Selective Inhibitor of Nuclear Export (SINE) Selinexor (KPT-330) in Patients With Myelodysplastic Syndromes: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Selective Inhibitor of Nuclear Export (SINE) Selinexor (KPT-330) in Patients With Myelodysplastic Syndromes (NCT02228525), a na phase 2 study. The primary outcome is Best Overall Response Rate.

2. Clinical Question

3. Trial Design

This is a completed phase II, single-group study of selinexor (KPT-330) in people with myelodysplastic syndromes. Memorial Sloan Kettering Cancer Center is listed as the sponsor. The registry gives a start date of 2014-08-27, a primary completion date of 2021-04-06, and enrollment of 25. Allocation is recorded as NA and masking as none. There is no control arm, so the design is not a randomized comparison.

The arm description identifies patients with MDS refractory to hypomethylating agents, naming decitabine and 5-azacytidine. It specifies oral selinexor at a starting dose of 60 mg twice weekly for 2 weeks, followed by 1 week without therapy. The description mentions permitted dose reductions but ends before fully describing the provision. Further details of dose modification and treatment exposure are not reported in the registry record.

The primary outcome is best overall response rate, expressed as the percentage of participants with response, with a 2-year timeframe. The registry’s endpoint description states that the design would use Simon’s two-stage minimax approach, with a maximum of 20 patients. It describes possible early termination if no responses are observed in the first 13 patients; if at least one response is observed, the study would continue to the maximum sample size. At the end, at least 3 responses would classify the strategy as promising, with type I and type II errors set at 0.10.

The registry separately reports enrollment of 25, while the design description specifies a maximum of 20. The record does not explain this difference. It also does not report whether the planned stopping rule was applied, whether any amendment changed the design, or what response results were observed. The named secondary outcomes are response duration, overall survival, and participants evaluated for adverse events.

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

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 Best Overall Response Rate, measured over 2 years.

Best overall response rate is the proportion of participants who meet the study’s response criteria at any point during the defined assessment period. The registry describes the measure as a percentage of participants with response and gives a 2-year timeframe. It does not state the detailed response criteria, assessment schedule, or rules for adjudicating response; those details are not reported in the registry record.

A response-rate endpoint is useful in a single-group study because it describes how often a predefined response is observed after the study intervention, without requiring a concurrent control arm. It can support an early assessment of whether further study may be worthwhile. Here, the registry’s design description sets a threshold of at least 3 responses for classifying the strategy as promising under the stated design. That planned decision rule is not itself an observed outcome.

The posted record does not report the number of participants who responded, the response percentage, or the stated 95% confidence interval. It therefore does not establish how frequently responses occurred or how precisely that frequency was estimated. The response criteria and the handling of participants without an evaluable assessment are also not reported in the registry record. Without those details and the observed result, the endpoint’s planned meaning can be described, but its empirical result cannot be interpreted.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does the response-rate endpoint measure?

The primary endpoint is a binary outcome summarized as a percentage: participants either meet the response definition or they do not. The registry calls it best overall response rate and assigns it a 2-year timeframe. “Best overall” ordinarily refers to the most favorable response recorded over a defined period, but the precise response categories, criteria, and assessment procedures are not reported in the registry record. Those operational details matter because the measured rate depends on what qualifies as a response and how assessments are conducted.

General statistical context: a percentage is a compact description of the observed frequency in a study group. It does not, by itself, show how precisely the underlying response frequency is known. The registry identifies a 95% confidence interval as the intended measure of dispersion. In general, a confidence interval expresses the uncertainty around an estimate under the assumptions of the statistical method. The actual interval and response estimate are not reported in the registry record, so no conclusion about their precision can be drawn.

What is the role of the two-stage design?

The endpoint description specifies Simon’s two-stage minimax design. In general, this design evaluates an early group before deciding whether to stop for insufficient activity or continue enrollment. “Minimax” refers to a design chosen to limit the maximum number of participants required while meeting its planned operating characteristics. The registry states that early termination may occur if no responses are observed in the first 13 patients. If at least one response is observed, the trial would continue to a maximum of 20 patients. At the end, at least 3 responses would meet the registry’s criterion for considering the strategy promising. The stated type I and type II errors are 0.10.

These figures describe the planned decision procedure. They do not report what happened during the study. Although the registry marks the study completed and gives enrollment of 25, it does not state whether the design was amended, whether the early rule was followed, or how the final response count related to the threshold. The difference between the design narrative’s maximum of 20 and reported enrollment of 25 is not explained in the registry record.

Why does the absence of a control group matter?

