Flotetuzumab for Relapsed Acute Myeloid Leukemia (AML) and Myelodysplastic Syndrome (MDS) Following Allogeneic Hematopoietic Cell Transplantation (Allo-HCT): Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Flotetuzumab for Relapsed Acute Myeloid Leukemia (AML) and Myelodysplastic Syndrome (MDS) Following Allogeneic Hematopoietic Cell Transplantation (Allo-HCT) (NCT04582864), a na phase 2 study. The primary outcome is Efficacy as Measured by Number of Participants With CR(Mrd), CR, and CRi.

2. Clinical Question

3. Trial Design

NCT04582864 is registered as a Phase 2, single-group trial sponsored by Washington University School of Medicine. Its title identifies flotetuzumab for relapsed AML and MDS following allo-HCT. The registry lists an enrollment of 11 and a terminated status. The recorded start date is 2021-05-20, and the primary completion date is 2024-03-29. The reason for termination is not reported in the registry record.

The intervention arm is flotetuzumab. The description specifies continuous intravenous administration beginning with a dose-escalation ramp on Cycle 1 Day 1, starting at 30 ng/kg/day and increasing daily toward 500 ng/kg/day by day 7. The available description then begins to state that participants continue at 500 ng/kg/day but is incomplete; the rest of the regimen is not reported in the registry record. Donor lymphocyte infusion is listed as a procedure. The study summary describes it as a possible addition if available, but the record does not specify how many participants received it or provide outcomes according to its use.

Allocation is recorded as not applicable, masking as none, and the model as single-group. Thus, the design does not include a randomized comparator in the registry record. Results from a single-group study can describe observed outcomes among treated participants, but do not by themselves separate treatment effects from the course of disease, other care, or differences among participants.

The planned primary endpoint is a participant count for CRmrd, CR, and CRi at the end of Cycle 1, defined as 28 days. The protocol-defined evaluability rule includes completing all Cycle 1 infusions or stopping because of drug toxicity or disease progression. The registry lists 13 outcome measures and no analyses. The primary endpoint count, the number evaluated for that endpoint, and the reason the trial was terminated 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.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Protocol defined evaluability for participants is defined as completing all Cycle 1 infusions of flotetuzumab (or discontinued treatment due to drug toxicity or disease progression).

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 Efficacy as Measured by Number of Participants With CR(Mrd), CR, and CRi, measured over At the end of Cycle 1 (each cycle is 28 days).

The primary endpoint is the number of participants with CRmrd, CR, or CRi at the end of Cycle 1, with each cycle lasting 28 days. These are response categories based on remission and hematologic criteria. CRmrd means complete remission without minimal residual disease, identified by negativity for a genetic marker by RT-qPCR or by MFC. CR denotes complete remission under the registry’s stated disease and blood-count criteria. CRi uses the CR criteria except that residual neutropenia or thrombocytopenia may remain.

Combining these categories into a participant count gives a clinically interpretable summary of early response under the trial’s definitions. It is a binary-outcome approach at the participant level: each participant either meets one of the specified categories or does not, according to the endpoint definition. In general, a response endpoint can summarize whether a prespecified clinical state was reached by a specified assessment time. Its interpretation depends on consistent assessment, clear criteria, and an explicit analysis population.

The registry defines evaluability as completing all Cycle 1 infusions or discontinuing due to drug toxicity or disease progression. This rule matters because a response count depends on who is considered evaluable and how participants without an assessment are handled. The number meeting the endpoint and the number included in its analysis are not reported in the registry record, nor is a missing-assessment rule. Therefore, the endpoint definition is available, but its observed frequency and precision cannot be assessed from this record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What kind of outcome is the primary endpoint? The endpoint is a count of participants meeting specified response criteria. This is a binary outcome at the participant level, even though the reported measure is a count: each participant is classified according to whether the endpoint definition is met. In general, binary outcomes are often summarized by counts and proportions, with uncertainty expressed using an interval estimate. The registry record does not report the endpoint count, denominator used in analysis, proportion, or interval estimate.

