Testing Oral Decitabine and Cedazuridine (ASTX727) in Combination With Venetoclax for Higher-Risk Acute Myeloid Leukemia Patients: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Testing Oral Decitabine and Cedazuridine (ASTX727) in Combination With Venetoclax for Higher-Risk Acute Myeloid Leukemia Patients (NCT04817241), a randomized phase 1, phase 2 study. The primary outcome is Event-free Survival (EFS) (Phase II).

2. Clinical Question

3. Trial Design

This is a randomized, parallel-group phase Ib/II trial with no masking listed in the registry record. The sponsor is the National Cancer Institute (NCI). The record lists enrollment of 5 and a status of active, not recruiting. The listed study start is 2022-02-10, and the listed primary completion date is 2025-06-06.

The two phase II arms contrast oral ASTX727 plus venetoclax with cytarabine and daunorubicin induction chemotherapy. The ASTX727/venetoclax arm description specifies daily oral treatment on a 28-day cycle, for up to 12 cycles. The comparator description specifies intravenous cytarabine on days 1-7 and intravenous daunorubicin on days 1-3 of a 28-day cycle, for up to 2 cycles. These are registry descriptions of the regimens, not evidence that every participant received the full stated course.

The phase Ib portion separately evaluates ASTX727 with venetoclax. Its description permits different schedules for ASTX727 and venetoclax and allows treatment for up to 12 cycles. The record says doses may be lowered to identify a dose for the randomized study that is safe and tolerable. It also lists bone marrow aspiration and biopsy and biospecimen collection. The registry does not report the allocation sequence, allocation concealment, or details of how participants entered the phase Ib and phase II portions.

The posted primary endpoint results list 2 participants in each randomized arm. A separate phase Ib safety group is also listed. The registry record does not report further details about the analysis population or how the small posted endpoint groups relate to the enrollment figure.

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

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: The Phase 1b enrolled 1 patient at dose level 1 (ASTX727 days 1-5 + venetoclax days 1-28). Enrollment was insufficient to determine a recommended Phase 2 dose, as the study transitioned to Phase 2 based on emerging external data supporting this combination.

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 Event-free Survival (EFS) (Phase II), measured over Up to 2 years after completion of study treatment.

Event-free survival (EFS) is a time-to-event endpoint. The registry defines an event as death, blasts >20%, myeloid sarcoma, or AML in the central nervous system; EFS is survival without any of these events. The listed timeframe is up to 2 years after completion of study treatment.

In general, time-to-event outcomes use both the timing of events and the time participants are observed without an event. This can retain information from participants whose event has not occurred by the end of their observed follow-up, provided the analysis handles censoring appropriately. The registry record does not report the censoring rules or how incomplete follow-up was handled.

The registry says EFS will be estimated using the Kaplan-Meier method and compared among treatments and other important prognostic groups using the log-rank test. A median is the time by which the estimated event-free proportion reaches its midpoint; it is one summary of the time-to-event curve, not a complete description of that curve. The record reports a median for the ASTX727/venetoclax arm but no median for the cytarabine/daunorubicin arm. No confidence intervals or comparative test results are posted.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry specifies Kaplan-Meier estimation and the log-rank test for EFS. These methods address time-to-event data, where the outcome is the time until an event rather than a simple yes-or-no status at a fixed point. The registry defines the EFS events as death, blasts >20%, myeloid sarcoma, or AML in the central nervous system.

What does Kaplan-Meier estimation do?

In general, the Kaplan-Meier method estimates the probability of remaining event-free over time. It updates that estimate as events occur and can incorporate participants whose observation ends before an event is recorded. Such an observation is usually treated as censored at the last known event-free time. This method depends on appropriate follow-up and censoring information. The registry record does not report its censoring rules, how follow-up ended, or whether the posted summaries use a particular censoring convention.

A median time-to-event value is the time at which the estimated event-free proportion reaches its midpoint. The median is a compact summary, but it does not describe the full pattern of event times or the shape of the estimated curve. It can also be unavailable when the estimated curve does not reach the point needed to calculate it. The registry does not explain the reason the comparator median is absent. Its reported full range is not a measure of sampling uncertainty and cannot substitute for a confidence interval.

What does the log-rank test assess?

In general, the log-rank test compares event experience over the follow-up period between groups. It uses information about event timing and participants still under observation, rather than comparing only the group medians. The registry lists this as the planned method for comparisons among treatments and important prognostic groups. However, the posted record includes no log-rank statistic or p-value and lists 0 analyses. The planned method should not be mistaken for a completed or reported test.

