MS-275 and GM-CSF in Treating Patients With Myelodysplastic Syndrome and/or Relapsed or Refractory Acute Myeloid Leukemia or Acute Lymphocytic Leukemia: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for MS-275 and GM-CSF in Treating Patients With Myelodysplastic Syndrome and/or Relapsed or Refractory Acute Myeloid Leukemia or Acute Lymphocytic Leukemia (NCT00462605), a na phase 2 study. The primary outcome is Response (Complete and Partial Response) in Patients With Myeloid Disorders.

2. Clinical Question

The study asked whether treatment with MS-275 and sargramostim was associated with complete or partial response in patients with myeloid disorders. The registry identifies this as a phase II study and describes the treatment combination as being studied in patients with myelodysplastic syndrome and relapsed or refractory acute myeloid leukemia. The listed conditions also include acute lymphoblastic leukemia and several other myeloid diagnoses. The record does not report how many participants had each diagnosis, so the mix of diseases represented in the enrolled group is unknown.

This question is descriptive in a single-group study: it concerns the observed response in the treated group, not a randomized estimate of the difference between treatments. The registry’s brief summary presents a biological rationale for combining the drugs, but the rationale is not itself evidence of clinical response. The actual response count and the analysis used to interpret it are not reported in the registry record.

3. Trial Design

This is a phase II, single-group study sponsored by the National Cancer Institute. The registry records enrollment of 24 and lists the study as completed. The recorded start is 2007-04, and primary completion is recorded as 2011-03. Allocation is listed as not applicable, and masking is listed as none. With no concurrent comparison arm, the design describes outcomes among participants receiving the combination rather than a treatment contrast between groups.

The intervention is MS-275, identified in the registry as entinostat, with sargramostim, identified as GM-CSF. The arm description says participants received oral MS-275 on days 1, 8, 15, and 22. Sargramostim was given subcutaneously once daily on days 1-42 in courses 3 and 5, and on days 1-35 in courses 1, 2, 4, and 6. Treatment was described as repeating every 6 weeks for 2-6 courses. The available arm description ends mid-word when describing a condition for continuing treatment, so the full wording of that condition is not reported in the registry record.

The primary outcome is response, defined in the record as complete and partial response in patients with myeloid disorders. Response was assessed after two cycles according to International Working Group criteria. The outcome timeframe is listed as up to 2 years; the registry does not clarify how this timeframe relates to the assessment after two cycles. Cytogenetic responses were monitored in participants with abnormalities at baseline.

Secondary outcomes cover changes in peripheral blood counts, transfusion requirements, detectable chromosomal abnormalities measured by FISH, and the percentage of cells with normal and abnormal myeloid phenotype measured by flow cytometry. The registry does not report the detailed analysis plan, sample-size justification, or whether any interim analyses were planned.

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 Response (Complete and Partial Response) in Patients With Myeloid Disorders, measured over Up to 2 years.

The primary endpoint counts participants with a complete or partial response among patients with myeloid disorders. The registry says response was assessed after two cycles using International Working Group criteria, and that cytogenetic responses were monitored in participants who had abnormalities at baseline. The endpoint is recorded as a participant count, not as a time-to-event measure or a continuous laboratory value. The stated outcome timeframe is up to 2 years.

Combining complete and partial responses into a response outcome can give a compact description of whether disease status met the specified response criteria. It does not, by itself, describe the duration of a response, the time until progression, or changes in symptoms or quality of life. Those concepts are distinct from the response count unless separately defined and reported.

General statistical interpretation: a participant-count endpoint needs a clear denominator. The numerator is the number meeting the response definition, while the denominator is the relevant analysis population. In a single-group study, a response proportion is often used to describe the observed frequency, but its precision depends on both the count and the number assessed. The registry record gives the enrollment count, but it does not report the primary response count, the analysis denominator, or an uncertainty interval. Therefore, the observed response frequency and its precision cannot be described from the registry record.

