A Phase 2 Multi-Center Study of Entinostat (SNDX-275) in Patient With Relapsed or Refractory Hodgkin's Lymphoma: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Phase 2 Multi-Center Study of Entinostat (SNDX-275) in Patient With Relapsed or Refractory Hodgkin's Lymphoma (NCT00866333), a na phase 2 study. The primary outcome is Percentage of Participants With Best Overall Response Based on the Participant's Best Response That is Documented Within the First 6 Cycles of Protocol Therapy.

2. Clinical Question

The study was intended to evaluate the efficacy and safety of entinostat in patients with relapsed or refractory Hodgkin's lymphoma. Its primary endpoint captured whether a participant's best documented response during the first 6 cycles met the stated response definition. Tumor response was assessed by investigators using the International Working Group revised response criteria for malignant lymphoma.

The registry record does not report the primary endpoint result, its numerator and denominator, or its 95% confidence interval. Consequently, the posted record does not quantify the proportion meeting the response definition or the precision of such an estimate. The response question is also distinct from the listed secondary outcomes, which include best overall response over the entire course of protocol therapy, duration of objective response among participants achieving CR or PR, and adverse events.

3. Trial Design

This was a Phase 2, multicenter study of entinostat in patients with relapsed or refractory Hodgkin's lymphoma. The registry identifies the study model as single-group, allocation as NA, and masking as none. It lists a planned enrollment of 49 and a terminated status. The study start date is 2009-04-13, and the primary completion date is 2013-02-08. The reason for termination is not reported in the registry record.

The intervention was entinostat, but the regimen depended on protocol version. The record describes Regimen 1 as entinostat 10 mg orally once every two weeks, on Days 1 and 15 of a 28-day cycle, until disease progression or unacceptable toxicity. It describes Regimen 2 as starting with 10 mg orally on Day 1 and then increasing to 15 mg, but the remainder of that regimen description is not reported in the registry record. A third regimen is identified as entinostat 15 mg; its full schedule is not reported in the registry record.

Although the record lists regimen-specific safety groups, it does not describe a randomized comparison among them. As a result, the regimens should not be interpreted as like-for-like control arms. The primary endpoint used a per-protocol population: participants had to complete at least 2 cycles of entinostat and undergo CT or PET scans at Screening and Day 1 of Cycle 3. The record does not explain how that population was selected for the secondary outcomes.

The registry lists four outcome measures and does not report analysis records. Detailed statistical methods, the rationale for the planned enrollment, and any 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.

Before assignment: Participants with a diagnosis of Relapsed or Refractory Hodgkin's Lymphoma (HL) were enrolled into one of three entinostat dosing regimens based on the version of the protocol at their time of enrollment in the study.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Per-Protocol (PP) population included all participants who met all of the following criteria: Completed at least 2 cycles of entinostat therapy and Underwent computed tomography (CT) or positron emission tomography (PET) scans at Screening and Day 1 of Cycle 3.

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 (FAS) included all participants who were enrolled in the study.

6. Primary Endpoint

The registry lists the primary outcome as Percentage of Participants With Best Overall Response Based on the Participant's Best Response That is Documented Within the First 6 Cycles of Protocol Therapy, measured over Up to 6 months.

The primary endpoint was the percentage of participants whose best overall response within the first 6 cycles was complete response (CR) or partial response (PR). It was assessed over a timeframe of up to 6 months. Investigators assessed tumors using the International Working Group revised response criteria for malignant lymphoma, cited in the registry record as Cheson, Pfistner et al. 2007.

Under the record's definition, CR required disappearance of detectable clinical and radiographic disease and disease-related symptoms, as well as normalization of biochemical abnormalities definitely assignable to Hodgkin's lymphoma. PR required at least a 50% decrease in the sum of the products of the greatest diameters of the six largest dominant nodes or nodal masses, with no increase in other nodes and no new disease sites.

A response proportion is used to describe how often a defined response category was documented in the assessed population. The registry record states that the primary measure was a percentage and identifies a 95% confidence interval as its dispersion measure. However, the actual response count, percentage, assessed denominator and confidence interval are not reported in the registry record. The endpoint definition therefore clarifies what was to be counted, but the posted record does not show the observed result.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does a percentage endpoint represent?

General statistical explanation: a percentage endpoint expresses the share of an assessed group meeting a defined outcome. For this study, the outcome was a best overall response of CR or PR documented within the first 6 cycles, and the assessed group was defined by the per-protocol criteria. Interpreting such a percentage requires knowing both the number meeting the endpoint and the number assessed. Neither is reported for the primary outcome in the registry record, so a percentage cannot be read from the posted results.

What does a confidence interval add?

