This page provides an independent statistical analysis and educational interpretation of publicly reported results. ClinicalTrials.gov provides the official trial registry record. Numerical trial results on this page are restricted to the results posted in the ClinicalTrials.gov record; calculations added by Clinical Biostats are labelled as such.
1. Trial at a Glance
This page covers the registry results for Decitabine (DAC) w/ or w/o Valproic Acid (VPA) in Myelodysplastic Syndrome (MDS) and Acute Myelogenous Leukemia (AML) (NCT00414310), a randomized phase 2 study. The primary outcome is Participant Response Rates to Decitabine With or Without Valproic Acid in MDS and AML.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT00414310 |
| Phase | Phase 2 |
| Condition | Myelodysplastic Syndrome, Acute Myelogenous Leukemia |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | None (open label) |
| Enrollment | 153 |
| Arms in the primary outcome | n/a |
| Lead sponsor | M.D. Anderson Cancer Center |
| Results posted | Yes |
2. Clinical Question
Population
Participants with myelodysplastic syndrome (MDS) or acute myelogenous leukemia (AML) were eligible for the study. The registry record reports enrollment of 153 participants. One enrolled participant assigned to the Decitabine arm was not treated and was not evaluable for response; the record does not give further detail about the response-evaluable population.
Intervention
The combination arm received decitabine 20 mg/m^2 intravenously over 1 hour daily for 5 days, plus valproic acid 50 mg/kg orally daily for 7 days. The study was open label, so masking was not used.
Comparator
The comparator arm received decitabine 20 mg/m^2 intravenously over 1 hour daily for 5 days without valproic acid. The registry describes a randomized, parallel-group Phase II study, but does not report how the random sequence was generated or how treatment assignments were concealed.
Primary question
The study asked whether response to decitabine, assessed at 1 Year, differed when valproic acid was added for participants with MDS or AML. The registered response measure includes complete remission, complete remission with incomplete platelet recovery, partial remission, and clinical benefit. The registry record does not report a single comparison of these categories or numerical response results, so the direction and size of any difference cannot be determined from the posted results.
3. Trial Design
This was a Phase II, randomized, open-label, parallel-group study sponsored by M.D. Anderson Cancer Center. It compared decitabine alone with decitabine plus valproic acid in participants with MDS or AML. The registry record reports enrollment of 153 and a completed status. It gives a start date of 2006-12 and a primary completion date of 2015-05.
Both groups received decitabine 20 mg/m^2 intravenously over 1 hour daily for 5 days. The combination group also received valproic acid 50 mg/kg orally daily for 7 days. Because masking was listed as none, participants and study personnel were not blinded to treatment assignment according to the registry record. Random allocation and a parallel model are reported, but the record does not describe the sequence-generation method, allocation concealment, stratification, or whether the groups were intended to be equal in size.
The primary outcome was participant response at 1 Year. Response encompassed multiple categories and definitions rather than a single binary comparison in the posted results. Response duration and overall survival rate were listed as secondary outcomes. The record lists three outcome measures but no analyses. It does not report the statistical analysis plan, the methods used to compare arms, or how follow-up and censoring were handled for the secondary outcomes.
The registry notes that one enrolled participant on the Decitabine arm was not treated and was not evaluable for response. The safety information lists the number at risk and the number affected by serious and other adverse events for each arm. The record does not explain whether those safety populations match the randomized, treated, or followed populations, nor does it give a participant-flow account. Thus, the design features and treatment schedules are described, but important operational details and the primary efficacy comparison 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: Of the 153 participants registered on the study for Decitabine (DAC) with or without Valproic Acid (VPA) in Myelodysplastic Syndrome (MDS) and Acute Myelogenous Leukemia (AML), three were screen failures therefore 150 patients were randomized with 149 participants treated.
Overall Study
| Stage | Decitabine | Decitabine + Valproic Acid |
|---|---|---|
| STARTED | 71 | 79 |
| COMPLETED | 70 | 79 |
| NOT COMPLETED | 1 | 0 |
Reasons for not completing this period:
| Reason | Decitabine | Decitabine + Valproic Acid |
|---|---|---|
| Not treated | 1 | 0 |
Analysis population for the primary outcome, as defined in the registry: One enrolled participant on the Decitabine arm was not treated, therefore not evaluable for response.
