A Phase I/II Study of ASTX660 in Patients With Relapsed or Refractory T-cell Lymphoma: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Phase I/II Study of ASTX660 in Patients With Relapsed or Refractory T-cell Lymphoma (NCT04362007), a non-randomized phase 1, phase 2 study. The primary outcome is Safety (Phase 1 Dose-escalation Part) - Number of Subjects With Dose-limiting Toxicities (DLTs), AEs, Abnormal Clinical Laboratory Values or Physical Exam Results.

2. Clinical Question

3. Trial Design

This was a Phase I/II, multicenter, open-label, nonrandomized study of ASTX660 in relapsed or refractory T-cell lymphoma. The registry classifies it as a single-group study with no masking. Because there was no randomized comparator, comparisons between cohorts cannot be read as controlled treatment effects.

The study had a Phase I dose-escalation part for participants with relapsed or refractory PTCL or CTCL. The registry says the starting dose was to be escalated stepwise in successive cohorts of 3 to 6 evaluable subjects. It also describes a Phase I ATLL expansion, in which participants were to receive ASTX660 at the recommended dose obtained from dose escalation. The Phase II part concerned participants with relapsed or refractory PTCL receiving ASTX660 at that recommended dose.

The described schedule was once-daily dosing for seven consecutive days every other week during each 28-day cycle, with doses on Days 1–7 and 15–21. This schedule and the study parts define the intended treatment structure; they do not establish how many participants completed treatment or the amount of exposure actually received.

The registry lists enrollment of 8 and records the study as terminated. It gives a start date of 2020-07-14 and a primary completion date of 2024-11-30. The reason for termination, the timing and circumstances of the termination, and whether the listed enrollment is final are not reported in the registry record. The record names Otsuka Pharmaceutical Co., Ltd. as sponsor.

The listed secondary outcomes concern pharmacokinetics: area under the concentration-time curve, maximum concentration, time to maximum concentration, elimination half-life, and clearance from plasma. These measures describe drug exposure and disposition rather than clinical benefit. The registry record does not report the numerical results for these outcomes.

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 DLT analysis population include all subjects who received at least 1 dose of IMP and have available data necessary for DLT assessment during the DLT assessment period.

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: Analysis population included subjects who had received at least one dose of the IMP.

6. Primary Endpoint

The registry lists the primary outcome as Safety (Phase 1 Dose-escalation Part) - Number of Subjects With Dose-limiting Toxicities (DLTs), AEs, Abnormal Clinical Laboratory Values or Physical Exam Results, measured over 28 days (Day1 to Day29).

The primary endpoint in the Phase I dose-escalation part is a count of participants meeting one or more safety-related criteria: dose-limiting toxicities (DLTs), adverse events, abnormal clinical laboratory values, or abnormal physical examination results. Its timeframe is 28 days, from Day 1 to Day 29. The stated analysis population includes participants who received at least one dose of investigational medicinal product and had data needed to assess DLTs during that period.

The DLT definition applies to adverse events in the assessment period that meet specified severity criteria, are not attributed to the primary disease, complications, or concomitant medications, and have a reasonable relationship with ASTX660. Severity was assessed using CTCAE v4.03. Examples in the definition include certain severe blood-count or bleeding events, febrile neutropenia or prolonged severe neutropenia, liver-associated abnormalities, and specified severe nonhematologic or hematologic toxicities. The definition also gives exceptions for some Grade 3 gastrointestinal symptoms lasting less than 48 hours.

A DLT endpoint is used in dose escalation to characterize treatment tolerability and inform selection of a dose for later study. It is a safety endpoint, not a measure of tumor response or comparative efficacy. The registry describes the recommended dose as an objective of Phase I, but the selected dose and the primary endpoint count are not reported in the registry record. The broader primary-outcome title also mentions adverse events, laboratory values, and physical examination results; the record does not give numerical results for those components.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does a participant count represent?

