Daratumumab in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia or High-Risk Myelodysplastic Syndrome: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Daratumumab in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia or High-Risk Myelodysplastic Syndrome (NCT03067571), a na phase 2 study. The primary outcome is Participants With a Response.

2. Clinical Question

The clinical question concerns observed response in a small, uncontrolled group, not a comparison of daratumumab with another treatment or with no treatment. Response could include several categories, including complete remission, complete remission without platelet recovery, partial remission, marrow complete remission for myelodysplastic syndrome, morphologic leukemia-free state for acute myeloid leukemia, and hematologic improvement. The criteria differ across categories and conditions, so the endpoint is broader than a single uniform response state.

The trial also listed time on treatment, overall survival, and progression-free survival as secondary outcomes. Those outcomes could describe treatment duration and the course of disease over time, but their results are not reported in the registry record. The primary response count and any accompanying estimate of uncertainty are also not reported in the registry record. The available information therefore identifies the question the study set out to address, but does not establish how many participants met the response criteria.

3. Trial Design

This was an open-label, phase 2, single-group trial of daratumumab in people with relapsed or refractory acute myeloid leukemia or high-risk myelodysplastic syndrome. The registry record lists enrollment of 7 and identifies M.D. Anderson Cancer Center as the sponsor. Allocation is listed as not applicable, masking as none, and the study model as single group. There was no randomized control arm, so the design does not provide a like-for-like treatment comparison.

The registered treatment was intravenous daratumumab. Participants received it over 3.25-6.5 hours on days 1, 8, 15 and 22 of cycles 1-2; on days 1 and 15 of cycles 3-6; and on day 1 of subsequent cycles. Cycles were scheduled to repeat every 28 days. These details describe the registered regimen, not how long any individual participant actually received treatment.

The study start date is 2017-10-27, and the primary completion date is 2022-11-21. Its current status is terminated. The reason for termination, actual treatment exposure for each participant, and any changes to the regimen are not reported in the registry record.

The primary outcome was the number of participants with a response, assessed using International Working Group recommendations, with a timeframe of up to 5 years. Secondary outcomes were time on treatment, overall survival, and progression-free survival. The registry lists 4 outcome measures, but 0 analyses. The response result, the secondary-outcome estimates, and details of any analysis actually performed are not reported in the registry record. A sample-size justification and details of interim analyses are also 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

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 Participants With a Response, measured over Up to 5 years.

The primary endpoint counts participants who meet the registered response definition. That definition draws on International Working Group recommendations and includes multiple kinds of response rather than a single measure of tumor size. Complete remission requires the specified marrow and blood-count criteria and absence of leukemia-related symptoms. Other categories relax or alter parts of those criteria: complete remission without platelet recovery allows a lower platelet count; partial remission allows residual abnormal marrow cells or a specified reduction in marrow blasts; and marrow complete remission applies to myelodysplastic syndrome. Morphologic leukemia-free state applies to acute myeloid leukemia, while hematologic improvement is described by the number of positively affected cell lines.

A response count can offer a direct description of how many participants met the criteria during the assessment timeframe. In a single-group trial, it does not by itself estimate a treatment contrast. The endpoint also combines categories with distinct criteria, so the meaning of a positive response depends on which category a participant met and the underlying condition.

Using a defined response endpoint is generally useful because it makes the outcome more explicit than an informal judgment of improvement. However, the registry record does not report the observed number of responders, category-specific counts, or an uncertainty estimate. It is therefore not possible to describe the observed response frequency from the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The study design and the kind of outcome determine what statistical conclusions are possible. This trial is single group, with one registered treatment arm and no comparator. Its primary outcome is a count of participants meeting a response definition. Those features make the main descriptive question a count of responses among enrolled participants. The registry record does not report the response count or an analysis of that endpoint, so no estimate can be interpreted.

What a single-group result can describe

General statistical explanation: a single-group study can describe outcomes observed among the people enrolled and assessed. It does not directly estimate how outcomes would differ under an alternative treatment, because there is no concurrent comparison group. Random allocation, when used, helps create comparable groups for a treatment contrast; this registry record lists allocation as not applicable and has no randomized comparison. As a result, any observed outcome in this study would need to be understood as an observation in this group, not as a controlled estimate of what daratumumab caused.

A response count is a binary-type endpoint at the participant level: each participant either meets the stated response definition or does not, assuming assessment is available. The result could be expressed as a count and, if the denominator and response data are available, as a proportion. The registry record reports enrollment but not the primary count, so the actual proportion cannot be stated. It also does not report how many participants were assessed for response or how missing assessments were handled.

What an uncertainty interval would mean

General statistical explanation: a confidence interval describes the statistical uncertainty around an estimate under the assumptions of the method used. For a response proportion, an interval would convey how much uncertainty remains about the underlying response frequency, given the observed participants and the chosen procedure. It would not correct for the absence of a comparator, resolve bias from participant selection, or account automatically for unreported outcomes. No confidence interval for the primary endpoint is reported in the registry record.

