Decitabine and Vorinostat Conditioning Followed by CD3-/CD19- NK Cells Infusion for High Risk Myelodysplastic Syndromes: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Decitabine and Vorinostat Conditioning Followed by CD3-/CD19- NK Cells Infusion for High Risk Myelodysplastic Syndromes (NCT01593670), a na phase 2 study. The primary outcome is The Number of Patients Who Achieved a Clinical Response.

2. Clinical Question

3. Trial Design

This was a Phase II therapeutic trial for people with high-risk MDS. The registry record identifies a single group, with no allocation to different trial arms and no masking. It lists an enrollment of 9 and a completed status. The trial start is recorded as 2013-03 and primary completion as 2018-10-23.

The treatment description combines decitabine, vorinostat, donor NK cells and IL-2. The schedule states that decitabine was given on days 1-5, vorinostat on days 6-15, and a single infusion of CD3-/CD19- enriched donor NK cells on day 17, followed by a short course of IL-2 intended to facilitate NK-cell survival and expansion. Two courses were planned, separated by 6-8 weeks. The registry describes the intent to administer treatment in the outpatient setting.

The arm description gives decitabine at 10 mg/m^2/day intravenously over 1 hour on days 1-5 and vorinostat at 200 mg by mouth twice a day on days 6-15. It describes an infusion of IL-2 activated donor NK cells intravenously over 15 to 60 minutes. Dosing details for IL-2 and the NK-cell infusion are not reported in the registry record.

Because the study has no recorded control group, its outcomes describe participants treated within this trial rather than a comparative treatment effect. The registry record does not report a statistical analysis plan, a sample-size justification, or details of how participants were selected for enrollment.

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 The Number of Patients Who Achieved a Clinical Response, measured over After 2 Courses of Treatment (Approx. 3 months).

The primary endpoint is a count: the number of participants who achieved a clinical response after 2 courses of treatment, at approximately 3 months. A count records how many people met the stated response definition; it is not, by itself, a comparison with an untreated group or another treatment.

The registry definition combines complete response, partial response and hematologic improvement. Complete response requires fewer than 5% myeloblasts in bone marrow and specified blood-count criteria. Partial response requires improvement in the response criteria if previously abnormal, with a reduction in bone-marrow myeloblasts of more than 50% over pretreatment levels while the proportion remains greater than 5%. Hematologic improvement can be based on changes in hemoglobin, red-cell transfusion requirements, platelets or neutrophils, according to the listed thresholds.

A composite response definition can capture more than one kind of change in disease status or blood counts. That can be useful when a single measure would not represent all clinically relevant response patterns. It also means the count depends on the exact criteria and assessment time specified in the registry. The posted record does not report how many participants met any response category, the category-specific counts, or how missing assessments were handled. The endpoint’s definition is therefore available, but its observed result cannot be interpreted from the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary outcome is recorded as a count of participants who achieved a defined clinical response. A count is a direct way to describe how many participants met the outcome criteria. To understand how common that outcome was in the trial group, readers would also need a denominator and a clearly specified analysis population. Although the registry gives an enrollment of 9, it does not report the primary response count or explain whether all enrolled participants were included in the primary endpoint analysis.

What does a count tell us?

In general, a count tells how many observed participants had an event or met a criterion. It does not, without context, describe the uncertainty in that count or the chance of the outcome in a broader population. A proportion can provide that context when an appropriate denominator is reported, and an interval estimate can show the precision of the proportion. Here, the registry record does not report the primary count, proportion or confidence interval, so none can be interpreted.

For safety outcomes, event counts should be read in relation to the population at risk and the way the registry defines each event category. The adverse-event record gives at-risk and affected counts for serious and other adverse events. Those are descriptive safety summaries; they do not by themselves estimate comparative risk because the study has no control group. An event’s occurrence during a trial also does not establish that the treatment caused it.

Why does the response definition matter?

The primary endpoint combines complete response, partial response and hematologic improvement. In general, a composite endpoint can represent several clinically relevant response patterns, but its overall count depends on the component definitions and on which assessments are available. The listed criteria include bone-marrow myeloblast levels and changes in hemoglobin, transfusion requirements, platelet counts and neutrophil counts. A participant could meet the composite definition through different components. The registry record does not provide counts by response category or further details about how overlapping categories were handled.

The assessment is tied to a specified time: after 2 courses of treatment, at approximately 3 months. In general, a fixed assessment time helps define when an outcome is evaluated. It does not indicate whether every participant had an assessment at that time, whether assessments outside that window were included, or how incomplete assessments were treated. Those details are not reported in the registry record.

What can a confidence interval contribute?