The categories named in the endpoint are CRmrd, CR, and CRi. The record defines CRmrd as complete remission without minimal residual disease, using the stated molecular or flow-cytometric criterion. CR is defined by marrow, disease, and blood-count criteria. CRi follows the CR criteria but permits incomplete neutrophil or platelet recovery. These definitions determine which participants qualify; they are not statistical tests. The record does not give separate observed counts for the categories.

What does the study design allow? The registered model is single-group, allocation is not applicable, and masking is none. In general, a single-group study can describe outcomes among participants receiving the intervention, but it cannot make a randomized comparison with a concurrent control group. Without that comparison, changes or outcomes cannot be attributed to treatment with the same strength as in a randomized controlled design. The registry also lists donor lymphocyte infusion as a procedure and notes its possible use if available. The number receiving it and any corresponding outcome analysis are not reported in the registry record.

In general, a confidence interval expresses the uncertainty around an estimate under the assumptions of the statistical method used. Narrower intervals indicate greater precision, while wider intervals indicate less precision. With a small enrollment such as the 11 listed in this record, estimates may be imprecise, especially if the endpoint is uncommon or the number evaluable is smaller than enrollment. This is a general statistical consideration, not an estimate of precision for this trial: the registry record does not provide the primary endpoint count or an interval.

What do the planning calculations represent? The record describes sample-size calculations as planning illustrations based on the observed effect, rather than the trial’s own design. Their stated 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. For time-to-event outcomes, the illustration gives the total number of events using the Schoenfeld approach, while other outcomes are expressed as participants per arm for 80% or 90% power, where those planning rows are shown. These are hypothetical planning quantities, not an estimate of the trial’s observed power. The record does not report a trial-specific sample-size justification, and the primary endpoint result needed to assess the observed effect is not reported in the registry record.

In general, power calculations depend on assumptions about the target effect, outcome frequency or event rate, variability, significance level, allocation, and analysis method. Changing those assumptions can change the required sample size. A planning illustration does not show that a study had a particular probability of detecting an effect after its data were collected, and it does not replace a confidence interval or a direct report of results. The registry’s description identifies the illustrations as planning calculations, so they should be interpreted in that limited way.

What is known about the analysis plan? The registry lists 13 outcome measures and zero analyses. The specific statistical methods for the primary endpoint, including any model, hypothesis test, confidence interval method, or covariate adjustment, are not reported in the registry record. The registry also does not report whether interim analyses were planned or conducted. These omissions mean that the analysis approach cannot be reconstructed from the record.

In general, an analysis plan specifies the endpoint definition, analysis population, handling of missing measurements, and methods for estimating effects and uncertainty. Prespecification helps readers distinguish planned analyses from exploratory ones. A registration record can describe outcomes without giving every analysis detail. Here, the available information defines the primary response categories and an evaluability rule, but does not report an analysis method or outcome estimate.

Why does evaluability matter? The primary endpoint’s population is defined as participants completing all Cycle 1 infusions or stopping due to drug toxicity or disease progression. This is a protocol-defined evaluability rule. It differs conceptually from simply assuming that every enrolled participant had an endpoint assessment. In general, exclusions or missing assessments can affect a response estimate if the likelihood of being assessed is related to prognosis, toxicity, or response. The record does not state how participants who did not meet the evaluability rule, or who lacked an assessment for another reason, were treated in the analysis. The number evaluated is not reported in the registry record.

How should over-dispersion be understood? Over-dispersion is a general issue for count data when variation is greater than a chosen statistical model expects. It can make standard errors too small if the model does not account for the extra variation. The primary endpoint is described as a participant count for response categories, not as a repeated-event count, and no model or dispersion estimate is reported. There is no basis in the registry record to say that an over-dispersion adjustment was used or needed. More generally, the appropriate method depends on the outcome’s distribution, design, and analysis objective.

