ADCT-301 in Patients With R/R AML, MDS, or MDS/MPN: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for ADCT-301 in Patients With R/R AML, MDS, or MDS/MPN (NCT04639024), a na phase 2 study. The primary outcome is Number of Participants With Complete Remission (CR) or Complete Remission With Incomplete Count Recovery (CRi).

2. Clinical Question

The trial was designed to assess safety and efficacy of ADCT-301 in the specified disease setting. The study summary describes administration after allogeneic transplantation, while the title identifies patients with relapsed or refractory AML, MDS, or MDS/MPN. Further details about how these characteristics were required or defined are not reported in the registry record.

In general, a single-group study can describe what occurred among participants receiving an intervention, but it cannot separate treatment effects from other explanations as a concurrent control comparison can. The clinical question is therefore descriptive: whether participants had the recorded remission outcomes and what safety events were observed during the study. It is not a direct comparison with another treatment or with no treatment.

3. Trial Design

NCT04639024 was an open-label phase 2 study of ADCT-301. The registry lists a single-group model, allocation as NA, and masking as NONE. Enrollment was 3. The study status is TERMINATED; the registry record gives a start date of 2021-12-07 and a primary completion date of 2022-11-03. The reason for termination is not reported in the registry record.

The intervention was ADCT-301 infusion. The arm description specifies 37.5 ug/kg on Days 1, 8 and 15 of a q3week cycle. Participants could receive up to 2 cycles for assessment of response and safety; those who were not progressing could continue for up to 6 cycles. The study summary describes blood tests following infusion, a bone marrow biopsy at the end of cycle 2/before cycle 3, and follow-up approximately every 12 weeks from the last disease assessment for up to 1 year from completion of therapy.

The registry describes efficacy evaluability as requiring eligibility, at least one dose of study agent, and 2 cycles of therapy, unless the participant withdrew early for safety. It reports that 1 subject received 2 cycles and was evaluated for response; that subject had refractory disease. The record does not report the full screening, enrollment, treatment-discontinuation, or follow-up disposition of every participant.

With no masking and no comparison arm, clinical assessments were not blinded to treatment assignment and there is no randomized control group. These design features matter when interpreting both response and adverse-event descriptions. The registry record does not report a detailed protocol for assessment timing beyond the summary information, nor does it report the reason for selecting the design or the sample size.

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

Analysis population for the primary outcome, as defined in the registry: 1 subject received 2 cycles of study medication and was evaluated for response. They had refractory disease.

5. Baseline Characteristics

The table reproduces the baseline characteristics posted in the registry, which describe the participants analysed at baseline and help show whether the randomized groups were comparable.

6. Primary Endpoint

The registry lists the primary outcome as Number of Participants With Complete Remission (CR) or Complete Remission With Incomplete Count Recovery (CRi), measured over duration of study, up to approximately 11 months.

The primary endpoint is the number of participants with complete remission (CR) or complete remission with incomplete count recovery (CRi), measured in participants over a timeframe described as the duration of the study, up to approximately 11 months. It is a binary response outcome at the participant level: a person either meets the recorded response definition or does not. The primary outcome is expressed as a count, not as a continuous measurement.

In general, remission endpoints are used in studies of blood cancers to capture a defined disease response. Counting CR together with CRi includes the response category in which remission is recorded despite incomplete count recovery. The registry record does not provide the detailed response criteria used to classify CR or CRi, so those criteria cannot be further described from this record.

The endpoint description says that participants were considered evaluable for efficacy if they were eligible and received at least one dose and 2 cycles of therapy, unless they withdrew early for safety. The registry identifies 1 subject who received 2 cycles and was evaluated for response. It does not report the number of participants achieving CR or CRi. Consequently, the endpoint's intended measure can be described, but the recorded primary response result cannot be interpreted as a remission count or rate from this information.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary outcome is a count of participants with CR or CRi. In statistical terms, each participant contributes a binary response classification, and the outcome can be summarized by the number meeting the endpoint. A response proportion could also be used in general, but the registry record reports the endpoint as a count and does not report the CR/CRi count. No rate should be inferred from the endpoint title alone.

What does a single-group design estimate?

In general, a single-group study describes outcomes in the participants who received the intervention. It does not estimate a randomized contrast against a control group because no control arm is present. Here, the allocation is listed as NA and the model as SINGLE GROUP. Comparisons with external experience would require suitable data and assumptions that are not reported in the registry record. The study therefore cannot, on its own, distinguish an intervention effect from the natural course of disease, participant selection, or other influences.

Why does the small enrollment matter?

The recorded enrollment is 3, while the registry identifies 1 subject evaluated for response. With so few observations, an individual outcome can strongly affect a descriptive summary. In general, estimates based on small samples are uncertain, and uncertainty should be made visible rather than hidden by a single point estimate. The registry record does not report a confidence interval for the primary outcome. A confidence interval is a statistical range intended to describe uncertainty around an estimate under specified assumptions; it is not a guarantee that the true value lies within the interval.