In general, a confidence interval expresses the precision of an estimated outcome under a stated statistical model. A wider interval indicates that a range of values remains compatible with the data; a narrower interval indicates more precision under that model. The interval does not guarantee that a result is true, and it cannot resolve limitations such as the lack of a comparison group. No interval for the primary response outcome is reported in the registry record, so its precision cannot be evaluated from that record.

Likewise, a p-value, in general, measures how unusual data would be under a specified null hypothesis and statistical model. Its interpretation depends on the hypothesis, analysis, and assumptions. A p-value is not a measure of clinical importance and does not replace an estimate with an interval. The registry record does not report an inferential analysis for the primary response outcome.

How should the sample-size illustrations be read?

The posted sample-size calculations are planning illustrations based on the observed effect, with assumptions of a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. They describe hypothetical sample-size planning for detecting a stated fraction of an observed effect. Such calculations can help illustrate how planning depends on the chosen target effect and design assumptions.

These calculations are not observed power. Observed power is not a substitute for interpreting the estimate and its uncertainty, and a planning illustration does not establish that the trial was designed using those assumptions. The registry record describes a single-group study, whereas the illustration assumes equal allocation between two arms. It should therefore be understood as a hypothetical planning comparison, not as a feature of the trial’s actual allocation or a comparison performed within it. The registry record does not report the original sample-size justification or a target enrollment based on a prespecified statistical plan.

Why does over-dispersion matter in general?

For count outcomes, a statistical model may assume that variability follows a particular relationship to the expected count. Over-dispersion means the observed variability is greater than that assumed by a simpler model. In general, ignoring over-dispersion can make uncertainty appear smaller than it is, affecting standard errors and interval estimates. This is a general modeling consideration, not a claim about the analysis used in this trial. The registry record does not report a count model, an over-dispersion assessment or a statistical analysis plan.

Overall, the registry record permits a description of the design, endpoint definition and safety counts, but it does not provide enough outcome-analysis detail to evaluate an estimated primary response rate or its precision. No adjustment method, modeling strategy or analysis-population definition is 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("Patients With High Risk MDS")
n      <- c(9)
events <- c(5)
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  Patients With High Risk MDS  9  5  55.6  21.2  86.3  26.7  81.1  26.2  81.3

11. Multiplicity, Missing Data and Analysis Populations

The registry lists a primary clinical-response outcome and secondary outcomes covering grade 3 or higher non-hematologic adverse events, transfusion independence, NK-cell expansion and overall survival. When a study evaluates several outcomes, multiplicity can arise: the more statistical questions examined, the greater the chance that at least one appears notable by chance if each is tested without adjustment. In general, prespecifying a primary outcome and describing any adjustment strategy helps readers interpret multiple tests.

The registry record does not report a multiplicity strategy, a hierarchy for secondary outcomes, or an inferential analysis plan. It also does not provide results for the listed secondary outcomes in the registry record for this analysis. The record lists zero analysis entries. The presence of an endpoint in the registry does not establish that it was analyzed or that a result was statistically significant.

Missing-data handling is not reported in the registry record. This matters because a response assessment may be unavailable, and the interpretation of a count can depend on whether participants without an assessment are excluded, counted as not responding, or handled in another way. The record does not state how the primary endpoint analysis population was defined, whether any participants were excluded from an outcome analysis, or how incomplete follow-up was treated.

These omissions limit assessment of how the reported enrollment relates to each endpoint and whether outcome estimates, if available elsewhere, would reflect all enrolled participants. No assumptions about missingness or analysis populations should be inferred from the single-group design or from the listed outcome definitions.

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: febrile neutropenia (22.2%), hypotension (11.1%), renal colic (11.1%), nausea (11.1%), ear pain (11.1%).

The registry’s adverse-event fields report serious adverse events for 6 participants among 9 at risk, other adverse events for 9 participants among 9 at risk, and 7 deaths. These are separate recorded summaries. Serious and other adverse-event categories should not be treated as interchangeable, and the record does not explain whether an individual could appear in both categories.

The serious-event terms listed include febrile neutropenia at 22.2%, and hypotension, renal colic, nausea, ear pain and otomastoiditis at 11.1% each. These percentages describe the listed terms in the registry record; they do not establish that the events were caused by the treatment. The record does not provide event-level timing, duration, recurrence, severity beyond the serious-event listing, or an attribution assessment for these terms.

The death count is not, on its own, an estimate of treatment-related mortality. The registry record does not report causes of death, timing in relation to treatment, or whether deaths were considered related to the study regimen. Without a comparison group, safety counts cannot show how event occurrence compares with another treatment or with the underlying condition. They should be read as descriptive records from this trial rather than as comparative risk estimates.