A hazard ratio is another common summary for time-to-event comparisons. In general, it expresses the relative event rate between groups over time under the assumptions of the model used. No hazard ratio is posted for this endpoint, and the available record therefore does not support interpretation of a relative hazard. The registry also does not report a proportional-hazards assessment or other model diagnostics.

How much precision do the posted summaries convey?

The endpoint results list 2 participants in each randomized arm. Such small groups provide little information about the range of outcomes that might occur in the target population. A single participant’s time or event status can strongly affect a median, and there is limited information for characterizing variation. The posted ranges are descriptive; without confidence intervals, they do not show the precision of the underlying estimates. The registry does not report an uncertainty interval for either arm.

General statistical interpretation also distinguishes estimation from hypothesis testing. An estimate describes an outcome or contrast, while a test evaluates data relative to a specified null hypothesis and assumptions. Here, the median for one arm is an estimate, but the missing comparator median and absent test result mean there is no posted treatment contrast to interpret. The absence of a reported p-value does not indicate that a comparison was nonsignificant; it indicates that no comparison result is posted.

What do planning illustrations mean?

In general, sample-size planning uses assumptions about an effect, significance level, allocation, and statistical model to illustrate the number of participants that might be needed for a future study. Those calculations are planning illustrations, not observed power and not evidence about the results of the current trial. The record describes assumptions for such illustrations, including a two-sided significance level of 0.05 and equal allocation, but no planning values are included in the registry record for this interpretation. The trial’s own sample-size justification is not reported in the registry record.

Over-dispersion is a general concern when data vary more than a statistical model assumes; ignoring it can make uncertainty appear smaller than it is. The registry information does not identify an over-dispersion model for EFS, and there is no basis to claim it was relevant to the sponsor’s analysis. More broadly, the registry does not report the detailed statistical analysis plan, software, model specifications, or sensitivity analyses. Those omissions limit independent assessment of how the planned methods were implemented.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists 7 secondary outcomes, including complete response rate, duration of response, progression-free survival, overall response rate, overall survival, stem-cell transplantation after treatment, and mutational burdens in sensitive versus resistant leukemia-initiating cells. The record does not report results for these outcomes in the information available for interpretation. It also does not report a multiplicity adjustment or a hierarchy for testing the primary and secondary outcomes. Without such details, the overall interpretation of multiple statistical tests cannot be assessed.

Missingness is important for the primary endpoint because EFS depends on event dates and follow-up. The registry provides arm-level median and range information but does not describe missing endpoint data, loss to follow-up, censoring rules, or methods for handling incomplete records. It is therefore not possible to determine whether missing information could affect the estimates or comparisons.

The registry record does not state which analysis population was used for the posted EFS results, such as whether participants were analyzed according to randomized assignment or another defined population. The primary population field is blank. The record also does not report exclusions from analysis, protocol deviations, or an intention-to-treat analysis definition.

These gaps matter because the estimated outcome can depend on who is included and how incomplete follow-up is treated. They do not establish that the analyses were inappropriate; they mean the relevant procedures are not reported in the registry record. With no inferential results posted, the effect of multiplicity and missing-data handling on a comparative conclusion cannot be evaluated.

11. 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: appendicitis (100.0%), bacteremia (100.0%), enterobacter septicemia (100.0%), failure to thrive (100.0%), febrile neutropenia (100.0%).

The registry lists serious adverse event counts by group. In Arm I, 2 participants were at risk and 2 were recorded as affected by serious adverse events. In Arm II, 2 were at risk and 1 was recorded as affected. In the phase Ib ASTX727/venetoclax group, 1 was at risk and 1 was recorded as affected. These are counts within the listed groups, not comparative estimates of safety.

The registry also lists other, non-serious adverse events: 2 of 2 in Arm I, 2 of 2 in Arm II, and 1 of 1 in the phase Ib group were recorded as affected. Deaths are listed as 2 for Arm I, 1 for Arm II, and 0 for the phase Ib group. The record does not establish that these deaths were caused by treatment, and these counts should not be interpreted as treatment-related mortality.

The listed serious-event terms are Appendicitis, Bacteremia, Enterobacter septicemia, Failure to thrive, Febrile Neutropenia, and Lethargy, each displayed with 100.0%. The registry information does not provide event-level counts for each term in this summary, so the percentages should not be read as estimates of risk in a broader population. Because the group counts are small, these safety figures are descriptive and do not support a precise comparison between regimens.

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

The registry record documents a randomized study of oral ASTX727 plus venetoclax and cytarabine/daunorubicin induction chemotherapy in higher-risk AML without a FLT3 change. It describes the treatment schedules and names EFS as the phase II primary endpoint. The posted EFS information is limited: a median of 64 days and range of 15 to 113 days are reported for the ASTX727/venetoclax arm, while the comparator arm has no reported median and a range of 0 to 816 days.