The primary outcome is expressed as a count of participants with specified safety findings. A participant count is different from an event count: one participant can experience more than one event, while a participant-level outcome may count that person once under a defined rule. The registry's primary outcome title refers to the number of subjects with DLTs, adverse events, abnormal laboratory values, or abnormal physical examination results. The record does not state the numerical count or provide enough detail to reconstruct the analysis.

The safety endpoint uses a defined observation window, from Day 1 to Day 29. Applying a consistent window can make it clearer which events contribute to a dose-escalation decision. It also means the endpoint describes events during that period, not every event that may occur later in treatment. The record does not give results by event onset or treatment duration.

How should DLT criteria be understood?

The DLT definition combines a time window, clinical attribution requirements, and severity thresholds. The registry says events must not be related to the primary disease, complications, or concomitant medication, and must have a reasonable relationship with ASTX660. It specifies CTCAE v4.03 for severity assessment and lists qualifying categories, alongside exceptions. These rules are important because they determine which events count toward the dose-escalation endpoint. The registry does not report how individual events were adjudicated or how many qualified.

In general, a dose-limiting toxicity is used in early-phase research to assess whether a dose can be administered with acceptable short-term tolerability under the study's rules. It is not a universal summary of all possible harms, and its interpretation depends on the protocol definition, assessment window, and completeness of follow-up. The record gives the definition and timeframe but does not report the DLT result, the dose levels tested, or the recommended dose.

What can cohort counts tell readers?

The adverse-event record gives cohort-level counts for participants at risk, participants affected by serious and other adverse events, and deaths. These are descriptive summaries. A count can indicate how many participants were recorded in a category, but without event descriptions, severity, timing, and exposure information it cannot convey the full clinical context. The serious-event terms are not listed in the record. The counts for other adverse events do not identify individual events or state whether every event was judged related to ASTX660.

In general, a denominator defines the group to which an event count refers. Different denominators can arise when participants have different eligibility, exposure, or follow-up for an outcome. The registry shows cohort-specific at-risk counts, but does not explain how they were derived or whether every participant had the same duration of observation. Counts should therefore be read as reported rather than expanded into assumptions about exposure or follow-up.

Why do confidence intervals and tests matter?

In general, a confidence interval describes the range of estimates that are reasonably compatible with the observed data under a statistical method. It communicates precision as well as the estimated value. A narrow interval generally indicates more precision than a wide interval, while a broad interval signals substantial uncertainty. No confidence interval for the primary endpoint or efficacy outcomes is reported in the registry record.

In general, a statistical test evaluates how compatible data are with a specified null model, subject to its assumptions. A p-value is not the probability that a treatment works, and it does not measure clinical importance. No p-value or inferential analysis is reported in the registry record. With a single-group, nonrandomized study, a test against a hypothetical value would not supply the missing concurrent control comparison.

What is the role of sample-size planning?

The record describes a planning illustration using a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation, with the effect to detect set as a stated fraction of the observed effect. Those assumptions are for a planning exercise, not a description of the study's single-group nonrandomized design. The record also states that non-time-to-event planning figures are participants per arm, while time-to-event illustrations use a total event count. These illustrations should not be read as observed power or as evidence about the study's actual design rationale. The sample-size justification and the trial's own statistical plan are not reported in the registry record.

In general, power is a design property describing the chance that a planned statistical procedure detects a specified effect under its assumptions. It is not a measure of how persuasive an observed result is, and it cannot repair missing outcome data or a lack of a control group. An illustration calculated from an observed effect is especially distinct from prospective design planning. No numerical planning outputs are reported in the registry record, and no estimate of observed power is appropriate.

Why does over-dispersion matter in general?

For count outcomes, some statistical models assume that variability follows a particular relationship to the expected count. Over-dispersion occurs when observed variability exceeds that assumption. If ignored, uncertainty estimates can be too small and statistical conclusions too confident. This is a general consideration for count-data analyses, not a claim about a model used in this study. The registry record lists no analyses, so it does not report a model choice or an assessment of over-dispersion.

