A Study to Assess the Clinical Efficacy and Safety of Daratumumab in Participants With Relapsed or Refractory Natural Killer/T-Cell Lymphoma (NKTCL), Nasal Type: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Study to Assess the Clinical Efficacy and Safety of Daratumumab in Participants With Relapsed or Refractory Natural Killer/T-Cell Lymphoma (NKTCL), Nasal Type (NCT02927925), a na phase 2 study. The primary outcome is Percentage of Participants With Overall Response.

2. Clinical Question

3. Trial Design

The registry describes a completed, open-label, phase 2 study of daratumumab in participants with relapsed or refractory natural killer/T-cell lymphoma, nasal type. It lists a single-group model and no masking. Enrollment is listed as 32. Because the study had no concurrent control group and was not a randomized comparison, its design can describe responses and safety events among participants treated in the study, but it cannot by itself estimate a treatment contrast against another group.

Participants received daratumumab by intravenous infusion at 16 milligram per kilogram once weekly for 8 weeks, then every 2 weeks for 16 weeks, then every 4 weeks thereafter. The listed stopping conditions were progressive disease, consent withdrawal, or unacceptable toxicity. The registry lists the study as completed. The dates recorded for study start and primary completion are 2017-02-14 and 2020-01-02.

The primary outcome was the percentage of participants with overall response. The registry defines response as complete response or partial response according to the LUGANO classification, using blinded independent central review. Other listed outcomes include complete response, progression-free survival, duration of response, time to response, overall survival, treatment-emergent adverse events, clinically significant vital-sign changes, and clinically significant electrocardiogram abnormalities. The registry record lists 11 outcome measures.

The design information does not establish how participants were selected, whether the study had interim analyses, or what sample-size justification was used. Those details are not reported in the registry record. The record also does not report the primary response estimate, its confidence interval, or numerical results for the listed secondary outcomes.

4. Participant Flow and Accounting

The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: All treated analysis set included all the participants who have received at least one dose of study drug.

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 treated analysis set included all the participants who have received at least one dose of study drug.

6. Primary Endpoint

The registry lists the primary outcome as Percentage of Participants With Overall Response, measured over Up to 2 years and 11 months.

The primary endpoint is the percentage of participants with an overall response. A response is defined as complete response or partial response under the Revised Criteria for Response Assessment of Hodgkin and non-Hodgkin lymphoma: LUGANO classification. Response classification was based on blinded independent central review. The listed timeframe is up to 2 years and 11 months.

The definition gives a clinical meaning to the binary outcome: a participant either met the response definition or did not. Complete response requires complete disappearance of all evidence of disease. Partial response requires a > 50 percent decrease in the sum of the products of the maximal perpendicular diameters of measured lesions, with no new sites. Measurements were based on computed tomography, including the CT portion of PET/CT where applicable.

In general, an overall response endpoint can provide a concise measure of tumor response during a study. Independent central review is intended to apply response criteria separately from the treating study team; the registry identifies the review as blinded. The measure does not, on its own, describe how long a response lasts, whether disease later progresses, or overall survival. Those are distinct outcomes, and the registry lists duration of response, progression-free survival, and overall survival separately.

The registry does not report the observed percentage with overall response or its 95% confidence interval. Thus, the endpoint definition and assessment approach are available, but the primary result and its precision cannot be assessed from the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry describes a binary primary outcome: whether a participant achieved overall response according to the stated criteria. A percentage for such an outcome is generally formed by counting participants who meet the definition and relating that count to the relevant analysis population. That general description does not establish which calculation procedure was used in this study. The registry identifies the all-treated analysis set as participants who received at least one dose of study drug, but it does not report the response count, the percentage, or the confidence interval.

What does the endpoint definition establish?

The primary endpoint combines complete response and partial response. The registry specifies complete response as complete disappearance of all evidence of disease. It specifies partial response as a > 50 percent decrease in the sum of the products of the maximal perpendicular diameters of measured lesions, with no new sites. These criteria give the response classification an operational definition, so that assessments can be made against stated rules rather than an undefined impression of improvement.

The record attributes response assessment to blinded independent central review. In general, independent review can separate assessment from the treating study team, while blinding can reduce the influence of knowledge that might affect classification. These features describe how the endpoint was assessed; they do not show that all measurement or classification error is eliminated. The registry does not describe adjudication procedures, handling of disagreements, or further details of the review process.

How should the confidence interval be understood?

A confidence interval is a statistical expression of uncertainty around an estimate. In general, it is calculated using a specified method and depends on the observed data and the method’s assumptions. The registry names a 95% confidence interval for the primary response measure, but does not report its limits or identify the interval method. It is therefore not possible to evaluate the interval’s width, determine whether it is compatible with a range of response percentages, or assess the method’s assumptions for this result.

