A Study Investigating the Safety, Tolerability and Efficacy of ASP7517 in Subjects With Relapsed/Refractory Acute Myeloid Leukemia (AML) and Relapsed/Refractory Higher Risk Myelodysplastic Syndrome (MDS): Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Study Investigating the Safety, Tolerability and Efficacy of ASP7517 in Subjects With Relapsed/Refractory Acute Myeloid Leukemia (AML) and Relapsed/Refractory Higher Risk Myelodysplastic Syndrome (MDS) (NCT04079296), a non-randomized phase 1, phase 2 study. The primary outcome is Number of Participants With Dose Limiting Toxicities (DLTs).

2. Clinical Question

This clinical question is principally about early-phase safety and dose evaluation, rather than a randomized estimate of treatment effect. The registry also lists clinical response and other measures of anticancer activity as study objectives. Its secondary outcomes include remission duration for AML and higher-risk MDS, event-free survival, overall survival, and response measures for each disease population. Those outcomes address different aspects of disease response and follow-up; they should not be conflated with the primary DLT count. The record does not report the numerical results for these secondary outcomes, so their values and precision cannot be assessed from the information posted.

3. Trial Design

This was a completed Phase 1/2, open-label study with non-randomized allocation and a sequential model. Enrollment was 43. The study began on 2019-09-19, primary completion was 2023-04-21, and the registry status is completed. The sponsor was Astellas Pharma Global Development, Inc. Participants had relapsed or refractory AML or relapsed or refractory higher-risk MDS.

The Phase 1 dose-escalation groups received ASP7517 at 1x10^6 cells/mL, 1x10^7 cells/mL, or 1x10^8 cells/mL. The descriptions for the 1x10^7 and 1x10^8 cells/mL groups specify intravenous infusion at 4 to 6 mL/minute on day 1 of each cycle for 2 doses, with 1 cycle= 28 days. The description of the 1x10^6 cells/mL group is incomplete in the registry record, ending after its infusion-rate detail begins, so its full administration schedule is not reported in the registry record.

The Phase 2 dose-expansion groups were separated by disease: AML and MDS. Both received ASP7517 at 1x10^8 cells/mL by intravenous infusion at 4 to 6 mL/minute on day 1 of each cycle for 6 doses, with 1 cycle= 28 days. The registry describes ASP7517 as human embryonic kidney (HEK293) cells transfected with encoding target WT-1.

Because allocation was not randomized and masking was absent, the dose groups should be read as components of a sequential early-phase study, not as balanced comparison arms. The record does not report how participants were assigned among dose groups, whether any particular enrollment target was set for each disease or group, or the rationale for the dose-escalation decisions. These details are not reported in the registry record. The phase structure and listed schedules establish what was planned for the groups, but do not by themselves establish how much treatment each participant received or the clinical outcomes that followed.

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: Participants who met all inclusion criteria and none of the exclusion criteria were enrolled in the study.

Dose Escalation Phase (56 Days)

Reasons for not completing this period:

Dose Expansion Phase (168 Days)

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: The safety analysis set (SAF) consisted of all participants who were enrolled and received at least 1 dose of study drug. SAF with available data was analyzed

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.

Population: The full analysis set (FAS) consisted of all participants who were enrolled and received at least one dose of study drug.

6. Primary Endpoint

The registry lists the primary outcome as Number of Participants With Dose Limiting Toxicities (DLTs), measured over Day 1 up to 28 days.

The primary endpoint is the number of participants with dose-limiting toxicities (DLTs), assessed from Day 1 up to 28 days. A DLT was defined as a qualifying event occurring within 28 days starting with the first dose on cycle 1 day 1 (C1D1), and considered related to study drug. The specified criteria include non-hematologic adverse events of grade 3 or higher; a confirmed Hy’s law case; new-onset grade 4 thrombocytopenia with a minimum of 2 grade worsening from baseline within 24 hours of dosing; and prolonged myelosuppression.

For this endpoint, prolonged myelosuppression means an absolute neutrophil count (ANC) < 500/microliter (μL) for more than 28 days off therapy, without evidence of active leukemia or MDS in marrow or blood. These criteria define what is counted as a DLT; they are not a summary of how many participants experienced one. The numerical primary result is not reported in the registry record.

General statistical context: early-phase dose studies use DLT assessment to characterize short-term tolerability within a defined observation window and to inform dose selection. A count of participants meeting prespecified criteria is directly interpretable as an observed safety outcome, but its meaning depends on the number evaluated, the completeness of observation, and the criteria used. The registry identifies the safety analysis set as enrolled participants who received at least 1 dose, with available data analyzed. It does not report the primary endpoint count, the number with evaluable DLT data, or additional handling rules for participants without complete observation. Thus the endpoint definition is available, but the result and its precision cannot be judged from the record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does a DLT count describe?

