An Efficacy and Safety Proof of Concept Study of Daratumumab in Relapsed/Refractory Mantle Cell Lymphoma, Diffuse Large B-Cell Lymphoma, and Follicular Lymphoma: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for An Efficacy and Safety Proof of Concept Study of Daratumumab in Relapsed/Refractory Mantle Cell Lymphoma, Diffuse Large B-Cell Lymphoma, and Follicular Lymphoma (NCT02413489), a na phase 2 study. The primary outcome is Overall Response Rate (ORR).

2. Clinical Question

This question is a treatment-activity question, rather than a comparison of daratumumab with another treatment. The planned response measure combines complete response and partial response, so it counts participants meeting either response definition. The study also aimed to identify a CD38 expression threshold above which daratumumab activity might be enhanced in each subtype. That aim does not establish that a threshold was identified: the threshold result is not reported in the registry record.

3. Trial Design

This was an open-label Phase 2 study of daratumumab in three relapsed or refractory lymphoma subtypes: mantle cell lymphoma, diffuse large B-cell lymphoma, and follicular lymphoma. The registry lists a total enrollment of 36. It describes a single-group design, with no control arm, and masking was listed as none. The study status is terminated. The registry lists a start date of 2015-09-02 and a primary completion date of 2017-06-01; the reason for termination is not reported in the registry record.

Participants received daratumumab as an intravenous infusion. The planned schedule began with administration once every week for 8 weeks, followed by once every other week for 16 weeks, and then once every 4 weeks until documented disease progression, unacceptable toxicity, or study end. These are the schedule details in the registry; actual treatment exposure and adherence are not reported in the registry record.

The primary outcome was overall response rate (ORR), defined as the percentage of participants achieving complete response or partial response. The stated timeframe ran from the first dose until disease progression, withdrawal of consent from study participation, or the end of study, described as approximately 1.9 years. The registry also lists duration of response, progression-free survival, overall survival, and time to response as secondary outcomes, but their numerical results are not reported in the registry record.

A single-group design can describe responses observed among treated participants, but it cannot directly estimate how those outcomes would compare with a concurrent control group. Open-label conduct also means that participants and study personnel were not masked to treatment. The registry does not report whether response assessment was independently reviewed, how treatment decisions were standardized, or what statistical procedures were planned for the subtype and CD38 analyses.

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.

Before assignment: In total 36 participants were treated (15 participants in the diffuse large B-cell lymphoma \[DLBCL\] cohort, 16 participants in the follicular lymphoma \[FL\] cohort, and 5 participants in the mantle cell lymphoma \[MCL\] cohort).

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: The analysis population was all participants that were treated with daratumumab.

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 Overall Response Rate (ORR), measured over After the first dose until disease progression, withdrawal of consent from study participation, or the end of study (approximately 1.9 years).

Overall response rate is the percentage of participants who achieve either a complete response (CR) or a partial response (PR). It is a binary-outcome summary at the participant level: each participant is classified according to whether the response definition was met during the stated assessment period. The registry defines CR as complete disappearance of all evidence of disease. PR requires a > 50 percent (%) decrease in the sum of the products of the maximal perpendicular diameters of measured lesions (SPD), with no new sites.

Lymph node measurements could be based on computed tomography (CT), the CT portion of positron emission tomography/computed tomography (PET/CT), or magnetic resonance imaging (MRI), where applicable. The endpoint therefore translates imaging assessments into a response category and then summarizes the proportion meeting either response criterion. This can be useful for describing antitumour activity in a study without a comparator, while not establishing what would have occurred under another treatment or no treatment.

The registry record gives the endpoint definition and timeframe but does not report the observed ORR, its confidence interval, or the underlying counts of participants with CR and PR. Consequently, the magnitude and precision of the response estimate cannot be assessed from the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

Overall response rate is a binary-outcome summary expressed as a percentage of participants. The response classification is based on whether an individual met either the complete-response or partial-response definition. In general, a binary endpoint reduces a participant's response assessment to an outcome category, which makes the resulting proportion relatively straightforward to describe. The endpoint still depends on consistent assessment of disease and on complete enough follow-up to classify participants. The registry defines the response criteria but does not report how missing or unevaluable assessments were handled.