General statistical explanation: a confidence interval describes uncertainty around an estimate. For a response percentage, it helps readers judge how precisely the observed proportion estimates the underlying response frequency in a broader population under the assumptions of the analysis. A narrower interval indicates greater precision, while a wider interval indicates more uncertainty. The registry identifies a 95% confidence interval as the intended dispersion measure for the primary outcome, but does not report its limits. It is therefore not possible to assess the precision of the response estimate from this record.

Why does the analysis population matter?

General statistical explanation: the population included in an analysis defines which participants contribute to its result. Different inclusion rules can yield results describing different groups, even when the endpoint definition is unchanged. Here, the per-protocol definition required completion of at least 2 cycles and CT or PET scans at Screening and Day 1 of Cycle 3. A response percentage for that population would answer a question about participants who met those conditions. The record does not report the number assessed or explain how participants with incomplete assessments were handled.

What can a single-group study estimate?

General statistical explanation: a single-group study can describe outcomes observed among participants receiving the study intervention. Without a comparator, it cannot directly estimate how those outcomes differ from what would have occurred under a different treatment or no treatment. This matters when interpreting a response proportion: the proportion would be a description of the study population and its treatment context, not by itself a controlled estimate of a treatment effect. The registry identifies this study as single-group and does not describe a randomized comparison of its regimens.

How should regimen groups be read?

General statistical explanation: comparisons between groups are most informative when the groups are formed and assessed in a way that supports a fair comparison. The registry lists three regimen-specific safety groups, but it identifies allocation as NA and does not report randomization. Regimen descriptions also differ, and at least some schedule details are incomplete in the record. Group-specific counts can be reported descriptively, but they do not by themselves establish that regimen differences caused differences in outcomes.

What does the registry's statistical detail establish?

The primary endpoint specifies a 95% confidence interval, but further statistical procedures are not reported in the registry record. The record does not report a hypothesis test, adjustment procedure, covariate model, or method for handling missing endpoint assessments. These omissions do not show that such procedures were or were not used; they mean that they cannot be described from the registry record.

General statistical explanation: prespecified methods help clarify how estimates are calculated, how uncertainty is quantified, and how multiple outcomes or analysis choices are handled. In their absence, readers should avoid inferring the analysis plan from the endpoint definition alone. The record lists four outcome measures and does not report analysis records, so no test statistics or model-based estimates can be interpreted from the posted results.

The record does not state a sample-size justification or describe a power calculation used to design the trial. Any planning illustrations based on an observed effect answer a different question: they show, under stated assumptions, the approximate sample size that might be needed for a future study to detect an effect of a chosen size. Such illustrations are not observed power and do not establish the rationale for the original enrollment. They also do not substitute for the missing primary endpoint estimate and confidence interval.

General statistical explanation: estimates from small groups tend to be less precise than estimates based on more information, all else being equal. Confidence intervals are one way to communicate that uncertainty. Since the primary endpoint estimate and its interval are not reported, readers cannot judge the observed response frequency's statistical precision, regardless of the enrollment figure.

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("Regimen 1: Entinostat 10 mg", "Regimen 2: Entinostat 10 mg/15 mg", "Regimen 3: Entinostat 15 mg")
n      <- c(12, 17, 12)
events <- c(1, 2, 2)
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  Regimen 1: Entinostat 10 mg  12  1  8.3  0.2  38.5  1.5  35.4  1.9  36.0
ARM  Regimen 2: Entinostat 10 mg/15 mg  17  2  11.8  1.5  36.4  3.3  34.3  3.6  34.7
ARM  Regimen 3: Entinostat 15 mg  12  2  16.7  2.1  48.4  4.7  44.8  5.0  45.4

11. Multiplicity, Missing Data and Analysis Populations

The registry lists four outcome measures: the primary response percentage within the first 6 cycles, best overall response over the entire course of protocol therapy, duration of objective response for participants achieving CR or PR, and counts of participants with serious adverse events and adverse events. The record does not report how statistical testing across these outcomes was handled. Any multiplicity adjustment, hierarchy among secondary outcomes, or distinction between confirmatory and exploratory analyses is not reported in the registry record.

The primary analysis population is described as per-protocol and requires completion of at least 2 cycles plus CT or PET scans at Screening and Day 1 of Cycle 3. The record does not report the population size used for the primary outcome, the number of missing response assessments, or how missing data were treated. It also does not state whether participants without an evaluable response were counted in a particular category or excluded from the calculation.

The population rules for the secondary outcomes are not reported in the registry record. No analysis records are reported, and the registry does not provide a statistical analysis plan, details of interim analyses, or a sample-size justification. These gaps limit assessment of how the endpoint was analyzed and how much confidence to place in any numerical result; in this case, the primary numerical result itself is not reported.

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 0% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: anemia (11.8%), thrombocytopenia (11.8%), acute respiratory distress syndrome (6.2%), cardio-respiratory arrest (6.2%), febrile neutropenia (6.2%).