The primary endpoint is a participant count, not a continuous measurement or a time-to-event estimate. The registry defines which events qualify and limits assessment to the period from the first dose on cycle 1 day 1 through 28 days. The count is intended to summarize participants meeting those criteria in the safety analysis set. The available record gives the definition but not the resulting count. Without that count and the number with evaluable data, neither the observed proportion nor a confidence interval can be assessed. No proportion should be calculated from the enrollment figure, because enrollment is not necessarily the same as the number with available endpoint data.

Why does the dose-group structure matter?

General statistical context: random allocation helps make groups comparable, on average, with respect to both measured and unmeasured characteristics. In a non-randomized sequential study, group differences may instead reflect the order and circumstances in which participants entered, the disease population, the dose level, or other factors. Here, the Phase 1 groups span dose levels, while the Phase 2 expansion groups are separated by AML and MDS at the same stated dose. An apparent difference between groups cannot therefore be attributed to dose or disease alone using these descriptive counts. The registry itself cautions that the arms are not a like-for-like control comparison.

Open-label conduct means masking was absent. General statistical context: knowledge of treatment can influence reporting, assessment, or decisions about care, depending on the outcome and its measurement. The record does not describe blinded outcome assessment or other procedures that might limit such influences, so those safeguards are not reported in the registry record. This is not evidence that assessment was biased; it is a limit on what can be evaluated from the information available.

How should uncertainty be understood?

General statistical context: an estimate is more informative when accompanied by an interval that describes its statistical uncertainty. A confidence interval reflects uncertainty under the assumptions of the analysis; it does not account for every source of bias, such as non-random allocation or incomplete outcome ascertainment. The record does not report a confidence interval or an analysis for the primary endpoint. The group-level safety counts alone do not supply a basis for constructing a valid interval, particularly when endpoint-specific evaluability and follow-up are not specified.

The sample-size planning illustrations associated with the posted results are not observed trial outcomes and are not the study’s stated design calculations. The illustration assumptions are a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation; the effect to detect is a stated fraction of the observed effect. Time-to-event illustrations give the total number of events using Schoenfeld, while other illustrations give participants per arm. These are conditional planning scenarios, not observed power and not evidence that the study was designed or powered in this way. The trial is non-randomized, so hypothetical equal allocation between two arms should not be mistaken for its actual design.

What do binary outcomes and event counts mean?

General statistical context: a binary outcome records whether a participant did or did not meet a defined event criterion over a stated period. A count of participants with an event is useful for describing burden in a group, but interpretation depends on the denominator, eligibility rules, and whether participants had adequate observation. When follow-up differs or is incomplete, raw counts may not be comparable even if group sizes appear similar. For time-to-event outcomes such as event-free survival or overall survival, timing and censoring matter; a simple event count does not replace a time-to-event analysis. The registry lists these outcomes but does not report their estimates or methods of analysis.

Why is over-dispersion sometimes relevant?

General statistical context: over-dispersion arises when observed variation in count data exceeds what a chosen statistical model expects. It can make standard errors too small if the model’s variability assumptions are not met. This issue is relevant to some analyses of counts, but the primary endpoint is a participant count and the record does not report a fitted count model, dispersion parameter, or inferential analysis. It would therefore be inappropriate to claim that over-dispersion was tested, present a model-based conclusion, or suggest that a particular adjustment was used.

More broadly, no statistical analysis plan, model specification, hypothesis test, confidence interval, or interim analysis is reported in the registry record. The record lists zero analyses. That does not show that no analysis occurred outside the registry; it means the posted registry information does not provide analysis details to evaluate. Statistical interpretation should remain descriptive and tied to what the record actually reports.

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("Dose Escalation (Phase 1): ASP7517 1x10^6 Cells/mL", "Dose Escalation (Phase 1): ASP7517 1x10^7 Cells/mL", "Dose Escalation (Phase 1): ASP7517 1x10^8 Cells/mL", "Dose Expansion (Phase 2: AML): ASP7517 1x10^8 Cell", "Dose Expansion (Phase 2: MDS): ASP7517 1x10^8 Cell")
n      <- c(4, 4, 6, 9, 11)
events <- c(0, 0, 0, 0, 1)
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  Dose Escalation (Phase 1): ASP7517 1x10^6 Cells/mL  4  0  0.0  0.0  60.2  0.0  49.0  0.5  52.2
ARM  Dose Escalation (Phase 1): ASP7517 1x10^7 Cells/mL  4  0  0.0  0.0  60.2  0.0  49.0  0.5  52.2
ARM  Dose Escalation (Phase 1): ASP7517 1x10^8 Cells/mL  6  0  0.0  0.0  45.9  0.0  39.0  0.4  41.0
ARM  Dose Expansion (Phase 2: AML): ASP7517 1x10^8 Cell  9  0  0.0  0.0  33.6  -0.0  29.9  0.3  30.8
ARM  Dose Expansion (Phase 2: MDS): ASP7517 1x10^8 Cell  11  1  9.1  0.2  41.3  1.6  37.7  2.1  38.5

