Phase II Study of the Combination of Mitoxantrone, Etoposide and Gemtuzumab Ozogamicin (MEGO) for Patients With Acute Myeloid Leukemia Refractory to Initial Standard Induction Therapy: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Phase II Study of the Combination of Mitoxantrone, Etoposide and Gemtuzumab Ozogamicin (MEGO) for Patients With Acute Myeloid Leukemia Refractory to Initial Standard Induction Therapy (NCT03839446), a na phase 2 study. The primary outcome is Complete Remission Rate.

2. Clinical Question

The study was designed to examine efficacy and toxicity of the combination in patients whose leukemia had not responded to first-line induction therapy. Its primary endpoint is a response proportion, not a direct comparison of MEGO with another treatment. The registry also lists progression-free survival and overall survival as secondary outcomes. Their definitions, estimates, and analysis details are not reported in the registry record.

This question needs to be read in light of the response-evaluable definition. It requires receipt of specified treatment and a follow-up marrow biopsy. The record does not report how many participants met that definition or how participants without an evaluable biopsy were handled. Consequently, the endpoint as described applies to the response-evaluable population, and the registry information does not establish how that population relates to all participants enrolled.

3. Trial Design

NCT03839446 is a phase II, open-label study of mitoxantrone, etoposide, and gemtuzumab ozogamicin for acute myeloid leukemia refractory to initial standard induction therapy. The registry classifies the design as single-group, with no allocation to separate arms and no masking. Enrollment is listed as 16. The study status is completed; the recorded start date is 2019-02-28 and the primary completion date is 2023-02-02.

The intervention is a combination regimen. The arm description specifies 10 mg/m2 mitoxantrone on days 1-5, 100mg/m2 etoposide on days 1-5, and 3mg/m2 gemtuzumab ozogamicin on day 6. The registry does not report a randomized comparison. Because there is no concurrent control arm, the study can describe outcomes among participants receiving the regimen, but it cannot directly estimate a between-arm treatment contrast from this design.

The primary endpoint is complete remission rate, expressed as the percentage of response-evaluable participants with complete responses, with a timeframe of up to six weeks. Response evaluation requires completion of the specified treatment and a follow-up bone marrow biopsy. The record also lists progression-free survival and overall survival as secondary outcomes, but does not report their result definitions or estimates in the information available for this analysis.

The record does not report the protocol’s sample-size justification, a statistical analysis plan, interim analyses, or details of how the primary endpoint was analyzed. Those omissions matter when interpreting a small phase II study: a design label and endpoint definition alone do not establish how precision, missing assessments, or analysis choices were handled. Any planning illustrations associated with the posted results should be distinguished from the trial’s original design and from observed 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

Analysis population for the primary outcome, as defined in the registry: To be evaluable for clinical response, a patient must have received a total of 5 days of mitoxantrone and etoposide, received 1 dose of GO and had a follow-up bone marrow biopsy to evaluate the response to therapy.

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: All trial participants

6. Primary Endpoint

The registry lists the primary outcome as Complete Remission Rate, measured over Up to six weeks.

The primary endpoint is complete remission rate: the estimated percentage of response-evaluable patients who achieved complete response within up to six weeks. It is a binary outcome at the participant level: each response-evaluable participant is categorized according to whether the remission criteria are met, and the endpoint expresses the proportion meeting those criteria as a percentage.

The registry’s definition requires normal absolute neutrophil count (>1000/microL) and platelet count (>100,000/microL), independence from red cell transfusion, and no clusters or collections of blast cells on bone marrow biopsy. It also specifies normal maturation of the erythrocytic, granulocytic, and megakaryocytic series; no requirement for bone marrow cellularity; and < 5 percent blast cells in the marrow, with none having a leukemic phenotype. Extramedullary leukemia must be absent. The absence of a previously detected clonal cytogenetic abnormality confirms the morphologic diagnosis but is not required for the stated complete remission definition.

Complete remission is used as a disease-response endpoint because it combines marrow findings with blood-count recovery and clinical criteria. It is not, by itself, a measure of how long remission lasts or of survival. The registry record does not report the observed remission percentage or its 95% confidence interval, so the degree of precision and the observed response rate cannot be assessed from the endpoint description alone.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does a single-arm design estimate?