The point estimate and its interval answer different questions. The point estimate would describe the response proportion observed in the analysis population; the interval would convey uncertainty about that estimate. Neither should be replaced by a statement based only on the study phase, enrollment, or endpoint definition. In this case, the point estimate itself is not reported in the registry record, so there is no numerical estimate to interpret.

What does a single-group design permit?

A single-group study can describe outcomes observed among participants who received the intervention. Without a concurrent comparator, it cannot estimate a between-group difference under the same study conditions. General comparisons with historical results are vulnerable to differences in eligibility, disease status, assessment, follow-up, and other features. The registry identifies this study as single-group and not a randomized comparison; it does not report an alternative control-based analysis.

The study is open label, with no masking listed, while the primary endpoint is described as based on blinded independent central review. These statements refer to different parts of the design: the study overall was open label, and the response assessment used a blinded independent review. The registry does not describe whether other outcome assessments were blinded.

How should planning calculations be distinguished from results?

In general, a sample-size calculation is a planning exercise about the information a proposed study might need under specified assumptions. It is not a result observed in participants, and it is not observed power. The stated planning assumptions describe a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation, with the effect to detect expressed as a fraction of the observed effect. For time-to-event outcomes, the stated planning approach uses the total number of events; other planning outputs are expressed as participants per arm.

Those assumptions do not describe the trial’s single-group design, which has no two-arm randomized comparison. The registry record does not report the trial’s own sample-size justification or its statistical plan. Any planning illustration using the stated assumptions should therefore be read as a hypothetical calculation, not as evidence that the study was designed or analyzed according to those assumptions. The registry record also does not report an interim analysis plan or interim results.

What remains unavailable?

The registry lists 11 outcome measures and no analysis entries. The primary response estimate, confidence interval limits, and numerical secondary-outcome results are not reported in the registry record. The record does not specify the statistical procedure used for the confidence interval, missing-outcome rules, sensitivity analyses, or adjustments for multiple outcomes. These omissions limit statistical interpretation: a defined endpoint and a named uncertainty measure do not substitute for the underlying result or a description of how missing observations and multiple analyses were handled.

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("Daratumumab")
n      <- c(32)
events <- c(8)
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  Daratumumab  32  8  25.0  11.5  43.4  13.3  42.1  13.3  42.3

11. Multiplicity, Missing Data and Analysis Populations

The registry lists 11 outcome measures, including the primary overall response endpoint and secondary outcomes covering complete response, progression-free survival, duration of response, time to response, overall survival, treatment-emergent adverse events, vital signs, and electrocardiogram abnormalities. When a study evaluates multiple outcomes, the chance of at least one apparently notable finding can increase if each is tested or interpreted separately. In general, a prespecified strategy can clarify which outcomes are confirmatory and whether any adjustment or hierarchical testing is used.

The registry record does not report a multiplicity strategy, the ordering of secondary analyses, or an inferential plan for the listed outcomes. It also does not provide analysis entries. It is therefore not possible to determine whether multiplicity was addressed, or how any reported inferential results should be interpreted across outcomes. Numerical results for the listed secondary outcomes are not reported in the registry record.

The primary analysis population is described as the all-treated analysis set, including participants who received at least one dose of study drug. The record does not report how missing response assessments, withdrawals, or unevaluable participants were handled. It does not describe imputation, censoring rules for time-to-event outcomes, sensitivity analyses, or whether analyses used other populations. These details matter because missing outcomes and analysis-population choices can affect the interpretation of an estimate.

The absence of these details does not show that a particular method was or was not used. It means the relevant approach is not reported in the registry record, so the robustness of the endpoint analyses to missing data and multiple outcomes cannot be assessed from the registry information.

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 2% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: pyrexia (15.6%), thrombocytopenia (9.4%), septic shock (9.4%), febrile neutropenia (6.2%), cellulitis (6.2%).

The registry safety figures list 17 participants with serious adverse events among 32 at risk in the daratumumab group. It lists 31 participants with other adverse events among 32 at risk and 21 deaths. The record also gives selected serious adverse event terms as percentages: pyrexia, 15.6%; thrombocytopenia, 9.4%; septic shock, 9.4%; febrile neutropenia, 6.2%; cellulitis, 6.2%; and pneumonia, 6.2%.

These counts and percentages describe events recorded in the study group. The selected event percentages are not a ranking of severity or proof that the events were caused by study drug. A participant may experience more than one event type, so event categories should not be added to estimate a participant total. The registry record does not report the attribution of the listed events to treatment, or details such as their timing and duration. The death count is reported, but its relationship to treatment is not reported in the registry record.

There is no concurrent control group for comparison. The safety figures therefore do not quantify how event frequency differed from another treatment group. They should be read as descriptive registry counts and percentages, not as comparative safety estimates or evidence of causation.