11. Multiplicity, Missing Data and Analysis Populations

The registry lists 44 outcome measures, including the primary DLT count and secondary outcomes covering remission duration, event-free survival, overall survival, and response measures. It reports zero analyses. The multiplicity approach—how the study would account for assessing many outcomes, or whether formal adjustment was planned—is not reported in the registry record. Without that information and without numerical outcome analyses, the chance of false-positive findings across multiple tests cannot be assessed. The listed outcome measures should not be treated as a set of statistically confirmed findings.

Missing-data handling is also not reported in detail. For the primary endpoint, the registry says the safety analysis set consisted of participants who enrolled and received at least 1 dose, and that available data were analyzed. It does not describe how missing or incomplete DLT observations were handled, whether participants with incomplete follow-up were excluded from a particular analysis, or how missing values were treated for secondary outcomes. Those details are not reported in the registry record.

The stated safety population differs conceptually from the enrollment count: enrollment identifies those enrolled, while the safety set requires receipt of at least 1 dose and the endpoint analysis uses available data. The record does not provide the endpoint-specific evaluable denominator. Consequently, enrollment should not be substituted for the number assessed for DLTs, and a missing result cannot be recovered from the group-level adverse event summaries.

Other analysis-population definitions, including populations for response or survival outcomes, are not reported in the registry record. Nor are rules for censoring, competing events, protocol deviations, or analysis exclusions. These omissions limit reproducibility and make it difficult to judge whether reported outcomes, if available elsewhere, were analyzed consistently with prespecified methods.

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 (60.0%), atrial fibrillation (20.0%), pneumonia fungal (20.0%), delirium (20.0%), pneumonia (16.7%).

The registry lists serious adverse event counts by study group, alongside the number at risk, counts for other adverse events, and deaths. For example, the Phase 2 AML expansion group has 12 participants at risk for serious events and 8 affected; the Phase 2 MDS expansion group has 12 at risk and 5 affected. The other-event counts and death counts are separately reported for each group. These are descriptive counts, not adjusted comparisons.

The serious adverse event terms are listed with percentages: febrile neutropenia at 60.0%; atrial fibrillation, pneumonia fungal, and delirium at 20.0%; pneumonia and sepsis at 16.7%. The denominator for these term percentages and whether a participant could contribute more than one event are not reported in the registry record. Do not infer a group-specific rate from these overall term summaries.

Deaths are listed by group, but the registry information does not specify a cause, relation to ASP7517, or a shared follow-up interval for these counts. A death count alone cannot establish whether deaths were treatment-related. Likewise, the serious-event counts do not show that ASP7517 caused an event. Disease severity, follow-up, and non-random group composition all matter, and the record does not provide adjusted analyses to address them.

General statistical context: safety counts are most interpretable when the population, observation period, event definition, and denominator are clear. Here, the primary endpoint has a defined DLT window, while the listed serious-event summaries do not provide an equivalent common window in the registry record. Keep the DLT endpoint and the broader adverse-event summaries distinct.

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

The posted record describes a completed early-phase study of ASP7517 in relapsed or refractory AML and higher-risk MDS. It specifies a primary safety endpoint based on DLTs during the period from Day 1 up to 28 days, defines qualifying events, and outlines dose escalation and disease-specific expansion. These are useful details for understanding the study’s question and structure.

The record does not report the numerical primary endpoint result, the recommended Phase 2 dose, or the maximum tolerated dose. It also does not report numerical results for the listed response, remission-duration, event-free-survival, or overall-survival outcomes. The study objectives and endpoint names therefore cannot be taken as evidence that a particular dose was tolerated or that a clinical response occurred. No efficacy conclusion can be drawn from the outcome descriptions alone.

The safety summaries document counts of participants affected by serious and other adverse events in the listed groups, as well as group-level death counts and selected serious event terms. They do not provide an adjusted comparison, event attribution, or a common follow-up interval in the registry record. Since the study was non-randomized, these figures do not isolate an effect of dose or treatment. The disease-specific expansion groups also should not be treated as interchangeable populations.

General statistical context: absence of a reported result is not the same as a result of zero events or no effect. It means the posted registry record does not enable the relevant estimate to be examined. Similarly, a descriptive count is not a causal estimate, and a planning illustration is not a measurement of trial performance. Conclusions should be limited to the design and descriptive details that are actually reported.