In a single-arm study, participants receive the study intervention and outcomes are described in that group. For a binary endpoint such as complete remission, the natural summary is the proportion of evaluable participants who meet the response definition. Such a proportion describes the observed group under the study’s eligibility criteria, treatment, and assessment procedures. Without a concurrent comparator, it is not a randomized estimate of how outcomes differ between treatments.

General statistical explanation: a comparison between groups is useful because it can help separate an intervention contrast from background changes and other influences. In an uncontrolled study, there is no within-study control group to make that comparison. Historical or external outcomes may sometimes provide context, but they are not part of the randomized single-arm contrast and can differ for reasons unrelated to treatment. No external comparison is reported in the registry record.

What does a confidence interval communicate?

The primary endpoint specifies a 95% confidence interval. General statistical explanation: a confidence interval describes uncertainty around an estimate under the assumptions of the method used to calculate it. For a remission proportion, the interval can show how compatible the data are with a range of underlying response probabilities. A narrower interval indicates greater statistical precision, while a wider interval indicates more uncertainty. A confidence interval does not correct for bias in the study design, missing assessments, or differences between the study population and another population.

The registry record does not report the remission estimate or the interval endpoints, nor does it identify the interval method. Precision therefore cannot be evaluated from the endpoint description. An interval’s interpretation would also depend on the analyzed denominator and on how the analysis handled participants who were not response-evaluable.

Why does the analysis population matter?

The primary endpoint population is defined by receiving a total of 5 days of mitoxantrone and etoposide, receiving 1 dose of gemtuzumab ozogamicin, and having a follow-up bone marrow biopsy. This definition focuses the response measure on participants who completed specified treatment and had an assessment. It also means that an enrolled participant may not necessarily meet the response-evaluable definition. The registry does not report the number evaluable, the number not evaluable, or the approach to missing response assessments.

General statistical explanation: restricting a response analysis to participants with an observed assessment can make the result depend on who remains evaluable. If participants with missing assessments differ in prognosis or response from those assessed, the analyzed proportion may not represent the enrolled group. Different missing-data rules can also lead to different interpretations. The registry record does not report whether missing response assessments were counted as nonresponses, excluded, or handled by another method.

How should the endpoint definition be read?

Complete remission is a composite clinical response definition. It combines blood-count recovery, marrow findings, absence of extramedullary leukemia, and other specified criteria. The registry notes that a previously detected clonal cytogenetic abnormality is not required to be absent for the morphologic diagnosis of complete remission. This detail matters because a response label depends on the stated operational definition; a different definition could classify outcomes differently.

The outcome is reported as a percentage of response-evaluable participants. General statistical explanation: a percentage is a way to express a binary outcome proportion, but its interpretation depends on both the number meeting the endpoint and the denominator used. The endpoint description gives the intended denominator concept, not the observed denominator or event count. Those results are not reported in the registry record.

What do the planning assumptions mean?

The stated planning assumptions describe an illustration based on an observed effect, with a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. The assumptions specify that the effect to detect is a stated fraction of the observed effect. They are planning assumptions, not evidence that the original study used that design. The trial itself is registered as single-group, so the hypothetical equal allocation between two arms should not be mistaken for the actual trial structure.

General statistical explanation: a planning calculation estimates the amount of information a hypothetical design would need to detect a chosen effect under specified assumptions. It does not describe an observed outcome, and it is not observed power. An illustration based on an observed effect is also dependent on that effect estimate, which can be uncertain. The registry does not report the study’s own sample-size justification, so the planning assumptions should not be treated as its protocol rationale.

Why can over-dispersion matter?

General statistical explanation: over-dispersion occurs when observed variability is greater than a statistical model expects. If a model assumes more regularity than the data support, standard errors may be too small and confidence intervals too narrow. This issue is relevant to some count and rate outcomes; it is not a substitute for evaluating the specific binary remission analysis. The registry record does not report an over-dispersion assessment or a model for the primary endpoint.

How should results and uncertainty be separated?