The endpoint’s diagnostic scope also matters. The primary outcome is expressly framed for myeloid disorders, although the listed conditions include other diagnoses. The record does not report which participants contributed to the primary endpoint or whether different diagnostic groups were assessed under different response rules.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The outcome is a count of participants meeting a response definition. The definition combines complete and partial response for patients with myeloid disorders, and the registry states that response was assessed according to International Working Group criteria after two cycles. This makes the endpoint binary at the participant level for a given assessment: each participant either meets the combined response definition or does not. The registry does not report the count in either category.

What does a participant count tell us?

General statistical explanation: for a binary endpoint, the count alone is not enough to describe the observed frequency unless its denominator is also known. The denominator should identify which participants were considered eligible for the endpoint and had an outcome assessed. A proportion can then describe the fraction meeting the response definition. This study’s registry record lists enrollment of 24, but it does not report the primary analysis denominator or the number with an assessed response. Enrollment and endpoint analysis populations are not necessarily identical, so they should not be treated as interchangeable.

In a single-group study, an estimated response proportion would describe the observed response frequency within the study group. A confidence interval is a range expressing the statistical uncertainty around an estimate under specified assumptions. General statistical explanation: a confidence interval for a proportion is typically wider when the information available is limited and narrower when the estimate is based on more observations, all else equal. No confidence interval or response estimate is reported in the registry record, so the precision of the primary result cannot be evaluated.

Why does the single-group design matter?

There is one treatment group and no concurrent control group. General statistical explanation: random allocation to a comparator can help balance prognostic factors across groups, on average, and supports a direct estimate of a between-group contrast. A single-group study instead describes what happened among participants who received the study regimen. It cannot, by itself, establish what would have happened to those same participants under a different treatment. This distinction applies even if a response count is available; the design determines the kinds of comparisons the data can support.

The registry lists allocation as not applicable and masking as none. It does not report further procedures for outcome assessment or steps intended to reduce assessment bias. The outcome is based on named response criteria, but the record does not describe how those criteria were operationalized, who assessed response, or whether assessments were independently reviewed. Those details should not be inferred from the endpoint label.

How should the timeframe be understood?

The primary outcome description says assessment occurred after two cycles, while the outcome timeframe is listed as up to 2 years. These entries do not, on their own, explain how response at the specified assessment relates to the longer timeframe. General statistical explanation: an outcome measured at a fixed assessment and an outcome tracked over follow-up answer different questions. A response count at an assessment concerns status at that assessment; duration of response concerns how long the response persists. The registry does not report a duration-of-response endpoint in the primary outcome description or clarify the relationship between the assessment and timeframe.

The record also says cytogenetic responses were monitored in participants with abnormalities at baseline. This is a distinct assessment from the combined complete-or-partial response endpoint. The registry lists secondary measures concerning blood counts, transfusion requirements, FISH-detected chromosomal abnormalities, and myeloid phenotype by flow cytometry. Each addresses a different aspect of clinical or laboratory activity. Their results are not reported in the registry entries.

What statistical analysis is reported?

The registry records zero analysis entries. It does not report a model, statistical test, adjustment strategy, significance threshold, confidence interval method, or analysis population for the primary response outcome. The absence of a reported analysis entry does not establish that no analysis was performed; it means the analysis details are not reported in the registry record.

General statistical explanation: a statistical test would address a specified hypothesis, while an estimate and confidence interval would convey the magnitude and precision of an outcome. In a single-group response study, the choice of a reference value or benchmark would need to be stated to make a hypothesis test interpretable. No benchmark or test is reported. It is therefore not appropriate to infer a hypothesis, calculate a test result, or treat a planning illustration as evidence about observed treatment performance.

The registry’s sample-size assumptions describe a planning illustration based on an observed effect, with a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. Those assumptions are not the design of this single-group trial: the registry lists no two-arm allocation. General statistical explanation: sample-size planning estimates describe hypothetical requirements under chosen assumptions; they are not observed power, and they do not add evidence to a trial’s outcome. The registry does not report the trial’s own sample-size justification. Since the primary response result is also not reported, a planning illustration cannot be used to reconstruct or interpret that missing result.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists the primary response outcome and secondary outcome domains involving peripheral blood counts, transfusion requirements, chromosomal abnormalities measured by FISH, and myeloid phenotype measured by flow cytometry. Considering several outcomes creates a multiplicity issue when statistical claims are made across them: the more comparisons or hypotheses examined, the greater the chance that at least one result appears notable by chance alone. General statistical explanation: methods such as prespecifying a primary endpoint or adjusting for multiple comparisons can address this concern, but the appropriate approach depends on the analysis plan. The registry record does not report a multiplicity strategy, testing hierarchy, or adjustment method.

