conducted outside the record. The statistical model, confidence-interval construction, missing-data handling, and any sensitivity analyses are not reported in the registry record.

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("Belinostat")
n      <- c(120)
events <- c(31)
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  Belinostat  120  31  25.8  18.3  34.6  18.8  34.3  18.8  34.4

11. Multiplicity, Missing Data and Analysis Populations

The registry record lists objective response rate as the primary endpoint and identifies several secondary outcomes, including time to response, duration of response, time to progression, progression-free survival, overall survival, and serious treatment-emergent adverse events. It does not report how statistical multiplicity was handled across these outcomes or whether any formal adjustment was planned. Without that information, the relationship among tests and any control of the chance of false-positive findings cannot be evaluated from the registry record.

The record does not report a missing-data strategy for the primary endpoint. It does not state how unevaluable response assessments, withdrawals, or participants without a recorded response assessment were handled. Nor does it provide the number analyzed for the endpoint. These omissions limit interpretation because the response proportion depends on both the classification of participants and the denominator used.

The stated efficacy analysis population includes participants who received at least one dose and had a confirmed PTCL diagnosis. The record does not explain whether every participant meeting those conditions was included, or whether additional analysis-population criteria applied. It also does not report separate intention-to-treat, per-protocol, or safety population definitions. The enrollment total of 129 should therefore not be assumed to be the denominator for every outcome.

The primary endpoint description says the analysis was based on Independent Review Committee assessment, but does not specify the analysis method or any sensitivity analysis comparing assessments. Such details are not reported in the registry record. A complete evaluation of missingness, population selection, and multiplicity would require the analysis results and fuller statistical documentation.

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 (7.8%), pyrexia (4.7%), infection (3.1%), anaemia (2.3%), blood creatinine increased (2.3%).

For the Belinostat group, the registry record lists 129 participants at risk for serious treatment-emergent adverse events and 61 participants with at least one such event. It also lists 129 participants at risk in the other adverse-event count and 125 participants affected. The record lists 22 deaths. It does not report the timing, causes, or treatment relationship for those deaths, so they should not be attributed to belinostat on the basis of these counts alone.

The serious-event terms listed with percentages are pneumonia, 7.8%; pyrexia, 4.7%; infection, 3.1%; anaemia, 2.3%; blood creatinine increased, 2.3%; and multi-organ disorder, 2.3%. These are descriptive entries in the registry record. They do not establish that each event was caused by treatment, and the record does not provide further detail about event severity, duration, recurrence, or the number of events per participant.

General statistical interpretation: safety counts describe what was recorded in the study group, while causal attribution requires more than observing an event after treatment. In a single-group study, there is no concurrent control group in this record to provide a direct comparison of event frequencies. The counts therefore characterize reported safety observations but do not quantify comparative risk.

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

The registry record establishes that this completed phase 2 study evaluated belinostat in relapsed or refractory PTCL, with objective response rate as the primary endpoint. It defines response using complete or partial response criteria and states that the Independent Review Committee assessment was used for the primary analysis. It also records an enrollment total of 129 and describes the treatment schedule and certain safety observations.

The record does not report the primary response percentage, the number of responders, the endpoint analysis denominator, or the 95% confidence interval. Consequently, it does not allow readers to assess the observed response frequency or the precision of that estimate. This is a limitation of the information recorded, not evidence that the response was either high or low.

The study design is single group, open label, and has no concurrent comparator. Any outcome described for the treated group would not, by itself, show what would have happened to similar participants under a different treatment or control condition. The trial record therefore does not support a randomized comparative estimate. The registry entry also does not provide a basis for inferring how the study result compares with outcomes from other populations or studies.

The safety counts show that serious treatment-emergent adverse events were recorded and list several event terms and percentages. They do not establish causation. The 22 deaths listed in the record have no accompanying information about cause, timing, or attribution in the registry record.