The record's efficacy evaluability description requires eligibility, at least one dose, and 2 cycles unless a participant withdraws early for safety. This rule matters because the analyzed population can differ from the enrolled population. The record notes the 1 subject who received 2 cycles and was evaluated, but does not fully report how the other participants were handled for efficacy or whether any withdrew early for safety. The exact primary analysis population and the response status of all enrolled participants are therefore not fully described.

What can the safety counts tell us?

Adverse-event counts are also binary participant-level summaries: whether a participant was affected by an event during the relevant reporting period. The record gives numbers at risk and numbers affected for serious and other adverse events. These are not event rates over person-time, and the registry record does not report exposure-adjusted rates. In general, event counts do not by themselves establish whether an event was caused by the intervention. A single-group study has no untreated comparison within the trial to help distinguish background events from events associated with treatment.

Febrile neutropenia and pneumonitis are listed as serious adverse-event terms, each with a reported percentage of 33.3%. The terms describe reported events; they do not quantify severity beyond the serious classification or establish a causal relationship. The registry does not report further event-level details, such as onset, duration, outcome, or attribution, in the information.

How should planning calculations be read?

In general, a sample-size planning calculation asks how many participants might be needed under specified assumptions to detect a chosen effect with a chosen error rate and power. The registry's planning assumptions describe a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation, with the target effect defined as a stated fraction of the observed effect. These are planning assumptions, not evidence that this single-group study had two randomized arms or used that design. The registry record does not report a sample-size justification for the actual trial.

Any sample-size outputs based on an observed effect are planning illustrations, not observed power and not evidence that the study was adequately powered. In general, power is a design property calculated under assumptions about an effect and variability; it cannot validate a result after the fact. The registry record reports no primary-endpoint analysis, p-value, or confidence interval, and it gives no sample-size justification. No effect size or additional planning result should be inferred from the assumptions alone.

The record reports 0 analyses. That means no analysis results are available in the registry information described for interpretation. A lack of reported inferential output does not show that no analyses were conducted outside the registry; it means their methods and results are not reported in the registry record. The sponsor's own analysis is not described in the available 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("ADCT-301 Infusion")
n      <- c(1)
events <- c(0)
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  ADCT-301 Infusion  1  0  0.0  0.0  97.5  0.0  79.3  1.3  84.2

11. Multiplicity, Missing Data and Analysis Populations

The registry lists 2 outcome measures, but the information available does not describe a multiplicity adjustment or a hierarchy for testing outcomes. Multiplicity arises in general when several outcomes or statistical hypotheses are assessed, because repeated testing can increase the chance of a false-positive finding. Without a reported analysis plan, it is not possible to determine whether or how that issue was addressed. The registry record does not report interim analyses or stopping rules.

Missing-data handling is also not reported in the registry record. The response endpoint description defines who is considered evaluable, including a provision for early withdrawal for safety, but it does not explain how missing response assessments or participants who did not meet the evaluability criteria were handled in the primary analysis. The record notes 1 subject who received 2 cycles and was evaluated, but does not provide a complete disposition for all 3 enrolled participants.

Analysis populations are not fully specified beyond the efficacy evaluability description. The record does not report whether the primary endpoint was analyzed in an intention-to-treat population, a treated population, or another defined set. These distinctions matter because the denominator and inclusion rules affect the interpretation of a participant count. No analysis population should be assumed beyond what the registry explicitly describes.

The registry record does not report a detailed statistical analysis plan, methods for handling incomplete follow-up, or sensitivity analyses. Consequently, the robustness of any response result to alternate assumptions cannot be assessed. Since the primary CR/CRi count itself is not reported, neither multiplicity adjustment nor missing-data methods can be linked to a reported primary result.

12. Safety Results

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

Deaths

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 0% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: febrile neutropenia (33.3%), pneumonitis (33.3%).

The adverse-event summary lists the ADCT-301 Infusion group with 3 participants at risk for serious adverse events and 2 affected. It also lists 3 participants at risk for other adverse events and 3 affected. The record lists 1 death. These are participant counts, not counts of the total number of separate events, and the record does not report exposure-adjusted rates.

Febrile neutropenia and pneumonitis are the leading serious adverse-event terms listed, each reported at 33.3%. These percentages are registry figures and should be interpreted as descriptive summaries of this small group. They do not establish the cause of an event. The record does not state whether the death was attributed to the study drug, and it does not provide enough detail to connect the death to any listed adverse-event term.

In general, serious adverse-event reporting concerns events meeting seriousness criteria, while an adverse event is not necessarily caused by the intervention. Attribution, timing, duration, and outcome help with interpretation, but further details are not reported in the registry record. The counts should therefore be read as safety observations recorded during the study, not as proof of a causal relationship or as a comparison with another treatment.