With enrollment of 7, each participant's outcome has substantial influence on a group-level description. This is a general property of small samples: estimates can be imprecise, and a change in one observed outcome can have a noticeable effect on the count. That does not mean a particular result occurred; the response count itself is not reported in the registry record. Precision cannot be assessed by enrollment alone, and an actual interval or estimate is needed to quantify it.

Planning illustrations and power

The registry record does not report the trial's sample-size justification, so the intended target precision or design assumptions cannot be described. Any planning illustration based on an observed effect is a separate calculation, not a record of the trial's original design. The stated planning assumptions are a two-sided significance level of 0.05, equal allocation between two arms, a normal approximation, and an effect defined as a stated fraction of the observed effect. For time-to-event planning, the illustration uses a total event count; other planning values are expressed as participants per arm. These are planning conventions, not observed trial outcomes.

General statistical explanation: power is a design-stage probability of detecting an effect under specified assumptions. It is not a measure of whether a result is true, and it cannot be recovered as an observed property of a completed study. A planning illustration based on an observed effect is particularly sensitive to that effect estimate and does not replace the original sample-size rationale. No calculated planning values or original sample-size justification are reported in the registry record.

Over-dispersion and outcome structure

General statistical explanation: over-dispersion occurs when observed variability exceeds what a particular statistical model expects. It can make model-based uncertainty estimates too narrow if not addressed. The primary outcome is described as participant counts, but the registry record does not report a fitted model or a variance analysis. There is therefore no basis to claim that over-dispersion was present or that a specific adjustment was used. The concept is relevant when counts are modeled, but it should not be mistaken for a reported feature of this trial's analysis.

Time-to-event outcomes

The listed secondary outcomes include overall survival and progression-free survival, as well as time on treatment. General statistical explanation: time-to-event analyses account for both the time until an event and the fact that some participants may not have an event observed during follow-up. Such methods often rely on definitions of the event, the start of follow-up, and censoring. The registry record does not report the event definitions in analysis-ready detail, the follow-up data, censoring rules, estimates, or methods used. No conclusion about these outcomes can be drawn from their names alone.

The registry lists 0 analyses. This means the available record does not provide analysis results to interpret; it does not reveal which analyses may have been conducted outside the posted record. Details of statistical tests, model specifications, covariate adjustment, confidence-interval procedures, and handling of interim looks 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("Treatment (Daratumumab)")
n      <- c(7)
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  Treatment (Daratumumab)  7  0  0.0  0.0  41.0  0.0  35.4  0.3  36.9

11. Multiplicity, Missing Data and Analysis Populations

The registry lists a primary response outcome and secondary outcomes of time on treatment, overall survival, and progression-free survival. It also lists 4 outcome measures and 0 analyses. The relationship among the outcome measures, any outcome hierarchy, and any adjustment for multiple statistical tests are not reported in the registry record. Without those details, it is not possible to determine whether multiplicity was addressed or how it would affect interpretation of any collection of results.

General statistical explanation: multiplicity arises when several outcomes, comparisons, or repeated analyses are considered. Looking at many results can increase the chance of finding an apparently notable result by chance, depending on the analysis plan. An explicit hierarchy or adjustment can help define how such results are interpreted. No multiplicity procedure or analysis plan is reported in the registry record, so none should be assumed.

The registry record does not report how missing outcome data were handled, the number of participants assessed for each outcome, or whether all enrolled participants were included in each analysis. It also does not report analysis populations, such as an intention-to-treat population or a population defined by treatment received. These details matter because missing assessments and differing analysis populations can change the denominator and the interpretation of a participant count.

General statistical explanation: missing outcome data can reduce precision and may introduce bias when the probability of missingness relates to participant condition or outcome. The impact depends on why data are missing and on the analytic approach. No missing-data assumptions, imputation methods, or sensitivity analyses are reported in the registry record. With enrollment of 7, the absence of participant-level assessment and missingness information limits assessment of how complete the outcome data were.

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 (42.9%), febrile neutropenia (28.6%), neutrophil count decreased (28.6%), angioedema (14.3%), dyspnea (14.3%).

In the treatment group, 6 of 7 participants were recorded as affected by serious adverse events, and 5 of 7 were affected by other adverse events. The registry also lists 2 deaths. These are counts for the study group, not comparisons with another treatment. The record does not state the cause of death or establish that deaths were caused by daratumumab.

The listed serious adverse-event terms and percentages are sepsis, 42.9%; febrile neutropenia, 28.6%; neutrophil count decreased, 28.6%; angioedema, 14.3%; dyspnea, 14.3%; and infection, 14.3%. They describe the entries reported for this group. The registry record does not provide enough detail to determine event timing, duration, recurrence, severity grading beyond serious-event classification, or attribution to treatment.

General statistical explanation: adverse-event percentages in a small group are descriptive and can be sensitive to individual events. Counts and percentages should be read with their denominator and with the study design in mind. Here, the group had 7 participants at risk in the reported categories. These figures do not estimate comparative risk, and they should not be interpreted as establishing that treatment caused or prevented an event. The record does not report a control group or a treatment-attribution analysis.

