Decitabine and Tretinoin in Treating Patients With Myelodysplastic Syndromes: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Decitabine and Tretinoin in Treating Patients With Myelodysplastic Syndromes (NCT00382200), a na phase 1, phase 2 study. The primary outcome is Number of Participants Evaluated for Hematologic and Nonhematologic Toxicities as Measured by NCI CTC v2.0.

2. Clinical Question

The clinical question is therefore about safety evaluation and dose selection for the combination in people with myelodysplastic syndromes, rather than a randomized comparison of the combination against another treatment. The registry rationale describes decitabine as a chemotherapy drug and proposes that decitabine and tretinoin may affect the growth or differentiation of myelodysplastic cells. That rationale is a statement of the study’s motivation, not evidence of a clinical effect.

Other registered outcomes examine bone marrow function, morphology and cytogenetics; differentiation and apoptosis; gene expression; and demethylation of specific genes. A further outcome concerns correlations between clinical response and laboratory measures. These objectives indicate that the study included both clinical and biological questions. The registry record does not report an analysis establishing whether these laboratory measures were associated with clinical outcomes.

Because there is no randomized comparator, differences between dose groups cannot be read as unbiased treatment effects. The record instead supports a descriptive reading of the study groups and their posted safety counts. It does not establish how the combination compares with an alternative treatment or what would have happened to the same participants under a different regimen.

3. Trial Design

This is a Phase I/II study registered as a single-group trial, with 54 participants enrolled. The study began in 2006-07, has primary completion listed as 2023-01-05, and is marked completed. Memorial Sloan Kettering Cancer Center is the sponsor. The condition listed is myelodysplastic syndromes.

The registered intervention combines decitabine and tretinoin. The arm description identifies a Phase I dose group at tretinoin 45 mg/m2/Day, another at 65 mg/m2/Day, and another at 85 mg/m2/Day. A Phase II group is listed at the MTD tretinoin dose of 65 mg/m2/Day. The registry’s stated purpose is to study side effects and the best dose of tretinoin when given with decitabine. The listed groups reflect the study’s dose structure, but do not create a randomized dose comparison.

Allocation is listed as NA, masking as none, and the model as single group. The registry explicitly cautions that the groups are not a like-for-like control comparison. There is no registered parallel control group against which to estimate a comparative treatment effect, and the record does not report random assignment among the dose groups.

The primary outcome is the number of participants evaluated for hematologic and nonhematologic toxicities as measured by NCI CTC v2.0, with a timeframe of up to 1 year. The registry also lists nine outcome measures overall, including clinical, laboratory, and molecular outcomes. The posted analysis count is 0. Details of the protocol, dose-escalation rules, sample-size justification, interim analyses, and statistical analysis plan are not reported in the registry record. The record’s completed status does not, by itself, supply those missing design details or establish that every listed outcome has a posted result.

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 Number of Participants Evaluated for Hematologic and Nonhematologic Toxicities as Measured by NCI CTC v2.0, measured over Up to 1 year.

The primary endpoint is the number of participants evaluated for hematologic and nonhematologic toxicities, using NCI CTC v2.0, over a timeframe of up to 1 year. This is a count endpoint: it concerns participants evaluated, not a continuous measurement or a time-to-event outcome. The endpoint title does not state the number evaluated or provide a result for this primary outcome in the registry record.

General explanation: toxicity monitoring is important in studies that explore a drug combination and different doses because it records safety-related events during treatment. A count of participants evaluated can describe the reach of the safety assessment, but it is not interchangeable with the number who experienced toxicity. Nor does the count alone communicate event severity, duration, recurrence, or attribution to a particular drug. Those interpretations require specific outcome definitions and results.

The registry lists serious and other adverse-event counts separately by group. Those entries provide safety information, but they should not be substituted for the primary endpoint: the primary endpoint is explicitly framed as participants evaluated for toxicities, while the adverse-event entries give participants at risk and affected for event categories. The registry record does not report a primary endpoint analysis linking these entries or describing a prespecified summary measure.

Using a named toxicity criteria version gives the registered endpoint a stated assessment framework. The record does not provide further details about how assessments were conducted, what thresholds were applied, or how missing evaluations were handled.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry identifies the study as Phase I/II and single-group, with no masking and allocation listed as NA. These features shape what statistical conclusions can be drawn. The treatment groups differ by phase and tretinoin dose, and the registry cautions that they are not a like-for-like control comparison. Accordingly, the group entries are best read descriptively. They do not support the same interpretation as a randomized comparison in which concurrent groups are assigned to different treatments under a prespecified allocation process.