The record supports understanding what investigators intended to assess and how the dose groups were organized. It does not, on its own, establish the magnitude or precision of clinical benefit, quantify the primary DLT result, or determine whether observed adverse events were caused by ASP7517.

14. Why This Trial Matters Statistically

This study illustrates a common statistical distinction in early-phase research: a trial can be designed to evaluate safety and dose selection without being structured to estimate a randomized treatment effect. Its Phase 1 dose escalation and Phase 2 disease-specific expansion address distinct questions. Dose escalation concerns tolerability across dose levels, while expansion can describe experience in a selected disease group at a specified dose. Neither feature creates a randomized control comparison.

The primary endpoint is explicitly defined, with a short assessment window and event criteria that include hematologic and non-hematologic toxicities. Clear operational definitions matter because they determine which events count toward a safety endpoint. At the same time, an endpoint definition is not a result. The registry record’s lack of a DLT count means readers cannot evaluate the central reported safety measure from the available information.

The record also illustrates why group-level safety counts require context. Counts may look comparable or different while reflecting differences in disease, dose, follow-up, or participant selection. Non-random allocation limits causal interpretation, and the lack of event attribution and a common observation window for the broader safety summaries further constrains comparison. Statistical caution is not merely about sample size; it also concerns how groups were formed and how outcomes were measured.

Finally, the registry lists numerous secondary outcomes, yet reports zero analyses. This highlights the difference between registering outcomes and posting analyzable estimates. For readers, transparent denominators, missing-data rules, analysis populations, and uncertainty intervals are important for judging the reliability and precision of findings. Their absence leaves the record useful for reconstructing the intended study structure, but insufficient for evaluating the efficacy outcomes or the primary DLT result.

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 main limitation for statistical interpretation is that the registry record does not report the numerical result for the primary DLT endpoint, despite defining its criteria and assessment window. The recommended Phase 2 dose and maximum tolerated dose are study aims, but their selected values are not reported in the registry record. Without endpoint results and evaluable denominators, the central dose-evaluation question cannot be answered from this record.

The study was open-label, sequential, and non-randomized. Dose groups are not balanced control groups, and the Phase 2 expansion groups differ by disease population. Descriptive differences in event counts cannot be separated from these design features. The record does not report adjustment methods or statistical comparisons that might address measured differences between groups.

Safety reporting is incomplete for comparative interpretation. The registry lists serious-event counts, other-event counts, deaths, and selected serious-event terms, but the listed information does not establish a shared follow-up period or causal attribution for the broader summaries. The denominators for the serious event term percentages are not reported in the registry record. Death counts should not be interpreted as treatment-related deaths without attribution information.

The registry provides the safety analysis-set definition and says available data were analyzed, but does not describe missing-data procedures or endpoint-specific evaluability. Analysis-population definitions for response and survival outcomes are not reported. The registry also lists no analyses, and does not report a statistical analysis plan, multiplicity strategy, confidence intervals, or interim analysis details. These gaps restrict reproducibility and precision assessment.

The description of the 1x10^6 cells/mL group’s administration schedule is incomplete in the registry record. The posted planning illustrations are hypothetical and based on stated assumptions, not evidence of the actual study’s design justification or observed power. Taken together, these limitations mean that the registry is more informative about the trial’s stated structure than about its outcome estimates.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: A Study Investigating the Safety, Tolerability and Efficacy of ASP7517 in Subjects With Relapsed/Refractory Acute Myeloid Leukemia (AML) and Relapsed/Refractory Higher Risk Myelodysplastic Syndrome (MDS) — NCT04079296.
• Registry record last updated 2024-11-26; status last verified 2024-11.
• Results first posted 2024-06-25.
• 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

NCT04079296 is a completed, open-label Phase 1/2 study of ASP7517 in relapsed or refractory AML and relapsed or refractory higher-risk MDS. The trial used non-randomized, sequential dose escalation and expansion, with enrollment of 43. Phase 1 tested ASP7517 at 1x10^6 cells/mL, 1x10^7 cells/mL, and 1x10^8 cells/mL; Phase 2 expansion groups addressed AML and MDS at 1x10^8 cells/mL.

The primary endpoint was the number of participants with DLTs from Day 1 up to 28 days. The registry defines qualifying toxicities but does not report the endpoint result. It lists group-level serious and other adverse event counts, deaths, and selected serious event terms, but these are descriptive and do not establish causation or a randomized comparison. Secondary outcomes include response and survival measures, but their numerical results are not reported in the registry record. The record therefore documents study structure and outcome definitions more fully than it documents analyzable clinical results.