The record does not report how missing outcome assessments were handled. It does not state whether participants without an assessment were excluded, counted as not responding, or handled through another method. These choices can affect a response estimate, especially if the likelihood of missingness is related to disease status or treatment experience. The number with an assessed primary outcome is not reported, so the extent of missing primary-outcome data cannot be determined.

The primary-outcome population field is blank. Although enrollment is recorded as 24, the registry does not define an intention-to-treat, modified intention-to-treat, per-protocol, or evaluable population for the response analysis. These labels describe different rules for deciding which participants contribute to an analysis. No one population should be assumed from the enrollment count alone.

Interim analyses, stopping rules, protocol deviations, and sensitivity analyses are not reported in the registry record. The statistical analysis plan and the trial’s sample-size justification are also not reported. These omissions limit assessment of whether the endpoint and analysis decisions were prespecified and how robust any reported result would be; the primary response result itself is not reported in the registry record.

11. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 4% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: neutropenic infection (20.8%), bone pain (12.5%), fatigue (8.3%), hypoxia (8.3%), pericardial effusion (4.2%).

The safety summary lists 24 participants at risk for serious adverse events and 19 participants affected. It separately lists 24 at risk for other adverse events and 6 affected. These are counts for the single study arm; they are not a comparison between treatment groups. The record lists no death count in the adverse-event summary.

The serious adverse event terms and their reported percentages are neutropenic infection, 20.8%; Bone Pain, 12.5%; Fatigue, 8.3%; hypoxia, 8.3%; Pericardial effusion, 4.2%; and Weakness, 4.2%. The registry does not give event-specific participant counts alongside these terms in the details. It also does not explain whether participants could contribute to more than one term, or provide the event definitions, severity grading, timing, or duration.

General statistical explanation: the overall count of participants affected by any serious adverse event and the percentages attached to individual event terms are different summaries. Event-term percentages should not be added to estimate the percentage of participants with any event, because one participant may have experienced multiple terms. The overall serious-event count describes how many participants were affected at least once under the registry’s reporting, while individual terms describe specific reported events.

These figures describe events recorded among participants in this study group. Without a comparator group and fuller event-level information, they do not establish whether the regimen caused an event or how the frequency compares with another treatment. The registry’s adverse-event summary should therefore be read as descriptive safety reporting rather than a comparative estimate.

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

The posted results establish that this was a completed phase II study with enrollment of 24, using a single group treated with MS-275 and sargramostim. They define the primary outcome as complete or partial response in patients with myeloid disorders, assessed after two cycles according to International Working Group criteria. The registry also records safety counts and lists serious adverse event terms with percentages.

The registry does not report the primary response count or an analysis of that endpoint. Consequently, the response frequency, its precision, and the number of participants included in the response assessment cannot be stated. The available information does not support a claim about how often response occurred in the study population. It also cannot establish that treatment did or did not cause a clinical effect.

General statistical interpretation: a single-group outcome is not a randomized treatment comparison. Even a complete response result would describe outcomes in participants receiving the regimen, not the difference between the regimen and an alternative. Disease subtype, baseline risk, prior treatment, and follow-up may influence the observed outcome. The registry does not report enough participant-level detail to assess these factors or interpret results by diagnosis.

The safety figures are similarly descriptive. They report participants affected by serious and other adverse events in the study group, but they do not provide a control rate, event-specific participant counts, or enough information to attribute events to a particular component of the combination. The listed event percentages should not be interpreted as evidence of comparative risk.