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.
| Characteristic | Unit | Decitabine | Decitabine + Valproic Acid | Total |
|---|---|---|---|---|
| Participants analysed | 71 | 79 | 150 | |
| Age, Continuous | years | 71 (39 to 85) | 66 (20 to 90) | 69 (20 to 90) |
| Sex: Female, Male: Female | Participants | 21 | 37 | 58 |
| Sex: Female, Male: Male | Participants | 50 | 42 | 92 |
| Region of Enrollment: United States | participants | 71 | 79 | 150 |
6. Primary Endpoint
The registry lists the primary outcome as Participant Response Rates to Decitabine With or Without Valproic Acid in MDS and AML, measured over 1 Year.
| Element | Registry entry |
|---|---|
| Result type | Number |
| Measure of spread | not applicable |
| Unit | Percentage of Participants |
| Endpoint classification | Binary Endpoint |
The primary outcome is participant response to decitabine with or without valproic acid, assessed at 1 Year and expressed as a percentage of participants. The definition combines several clinically distinct response categories. Complete remission requires normalization of peripheral blood and bone marrow, with bone marrow blasts < 5%, a peripheral blood granulocyte count > (1.0 x 10^9/ L, and a platelet count > 100 x 10^9/L. CRi uses the stated remission definition but allows platelets <100 x 109/L. Partial remission uses the stated criteria with 6-15% marrow blasts, or a 50% reduction if the starting value is <15%.
Clinical benefit is also included. In MDS/CMML, the record defines it through specified changes in platelets, granulocytes, hemoglobin, transfusion independence, splenomegaly, or monocytosis. In AML, a decrease in bone marrow blasts to <5% is also considered clinical benefit.
A response endpoint is used to describe whether participants meet prespecified disease-response criteria within the stated assessment period. Combining categories can summarize activity, but the categories do not represent identical states. The registry record does not report category-specific counts, the rule used to combine categories into a comparison, or the numerical response results. Consequently, the endpoint definition is available, but the size and precision of the treatment comparison are not.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record establishes the question and the response definitions, but it does not provide a single primary-response comparison. Although the primary outcome is described as a percentage of participants at 1 Year, no response percentages or category counts are reported in the posted results. The record also states that the primary outcome has several categories or time points and was not reduced to one comparison. Therefore, no direction or magnitude of an efficacy difference can be stated from this record.
Without response counts or percentages, a reader cannot assess how often participants met the response criteria in either arm, whether the arms differed, or how precise an estimated difference might be. A confidence interval would ordinarily describe the range of effect sizes compatible with the data under the analysis assumptions. No confidence interval is reported for this primary comparison. There is also no reported test statistic or p-value for it. This absence does not establish that the treatments had equal results; it means the registry record does not report a result that permits that assessment.
The outcome definition itself requires care in interpretation. Complete remission, CRi, partial remission, and clinical benefit are grouped under response, but each category has different criteria. The clinical-benefit criteria also differ by disease context. The record does not provide the number of participants meeting each category or explain how overlapping categories, if any, were handled. It therefore does not support separating remission from clinical benefit or examining response patterns by diagnosis.
Safety data are reported as affected counts and at-risk counts for serious and other adverse events. These figures describe events recorded in the registry, not a causal estimate of treatment harm. The record does not give event-level timing, severity grading, duration, or an adjusted comparison. The listed serious-event terms and percentages should be read as registry summaries; the denominator and calculation details for those term percentages are not reported in the registry record.
Randomization is a design feature intended to support comparisons between assigned groups, but it does not by itself resolve limitations in reporting. The record does not describe allocation procedures, follow-up completeness, analysis populations, or the statistical plan. It also notes that one participant assigned to Decitabine was not treated and was not evaluable for response. Without the complete analysis details and numerical response results, neither the strength nor the precision of the primary comparison can be evaluated.
Overall, the posted information supports a description of the trial question, schedules, endpoint criteria, and selected safety counts. It does not support a quantitative conclusion about comparative response, statistical significance, or the clinical importance of a difference. Those conclusions require results and analysis details that are not reported in the registry record.
9. Statistical Methods Explained
What does randomization contribute?
Randomization assigns participants to treatment groups by chance. In general, this can reduce systematic differences between groups at the time of assignment and makes a treatment comparison more interpretable than a comparison in which treatment choice is determined by participant characteristics. It does not guarantee that every relevant characteristic will be balanced, especially in a study of limited size. Nor does randomization remove the need to report how assignment was generated, concealed, and analyzed. The registry record identifies the study as randomized but does not describe those procedures.
