E7070, Idarubicin and Cytarabine in Relapsed AML and High-Risk Myelodysplastic Syndromes: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for E7070, Idarubicin and Cytarabine in Relapsed AML and High-Risk Myelodysplastic Syndromes (NCT01692197), a na phase 2 study. The primary outcome is Overall Response.

2. Clinical Question

3. Trial Design

This was a phase 2, single-group study sponsored by M.D. Anderson Cancer Center. The registry record gives enrollment as 43 and status as completed. The recorded start date is 2013-02-01, and the primary completion date is 2017-06-07. These dates describe the study record, not the length of follow-up for an individual participant.

Participants received a combination of E7070, idarubicin, cytarabine, and dexamethasone. The named arm is E7070 + Idarubicin + Cytarabine, while dexamethasone is included in the intervention list and described in the regimen. E7070 is specified as an intravenous infusion on day 1 and day 8, with the day 8 timing allowing a stated variation. Idarubicin is scheduled after E7070, and the cytarabine schedule varies by age. The registry record truncates the dexamethasone schedule, so its complete timing and duration are not reported there.

The study has no listed control group. Allocation is marked not applicable, and masking is recorded as none. Thus the design is not a randomized comparison, and there is no like-for-like concurrent group against which to compare response or adverse events. The study can document outcomes recorded among treated participants, but differences from an external group or from an assumed alternative treatment cannot be interpreted as randomized treatment effects.

The primary endpoint is overall response, with a registry timeframe of 2 cycles (60 days). The endpoint description also refers to response categories during cycle 1, leaving the timing description internally unclear. The record says 37 patients are evaluable for this endpoint, but does not report the response count or explain the evaluability criteria, exclusions, or follow-up completeness. Disease-free survival, duration of response, and overall survival are listed as secondary outcomes. Their results and analysis details 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 43 participants registered, three never received the study medication.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Thirty seven patients are evaluable.

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 Overall Response, measured over 2 cycles (60 days).

The primary endpoint is overall response, recorded as a count of participants. The registry definition combines complete response, complete response with incomplete platelet recovery, partial response, and marrow clearance of blast. These categories represent different response descriptions, and the endpoint groups them into a single response measure. The registry record does not provide separate counts for the component categories.

Response is used as an efficacy endpoint because it records whether participants meet a specified disease-response definition over a stated treatment period. In general, a count can be converted to a proportion when the relevant denominator is clear, and a confidence interval can describe uncertainty around that estimate. The registry record says 37 patients are evaluable, but does not report the response count, proportion, or confidence interval; none can therefore be described from this record.

The timing is not fully consistent in the record. The stated timeframe is 2 cycles (60 days), while the outcome definition says the response categories apply during cycle 1. The registry record does not clarify how those statements relate or which assessment time determines the primary endpoint. That matters when interpreting response because an endpoint depends not only on its categories, but also on when and how they are assessed.

Overall response is distinct from the listed secondary outcomes of disease-free survival, duration of response, and overall survival. Those outcomes concern different aspects of the clinical course and require their own definitions and analysis details. Such details and results are not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

General statistical explanation: A clinical endpoint needs a clear definition, a population in which it is assessed, and an assessment time. For this study, the endpoint is a participant count based on a combined response definition. The record identifies 37 evaluable patients and gives a timeframe of 2 cycles (60 days), but the description also refers to cycle 1. It does not clarify the timing discrepancy or state the criteria used to determine evaluability.

What does a count of participants represent?

General statistical explanation: A count reports how many people meet an event or response definition. A count alone does not convey the frequency in the study group unless its denominator is clear. A proportion uses a count and a defined denominator; an interval estimate can then express uncertainty in that proportion. The registry record reports the evaluable population size but not the number meeting the primary response definition. A response proportion or its confidence interval is therefore not reported in the registry record.

The endpoint is a composite: it includes complete response, complete response with incomplete platelet recovery, partial response, and marrow clearance of blast. In general, combining categories can make a single summary endpoint, but interpretation depends on the exact category definitions and assessment rules. The registry description names its component categories but does not report separate results for them. It also does not explain how a participant meeting more than one listed description would be classified, if that situation arose.

What can a single-group study estimate?

General statistical explanation: A single-group study can describe outcomes observed among enrolled participants. It does not directly estimate a randomized contrast between treatment strategies because it has no concurrent control group. Without random allocation to comparison groups, differences from other populations or historical results can reflect differences in participant characteristics, care, assessment, or follow-up as well as treatment. Such factors cannot be disentangled by the design alone.

This study is recorded as single-group, with allocation not applicable and masking none. The posted information does not identify a comparator. Accordingly, the design does not support a like-for-like randomized treatment comparison. This is relevant both to the primary response endpoint and to adverse-event counts: a recorded event count describes the study group, but does not provide a comparative risk estimate.

How should uncertainty be understood?