What does a count endpoint describe?

The primary outcome is the number of participants evaluated for hematologic and nonhematologic toxicities, with assessment framed by NCI CTC v2.0 and a timeframe of up to 1 year. General explanation: a count records how many people meet a stated definition or are assessed. It does not automatically describe the rate of events over time, the number of repeated events per person, or the severity distribution. Those require separate definitions and data. In this record, the outcome title states the count to be evaluated, but no primary endpoint count or analysis is reported.

The serious adverse-event summaries use participants at risk and participants affected. General explanation: the at-risk count indicates the group denominator used for an event summary, while the affected count represents participants with a recorded event in that category. These counts do not reveal whether an individual had more than one event, how long an event lasted, or whether several terms describe related events in the same person. Those details are not reported in the registry record.

Why does the design matter for interpretation?

In a randomized trial, allocation can help make treatment groups comparable on average, so differences in outcomes can be interpreted in relation to the assigned treatment, subject to the analysis and its assumptions. This study is not registered as a randomized comparison. The dose groups are associated with different phases and are not registered as concurrent, like-for-like controls. Differences in their safety counts could reflect more than dose alone; the registry does not provide an analysis that separates such influences.

General explanation: confounding occurs when factors other than the treatment of interest differ between groups and also relate to outcomes. In a nonrandomized dose-group comparison, this possibility limits causal interpretation. The record does not report an adjusted comparison or a statistical model for group differences. It also does not report the dose-escalation rules, so the sequence and decision process behind the listed groups cannot be reconstructed from this record.

How should uncertainty be assessed?

General explanation: an estimate is more informative when accompanied by a measure of uncertainty, such as a confidence interval, and by a clear account of the model and analysis population. A confidence interval gives a range of values compatible with the data and model at a stated confidence level; it is not a guarantee that the true value lies within that range. The registry record does not report confidence intervals or p-values for the primary outcome, and its posted analysis count is 0. No formal estimate of a dose contrast is available in the record.

Over-dispersion is a general issue for count data: it occurs when observed variability exceeds what a chosen count model assumes. If counts are analyzed with a model that underestimates variability, standard errors may be too small and uncertainty may appear narrower than it is. This concept is relevant only if such a model is used; no count model or dispersion assessment is reported in this registry record.

What do the planning illustrations mean?

General explanation: a planning sample size is an assumption-based illustration of how many participants might be needed for a specified statistical objective. It is not the number of participants observed, and it is not observed power. The registered sample-size assumptions describe two-sided significance level 0.05, equal allocation between two arms, and a normal approximation, with the target effect expressed as a fraction of the observed effect. Those assumptions do not make this single-group study a randomized two-arm comparison. The registry record does not report the trial’s own sample-size justification or a primary observed effect from which to judge such planning illustrations.

Sample-size calculations depend on the outcome, the target effect, the statistical model, and the design. General explanation: a calculation based on an assumed effect can show the consequences of that assumption, but it does not prove that the study had adequate power or that a result is clinically meaningful. No sample-size illustration values or trial-specific justification are reported in the registry record.

What can be inferred from the registered analyses?

The registry lists nine outcome measures and includes clinical and laboratory objectives. It also lists an intended correlation between clinical response and molecular or cellular measures. A correlation analysis would describe how measured variables vary together; by itself, it would not establish that one measure causes another. The registry record reports no analyses for these outcomes. It therefore does not support claims about such associations, changes in biological markers, or clinical response patterns.

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("Phase I: Tretinoin 45 mg/m2/Day", "Phase I: Tretinoin 65 mg/m2/Day", "Phase I: Tretinoin 85 mg/m2/Day", "Phase II: MTD Tretinoin 65 mg/m2/Day")
n      <- c(5, 14, 7, 28)
events <- c(5, 14, 7, 28)
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  Phase I: Tretinoin 45 mg/m2/Day  5  5  100.0  47.8  100.0  56.6  100.0  54.1  99.6
ARM  Phase I: Tretinoin 65 mg/m2/Day  14  14  100.0  76.8  100.0  78.5  100.0  78.2  99.8
ARM  Phase I: Tretinoin 85 mg/m2/Day  7  7  100.0  59.0  100.0  64.6  100.0  63.1  99.7
ARM  Phase II: MTD Tretinoin 65 mg/m2/Day  28  28  100.0  87.7  100.0  87.9  100.0  88.1  99.9

11. Multiplicity, Missing Data and Analysis Populations

The registry lists nine outcome measures spanning toxicity, bone marrow function, morphology, cytogenetics, differentiation, apoptosis, gene expression, demethylation, and correlations between clinical response and laboratory indicators. Considering multiple outcomes raises a general multiplicity issue: if many hypotheses are tested, the chance of at least one apparently notable result can increase. Statistical plans may address this through a prespecified primary outcome, a testing hierarchy, or an adjustment procedure. The multiplicity strategy is not reported in the registry record.