The parallel-group design means the record describes separate groups receiving the two assigned regimens. Open-label status means masking was listed as none. In general, lack of masking can affect outcomes that depend on clinical judgment, reporting, or decisions about assessment. Whether or how that affected this study cannot be determined from the registry record, which does not describe outcome-assessment safeguards.
How should a response percentage be understood?
A percentage of participants with an event or response describes the frequency of that outcome in a defined group. It depends on the numerator, the number meeting the definition, and the denominator, the number included in the analysis. The registry defines the primary outcome as a percentage of participants and identifies one Decitabine-assigned participant who was not treated and was not evaluable for response. It does not report response numerators, arm-specific response percentages, or the full analysis denominators. The response frequency and a between-arm effect therefore cannot be reconstructed from the record.
In general, a treatment comparison might report each arm’s response proportion and a measure of the difference or relative effect. A confidence interval would indicate the uncertainty around that estimate, while a statistical test could assess compatibility with a null hypothesis under specified assumptions. These are general concepts, not reported analyses for this trial. No primary comparison estimate, confidence interval, or p-value is reported in the registry record.
Why do endpoint definitions matter?
The endpoint includes complete remission, CRi, partial remission, and clinical benefit. A composite or multi-category endpoint can capture more than one form of response, but its interpretation depends on the exact criteria and the rule for combining categories. The record supplies clinical criteria, including marrow blast thresholds, blood-count criteria, and disease-specific clinical-benefit criteria. It does not give category counts or explain whether the reported outcome was intended to combine categories into one binary response variable. The registry explicitly notes that several categories or time points were not reduced to one comparison.
Different categories may carry different clinical meanings and may have different frequencies. In general, reporting them separately can show whether an overall response measure is driven by remission categories or by clinical benefit. That breakdown is not reported in the registry record, so the separate contributions cannot be assessed.
What do the safety denominators represent?
For each arm, the registry lists people at risk and people affected for serious and other adverse events. A count of affected participants is not necessarily the same as a count of individual events: one participant may experience more than one event. The record does not specify whether its counts represent people, event episodes, or a particular coding convention beyond the labels used. It also does not provide a detailed safety-analysis population definition. The numbers should therefore be read as the registry’s reported affected counts, not as an independently calculated event rate.
In general, an adverse-event comparison requires consistent definitions, observation periods, and denominators. Follow-up duration can influence the chance of recording an event, and differences in exposure can affect interpretation. The registry record does not describe these details, nor does it provide adjusted safety estimates. Seriousness and frequency are also distinct concepts: a serious event is categorized by seriousness criteria, while a percentage describes frequency in a stated group. The listed serious-event terms do not by themselves establish that an event was caused by a treatment.
What can planning assumptions tell us?
The registry includes a general planning illustration based on the observed effect, with a two-sided significance level of 0.05, equal allocation between the arms, and a normal approximation. The effect to detect is described as a stated fraction of the observed effect. Such sample-size calculations are planning illustrations: they describe the group size associated with specified assumptions and a target power. They are not observed power and do not show that the trial was designed using those assumptions. The registry record does not report the trial’s own sample-size justification or statistical plan. No numerical planning results are stated in the registry record.
More generally, a planning calculation depends on the assumed effect, outcome variability or event frequency, allocation, significance criterion, and analysis method. If those assumptions differ from the eventual data or intended analysis, the planning result may not describe the trial’s actual operating characteristics. Since the record does not report the protocol rationale or a complete statistical plan, the planning assumptions should not be treated as evidence about the original design choices.
10. Multiplicity, Missing Data and Analysis Populations
The primary outcome is described using several response categories and the registry notes several categories or time points, without reducing them to one comparison. That creates an interpretive issue: a reader needs to know which response definition, time point, and contrast were designated as primary for inference. Those details are not reported in the registry record. The record also does not report a multiplicity strategy for handling multiple response categories, time points, or secondary outcomes. Without that information, the control of false-positive findings across analyses cannot be assessed.
Missing-data handling is also not described. The registry identifies one enrolled participant on the Decitabine arm who was not treated and was not evaluable for response. It does not report other reasons for missing response assessments, the extent of missing outcome data, or how participants without an assessment were handled. The record does not state whether the response analysis followed an intention-to-treat, treated-participant, or other population definition.
These distinctions matter because the analysis population and handling of unavailable outcomes can affect a response percentage and a comparison between groups. The record provides no participant-flow account or sensitivity analysis for missing outcomes. The number of outcome measures and the absence of reported analyses do not establish which analyses were conducted outside the registry; they indicate that such details are not reported in the registry record. Accordingly, the robustness of any response estimate to missingness or multiplicity cannot be evaluated from the posted information.