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

The record establishes that a Phase II, single-group study was conducted in people with high-risk MDS and that its intended regimen combined decitabine and vorinostat conditioning with donor NK cells and IL-2. It also defines a primary clinical-response outcome assessed after 2 courses, at approximately 3 months. These design details explain what the study set out to evaluate.

The registry record does not report the primary response count. Consequently, it does not support a numerical statement about how many participants achieved clinical response, the response proportion, or the precision of an estimate. A treatment effect relative to another approach cannot be estimated from a single-group design without a concurrent comparator. No causal conclusion should be drawn from the response definition or the existence of a completed trial alone.

The record reports adverse-event and death counts, but not treatment attribution or comparative safety estimates. Those figures describe events recorded for participants in the study; they do not establish that the regimen caused the events or deaths. The registry also lists several secondary outcomes, but their results are not reported in the registry record for this analysis.

More broadly, a registry record is useful for understanding intended design and registered outcomes, but it may not contain every detail needed to assess execution or analysis. Here, the statistical plan, missing-data handling, analysis populations and primary outcome estimate are not reported in the registry record. The appropriate interpretation is therefore limited: the design and endpoint are documented, while the main efficacy result and its uncertainty cannot be assessed from the record.

14. Why This Trial Matters Statistically

This trial is statistically notable for the distinction between a clearly defined endpoint and a reported endpoint result. The registry specifies a composite clinical-response definition and an assessment time after 2 courses of treatment, at approximately 3 months. Yet the primary response count is not reported in the registry record. A detailed definition is important, but it cannot substitute for the observed result needed to describe the outcome.

The single-group design also highlights the difference between describing outcomes and estimating comparative effects. A one-arm study can document what was observed among treated participants, but it does not provide a concurrent reference group. Changes in disease status or blood counts cannot be attributed to the regimen by design alone. This distinction is especially important when interpreting a therapeutic study’s stated intent alongside its statistical evidence.

The record further illustrates why safety counts need context. Counts of affected participants, serious-event terms and deaths are descriptive. Attribution, timing and comparison information affect how those observations can be interpreted, and those details are not reported in the registry record.

Finally, the registry includes multiple secondary outcomes but does not report an analysis plan or multiplicity approach. Clear reporting of analysis populations, missing-data methods, estimates and uncertainty would help readers understand how the registered questions were addressed. The available record documents important design features but leaves the primary outcome result and several elements needed for statistical interpretation 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.

Several limitations are specific to the information recorded for this trial. The primary endpoint is defined, but its observed count is not reported in the registry record. There is therefore no primary response estimate or interval to assess. Results for the listed secondary outcomes are also not reported in the registry record for this analysis.

The study is described as a single group, with allocation listed as not applicable and masking listed as none. There is no concurrent control group in the registry record, so the design does not support a direct comparison with another treatment. The record does not report further information about outcome-assessment procedures or whether assessors were independent.

The registry gives an enrollment of 9 but does not report the primary endpoint analysis population, participant flow, exclusions, or how participants with missing assessments were handled. It also does not report baseline characteristics that would help describe the enrolled group. The timing and completeness of outcome follow-up are not detailed beyond the primary assessment timeframe.

The analysis plan, original sample-size justification, multiplicity handling and statistical methods are not reported in the registry record. Safety summaries include affected counts, serious-event terms and deaths, but the record does not report event attribution, timing, causes of death or treatment relationship. These limitations constrain interpretation of both efficacy and safety; they should not be filled in by assumptions based on the intervention or disease.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Decitabine and Vorinostat Conditioning Followed by CD3-/CD19- NK Cells Infusion for High Risk Myelodysplastic Syndromes — NCT01593670.
• Registry record last updated 2019-05-21; status last verified 2019-05.
• Results first posted 2017-06-14.
• 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 NCT01593670 as a completed Phase II, single-group trial for high-risk MDS, with an enrollment of 9. The regimen combined decitabine and vorinostat conditioning, donor NK-cell infusion and IL-2, with two courses planned 6-8 weeks apart. The primary outcome was the number of participants achieving clinical response after 2 courses, at approximately 3 months.

The record does not report the primary response count, an estimate of its precision, or an inferential analysis. It lists secondary outcomes for serious non-hematologic adverse events, transfusion independence, NK-cell expansion and overall survival. Safety fields report 6 participants with serious adverse events among 9 at risk, 9 with other adverse events among 9 at risk, and 7 deaths. Attribution and comparative safety information are not reported. The design and endpoint are documented, but the primary outcome result cannot be assessed from the registry record.