General statistical context: a single-group design estimates outcomes within the group receiving the intervention. It lacks a concurrent group to show what outcomes would have been under a different treatment or control condition. Randomization is one way trials create a balanced comparison, but this record reports a single group, allocation NA, and masking none. Thus, an observed response rate—if reported—would describe the enrolled group and would not be a randomized estimate of a treatment difference.

The lack of a comparator does not make a response-rate endpoint meaningless. It does shape the question it can answer. The endpoint can describe the frequency of responses under the study conditions, while causal attribution and comparative benefit require evidence beyond a single group. The registry record does not report a comparative analysis.

How should sample-size illustrations be understood?

General statistical context: sample-size calculations are planning exercises that estimate the group size needed to detect a chosen effect under specified assumptions. Any sample-size illustrations associated with these results are explicitly planning illustrations based on the observed effect, not the trial’s own design. Their assumptions are a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation; the target effect is a stated fraction of the observed effect. For time-to-event outcomes, the illustration concerns the total number of events, while other outcomes use participants per arm.

These assumptions are distinct from the registry’s single-group Simon design, whose type I and type II errors are stated as 0.10. The illustrations do not mean that this trial randomized participants between two arms, and they are not observed power. A planning calculation cannot compensate for an unreported primary result or turn a single-group study into a controlled comparison.

What can be inferred from the analysis record?

The registry lists no analysis entries. This means analysis details and statistical results are not available in the record, rather than showing that no analysis was conducted. It does not report the method used to calculate the 95% confidence interval, the response analysis population, or how participants with incomplete assessments were handled. General statistical context: confidence intervals and percentages depend on the analyzed denominator and the method used; without those details, an estimate cannot be independently assessed. No recalculated response estimate is possible from the posted information because the response count and denominator for the endpoint are not reported.

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("Selinexor (KPT-330)")
n      <- c(25)
events <- c(6)
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  Selinexor (KPT-330)  25  6  24.0  9.4  45.1  11.5  43.4  11.6  43.6

11. Multiplicity, Missing Data and Analysis Populations

The registry lists best overall response rate as the primary outcome and names response duration, overall survival, and participants evaluated for adverse events as secondary outcomes. It reports four outcome measures in total, but gives no analysis entries. The statistical plan for evaluating the secondary outcomes, including any adjustment for multiple comparisons, is not reported in the registry record.

Multiplicity arises when several outcomes or analyses are examined: the chance of at least one apparently noteworthy result can increase as the number of evaluations grows. General statistical context: prespecifying a primary endpoint and distinguishing it from secondary outcomes helps readers understand which question is central, but it does not reveal whether additional analyses were planned or how they were handled. The registry states a primary endpoint and the design’s decision thresholds, but does not report an adjustment strategy for multiple testing.

Missing-data procedures are not reported in the registry record. The record does not state how participants without a response assessment, incomplete follow-up, or withdrawals were handled for the primary endpoint. Nor does it specify the analysis population—for example, whether the response-rate denominator included everyone enrolled or only participants with an evaluable assessment. These details are important because the denominator and the treatment of missing outcomes can change the interpretation of a percentage.

The registry’s enrollment count is 25, but it is not identified as the analysis denominator for response. The response count, denominator, and interval estimate are not reported. Consequently, a reader cannot assess the impact of missing observations or reconstruct the primary analysis from the registry record.

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 non-serious adverse event terms

The registry’s safety figures list 25 participants at risk for serious adverse events and 0 affected. For other adverse events, it lists 25 at risk and 25 affected. These are counts recorded for the selinexor group. The registry also records 7 deaths. The record does not provide a timing or causal attribution for the deaths, so the deaths field should not be interpreted as showing that selinexor caused them.

No top serious adverse-event terms are listed. The absence of listed terms does not supply detail about event types, severity gradations, timing, or duration; those particulars are not reported in the registry record. Likewise, the broad “other adverse events” count does not describe which events occurred or how often each type occurred.

General statistical context: a count of participants affected is not the same as a count of separate events, because an individual may experience more than one event. The record’s figures do not clarify event-level counting rules or the observation period used for these summaries. These safety entries are descriptive registry data and do not provide a comparison with another group. They should not be read as a comparative estimate of risk or as proof of a causal relationship.

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

The registry record supports a limited description of this completed phase II study: it enrolled 25 participants in a single group receiving selinexor, and it specified best overall response rate as the primary endpoint. The planned endpoint timeframe was 2 years. The study description also set out a Simon’s two-stage minimax decision rule, including early stopping conditions and a threshold of at least 3 responses for classifying the strategy as promising.

Those design details do not show the observed primary result. The registry does not report the response count, response percentage, or 95% confidence interval. Therefore, the posted information cannot establish whether the response threshold was met, what response frequency was observed, or how precise that frequency was. A design threshold is a rule for interpreting a result, not the result itself.