The registry record also leaves important analytic details unspecified, including the analysis population, handling of missing response assessments, multiplicity strategy, and statistical analysis plan. These limitations do not show that the study lacked analyses; they indicate that these details are not reported in the registry record. The appropriate interpretation is therefore bounded: the record documents the study design, intended response measure, regimen, and selected safety summaries, but does not supply the primary response result needed to describe the principal clinical outcome.

13. Why This Trial Matters Statistically

This trial is statistically notable as a single-group phase II study asking a response question across a broad set of listed blood cancer diagnoses. The primary endpoint is specifically framed around myeloid disorders, while the conditions list also includes acute lymphoblastic leukemia and multiple myeloid and myelodysplastic diagnoses. Because diagnosis-specific enrollment is not reported, the composition of the study group and the reach of any overall response result cannot be assessed from the registry entries.

The design illustrates the distinction between observing an outcome and estimating a treatment contrast. A single-group study can record whether participants meet a response definition and can describe adverse events in the treated group. It does not create a contemporaneous randomized comparison. General statistical explanation: without that comparison, observed outcomes cannot isolate the effect of the intervention from other influences, and comparisons with external experience would require additional assumptions and suitable data.

The endpoint description also highlights why reporting the denominator and assessment timing matters. Response was assessed after two cycles, while the timeframe is listed as up to 2 years. The registry does not clarify the relationship between those entries or report the number assessed. Clear reporting of the analysis population, missing assessments, and timing would help readers determine exactly what a response count represents.

Finally, this record demonstrates the limits of registry outcome summaries when the primary result and analysis details are absent. Enrollment, design, endpoint definitions, and safety counts are useful for understanding the study, but they do not replace the response estimate and its uncertainty. Without those elements, readers cannot judge the magnitude or precision of the principal outcome from the registry record. The statistical importance of the study therefore lies both in its single-group design and in the reporting information needed to interpret its stated endpoint.

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 most direct limitation is that the registry does not report the primary response count, response estimate, or uncertainty interval. The record identifies response as complete or partial response in patients with myeloid disorders, but does not show how many met that definition. The primary analysis denominator is also not reported, so the enrollment count cannot stand in for the number assessed.

The study has one treatment group and no comparator. This limits interpretation to description of outcomes in the enrolled group and prevents a direct randomized comparison. The registry does not report participant characteristics or diagnosis-specific counts, despite listing a broad set of conditions. It is therefore not possible to assess the disease composition of the cohort or whether results differed across diagnoses.

The endpoint timing is not fully clear from the record: response is described as assessed after two cycles, and the timeframe is listed as up to 2 years. The registry does not explain whether these refer to separate assessments or how follow-up relates to the primary response measure. It also does not report the duration of response or the number of participants with baseline chromosomal abnormalities who were monitored for cytogenetic response.

Analysis methods, the analysis population, handling of missing assessments, multiplicity procedures, and interim analyses are not reported in the registry record. The study’s sample-size justification is also not reported. The adverse-event summary does not include event-specific participant counts, definitions, timing, or duration, and does not provide a control group for comparison.

These are limitations of what the registry record reports; they do not establish what was or was not done in the study outside the registry. They do, however, constrain independent statistical interpretation of the posted results.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: MS-275 and GM-CSF in Treating Patients With Myelodysplastic Syndrome and/or Relapsed or Refractory Acute Myeloid Leukemia or Acute Lymphocytic Leukemia — NCT00462605.
• Registry record last updated 2017-07-18; status last verified 2017-06.
• Results first posted 2017-04-17.
• 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 identifies NCT00462605 as a completed phase II, single-group study sponsored by the National Cancer Institute, with enrollment of 24. The intervention combined oral MS-275, also called entinostat, and sargramostim, also called GM-CSF. The primary outcome was complete or partial response in patients with myeloid disorders, assessed after two cycles using International Working Group criteria; its timeframe is listed as up to 2 years.

The registry lists secondary outcomes related to blood counts, transfusion requirements, chromosomal abnormalities, and myeloid phenotype. It reports serious adverse events in 19 participants and other adverse events in 6 participants, among 24 at risk for each category, along with selected serious-event terms and percentages. The primary response result, analysis denominator, inferential analysis, missing-data approach, multiplicity strategy, and sample-size justification are not reported in the registry record.