In general, statistical results should be interpreted together with their endpoint definitions, analysis populations, uncertainty, missing-data handling, and study design. Several of those details are not reported in the registry record, and the primary efficacy result itself is absent. The information available supports a description of the trial’s design and recorded safety figures, but not a numerical judgment about the primary response outcome or a causal treatment effect.

14. Why This Trial Matters Statistically

This trial is statistically informative as an example of how a clearly defined binary endpoint can be used in a single-group clinical study. The registry defines objective response as complete or partial response and specifies clinical and radiological assessment under International Working Group criteria. It also states that the primary endpoint assessment was based on an Independent Review Committee. These details establish what the primary outcome was intended to summarize, even though the estimate is not reported.

The design distinction is important. A single-group study can describe an outcome among treated participants, but it does not include the concurrent randomized comparator needed for a direct between-group treatment contrast. The registry lists allocation as NA and masking as none. Statistical interpretation should therefore focus on the design actually recorded rather than treating the study as if it were a controlled comparison.

The entry also illustrates why endpoint results require more than a study enrollment count. The registry gives an enrollment total of 129, but does not report the number analyzed for the primary endpoint, the response count, or the response percentage. It specifies a 95% confidence interval but does not post its limits. Without those elements, neither the magnitude nor precision of the primary result can be assessed.

Finally, safety counts and event terms need careful interpretation. Counts describe events recorded in the treatment group, but do not by themselves prove causation or establish a comparative risk. The absence of key analysis details, including missing-data and multiplicity methods, also limits how fully the registry entry can be evaluated. These are general lessons in reading clinical trial records: distinguish design from outcome, estimate from uncertainty, and recorded events from causal conclusions.

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 principal limitation for interpreting efficacy is that the registry record does not report the primary objective response rate, responder count, analysis denominator, or confidence interval. Although the endpoint definition and 24-month timeframe are stated, the result and its precision cannot be assessed from the record.

The study is listed as single group, with no concurrent comparator, allocation listed as NA, and masking listed as none. This design does not provide a randomized, like-for-like control comparison. The registry record also does not report detailed procedures for response assessment beyond the criteria and Independent Review Committee basis, including whether committee members were masked or how disagreements were resolved.

The record gives an enrollment total of 129 and defines the efficacy population as participants who received at least one dose and had a confirmed PTCL diagnosis. It does not report the number meeting that definition, the number evaluated for response, or how missing and unevaluable assessments were handled. This leaves the endpoint denominator and potential effects of incomplete data unclear.

Although secondary outcomes are listed, their results and analysis details are not reported in the registry record. The statistical methods, multiplicity approach, sample-size justification, interim analyses, and sensitivity analyses are also not reported. The safety information lists event counts, percentages, and deaths, but does not provide timing, causes, or treatment attribution for deaths, or enough detail to establish causal relationships for adverse events. These limitations restrict interpretation to the design and descriptive information recorded.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Belinostat in Relapsed or Refractory Peripheral T-Cell Lymphoma — NCT00865969.
• Registry record last updated 2021-10-29; status last verified 2021-10.
• Results first posted 2021-09-16.
• 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

The registry record describes a completed, multicenter, open-label, phase 2, single-group trial of belinostat in relapsed or refractory peripheral T-cell lymphoma. Enrollment was 129. Belinostat was administered as a 30 minute intravenous infusion on Days 1-5 of every 3-week cycle, with treatment continuing until disease progression or unmanageable treatment-related toxicities.

The primary endpoint was objective response rate at 24 months, defined as the percentage of participants with complete or partial response under International Working Group criteria. The primary analysis was based on the Independent Review Committee assessment. The registry record does not report the response estimate, responder count, analysis denominator, or confidence interval.

Safety information includes 61 participants with at least one serious treatment-emergent adverse event among 129 at risk, and 22 deaths. The registry record does not report causal attribution or detailed context for the deaths. The single-group design has no concurrent comparator.