General statistical explanation: A confidence interval is a range of estimates compatible with the data under a specified statistical procedure. It is used to communicate how precisely an estimate has been measured, rather than to guarantee that a true value lies within the interval. For a binary endpoint, an interval around a response proportion would help show uncertainty in the observed response frequency. The registry record does not report a primary response estimate or confidence interval, so the precision of the response result cannot be evaluated from the record.

The record lists no analysis count and does not report a primary hypothesis test, p-value, or adjusted analysis. This absence does not establish what analyses were planned or conducted outside the registry record; those details are not reported there. There is likewise no reported statistical model for the primary endpoint. No assumptions about adjustment, stratification, or interim monitoring can be made from the posted information.

What does the sample-size illustration mean?

General statistical explanation: The record describes a planning illustration based on the observed effect, using a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. It says the effect to detect is a stated fraction of the observed effect; time-to-event illustrations use a total event count, while other illustrations use participants per arm. These are planning assumptions for an illustration, not a description of the actual single-group design. They do not establish the study’s original sample-size justification and do not represent observed power. The actual trial has no listed second arm, so an equal-allocation, two-arm scenario should not be read as a feature of the enrolled study. Numerical illustration results and the trial’s own sample-size justification are not reported in the registry record.

In general, over-dispersion occurs when count variability exceeds what a simple model assumes. If present, it can affect standard errors and interval estimates, and a method that accounts for it may be needed. The registry record does not report a count model, an over-dispersion assessment, or a model-based primary analysis. No conclusion about whether over-dispersion was relevant to this study can be drawn from the record.

How do the safety counts differ from efficacy estimates?

General statistical explanation: Adverse-event counts summarize participants or events meeting a safety definition; their meaning depends on the reporting period, denominator, severity rules, and attribution procedures. The record gives participants at risk and affected for serious and other adverse events, plus a death count and selected serious-event terms. It does not give detailed event-level analyses, timing, attribution, or a comparative group. These counts should therefore be read descriptively, not as adjusted comparisons or proof of causation.

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("E7070 and Idarubicin and Cytarabine")
n      <- c(37)
events <- c(11)
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  E7070 and Idarubicin and Cytarabine  37  11  29.7  15.9  47.0  17.5  45.8  17.5  45.9

11. Multiplicity, Missing Data and Analysis Populations

The primary endpoint is overall response. Disease-free survival, duration of response, and overall survival are listed as secondary outcomes. Testing or estimating several outcomes can raise multiplicity concerns because repeated statistical comparisons can increase the chance of at least one apparently notable result. General approaches include prespecifying a hierarchy or adjusting the interpretation of multiple tests, but the registry record does not report a multiplicity procedure, a testing hierarchy, or results for the secondary outcomes.

The registry record reports zero analyses. It does not describe a statistical analysis plan, identify planned hypothesis tests, or state whether interim analyses were planned or conducted. Those procedures are not reported in the registry record, so it is not possible to determine how multiplicity was considered or whether the posted endpoint was analyzed according to a prespecified plan.

The primary endpoint description says 37 patients are evaluable, while enrollment is 43. The registry record does not explain the difference, define the evaluable population, or state whether all enrolled participants were included in any analysis. It does not report reasons for missing assessments, missing-data assumptions, imputation procedures, or sensitivity analyses. Therefore, the potential effect of missing response information cannot be assessed from the record.

For time-to-event outcomes, interpretation generally depends on follow-up duration, event definitions, censoring rules, and the population included. The record lists disease-free survival, duration of response, and overall survival, but does not report their estimates, analysis populations, follow-up details, or censoring methods. These details are not reported in the registry record. No assumptions about how incomplete follow-up or missing outcome data were handled can be made.

12. Safety Results

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

Deaths

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: febrile neutropenia (35.0%), lung infection (27.5%), sepsis (22.5%), skin infection (7.5%), death (5.0%).

The registry record gives safety counts for the E7070 and idarubicin and cytarabine group. Serious adverse events are recorded for 30 participants among 40 at risk; other adverse events are recorded for 38 among 40 at risk. The record also lists 11 deaths. These are distinct entries in the safety summary, and the registry record does not explain how the death count relates to the adverse-event categories or specify whether deaths were attributed to treatment.

The leading listed serious-event terms are febrile neutropenia at 35.0%, lung infection at 27.5%, sepsis at 22.5%, skin infection at 7.5%, death at 5.0%, and allergic reaction at 2.5%. The record does not describe the term-specific denominator or provide event-level timing and attribution details. The percentages should therefore be read as the registry’s reported figures, not as a basis for calculating an unreported risk or comparing groups.

In general, an adverse event is an event recorded during a study; recording alone does not establish that treatment caused it. The single-group design provides no concurrent comparator for evaluating whether these events occurred more or less often than they would under another treatment. The safety figures describe reported experience in the study group and should not be treated as causal estimates.

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

The record describes a completed phase 2 study of a four-drug combination in patients with relapsed or refractory AML or high-risk MDS. It specifies a single-group design and defines overall response as the primary endpoint. It also reports that 37 patients were evaluable for that endpoint, while enrollment was 43. The endpoint definition, study design, and safety counts are useful for understanding what the registry record set out to describe.