What does a confidence interval convey?

General explanation: a confidence interval describes statistical uncertainty around an estimate. For a response proportion, the interval gives a range of values compatible with the observed data under the method used to construct it. It is not a guarantee that the true value lies within that range, and it does not correct for bias in study design or assessment. The registry identifies the primary endpoint's dispersion as a 95% confidence interval, but the interval itself and the response estimate are not reported in the registry record. The method used to calculate that interval is also not reported.

What can a single-group design estimate?

General explanation: in a single-group study, an outcome proportion can describe the participants who received the intervention, subject to the analysis population and completeness of outcome assessment. There is no concurrent control arm to provide a direct estimate of what would have happened to similar participants under another intervention. As a result, a response proportion in this design is not a randomized treatment-effect contrast. The registry describes no allocation to different arms and lists allocation as not applicable. It does not report a planned comparative model or an adjusted effect estimate.

Open-label conduct is another design feature. General explanation: when treatment assignment is known, knowledge of treatment may influence subjective decisions or assessments. The registry lists masking as none. It does not report whether response assessments were reviewed by an independent committee, whether assessors were otherwise masked, or what steps were used to standardize imaging interpretation. The response definitions and imaging modalities are stated, but those details alone do not establish how consistently assessments were conducted.

How should the response definition be read?

Complete response requires complete disappearance of all evidence of disease. Partial response requires a > 50 percent (%) decrease in the sum of the products of maximal perpendicular diameters of measured lesions (SPD), and no new sites. The registry says lymph node measurements were taken from CT, the CT portion of PET/CT, or MRI where applicable. These criteria define the endpoint's classification rule; they do not provide the number of participants who met either category. The ORR estimate, CR and PR counts, and their subtype-specific breakdown are not reported in the registry record.

The record describes the analysis population for the primary outcome as all participants treated with daratumumab. General explanation: an analysis population specifies which participants contribute to an estimate. A treated-participant population may differ from an enrolled population if some enrolled participants did not receive treatment. The registry does not report the number treated, the number with evaluable responses, or how participants without response assessments were included. It is therefore not possible to determine from the record whether every enrolled participant contributed to the primary analysis.

What can the registry establish about the statistical plan?

The registry lists five outcome measures and names the primary endpoint and secondary outcomes. It does not report numerical results for these outcomes, and it does not report analysis results. The planned association between ORR and CD38 expression is described as an objective, but details such as the statistical model, expression measurement, handling of expression as a continuous or categorical measure, and method for selecting a threshold are not reported in the registry record. Without those details and results, the association and any proposed threshold cannot be evaluated.

General explanation: when a study examines multiple endpoints, subgroups, or candidate thresholds, many analyses can create opportunities for chance findings. Statistical methods may address this through prespecified testing strategies or other adjustments, but the appropriate approach depends on the design and questions. The registry record does not report a multiplicity plan, interim analyses, a sample-size justification, or a detailed statistical analysis plan. No specific procedure should be inferred from the Phase 2 label or from the presence of several outcome measures.

General explanation: over-dispersion is relevant when observed variability in count data exceeds what a simple statistical model expects. It can affect standard errors and confidence intervals if a model assumes less variability than is present. The primary endpoint is a participant-level response percentage, and no count-model method or over-dispersion assessment is reported in the registry record. Therefore, over-dispersion should not be presumed to have been present or to have affected the analysis. The information available supports explaining the endpoint definition and design, but not reconstructing the unreported analysis.

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("Diffuse Large B-cell Lymphoma (DLBCL)", "Follicular Lymphoma (FL)", "Mantle Cell Lymphoma (MCL)")
n      <- c(15, 16, 5)
events <- c(1, 2, 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  Diffuse Large B-cell Lymphoma (DLBCL)  15  1  6.7  0.2  31.9  1.2  29.8  1.6  30.2
ARM  Follicular Lymphoma (FL)  16  2  12.5  1.6  38.3  3.5  36.0  3.8  36.4
ARM  Mantle Cell Lymphoma (MCL)  5  0  0.0  0.0  52.2  0.0  43.4  0.4  45.9

11. Multiplicity, Missing Data and Analysis Populations

The registry lists ORR as the primary outcome and duration of response, progression-free survival, overall survival, and time to response as secondary outcomes. It also states an objective of assessing the association between ORR and CD38 expression and determining a threshold within each lymphoma subtype. The statistical plan for handling multiple outcomes, subtype-specific analyses, or threshold exploration is not reported in the registry record. It is therefore not possible to tell whether these analyses were confirmatory, exploratory, adjusted for multiple testing, or governed by a prespecified hierarchy.