Overall, the methods information identifies the endpoint definition, assessment window, and selected safety-count categories, but not the statistical analysis used to produce primary or efficacy results. Those results, along with confidence intervals, p-values, and details of any adjustment, are not reported in the registry record.

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("Cohort 1")
n      <- c(6)
events <- c(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  Cohort 1  6  1  16.7  0.4  64.1  3.0  56.4  3.7  57.9

11. Multiplicity, Missing Data and Analysis Populations

The registry lists a safety primary outcome and secondary pharmacokinetic outcomes: area under the concentration-time curve, maximum concentration, time to maximum concentration, elimination half-life, and clearance from plasma. The brief summary also describes a Phase II efficacy objective in PTCL. The record does not report a multiplicity strategy for interpreting several outcomes or for any repeated testing. It does not describe a hierarchy of endpoints, adjustment method, or prespecified rules for drawing conclusions across outcomes.

Missing-data handling is not reported in the registry record. The primary outcome population is described as participants who received at least one dose and had data needed for DLT assessment during the assessment period. That definition identifies who is included in the stated DLT analysis population, but it does not explain how incomplete assessments, early discontinuation, or missing laboratory and examination results were handled. The record does not report how many participants lacked evaluable data.

The registry lists no analyses. It therefore does not provide analysis populations or numerical results for the primary endpoint, efficacy, or pharmacokinetic outcomes. The listed enrollment of 8 should not be assumed to be the denominator for every outcome; the relevant at-risk counts vary by cohort and adverse-event category. No imputation method, sensitivity analysis, or approach to incomplete follow-up is described.

In general, multiplicity matters because examining several outcomes or statistical tests can increase the chance of a false-positive finding if each is interpreted independently. Missing-data methods matter because an analysis can be affected when outcome availability is related to participants' health, treatment exposure, or other factors. These are general statistical concerns; the registry record does not report how they were addressed in this study.

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 non-serious adverse event terms

The serious adverse-event figures are 0 affected in Cohort 1, among 7 at risk, and 0 affected in Cohort 2, among 1 at risk. The record lists 0 deaths in each cohort. These counts describe what is posted for the recorded categories; they do not show that no adverse events of any kind occurred. The other-adverse-event counts are 7 affected among 7 at risk in Cohort 1 and 1 affected among 1 at risk in Cohort 2.

The registry does not list the serious adverse-event terms, event severity, timing, duration, outcome, or relationship to ASTX660. It also does not report the completeness or duration of follow-up for these counts. The two cohorts are not described as randomized treatment and control groups, so their counts do not support a comparative safety estimate. A zero count in the posted serious-event category should be read as a recorded count, not as proof that serious risk is absent or that future participants would have the same experience.

These summaries also differ from the primary DLT endpoint. DLTs use a defined 28-day assessment window and specific severity and attribution criteria. The reported adverse-event figures do not provide the primary DLT count. That count and the detailed primary safety results are not reported in the registry record.

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

The registry record describes an early-phase study designed to investigate ASTX660 safety and tolerability, select a recommended dose, assess safety in an ATLL expansion, and evaluate efficacy in PTCL at the recommended dose. The study is listed as terminated, and its enrollment is recorded as 8. The posted adverse-event counts include no serious adverse events and no deaths in either listed cohort, alongside other adverse events affecting participants in both cohorts. Those are descriptive safety counts, not a complete account of all possible risks or event details.

The record does not report the primary endpoint count, the recommended dose, or a numerical efficacy result. It therefore cannot establish from the posted information how often DLTs occurred, whether the Phase II efficacy objective was met, or how precise any treatment-effect estimate might be. Pharmacokinetic outcomes are listed, but their numerical results are not reported either.

The single-group, nonrandomized design has no concurrent control group. Even if an outcome result were available, changes observed in participants could not be attributed to ASTX660 alone using a randomized comparison in this study. Disease course, prior treatment, supportive care, participant selection, and other factors can affect outcomes. No such causal conclusion should be drawn from the cohort counts.