An observed estimate and its uncertainty answer different questions. The estimate describes the observed proportion, while the confidence interval conveys sampling uncertainty under the chosen method. Neither, on its own, resolves the limitations of a single-arm design or determines whether an observed outcome is attributable to the intervention. Here, the registry record contains the endpoint definition and confidence-level specification, but not the remission estimate, interval limits, denominator, or analysis method. As a result, the statistical precision of the primary result cannot be evaluated from the registry information.

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("Mitoxantrone + Etoposide + Gemtuzumab Ozogamicin")
n      <- c(14)
events <- c(5)
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  Mitoxantrone + Etoposide + Gemtuzumab Ozogamicin  14  5  35.7  12.8  64.9  16.3  61.2  16.3  61.6

11. Multiplicity, Missing Data and Analysis Populations

The registry lists complete remission rate as the primary outcome and progression-free survival and overall survival as secondary outcomes. The statistical analysis plan and any multiplicity procedure are not reported in the registry record. It is therefore not reported whether the study prespecified a hierarchy among outcomes, adjusted for multiple testing, or treated secondary analyses as descriptive. When several outcomes are examined, general statistical reasoning recognizes that the chance of at least one apparently notable result can increase if each is tested independently without adjustment. That principle does not establish what was done in this study.

The record does not report interim analyses, stopping rules, or whether repeated looks at the data were planned. It also does not report the primary endpoint estimate, confidence interval limits, or analysis population count. The stated 95% confidence level identifies the intended interval level, but without the interval method and analysis details, the calculation cannot be evaluated.

Missing response data are especially relevant because evaluability requires a follow-up bone marrow biopsy as well as receipt of specified treatment. The registry does not report the number of participants without an evaluable assessment, reasons for missingness, or how missing assessments were handled. It also does not report whether all enrolled participants were included in another analysis population or whether any participants were excluded after enrollment.

These omissions limit assessment of selective availability of response measurements and the impact of analysis choices. They do not show that the study used an inappropriate method; they mean the registry record does not describe the method sufficiently to judge it. The same applies to the secondary survival outcomes: their analysis populations, follow-up details, and handling of censoring are not 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: sepsis (6.2%), platelet count decreased (6.2%), nervous system disorders - other, specifyepidural, subdural, subarachnoid hematoma (6.2%).

The registry reports one MEGO group with 16 at risk for serious adverse events and 2 affected. In the separate “other” adverse-event category, it reports 16 at risk and 16 affected. It also reports 7 deaths. These are descriptive entries in the registry record; they should not be read as evidence about causality or treatment effect.

The listed serious adverse-event terms are Sepsis, Platelet count decreased, and Nervous system disorders - Other, specifyEpidural, subdural, subarachnoid hematoma. Each term is accompanied by a reported value of 6.2%. The registry does not report further detail in the information about timing, duration, severity grading, recurrence, or whether an event was judged related to study treatment.

The deaths entry is not accompanied by a cause or attribution in the record, so it cannot be assumed that deaths were caused by the intervention or by the underlying disease. The record also does not establish how the adverse-event categories relate to one another or to deaths. Counts in separate categories should not be added together to estimate a total number of affected participants; the same participant may appear in more than one category. These safety entries are useful as a description of what the registry reports, but they do not replace a detailed safety analysis.

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

The study addresses an important clinical research question: the complete remission rate after a specified combination regimen among patients with acute myeloid leukemia refractory to initial standard induction therapy. The registry record clearly identifies the intervention, the response-evaluable criteria, and the clinical features required for complete remission. It also lists progression-free survival and overall survival as secondary outcomes.

What the registry record does not report is the observed primary remission estimate or its confidence interval. Without those values, the posted information cannot establish the response proportion or its precision. It also does not report the number of participants who met the response-evaluable criteria, so the endpoint denominator cannot be assessed. The endpoint definition should not be mistaken for an outcome result.

The single-arm design also sets a boundary on interpretation. Even if an outcome proportion were available, it would describe participants in this study and would not by itself establish how their outcomes compare with those under another treatment. No randomized comparator is described. The registry therefore does not provide a direct treatment contrast, and differences from other studies cannot be attributed to this regimen based on this record alone.

The listed safety information includes counts for serious and other adverse events and a death count, alongside several named serious adverse-event terms. These descriptive records do not establish that the intervention caused any event or death. The record does not provide the context needed to assess attribution or timing.