General explanation: multiplicity arises when several statistical questions are examined. Without an appropriate plan, interpreting an isolated finding among many tests can overstate how compelling it is. The issue is particularly relevant when outcomes, subgroups, or possible biomarker thresholds are considered together. This is a general concern, not evidence that a particular analysis in this study produced a false-positive result.

The primary analysis population is described as all participants treated with daratumumab. How missing response assessments, withdrawals, or participants without evaluable imaging were handled is not reported in the registry record. The registry's primary-outcome timeframe includes progression, withdrawal of consent, or study end, but it does not state the number of participants with missing data or the method used to classify them. Missing-data assumptions can affect a response proportion, so the absence of this information limits assessment of the endpoint analysis.

The registry does not report a sample-size justification, interim-analysis plan, or detailed statistical analysis plan. The study is listed as terminated, but the reason and its implications for the planned analyses are not reported in the registry record. These omissions do not show that the analyses were inadequate; they mean the available record does not establish how multiplicity, missingness, or analysis populations beyond the stated treated-participant population were addressed.

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 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: pyrexia (40.0%), febrile neutropenia (20.0%), general physical health deterioration (20.0%), thrombocytopenia (6.7%), abdominal pain lower (6.7%).

The registry reports serious adverse-event figures separately for diffuse large B-cell lymphoma, follicular lymphoma, and mantle cell lymphoma. For diffuse large B-cell lymphoma, 6 participants were affected among 15 at risk; for follicular lymphoma, 6 were affected among 16 at risk; and for mantle cell lymphoma, 3 were affected among 5 at risk. These are group-specific counts, not comparisons with an untreated or alternative-treatment group. The record also reports deaths of 11, 3, and 4 participants in those groups, respectively. The cause, timing, and relationship of these deaths to treatment are not reported in the registry record.

The listed serious-event terms include pyrexia at 40.0%, febrile neutropenia at 20.0%, general physical health deterioration at 20.0%, thrombocytopenia at 6.7%, abdominal pain lower at 6.7%, and pneumonia at 6.7%. The registry does not report the denominator or whether a participant could contribute to more than one term in this list. These percentages should therefore be read as reported event-term figures, not as mutually exclusive categories or as a complete description of all adverse events.

General explanation: adverse-event counts describe events recorded during a study; they do not, on their own, establish that treatment caused an event. The single-group design provides no control rate for comparison, and the registry figures do not include a causal assessment. The numbers at risk also differ across lymphoma subtypes, so raw counts across groups should not be interpreted as directly comparable rates.

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

The registry record establishes that a Phase 2, open-label, single-group study was conducted to assess daratumumab in participants with relapsed or refractory mantle cell lymphoma, diffuse large B-cell lymphoma, and follicular lymphoma. It defines ORR as the percentage achieving complete or partial response and specifies the response criteria. It also describes an objective involving the relationship between ORR and CD38 expression. These registry entries explain the study question, but they do not show the observed response rate or whether a CD38 threshold was found.

The primary ORR result and its 95% confidence interval are not reported in the registry record. The record also does not report the counts of complete and partial responses, response results by subtype, or numerical findings for the listed secondary outcomes. Accordingly, the size and precision of the observed response estimate, and the pattern of outcomes across the three lymphoma subtypes, cannot be assessed from the registry information.

Even if a response proportion were available, the single-group design would describe outcomes among treated participants rather than estimate a randomized difference against a comparator. The open-label design and the unreported details about response review and missing assessments also limit what can be established about measurement and analysis. The reported serious adverse-event counts and deaths are descriptive safety information; they do not by themselves establish treatment causation or permit comparison with another treatment.