11. Safety Results
The registry reports serious adverse events as affected participants divided by participants at risk.
| Arm | Participants with serious adverse events | Participants at risk | Percentage |
|---|---|---|---|
| Decitabine | 43 | 71 | 60.6% |
| Decitabine + Valproic Acid | 49 | 79 | 62.0% |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 0% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Decitabine | 27 of 71 |
| Decitabine + Valproic Acid | 36 of 79 |
Most frequent serious adverse event terms
| Event term | Organ system | Decitabine | Decitabine + Valproic Acid |
|---|---|---|---|
| Neutropenic Fever | Infections and infestations | 11 of 71 | 22 of 79 |
| Pneumonia | Infections and infestations | 10 of 71 | 11 of 79 |
| Infection other | Infections and infestations | 10 of 71 | 9 of 79 |
| Death | Gastrointestinal disorders | 9 of 71 | 5 of 79 |
| Congestive Heart Failure | Cardiac disorders | 2 of 71 | 3 of 79 |
| Bacteremia | Infections and infestations | 1 of 71 | 4 of 79 |
| Cardiac Arrhythmia | Cardiac disorders | 2 of 71 | 2 of 79 |
| Nausea and Vomiting | Gastrointestinal disorders | 1 of 71 | 3 of 79 |
| Somnolence | Nervous system disorders | 0 of 71 | 4 of 79 |
| Gastrointestinal Hemorrhage | Blood and lymphatic system disorders | 3 of 71 | 0 of 79 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Decitabine | Decitabine + Valproic Acid |
|---|---|---|---|
| Neutropenic Fever | Infections and infestations | 10 of 71 | 12 of 79 |
| Infection | Infections and infestations | 8 of 71 | 8 of 79 |
| Fatigue | General disorders | 6 of 71 | 9 of 79 |
| Nausea | Gastrointestinal disorders | 3 of 71 | 10 of 79 |
| Diarrhea | Gastrointestinal disorders | 4 of 71 | 4 of 79 |
| Somnolence | Nervous system disorders | 0 of 71 | 6 of 79 |
| Pain | General disorders | 3 of 71 | 2 of 79 |
| Opportunistic infection | Infections and infestations | 2 of 71 | 3 of 79 |
| Dizziness | Nervous system disorders | 0 of 71 | 5 of 79 |
| Renal Failure | Renal and urinary disorders | 4 of 71 | 1 of 79 |
Serious events with the highest arm-level rate: neutropenic fever (27.8%), infection other (14.1%), pneumonia (14.1%), death (12.7%), bacteremia (5.1%).
The registry lists serious adverse events and other adverse events separately. For Decitabine, it reports 71 at risk and 43 affected by serious adverse events, and 71 at risk and 27 affected by other adverse events. For Decitabine + Valproic Acid, it reports 79 at risk and 49 affected by serious adverse events, and 79 at risk and 36 affected by other adverse events. These are the recorded counts; the registry does not report an adjusted comparison or explain the safety-population definition.
The most frequent serious-event terms listed are Neutropenic Fever at 27.8%, Infection other at 14.1%, Pneumonia at 14.1%, Death at 12.7%, Bacteremia at 5.1%, and Somnolence at 5.1%. The registry record does not state the denominator or calculation details for these term percentages in the information, so they should not be treated as arm-specific rates.
Serious-event counts and term percentages are descriptive. They do not establish that treatment caused an event, and they do not convey timing, duration, or the number of repeated episodes. The record does not provide those details or a formal safety comparison. The counts should therefore be interpreted within the limits of the registry reporting rather than as a complete assessment of comparative risk.
12. What the Result Does, and Does Not, Mean
The record describes a randomized Phase II study comparing decitabine alone with decitabine plus valproic acid for MDS and AML. It specifies treatment schedules, a 1 Year response assessment, response criteria, selected adverse-event counts, and secondary outcomes. These details establish the intended clinical question and provide context for interpreting the registered endpoints.
However, the primary response outcome is not reported as a single comparison, and numerical response results are absent from the registry record. It is therefore not possible to say from the posted results whether response was more frequent in either arm, how large any difference was, or how precisely it was estimated. No conclusion about statistical significance can be drawn without a reported estimate and its uncertainty or a reported test.