The record does not report the primary response count, an estimated response proportion, or a confidence interval. It therefore does not show the magnitude of the primary response outcome or its statistical precision. Nor does it report results for the listed secondary outcomes. A treatment effect cannot be inferred from an outcome count that is not reported, and the record does not provide a randomized comparison from which to estimate a comparative effect.

The listed safety counts indicate that serious and other adverse events were recorded among participants at risk, and the registry lists selected serious-event terms and percentages. Those observations describe reported events. Without event attribution and a comparator, they do not establish that the combination caused any specific event or quantify how safety would differ under another treatment.

Some interpretation details remain unresolved in the registry record. The endpoint timeframe is stated as 2 cycles (60 days), while the definition refers to cycle 1. The record does not explain how the 37 evaluable patients relate to enrollment of 43, define evaluability, or describe missing-data handling. It also does not report the analysis methods or results for the secondary outcomes.

In general, a registry record can document study features and posted outcomes, but its completeness determines what can be inferred. Here, the available information supports a description of the study’s design, endpoint definition, and selected safety summaries. It does not support a conclusion about the primary response estimate, the uncertainty around that estimate, or a causal or comparative treatment effect.

14. Why This Trial Matters Statistically

This study illustrates why trial design and outcome reporting need to be considered together. The registry describes a phase 2 study in a clinically defined population and identifies an overall response endpoint, but the record does not report the response count or an uncertainty estimate. Knowing the endpoint definition is not the same as knowing the observed result. Without the result, readers cannot evaluate its size or precision.

The single-group design is also central to interpretation. It can document outcomes among participants receiving the combination, but does not provide a concurrent comparison group. A response, if reported, would not by itself establish what would have occurred under another strategy. This distinction between describing an outcome and estimating a comparative effect is a basic statistical issue in clinical research.

The record additionally shows why analysis populations and endpoint timing matter. It reports 43 enrolled and 37 evaluable for the primary endpoint, without explaining the difference. Its primary timeframe is listed as 2 cycles (60 days), while the endpoint description mentions cycle 1. These are not minor details: the denominator and assessment timing define what an outcome estimate would mean.

Finally, the safety summary gives affected-participant counts and selected serious-event percentages, but does not report attribution or a comparator. Reading those figures descriptively, rather than causally, preserves the distinction between events observed during a study and effects attributable to treatment. The posted information makes these design and reporting limits important to any statistical interpretation.

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 registry record does not report the primary response count, proportion, or confidence interval. Although 37 patients are described as evaluable, the record does not define the evaluable population or explain how it relates to the enrollment of 43. Reasons for non-evaluability and missing-data handling are not reported in the registry record.

The endpoint timing is not fully resolved. The timeframe is listed as 2 cycles (60 days), while the outcome description refers to response during cycle 1. The record does not clarify which assessment period defines the primary endpoint. It also does not provide separate results for complete response, complete response with incomplete platelet recovery, partial response, or marrow clearance of blast.

The study has one group and no listed comparator. Consequently, it cannot provide a randomized comparison. Masking is recorded as none, and the registry record does not report details of response assessment procedures or whether assessors were independent. The potential influence of assessment procedures cannot be evaluated from the posted information.

The full dexamethasone schedule is truncated in the arm description. The record lists disease-free survival, duration of response, and overall survival as secondary outcomes but does not report their results, analysis methods, or follow-up details. It also does not report a statistical analysis plan, multiplicity procedures, interim analyses, or the trial’s own sample-size justification.

For safety, the record gives participant counts and selected serious-event percentages, but does not report detailed event timing, attribution, or the term-specific denominator. The 11 deaths are not characterized further in the registry record. These limitations restrict interpretation to the information recorded and do not establish whether unreported analyses or details exist elsewhere.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: E7070, Idarubicin and Cytarabine in Relapsed AML and High-Risk Myelodysplastic Syndromes — NCT01692197.
• Registry record last updated 2018-07-03; status last verified 2018-06.
• Results first posted 2018-07-03.
• 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

NCT01692197 is a completed phase 2, single-group study sponsored by M.D. Anderson Cancer Center. It enrolled 43 participants with relapsed or refractory AML or high-risk MDS and evaluated E7070 with idarubicin, cytarabine, and dexamethasone. Allocation is recorded as not applicable and masking as none.

The primary endpoint was overall response, defined using complete response, complete response with incomplete platelet recovery, partial response, and marrow clearance of blast. The record says 37 patients were evaluable, but does not report the response count or an inferential result. The stated timeframe of 2 cycles (60 days) is not reconciled with the description’s reference to cycle 1.

Disease-free survival, duration of response, and overall survival are listed as secondary outcomes, without reported results in the registry record. Safety entries include 30 participants with serious adverse events among 40 at risk, 38 with other adverse events among 40 at risk, and 11 deaths. The record does not report a comparator, analysis details, or event attribution.