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("Flotetuzumab")
n      <- c(10)
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  Flotetuzumab  10  0  0.0  0.0  30.8  0.0  27.8  0.2  28.5

11. Multiplicity, Missing Data and Analysis Populations

The registry lists 13 outcome measures, including the primary response endpoint and secondary measures such as overall response rate, morphologic leukemia-free state, partial remission, stable disease, progression-free survival, overall survival, and adverse events. Considering many outcomes can raise multiplicity concerns: when several hypotheses are tested, the chance of at least one apparently positive result can increase unless the analysis strategy accounts for the testing structure. This is a general statistical issue, not evidence that a particular error occurred in this trial.

The registry record does not report a multiplicity adjustment, hierarchical testing strategy, distinction between confirmatory and exploratory analyses, or statistical analysis plan. It also lists no analyses. Therefore, it is not possible to determine how the outcomes would be interpreted jointly, whether any tests were planned, or whether adjustment was intended.

The primary endpoint population is defined by completion of all Cycle 1 infusions or treatment discontinuation due to drug toxicity or disease progression. However, handling of missing response assessments is not reported in the registry record. The record does not state whether missing outcomes were excluded, counted as nonresponse, imputed, or addressed through another method. The number evaluable for the primary endpoint is also not reported.

In general, missing-data methods rely on assumptions about why measurements are absent. Those assumptions matter because participants without an assessment may differ from those assessed. The evaluability rule gives some information about who qualifies, but it does not fully describe the analysis population or missing-data procedure. No intention-to-treat analysis population or alternative analysis population is reported in the registry record.

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: disease progression (36.4%), respiratory failure (18.2%), febrile neutropenia (9.1%), cytokine release syndrome (9.1%), gvhd of the gut (9.1%).

The registry reports a flotetuzumab safety group with 11 participants at risk for serious adverse events and 8 affected. In the other adverse-event category, 11 were at risk and 11 were affected. The deaths count is 10. These are registry counts; they should be interpreted according to the categories recorded rather than treated as a comparative risk estimate. The record does not provide a control group for comparison.

The listed serious adverse-event terms and percentages are disease progression, 36.4%; respiratory failure, 18.2%; febrile neutropenia, 9.1%; cytokine release syndrome, 9.1%; GvHD of the gut, 9.1%; and sepsis, 9.1%. These are the terms identified among the top serious events. The record does not clarify whether participants could contribute more than one term, so the entries should not be read as mutually exclusive categories or added together.

In general, adverse-event counts and percentages describe what was recorded during a study; they do not alone establish causation. Interpretation also depends on event definitions, observation time, baseline illness, attribution, and follow-up. The registry record does not report the relationship of these events or deaths to treatment, their timing, or the reason for trial termination. These safety data therefore describe recorded events but do not provide a complete causal or comparative safety assessment.

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

The record identifies a clinical question: whether flotetuzumab could be used in a Phase 2 study of relapsed AML or MDS following allo-HCT, with a primary response assessment at the end of Cycle 1. It also records the investigators’ hypothesis that flotetuzumab might be safe and tolerable and could facilitate immune-effector retargeting, with possible additional use of donor lymphocyte infusion if available. These are trial aims and hypotheses, not demonstrated findings.

The registry lists enrollment of 11, a terminated status, a primary endpoint definition, and safety counts. It does not report how many participants achieved CRmrd, CR, or CRi, nor does it provide an estimate of response frequency or uncertainty. Without that result, the primary clinical outcome cannot be judged from the registry record. The listed adverse-event counts and terms are descriptive and do not by themselves establish that the intervention caused those events.

The single-group design also limits what any observed outcome could establish. In general, outcomes within a treated group cannot provide the same causal contrast as outcomes compared between randomized groups. The registry does not provide a concurrent comparator or report outcomes according to donor lymphocyte infusion use. Therefore, the record cannot establish comparative effectiveness or isolate the contribution of flotetuzumab from other factors.

The status “terminated” is a record status, not an explanation. The reason for termination, whether the planned primary assessment was completed, and how missing assessments were handled are not reported in the registry record. The registered information therefore supports a description of the study design and its recorded safety counts, but not a conclusion about the primary response result, treatment effect, or comparative benefit.

In general, a clinical trial result should be read alongside its endpoint definition, analysis population, uncertainty, missing-data approach, and design. Those details determine how far an estimate can be generalized and what comparisons it supports. Here, the response endpoint is defined, but the result and statistical analysis are not reported. The registry record should therefore be treated as an incomplete basis for interpreting efficacy, rather than as evidence for or against a treatment effect.