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

The record establishes that this was a small, open-label, single-group phase 2 study of ADCT-301 in patients with relapsed or refractory AML, MDS, or MDS/MPN. It reports enrollment of 3 and identifies 1 subject who received 2 cycles and was evaluated for response. The primary endpoint was the count of participants with CR or CRi, but that count is not reported in the registry record. Therefore, the available information does not establish how many participants met the primary endpoint.

The safety information records participants affected by serious and other adverse events, along with a death and two leading serious-event terms. These data describe what was reported in the study group. They do not by themselves show that ADCT-301 caused an event, nor do they allow a safety comparison with another treatment because there was no comparator arm.

The design and enrollment do not support a precise estimate of response frequency or broad conclusions for other patients. In general, a larger study with a comparison group and clearly reported outcome data can address different questions from a small single-group study. That general point does not imply that any unreported study feature was planned or used in this trial.

The study status is TERMINATED. The reason for termination, the full participant disposition, the primary response count, and inferential results are not reported in the registry record. The most defensible reading is therefore limited: the registry describes the intended endpoint and some participant-level safety findings, but does not provide the primary efficacy result needed to characterize remission outcomes.

14. Why This Trial Matters Statistically

This trial illustrates why study design and reporting details are essential to statistical interpretation. The primary question concerns a participant count for CR or CRi, but the registry record does not report that count. Without the outcome itself, a reader cannot estimate the observed response frequency, assess its precision, or relate it to the study's intended clinical question.

The single-group design is another important feature. It can document outcomes and adverse events among people receiving ADCT-301, but it does not create a concurrent control comparison. That distinction helps prevent descriptive observations from being mistaken for evidence of a comparative treatment effect. The open-label design also makes it important to know how response assessments were defined and conducted; detailed assessment criteria are not reported in the registry record.

The record also shows how evaluability rules shape what an endpoint means. Efficacy evaluation was described as requiring eligibility, at least one dose, and 2 cycles unless early withdrawal occurred for safety. The record identifies 1 evaluated subject but does not give full disposition information for all participants. Clear reporting of denominators, exclusions, missing assessments, and analysis populations is necessary to understand how a study's outcome count was formed.

Finally, the safety counts demonstrate the value of separating event reporting from causal interpretation. A reported serious event is important descriptive information, but attribution and context are needed to assess its relationship to treatment. This trial is statistically informative as an example of the limits created by a small enrollment, missing primary outcome reporting, and no comparison group; it does not permit conclusions beyond the information recorded.

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.

Several trial-specific limitations restrict interpretation. Enrollment was 3, and the registry identifies only 1 subject as having received 2 cycles and been evaluated for response. The primary CR/CRi count is not reported, so the central efficacy outcome cannot be assessed. The record does not give a complete participant flow, including the response status or treatment exposure of every enrolled participant.

The study was open-label and single-group, with no comparator. There is consequently no randomized comparison to help distinguish outcomes under ADCT-301 from outcomes that might occur for other reasons. The registry record does not report detailed response criteria, adjudication procedures, or masking of outcome assessment. The record does not report the reason the study was terminated.

Safety information is limited to participant counts and selected serious-event terms. Event timing, duration, outcomes, attribution, and exposure-adjusted rates are not reported in the registry record. The death is recorded, but its relationship to treatment is not stated. These omissions prevent a fuller assessment of safety context or causality.

The record also does not report a detailed statistical analysis plan, sample-size justification, interim analyses, missing-data methods, or complete analysis-population definitions. The available efficacy evaluability description does not resolve how all enrolled participants were treated in the primary analysis. These are limitations of the registry information available for interpretation and should not be replaced by assumptions about the protocol or the conduct of the study.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: ADCT-301 in Patients With R/R AML, MDS, or MDS/MPN — NCT04639024.
• Registry record last updated 2026-05-01; status last verified 2026-04.
• Results first posted 2026-05-01.
• 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

NCT04639024 is a terminated, open-label phase 2, single-group study of ADCT-301 in patients with relapsed or refractory AML, MDS, or MDS/MPN. Enrollment was 3. The intervention description specifies 37.5 ug/kg on Days 1, 8 and 15 of a q3week cycle, with response and safety assessment after up to 2 cycles and possible continuation for up to 6 cycles for participants who were not progressing.

The primary endpoint was the number of participants with CR or CRi. The registry identifies 1 subject who received 2 cycles and was evaluated for response, but does not report the primary response count. Serious adverse events affected 2 of 3 participants at risk; other adverse events affected 3 of 3, and 1 death is listed. Febrile neutropenia and pneumonitis are each reported as serious adverse-event terms at 33.3%. The study has no comparator arm, and the registry record does not report a reason for termination or a primary-endpoint analysis.