The study's terminated status is recorded, but the reason is not reported. That status should not be treated as an explanation for the absence of particular findings or as evidence about the study's results. The registry record is useful for identifying the design, intervention schedule, endpoint definitions, and some safety counts, while leaving key efficacy estimates and analysis details unavailable. It does not support a conclusion about comparative benefit or harm.

14. Why This Trial Matters Statistically

This trial illustrates an important distinction between defining an endpoint and reporting its result. The registry gives a clear operational definition of ORR: a participant must meet the complete-response or partial-response criteria, with partial response requiring a specified reduction in measured lesions and no new sites. Yet the numerical ORR, the response counts, and the confidence interval are not reported in the registry record. Without those quantities, readers cannot judge either the observed response proportion or its statistical precision.

The single-group design also clarifies what a study can and cannot answer. It can be structured to describe outcomes among treated participants, but it does not supply a randomized comparison with another intervention. That distinction matters when interpreting activity: an outcome proportion is not the same as a treatment-effect contrast. The open-label design adds another reason to consider how outcomes were assessed, while the registry does not describe independent response review or other assessment safeguards.

The study's three lymphoma subtypes and its CD38 objective raise questions about subgroup and biomarker analysis. Those questions require appropriate methods and careful interpretation, particularly when several outcomes or candidate thresholds are considered. The registry record does not report the relevant statistical plan or numerical CD38 findings, so no threshold or subtype-specific association can be assessed.

Finally, safety counts require context. The record gives serious-event figures and deaths by subtype, but no comparator or reported causal attribution. These numbers are descriptive, and their interpretation depends on denominators, follow-up, and event definitions. The record's mixture of defined endpoints, incomplete outcome reporting, and uncontrolled safety summaries makes this trial a useful example of why design, analysis, and reporting details must be read together.

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 for interpretation is that the registry record does not report the primary ORR estimate, its confidence interval, or the counts of complete and partial responses. It also does not report numerical results for the secondary outcomes or the planned CD38 association. The study's stated efficacy question therefore cannot be answered from the reported registry information.

The study had no comparator arm and was open-label. A single-group study cannot directly estimate a difference in outcomes against a concurrent control, and open-label conduct can matter when outcomes depend on assessment. The registry defines imaging-based response criteria but does not report whether assessments were independently reviewed or how assessment consistency was maintained.

The enrollment was 36, with safety denominators reported separately by lymphoma subtype. The registry does not report response counts by subtype or the number of treated participants with evaluable response assessments. It also does not describe how missing assessments or withdrawals were handled. Thus, the completeness of the primary analysis and the precision of any subtype-specific estimates cannot be evaluated.

The study is listed as terminated, but the reason for termination and its effect on planned analyses are not reported in the registry record. A sample-size justification, interim-analysis plan, detailed statistical analysis plan, and multiplicity approach are also not reported. These missing details constrain interpretation; they do not establish that a particular analysis was or was not performed. The safety figures lack a comparator and do not report the cause or treatment relationship of deaths, limiting causal interpretation of those counts.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: An Efficacy and Safety Proof of Concept Study of Daratumumab in Relapsed/Refractory Mantle Cell Lymphoma, Diffuse Large B-Cell Lymphoma, and Follicular Lymphoma — NCT02413489.
• Registry record last updated 2025-02-04; status last verified 2025-01.
• Results first posted 2018-06-26.
• 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

NCT02413489 is a Phase 2, open-label, single-group study of daratumumab in relapsed or refractory mantle cell lymphoma, diffuse large B-cell lymphoma, and follicular lymphoma. Enrollment was 36. The intervention schedule began with intravenous infusion at 16 milligram per kilogram [mg/kg] once every week for 8 weeks, then once every other week for 16 weeks, followed by once every 4 weeks until progression, unacceptable toxicity, or study end.

The primary outcome was ORR, defined as the percentage of treated participants achieving complete or partial response. The record lists duration of response, progression-free survival, overall survival, and time to response as secondary outcomes. It also describes an objective to assess the association between ORR and CD38 expression. Numerical efficacy results, the ORR confidence interval, and CD38 findings are not reported in the registry record.

The study status is terminated. The reason for termination and detailed statistical methods are not reported. Serious adverse-event counts and deaths are listed by lymphoma subtype, without a comparator or reported causal attribution.