The registry reports serious adverse event counts by regimen group: 2 of 16 participants in Regimen 1, 7 of 17 in Regimen 2, and 3 of 16 in Regimen 3. It reports other adverse events for 16 of 16, 17 of 17, and 16 of 16 participants, respectively. The listed death counts are 0, 0 and 1, respectively. These are descriptive counts within the registry's groups, not results from a randomized comparison.

The record also lists serious adverse event terms with percentages: Anemia and Thrombocytopenia at 11.8% each, and Acute respiratory distress syndrome, Cardio-respiratory arrest, Febrile neutropenia and Hypercalcaemia at 6.2% each. It does not provide enough context alongside these terms to assign them to a particular regimen group. The listed terms should not be taken as a complete account of all safety events.

General statistical explanation: adverse event counts describe events recorded during a study, while causal attribution requires additional clinical assessment and study context. These figures alone do not establish that entinostat caused an event or death. The record does not report further details needed to interpret event timing, severity beyond the serious classification, or causal attribution.

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

The registry record documents a Phase 2 study of entinostat in patients with relapsed or refractory Hodgkin's lymphoma and defines a primary response endpoint. That endpoint counted participants whose best response within the first 6 cycles was CR or PR, using investigator assessment under the stated lymphoma response criteria. The record also defines the per-protocol population used for the primary outcome and lists regimen-specific safety counts.

However, the primary response count, percentage and 95% confidence interval are not reported in the registry record. The endpoint definition is not a result: it explains what the study intended to measure, not how participants actually responded. Without the numerical outcome, the posted record cannot establish the response frequency or its precision.

The single-group design also limits what can be inferred. No comparator is described, and the registry does not identify a randomized comparison among regimens. The safety counts can be described within their listed groups, but they do not provide a controlled estimate of relative safety or evidence of causation. The study's terminated status does not explain why it ended, because the reason is not reported in the registry record.

General statistical explanation: a trial result is most informative when the outcome estimate is read alongside its analysis population, uncertainty, design and analysis methods. Here, important pieces of that interpretation—including the primary estimate, its interval, missing-data handling and detailed statistical plan—are not reported in the registry record. The appropriate conclusion is about the limits of the posted information, not about whether entinostat did or did not produce a clinical effect.

14. Why This Trial Matters Statistically

This study illustrates why an endpoint definition and an endpoint result are not interchangeable. The registry specifies a response category, assessment criteria, timeframe and per-protocol population. Those details describe what was to be measured. But without the response count, percentage and confidence interval, readers cannot assess the observed frequency or its statistical precision.

It also shows why design labels matter when reading treatment groups. The registry identifies a single-group study and lists allocation as NA. Although safety outcomes are broken out by regimen, the record does not describe a randomized comparison. Descriptive differences between groups should not be interpreted as causal dose comparisons.

Finally, the record highlights the role of population definitions and reporting completeness. The primary endpoint applied to participants meeting treatment and scan criteria, while the size of that analysis population and the handling of missing assessments are not reported. The terminated status is recorded, but its reason is not. Together, these features make the registry useful for understanding the study's question and some of its conduct while leaving central information needed to interpret the primary outcome unavailable.

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 main limitation for interpretation is that the primary endpoint result is not reported in the registry record. The response numerator, assessed denominator, percentage and 95% confidence interval are all absent. The record therefore does not permit evaluation of the observed response frequency or its precision.

The study is listed as terminated, but the reason for termination is not reported. The registry also does not provide the primary analysis population size, the number of participants with missing or unevaluable assessments, or the approach used to handle them. Its per-protocol criteria are specified, but the record does not explain how those criteria affected inclusion in the final analysis.

The single-group design, allocation listed as NA, and lack of masking limit comparative interpretation. Regimen-specific safety counts are descriptive; the record does not identify a randomized comparison among regimens. Some regimen schedule details are incomplete, and the record does not report a detailed statistical analysis plan, multiplicity strategy, interim analyses, or sample-size justification. These absences should be read as gaps in registry reporting, not as evidence that a procedure was or was not performed.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: A Phase 2 Multi-Center Study of Entinostat (SNDX-275) in Patient With Relapsed or Refractory Hodgkin's Lymphoma — NCT00866333.
• Registry record last updated 2019-10-22; status last verified 2019-10.
• Results first posted 2019-10-22.
• 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.

19. Record Summary

The registry describes a Phase 2, multicenter, single-group study of entinostat in patients with relapsed or refractory Hodgkin's lymphoma. It lists a planned enrollment of 49, no masking, and terminated status. The primary endpoint was the percentage of the per-protocol population with a best response of CR or PR within the first 6 cycles.

The record defines the response criteria and per-protocol population and reports safety counts for three regimen groups. It does not report the primary response result, its confidence interval, the reason for termination, or a detailed statistical analysis plan. The posted safety counts are descriptive and do not establish causal effects or randomized regimen comparisons.