The primary outcome is identified as the number of participants evaluated for hematologic and nonhematologic toxicities, but the registry record does not report a primary result or a statistical analysis for it. The number of analyses listed is 0. No p-values or confidence intervals are posted for the outcomes in the record. It is therefore not possible to assess how any potential multiplicity procedure affected reported inferences.

Missing-data methods and analysis populations are also not reported in the registry record. The record does not specify which participants were included in each outcome analysis, how participants with incomplete follow-up were handled, or whether any analysis population was defined by treatment received or another criterion. These omissions matter because outcome counts and estimates can depend on who was observed and how unavailable measurements are treated.

General explanation: missingness can affect interpretation when the probability of an unavailable measurement is related to health status, treatment exposure, or the outcome itself. A complete-case summary may not represent all enrolled participants if those with missing measurements differ systematically. The registry record does not describe missingness or a method for addressing it, so no assumption about the pattern or handling of missing data can be made.

The completed status and enrollment count do not fill these reporting gaps. They do not establish that every planned measure was analyzed or that missing observations were absent. Details of the statistical analysis plan, multiplicity control, and analysis populations are not reported in 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 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 (42.9%), infection with febrile neutropenia (40.0%), pain (28.6%), constipation (20.0%), dyspnea (20.0%).

The serious adverse-event entries are reported separately for the Phase I groups at tretinoin 45 mg/m2/Day, 65 mg/m2/Day, and 85 mg/m2/Day, and for the Phase II group at the MTD tretinoin dose of 65 mg/m2/Day. Each entry gives participants at risk, participants affected, and deaths. These are counts within the registered groups, not comparative treatment effects.

For serious adverse events, the posted at-risk and affected counts are 5 and 5 in the 45 mg/m2/Day Phase I group; 14 and 9 in the 65 mg/m2/Day Phase I group; 7 and 5 in the 85 mg/m2/Day Phase I group; and 28 and 21 in the Phase II group. The corresponding death counts are 0, 2, 1, and 10. The record does not attribute deaths to treatment, so these counts should not be interpreted as treatment-caused deaths.

The registry also lists Febrile Neutropenia, 42.9%; Infection with febrile neutropenia, 40.0%; Pain, 28.6%; Constipation, 20.0%; Dyspnea, 20.0%; and Fatigue, 20.0% as serious adverse-event terms. The record does not provide additional event-level context or an adjusted comparison. Seriousness and severity are distinct concepts in general safety reporting; the registry’s serious-event listing alone does not give a severity distribution or establish causality. Since the groups are not a randomized comparison, their counts should not be used to rank doses by safety.

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

The registry record establishes that a phase I/II study of decitabine with tretinoin was conducted in participants with myelodysplastic syndromes and was marked completed. It identifies the primary outcome as the number of participants evaluated for hematologic and nonhematologic toxicities using NCI CTC v2.0, up to 1 year. It also posts serious adverse-event counts for its dose groups and lists several serious adverse-event terms with percentages.

These registry entries allow a reader to describe what was registered and the safety counts displayed in the record. They do not show the result of the primary endpoint, because that result is not reported in the registry record. Nor do they provide a randomized comparison of decitabine and tretinoin against another treatment. The study’s rationale and purpose do not establish clinical benefit, and the posted safety counts alone do not demonstrate harm caused by the combination.

The dose groups cannot be treated as interchangeable controls. The record identifies different phases and doses, and explicitly notes that this is not a like-for-like control comparison. Group differences may be influenced by factors beyond dose; no comparative analysis or adjustment is reported. The record also does not report the protocol’s dose-selection rules or a trial-specific statistical analysis plan.

General explanation: a treatment effect is a comparison between outcomes under different treatment strategies, ideally supported by a design and analysis that address confounding and uncertainty. Descriptive counts from a single-group study do not, on their own, estimate that counterfactual comparison. A sample-size planning illustration likewise does not turn an observed count into evidence of efficacy or establish observed power.