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

The registry record establishes that a phase 2, open-label, single-group trial evaluated daratumumab in people with relapsed or refractory acute myeloid leukemia or high-risk myelodysplastic syndrome. It reports enrollment of 7, the response criteria planned for the primary outcome, several secondary outcomes, and adverse-event counts. It also lists the study as terminated.

It does not report the number of participants who had a response, the response categories observed, or an estimate of uncertainty. It therefore cannot show from the posted results how many participants met the primary endpoint or how precisely any response frequency was estimated. The listed secondary outcomes likewise have no reported results in the registry record.

Even if a response count were available, the single-group design would describe outcomes in the enrolled group rather than provide a randomized treatment comparison. There is no concurrent comparator arm, and allocation is listed as not applicable. A response observed during treatment would not, on its own, separate the contribution of treatment from other influences or establish a causal effect.

The serious and other adverse-event counts describe events recorded among participants in the treatment group. They do not provide comparative safety estimates or establish treatment attribution. The listed deaths are not accompanied by causes or attribution details in the registry record.

General statistical explanation: results from small studies can be useful for describing feasibility and generating questions, but their estimates may be imprecise. The registry record does not provide enough outcome or analysis information to assess the size, precision, or robustness of the primary result. It also does not report the reason for termination, sample-size justification, missing-data approach, or analysis populations. Those absences constrain interpretation; they do not supply evidence for a particular response or safety conclusion.

14. Why This Trial Matters Statistically

This trial is statistically notable because it asks a clinically focused response question in a single group but has no comparator arm. That structure makes the distinction between describing an outcome and estimating a treatment effect especially important. The registered endpoint can, in principle, count participants who meet defined response criteria, but that count is not reported in the registry record.

Enrollment of 7 also makes the importance of precision clear. General statistical explanation: when a study includes few participants, individual outcomes can strongly influence an estimate, and uncertainty can remain substantial. A count alone would not convey that uncertainty; an interval and clear information about who was assessed would help. Neither the response count nor a precision estimate is reported in the registry record.

The response definition spans several categories, including categories specific to acute myeloid leukemia or myelodysplastic syndrome. This matters statistically because a combined endpoint can bring together clinically distinct outcomes. Category-level results would help readers understand what contributed to any combined count, but such results are not reported in the registry record.

The record also illustrates why outcome names and outcome results are different. Time on treatment, overall survival, and progression-free survival are listed, but no analyses are reported. Without follow-up estimates, event definitions, and analysis details, those outcomes cannot be interpreted quantitatively. The registry status of terminated does not explain whether follow-up was complete or why the study ended.

Finally, the adverse-event information is descriptive. Counts in a single group can identify what was recorded among participants, but they cannot establish a relative safety profile without a comparator. The design and reporting gaps matter as much as the endpoint definitions when deciding what statistical conclusions are supported.

15. Limitations

• The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
• Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.

The main trial-specific limitation is the absence of a comparator group. With a single treatment group, the design cannot provide a randomized estimate of the difference between daratumumab and another treatment. The open-label design also means masking was absent, as recorded in the registry. The record does not report whether outcome assessment was independently reviewed or otherwise protected from knowledge of treatment.

Enrollment was 7, limiting how much information the study can contribute to precise estimates. More importantly, the registry record does not report the primary response count, its uncertainty, or category-specific response data. The listed secondary outcomes have no reported analysis results. Consequently, the available record does not allow numerical interpretation of efficacy outcomes.

The study is listed as terminated, but the reason for termination is not reported in the registry record. The record also does not report whether outcome follow-up was complete, how many participants contributed data to each outcome, or how missing data were handled. Sample-size justification, interim analyses, statistical tests, analysis populations, and model specifications are not reported in the registry record.

The primary endpoint includes multiple response categories with differing criteria. Without category-level counts, a combined result—if reported—would be difficult to interpret in detail. The adverse-event information is limited to group counts and listed terms and percentages; timing, treatment attribution, causes of deaths, and comparative safety results are not reported in the registry record. These limitations concern what can be concluded from the record and do not establish that particular unreported analyses or outcomes occurred.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Daratumumab in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia or High-Risk Myelodysplastic Syndrome — NCT03067571.
• Registry record last updated 2023-09-21; status last verified 2023-09.
• Results first posted 2023-09-21.
• 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

This phase 2, open-label, single-group trial evaluated intravenous daratumumab in people with relapsed or refractory acute myeloid leukemia or high-risk myelodysplastic syndrome. The registry lists enrollment of 7, no masking, and no comparator arm. The primary outcome was participants with a response by International Working Group recommendations, with a timeframe of up to 5 years. Secondary outcomes were time on treatment, overall survival, and progression-free survival.

The study is listed as terminated. The registry record reports serious adverse events affecting 6 participants, other adverse events affecting 5 participants, and 2 deaths in the treatment group. It lists 4 outcome measures and 0 analyses. The primary response result, secondary-outcome results, reason for termination, and detailed analysis methods are not reported in the registry record. Interpretation is therefore limited to the registered design and the posted safety counts.