In general, an early-phase study can provide information about short-term tolerability and guide subsequent research, while a later efficacy assessment typically needs an outcome definition and analysis suited to its clinical question. This general distinction does not fill in the missing results for this trial. The registry record supports describing the planned study structure and the adverse-event counts that were posted; it does not support a conclusion about whether ASTX660 is effective or whether its benefits outweigh its risks.

14. Why This Trial Matters Statistically

This trial is statistically informative as an example of why design and outcome reporting must be read together. Its Phase I dose-escalation part had a defined DLT assessment window and criteria, with the stated purpose of determining a recommended dose. The subsequent ATLL expansion and PTCL Phase II part were also described. These parts ask different questions: short-term tolerability and dose selection are not the same as efficacy, and pharmacokinetic measures address exposure rather than clinical response.

The registry's nonrandomized, single-group classification limits what can be inferred from outcomes. Cohort-specific counts are useful descriptions of recorded events, but there is no randomized comparator for estimating a relative treatment effect. This remains true even when a count appears straightforward. Denominators, event definitions, follow-up, and missing outcome information all shape what a descriptive count means.

Reporting also determines whether the intended statistical question can be answered. Here, the record describes a primary safety endpoint but does not report its numerical result. It states an efficacy objective but does not report an efficacy estimate. It lists pharmacokinetic outcomes without their numerical results. Those gaps make precision, uncertainty, and consistency across outcomes impossible to assess from the registry record.

The listed enrollment and termination status provide context, but do not explain why the trial ended or whether the planned objectives were completed. The reason for termination and the trial's statistical plan are not reported in the registry record. Accordingly, the study's statistical importance lies in clarifying the distinction between a trial's aims, its design, and the results that are actually available—not in supporting a treatment conclusion.

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 numerical result for the primary safety endpoint, including the number of participants meeting the DLT definition. It also does not report a numerical efficacy result for Phase II PTCL or numerical results for the listed pharmacokinetic outcomes. The recommended dose is not stated. These omissions prevent assessment of the primary dose-escalation result, efficacy, and drug-exposure findings.

The record lists 8 for enrollment and marks the study terminated, but does not explain the reason for termination or whether all planned parts and assessments were completed. The listed at-risk counts differ across the two adverse-event cohorts, and the record does not explain their derivation, exposure, or follow-up. Serious adverse-event terms are not listed; other event details, severity, timing, duration, and relationship to ASTX660 are also not reported.

The study is nonrandomized and single-group, with no like-for-like control comparison. Cohort-level event counts cannot be treated as treatment-versus-control results. The record also does not report a statistical analysis plan, confidence intervals, p-values, missing-data methods, multiplicity handling, or analysis populations for efficacy and pharmacokinetic outcomes. The sample-size justification is not reported in the registry record.

These limitations are specific to the information recorded for this study. They do not show that unreported analyses were never conducted; they mean that such analyses and details are not reported in the registry record. Conclusions should therefore remain limited to the design and posted counts.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: A Phase I/II Study of ASTX660 in Patients With Relapsed or Refractory T-cell Lymphoma — NCT04362007.
• Registry record last updated 2026-02-25; status last verified 2026-02.
• Results first posted 2026-02-25.
• 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

The registry describes a multicenter, open-label, nonrandomized Phase I/II study of ASTX660 in relapsed or refractory PTCL, CTCL, and ATLL. Phase I included dose escalation in PTCL and CTCL and an ATLL expansion; Phase II concerned PTCL at the recommended dose. The listed schedule was once daily for seven consecutive days every other week in each 28-day cycle.

The primary Phase I dose-escalation outcome was a count of participants with DLTs and other specified safety findings during 28 days from Day 1 to Day 29. Enrollment is listed as 8, and the study status is terminated. The posted adverse-event counts show 0 serious adverse events and 0 deaths in each cohort, with other adverse events affecting participants in both cohorts. The primary endpoint result, recommended dose, efficacy results, reason for termination, and statistical analysis plan are not reported in the registry record.