Accordingly, the record is useful for understanding the study’s objectives, structure, registered outcomes, and posted safety summaries. It does not support a conclusion about whether the regimen works, whether it is better than an alternative, or which dose has a superior benefit-risk profile. Those questions would require appropriately reported outcome results and analyses that are not present in the registry record.

14. Why This Trial Matters Statistically

This trial is statistically instructive because it combines a dose-focused Phase I/II design with a primary outcome framed as a count of participants evaluated for toxicities. It makes clear why the endpoint definition matters: the number evaluated is not itself a count of participants with toxicity, a severity summary, or a comparative effect estimate. Distinguishing these quantities prevents a safety assessment from being interpreted more broadly than its stated measure permits.

The study also illustrates the limits of comparisons across nonrandomized groups. The registry lists different tretinoin doses across phases and warns that the groups are not a like-for-like control comparison. Group-specific counts can describe what was posted, but they cannot isolate dose effects from other differences in the study structure. This is a useful distinction for clinical researchers reading safety data from early-phase or single-group studies.

Another statistical lesson is that a completed study status and a substantial set of registered outcomes do not guarantee that an interpretable analysis is available. The registry lists nine outcome measures but reports an analysis count of 0, and it does not report a primary endpoint result, a statistical analysis plan, missing-data methods, or multiplicity procedures. Readers need outcome estimates, denominators, uncertainty, and analysis details to evaluate the evidence beyond a descriptive summary.

Finally, planning assumptions should be separated from observed evidence. A sample-size illustration based on a hypothetical effect and two-arm assumptions is a planning exercise, not observed power and not a substitute for a trial-specific justification. The record’s design and reporting gaps make this distinction especially important. Clearer reporting of outcome results and analytic methods would be needed to support stronger statistical conclusions.

15. Limitations

• The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
• Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.

The key limitation is that the registry record does not report the primary endpoint result or any primary endpoint analysis. Although the endpoint is defined as the number of participants evaluated for hematologic and nonhematologic toxicities, the record does not give that outcome count. It lists nine outcomes overall and an analysis count of 0, leaving the registered clinical and laboratory objectives without reported analyses in this record.

The single-group design and lack of randomization limit comparative interpretation. The registry lists dose groups from different phases and explicitly cautions that they are not a like-for-like control comparison. As a result, the adverse-event counts cannot establish a causal dose effect or a difference relative to another treatment. No adjusted comparison is reported.

The safety entries do not provide all context needed for detailed assessment. The record lists participants at risk and affected, deaths, and selected serious adverse-event terms with percentages, but it does not report event-level timing, recurrence, severity distributions, or causal attribution in these entries. The serious-event percentages are not accompanied by additional denominator context in the registry record.

Important methods are also not reported: the protocol, dose-selection rules, sample-size justification, interim analyses, statistical analysis plan, analysis populations, missing-data handling, and multiplicity strategy. The record does not provide confidence intervals or p-values for the outcomes. These reporting limitations prevent assessment of precision, robustness, and how the analyses were intended to address multiple outcomes or incomplete follow-up.

The study’s rationale and registered objectives describe intent, not results. The record should therefore be read as a limited account of design and posted safety summaries, rather than a complete statistical report of the trial.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Decitabine and Tretinoin in Treating Patients With Myelodysplastic Syndromes — NCT00382200.
• Registry record last updated 2024-05-20; status last verified 2023-01.
• Results first posted 2024-05-20.
• 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

NCT00382200 is a completed Phase I/II, single-group study sponsored by Memorial Sloan Kettering Cancer Center. It enrolled 54 participants with myelodysplastic syndromes and studied decitabine with tretinoin. The record lists no masking and allocation as NA.

The primary outcome is the number of participants evaluated for hematologic and nonhematologic toxicities using NCI CTC v2.0, up to 1 year. Dose groups include Phase I tretinoin doses of 45 mg/m2/Day, 65 mg/m2/Day, and 85 mg/m2/Day, and a Phase II MTD group at 65 mg/m2/Day. The registry lists nine outcome measures and an analysis count of 0.

Serious adverse-event counts and selected event-term percentages are posted by group. The record does not report a primary endpoint result, comparative analysis, or the statistical methods needed to interpret treatment effects. The group counts are descriptive and are not a randomized comparison.