14. Why This Trial Matters Statistically

This trial addresses a setting identified in its title: relapsed AML and MDS following allo-HCT. The primary endpoint focuses on response categories at the end of Cycle 1, while the registered secondary outcomes span remission measures, progression-free survival, overall survival, and adverse events. That range illustrates a common statistical challenge in clinical research: several outcome types can be relevant, but each requires clear definitions, an appropriate analysis population, and a transparent plan for uncertainty and multiplicity.

The record also shows why design is central to interpretation. A single-group Phase 2 study can describe responses and safety events among treated participants, but without a randomized comparator it cannot provide a direct controlled estimate of treatment effect. This distinction remains important even when the clinical question is urgent or the intervention has a plausible rationale. Rationale and observed outcomes are different kinds of evidence.

For biostatistical interpretation, the missing primary result is especially consequential. A precise endpoint definition cannot substitute for the number meeting that endpoint, the number assessed, and an estimate of uncertainty. The registry lists 11 enrolled participants and a protocol-defined evaluability rule, but does not report the primary count or analysis. This prevents readers from assessing response frequency or precision from the record.

The safety information likewise needs context. Counts and selected serious-event terms can identify what the registry records, but causal attribution and comparison require additional details. The trial’s terminated status adds a reason for readers to seek clarification, yet the reason is not reported in the registry record. Together, these features make transparent reporting of outcomes, analysis populations, missingness, and study conduct particularly important for interpreting the trial.

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 most direct limitation is that the registry record does not report the primary endpoint result. Although it defines CRmrd, CR, and CRi and specifies assessment at the end of Cycle 1, it gives no count of participants meeting those criteria, no denominator for the endpoint analysis, and no estimate of uncertainty. The record therefore does not permit assessment of the observed response frequency or its precision.

The trial is single-group, with allocation recorded as not applicable and masking as none. There is no registered concurrent comparator, so the design cannot provide a direct randomized contrast. Donor lymphocyte infusion is listed as a possible procedure, but the record does not report who received it or separate outcomes by its use. The contribution of flotetuzumab and any additional treatment cannot be distinguished from these data.

Enrollment is listed as 11, and the trial status is terminated. The reason for termination is not reported in the registry record. The record does not state whether all planned assessments were completed, how long participants were followed for each outcome, or how missing measurements were handled. It also does not report participant characteristics, baseline disease details, or the analysis population beyond the primary evaluability definition.

The record lists safety counts and selected serious-event terms, but does not report event timing, treatment attribution, or a detailed account of the deaths. It does not report the statistical analysis plan, an interim-analysis plan, multiplicity procedures, or a trial-specific sample-size justification. These limitations restrict both statistical and clinical interpretation and should not be filled in by assumption.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Flotetuzumab for Relapsed Acute Myeloid Leukemia (AML) and Myelodysplastic Syndrome (MDS) Following Allogeneic Hematopoietic Cell Transplantation (Allo-HCT) — NCT04582864.
• Registry record last updated 2024-12-06; status last verified 2024-12.
• Results first posted 2024-12-06.
• 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.

19. Record Summary

NCT04582864 is a Phase 2, single-group trial sponsored by Washington University School of Medicine, registered for flotetuzumab in relapsed AML and MDS following allo-HCT. Enrollment is listed as 11. The recorded start date is 2021-05-20, the primary completion date is 2024-03-29, and the status is terminated.

The primary endpoint is the number of participants with CRmrd, CR, or CRi at the end of Cycle 1, defined as 28 days. The protocol-defined evaluability rule includes completing Cycle 1 infusions or stopping due to drug toxicity or disease progression. The registry lists 13 outcome measures and no analyses. The primary endpoint result, statistical analysis plan, missing-data handling, and reason for termination are not reported in the registry record.

The safety record lists serious and other adverse-event counts, deaths, and selected serious-event terms. These entries are descriptive; the record does not provide a concurrent control or enough information to establish treatment causality.