In general, the strength of an inference depends on the design, completeness of outcome reporting, analysis methods, and precision as well as on the endpoint definition. For this study, the registry supports a description of the intended question and design, but not a conclusion about the magnitude or certainty of the primary efficacy outcome. Absence of an outcome estimate from the registry record is not evidence that no responses occurred; it means the result is not reported in the registry record.

14. Why This Trial Matters Statistically

This trial is statistically notable for the distinction between a clearly specified response endpoint and an unavailable registry estimate. A detailed clinical definition helps readers understand what counts as complete remission, including blood-count recovery, marrow morphology, and absence of extramedullary leukemia. But a definition alone cannot answer how often the endpoint occurred or how precise the estimate was.

The response-evaluable rule also illustrates why analysis populations need explicit reporting. Participants must receive the specified treatment and have a follow-up marrow biopsy to qualify for the primary endpoint population. Without the evaluable denominator and information about missing assessments, readers cannot judge how much of the enrolled group contributed to the response analysis or whether missingness could affect interpretation.

The single-arm design makes the estimand descriptive rather than a randomized comparison. This is a different statistical question from whether outcomes differ between treatments. A single-group study can characterize outcomes under its eligibility and assessment procedures, but it cannot supply a concurrent control contrast. Recognizing that boundary prevents an observed group outcome from being interpreted as a causal treatment effect.

The record also separates efficacy and safety evidence. It includes some adverse-event and death counts, but not the primary efficacy estimate or detailed analysis information. These elements show why a registry entry should be read as a record of specified design features and posted results, not as a complete account of every analysis needed to judge response, precision, missingness, or causality.

Finally, the planning assumptions describe an illustration and should not be confused with the actual single-arm design or with observed power. Keeping design, outcome estimation, uncertainty, and planning calculations distinct is central to sound statistical interpretation.

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 limits follow from the registry record. The study is open-label and single-arm, with no concurrent comparator. The design can describe outcomes among treated participants but cannot provide a randomized comparison. The registry does not report a primary remission estimate or its confidence interval, so the central efficacy outcome cannot be assessed from the recorded information.

Response evaluability requires receipt of specified treatment and a follow-up bone marrow biopsy. The number meeting these criteria and the handling of participants without an evaluable biopsy are not reported in the registry record. This leaves the relationship between enrollment and the endpoint analysis unclear. The record also does not report the statistical analysis plan, method for calculating the confidence interval, or the study’s sample-size justification.

Although progression-free survival and overall survival are listed as secondary outcomes, their definitions, estimates, follow-up details, and analysis methods are not reported in the registry record. Interim analyses and multiplicity handling are also not reported. These omissions make it difficult to assess the planned scope of inference or how uncertainty across outcomes was addressed.

The safety information is limited to registry counts and listed terms. The record does not report event timing, attribution, duration, or the relationship between the adverse-event categories and deaths. It therefore does not support causal interpretation of those entries. These limitations describe what is not reported; they do not establish that the trial did not collect or analyze the information outside the registry record.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Phase II Study of the Combination of Mitoxantrone, Etoposide and Gemtuzumab Ozogamicin (MEGO) for Patients With Acute Myeloid Leukemia Refractory to Initial Standard Induction Therapy — NCT03839446.
• Registry record last updated 2025-02-20; status last verified 2025-01.
• Results first posted 2024-04-18.
• 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

NCT03839446 is a completed, open-label, single-arm phase II study of mitoxantrone, etoposide, and gemtuzumab ozogamicin in acute myeloid leukemia refractory to initial standard induction therapy. Enrollment is listed as 16. The primary endpoint is complete remission rate within up to six weeks among response-evaluable participants, with response evaluability requiring specified treatment and a follow-up bone marrow biopsy.

The registry lists progression-free survival and overall survival as secondary outcomes. The primary remission estimate, confidence interval limits, analysis denominator, and statistical analysis details are not reported in the registry record. Safety entries include 2 affected among 16 at risk for serious adverse events, 16 affected among 16 at risk in the other adverse-event category, and 7 deaths. These entries are descriptive and do not establish causation.