The single-group design also limits what a response result could establish. Without a concurrent control group, the study would not provide a randomized comparison with another treatment or control condition. It could describe outcomes among enrolled participants, but it could not by itself identify a comparative treatment effect.

The reported safety entries show 0 of 25 affected by serious adverse events and 25 of 25 affected by other adverse events, alongside 7 deaths. The registry does not provide event terms for serious events or state the timing and attribution of deaths. These figures should not be extended into causal conclusions.

The record is marked completed, but completion does not supply missing outcome results. It reports enrollment of 25 while the endpoint narrative describes a maximum of 20; the reason for the difference is not reported. Details on response criteria, missing-data handling, analysis populations, and statistical analyses are also absent. The appropriate interpretation is therefore that the registry describes a planned response question and reports limited safety counts, but leaves the primary observed response result unavailable.

14. Why This Trial Matters Statistically

This trial is statistically informative as an example of the distinction between a design rule and an observed result. The endpoint narrative lays out a Simon’s two-stage minimax approach, including an early stopping condition, a maximum sample size, and a response threshold for classifying the strategy as promising. Those features show how a single-group phase II study can be structured to make a decision using a binary response outcome. They do not tell readers whether the decision threshold was reached.

The registry’s lack of an observed response estimate is central. A planned percentage endpoint and a stated 95% confidence interval are not enough to assess the result without the response count, denominator, and interval. Reporting those elements would allow readers to distinguish an estimate from its uncertainty and to understand how the design’s rule relates to the observed data.

The design also illustrates why the target question needs to be described precisely. A single-group response rate is a within-group description. It is not a randomized comparison, and it does not alone quantify a difference against an alternative. The registry’s allocation and masking entries reinforce that this is not a controlled, masked comparison.

Finally, the record gives enrollment of 25 despite describing a planned maximum of 20. Because no explanation is recorded, readers cannot tell whether this reflects a change in conduct, a design update, or another reporting issue. This makes clear why complete reporting should connect planned methods with the conduct and analysis actually performed. The available information supports discussion of the design and safety counts, but not a conclusion about the primary response outcome.

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.

Several trial-specific limitations affect interpretation of the registry record. Most importantly, the observed best overall response rate is not reported. Neither the response count nor its percentage or 95% confidence interval is available. The criteria defining response and the assessment procedures are also not reported, so the endpoint cannot be independently interpreted from its label alone.

The study is single-group, with allocation recorded as NA and masking as none. There is no concurrent comparator for a randomized treatment contrast. Even if the primary response result were available, the design would support a description of outcomes in the enrolled group rather than a controlled comparison.

The endpoint narrative describes a maximum of 20 patients, but the registry reports enrollment of 25. The registry does not explain this difference or state whether the Simon’s two-stage design or its stopping rules changed. It does not say whether early stopping was considered or applied. As a result, the relationship between the planned decision procedure and the completed study is unclear.

The statistical analysis details are sparse. The registry records no analysis entries and does not report the response analysis population, missing-data rules, confidence-interval method, or procedures for the secondary outcomes. The named secondary outcomes are response duration, overall survival, and participants evaluated for adverse events, but their results and analysis details are not reported in the registry record.

Safety reporting is also limited to summary counts. No top serious adverse-event terms are listed, and timing or attribution for the 7 deaths is not reported. These gaps prevent detailed interpretation of the safety entries and do not permit causal conclusions.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Selective Inhibitor of Nuclear Export (SINE) Selinexor (KPT-330) in Patients With Myelodysplastic Syndromes — NCT02228525.
• Registry record last updated 2022-03-09; status last verified 2021-04.
• Results first posted 2022-03-09.
• 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

NCT02228525 is a completed phase II, single-group study of oral selinexor (KPT-330) in people with myelodysplastic syndromes. The sponsor is Memorial Sloan Kettering Cancer Center. The registry reports enrollment of 25, a start date of 2014-08-27, and a primary completion date of 2021-04-06. The arm description identifies patients refractory to decitabine or 5-azacytidine and states a starting schedule of 60 mg twice weekly for 2 weeks, followed by 1 week without therapy.

The primary endpoint is best overall response rate over 2 years. Its description specifies a Simon’s two-stage minimax design, while the registry reports a planned maximum of 20 patients. The response result and 95% confidence interval are not reported. Registry safety counts are 0 of 25 affected by serious adverse events, 25 of 25 affected by other adverse events, and 7 deaths. The reason for the difference between planned maximum and reported enrollment, and the timing or attribution of deaths, are not reported in the registry record.