The same caution applies to safety. Affected counts and listed event terms describe what the registry records, but they do not establish that treatment caused those events or quantify a comparative treatment effect. The record does not provide event timing, a detailed safety analysis population, or an adjusted comparison.
In general, a treatment result is interpreted by considering the estimated effect, its uncertainty, the endpoint definition, the analysis population, and the study’s design and limitations. Here, important numerical results and methodological details are not reported in the registry record. The absence of a reported result is not evidence of no difference. It means that the comparative efficacy and the precision of any effect cannot be determined from this record alone.
The registry record also does not establish how the findings should guide care for an individual. It describes a study and its reported information; it does not replace a full clinical report or provide individualized medical advice. The most defensible reading is limited to the documented design, outcome definitions, and descriptive safety information, while recognizing that the central response comparison is unavailable.
13. Why This Trial Matters Statistically
This trial is statistically notable because its registry record describes a randomized comparison but does not report a single primary-response contrast. Randomization can support an interpretable comparison when allocation, outcome definitions, analysis populations, and results are fully documented. Here, the design label and treatment schedules are present, while important details needed to evaluate the primary analysis are not reported.
The endpoint also illustrates why outcome construction matters. Response includes remission categories and clinical benefit, with criteria that differ by diagnosis and response type. A single percentage can be useful as a summary, but its meaning depends on how categories and assessment times are combined. The registry notes multiple categories or time points without reducing them to one comparison. Without category-level results and an explicit analysis rule, readers cannot tell what response pattern the primary summary was intended to represent.
The record further highlights the distinction between descriptive safety counts and comparative inference. Counts of participants affected can communicate the recorded burden of events, but causal interpretation and arm-to-arm comparison require clear definitions, exposure and follow-up information, and an appropriate analysis. Those details are not reported in the registry record.
Finally, statistical planning and completed analysis are different. Planning illustrations based on an observed effect do not establish the original sample-size rationale or the trial’s observed power. A transparent report would ordinarily connect the planned hypothesis and analysis to the reported estimates, uncertainty, and handling of missing data. The available record does not provide that connection, so its value is primarily in documenting the study question and selected design and safety information rather than enabling a quantitative assessment of the primary response comparison.
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 principal limitation for interpreting efficacy is that the registry does not report a single primary-response comparison or numerical response results. The response endpoint includes multiple categories and definitions, and the record states that several categories or time points were not reduced to one comparison. Without arm-specific response counts, percentages, or an effect estimate, the comparative result and its precision cannot be assessed.
The registry does not report the analysis plan, the method used to compare groups, confidence intervals, p-values, multiplicity handling, or the analysis population. It also does not describe allocation concealment, sequence generation, follow-up completeness, or how missing response assessments were handled. One participant assigned to Decitabine was not treated and was not evaluable for response, but the record does not give a broader participant-flow account.
The open-label design is reported as having no masking. The registry does not describe whether outcome assessment was protected from knowledge of assignment or whether that could have influenced response classification. Response includes clinical criteria, and the record does not report category-specific results or diagnostic subgroup results.
Safety information is limited to affected and at-risk counts and selected serious-event terms. Definitions of the safety population, event timing, exposure duration, and term-percentage denominators are not reported in the registry record. These limitations restrict causal and comparative interpretation of adverse events. The registry also does not report a sample-size justification or the trial’s own statistical plan; planning assumptions are not a substitute for those details.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Decitabine (DAC) w/ or w/o Valproic Acid (VPA) in Myelodysplastic Syndrome (MDS) and Acute Myelogenous Leukemia (AML) — NCT00414310.
- Registry record last updated 2019-05-21; status last verified 2019-05.
- Results first posted 2015-08-13.
- 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.
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18. Record Summary
NCT00414310 is a completed Phase II randomized, open-label, parallel-group study sponsored by M.D. Anderson Cancer Center. It enrolled 153 participants with MDS or AML and compared decitabine with decitabine plus valproic acid. Both arms received decitabine 20 mg/m^2 intravenously over 1 hour daily for 5 days; the combination arm also received valproic acid 50 mg/kg orally daily for 7 days.
The primary outcome was participant response at 1 Year, defined using complete remission, CRi, partial remission, and clinical-benefit criteria. Response duration and overall survival rate were listed as secondary outcomes. The registry reports safety counts and selected serious-event terms, and notes that one Decitabine-assigned participant was not treated and was not evaluable for response.
The registry record does not report a single primary-response comparison, numerical response results, or a statistical analysis plan. As a result, the comparative response and its precision cannot be determined from the posted results.