These values describe the small groups listed in the registry, rather than establishing what would happen in a larger population. The registry does not post a hazard ratio, confidence interval, log-rank result, or other inferential comparison. The available information therefore cannot show whether EFS differs between treatments, how large any difference might be, or how precisely a comparative effect has been estimated.

It would also be incorrect to treat an absent comparator median as proof of a favorable or unfavorable result, or as evidence that the arms are equivalent. The record does not explain why the median is not available. Likewise, the adverse-event counts and listed death counts are not enough to establish causal relationships or to make a precise comparative safety assessment.

The trial’s listed secondary outcomes may address other aspects of response and longer-term outcomes, but their results are not reported in the information. Overall, the registry supports a cautious account of the design and the posted descriptive summaries. It does not support medical recommendations or a conclusion that either treatment is superior, equivalent, or ineffective.

13. Why This Trial Matters Statistically

This study raises a clinically relevant statistical question: how outcomes with an oral ASTX727/venetoclax regimen compare with outcomes under cytarabine/daunorubicin induction chemotherapy in the stated higher-risk AML population. The randomized parallel design is intended to support a treatment comparison, while the phase Ib component addresses dose evaluation before the phase II comparison. The registry also identifies EFS and several response and survival outcomes, making clear that the research question includes both event timing and other clinical endpoints.

Statistically, the record is a reminder that naming an appropriate method does not itself provide evidence from that method. Kaplan-Meier estimation and log-rank testing are listed for EFS, but no comparative analysis result is posted. The reported median and range in one arm, alongside a range but no median in the other, cannot answer the randomized comparison on their own.

The small endpoint groups make precision central to interpretation. Descriptive values from 2 participants per randomized arm are highly limited as estimates for a broader population. The absence of confidence intervals and comparative results further constrains what can be concluded. The safety counts likewise need to be read with their group denominators rather than as stable estimates of event frequency.

For researchers, the record illustrates why reporting analysis populations, missing-data procedures, uncertainty intervals, and completed comparative analyses matters. Those details allow readers to distinguish a planned analysis from a reported finding and to assess how much information supports an estimate. In this record, those elements are not reported, so statistical interpretation should remain descriptive.

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 primary limitation is the sparse posted EFS information. The registry lists 2 participants in each randomized arm, reports a median only for the ASTX727/venetoclax arm, and provides no confidence intervals or comparative test results. The comparator’s full range of 0 to 816 days does not resolve the lack of an estimable median. The record does not explain why that median is absent.

The registry status is active, not recruiting, while the listed primary completion date is 2025-06-06. The record does not clarify whether the posted outcome values are final, interim, or otherwise subject to update. No interim-analysis plan is reported. No interpretation should assume one.

The primary population field is blank, and the record does not specify the analysis population, exclusions, censoring rules, or procedures for missing endpoint data. It also does not provide the detailed statistical plan, sample-size justification, hazard ratio, or uncertainty intervals. Consequently, the planned Kaplan-Meier and log-rank methods cannot be evaluated as implemented from the posted information.

The registry lists a phase Ib group in addition to the two phase II arms, and the safety summaries include all three groups. The registry entries do not report how participants moved between study portions or how the posted endpoint groups relate to enrollment. Safety counts have small denominators and do not establish causation. Finally, although multiple secondary outcomes are listed, their results and any multiplicity strategy are not reported in the registry record.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Testing Oral Decitabine and Cedazuridine (ASTX727) in Combination With Venetoclax for Higher-Risk Acute Myeloid Leukemia Patients — NCT04817241.
• Registry record last updated 2026-11-03; status last verified 2026-05.
• Results first posted 2026-10-06.
• 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 record describes NCT04817241, a randomized, parallel, unmasked phase Ib/II study sponsored by the National Cancer Institute (NCI). It evaluates oral ASTX727, decitabine and cedazuridine, with venetoclax against cytarabine and daunorubicin in higher-risk AML without a FLT3 change. Enrollment is listed as 5; the study status is active, not recruiting.

The phase II primary endpoint is EFS, defined by death, blasts >20%, myeloid sarcoma, or AML in the central nervous system. The registry lists Kaplan-Meier estimation and log-rank comparison as planned methods. Posted EFS summaries include a median of 64 days for the ASTX727/venetoclax arm and no reported median for the cytarabine/daunorubicin arm. No comparative analysis or confidence interval is posted. The record lists 7 secondary outcomes, but their results are not reported in the information.