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

The study addresses a defined clinical question: the percentage of participants with relapsed or refractory natural killer/T-cell lymphoma, nasal type, who achieved complete or partial response while receiving daratumumab. The endpoint criteria and assessment approach are described, and the registry records selected safety counts. However, the primary response percentage and its 95% confidence interval are not reported in the registry record. The central efficacy result therefore cannot be summarized from the available registry information.

Even if a response estimate were available, a single-group study would describe outcomes among participants treated in the study rather than establish a comparative treatment effect. A concurrent randomized comparator helps distinguish outcomes in the treatment group from outcomes that might occur under another treatment or usual care. This study is not a randomized comparison and has no concurrent control group listed.

The endpoint also has a specific scope. Overall response records whether a participant met the complete-response or partial-response definition. It does not by itself describe response duration, progression-free survival, or overall survival. The registry lists these as separate outcomes, but their numerical results are not reported in the registry record. A response classification should not be treated as interchangeable with those other outcomes.

The safety counts are likewise descriptive. They identify recorded adverse events and deaths in the study group, but the registry information does not establish that the events were caused by daratumumab. The absence of a comparison group and the lack of reported event attribution limit causal interpretation.

In general, statistical evidence should be interpreted using the outcome estimate, its uncertainty, the analysis methods, and the design that generated the data. Here, the endpoint definition and design are described, but the primary estimate and several analytic details are unavailable in the registry record. The record therefore supports a description of what the study set out to assess, not a conclusion about the magnitude or comparative effect of treatment.

14. Why This Trial Matters Statistically

This study is statistically informative as an example of the distinction between defining an endpoint and reporting its result. The registry gives a detailed overall-response definition, including complete and partial response criteria, and identifies blinded independent central review. Those features help readers understand what the primary measure was intended to capture. Without the observed response percentage and its confidence interval, however, the endpoint cannot be quantified or assessed for precision.

The single-group design also shapes what can be learned. A study can document outcomes among participants receiving an intervention, but a concurrent comparator is needed to estimate a direct contrast under shared study conditions. The registry explicitly describes a single-group study and not a randomized comparison. That design limitation remains even when outcome assessment is carefully specified.

There is also a useful distinction between efficacy outcomes and safety descriptions. The registry lists response, disease-control, survival, and safety outcomes, but the numerical results available in the record are limited to selected safety counts and percentages. Those figures are descriptive, and they do not establish causation. Reading each measure according to its role prevents a safety count, response definition, or study completion status from being mistaken for a comparative result.

Finally, the record illustrates why analysis details matter alongside outcome definitions. Information about missing observations, multiplicity, confidence-interval methods, and the statistical plan can affect how estimates should be understood. These details are not reported in the registry record. The absence of the primary result and analytic details makes careful separation of documented details from unreported findings especially important.

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 limitation for interpretation is that the registry record does not report the primary overall-response percentage or its 95% confidence interval. The endpoint is defined, but neither its observed frequency nor its precision can be assessed. Numerical results for the listed secondary outcomes are also not reported in the registry record.

The study was open label and single group, with no concurrent control group listed. It therefore cannot provide a direct randomized comparison. The primary outcome used blinded independent central review, but the registry does not report further details of that process, such as how disagreements were handled. It also does not describe masking for the other outcome assessments.

The registry defines the all-treated analysis set as participants who received at least one dose of study drug. It does not report how missing or unevaluable response assessments were handled, how withdrawals were treated in each analysis, or which analysis populations were used for outcomes beyond the primary population definition. The statistical plan, confidence-interval method, multiplicity approach, and interim-analysis details are not reported in the registry record.

The safety information is limited to listed counts and selected event percentages. Event attribution, timing, duration, and comparative safety results are not reported. The death count is present, but its relationship to treatment is not reported in the registry record. These limitations prevent causal interpretation of safety events as well as comparative interpretation of efficacy.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: A Study to Assess the Clinical Efficacy and Safety of Daratumumab in Participants With Relapsed or Refractory Natural Killer/T-Cell Lymphoma (NKTCL), Nasal Type — NCT02927925.
• Registry record last updated 2021-01-14; status last verified 2020-12.
• Results first posted 2021-01-14.
• Data retrieved from ClinicalTrials.gov on 2026-11-09.
• Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.

19. Record Summary

The registry describes a completed, open-label, single-group phase 2 study of daratumumab in relapsed or refractory natural killer/T-cell lymphoma, nasal type. Enrollment is listed as 32. Daratumumab was administered by intravenous infusion on a schedule that began weekly, changed to every 2 weeks, and then every 4 weeks until a listed stopping condition.

The primary endpoint was the percentage of participants with complete or partial response according to the LUGANO classification, based on blinded independent central review. The response estimate and its 95% confidence interval are not reported in the registry record. The registry lists 11 outcome measures and no analysis entries.

Safety listings include serious and other adverse-event counts, selected serious-event percentages, and a death count. These are descriptive figures from a single-group study; event attribution and comparative safety results are not reported in the registry record.