Denintuzumab Mafodotin (SGN-CD19A) Combined With RCHOP or RCHP Versus RCHOP Alone in Diffuse Large B-Cell Lymphoma or Follicular Lymphoma: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Denintuzumab Mafodotin (SGN-CD19A) Combined With RCHOP or RCHP Versus RCHOP Alone in Diffuse Large B-Cell Lymphoma or Follicular Lymphoma (NCT02855359), a randomized phase 2 study. The primary outcome is Part B Outcome Measure: Complete Response Rate (CR).

2. Clinical Question

This clinical question concerns a proposed treatment comparison, not an estimate of treatment effect. Although the registry describes a randomized study, it does not report Part B outcome results, a complete response rate, or a comparative estimate. It therefore does not establish whether the groups differed on complete response. The planned secondary Part B outcomes included event-free survival, progression-free survival, overall survival, objective response rate at end of treatment, and duration of objective and complete response. Those outcomes also lack reported Part B comparisons in the registry record.

The study record describes two combination approaches in Part A: denintuzumab mafodotin with RCHOP and denintuzumab mafodotin with RCHP. Part B was described as denintuzumab mafodotin with RCHOP or RCHP compared with RCHOP alone. The registry does not report Part B results, so the intended comparison cannot be interpreted as an observed randomized treatment effect. The disease population, regimens, and planned endpoint describe the question the study set out to address; they do not fill the gap left by the unassessed endpoint.

3. Trial Design

This was a randomized, open-label phase 2 study with a parallel design. The registry lists enrollment of 24 and status as terminated. The study started in 2016-08, and primary completion is recorded as 2018-01. The reason for termination is not reported in the registry record.

The study plan had a Part A and a Part B. Part A included denintuzumab mafodotin with RCHOP and denintuzumab mafodotin with RCHP. Part B was intended to compare denintuzumab mafodotin with RCHOP or RCHP against RCHOP alone. The registry states that the study did not progress to Part B. Consequently, the Part B complete response endpoint was not assessed, and the planned Part B comparison is not available as a reported clinical outcome.

Open-label means that masking was not used, as also stated in the registry. Randomized allocation describes the intended assignment method, but the record does not report allocation details or how assignment was implemented. It also does not report the number assigned to each study group as a planned design feature. The safety record lists group-specific numbers at risk, which describe the safety summaries rather than a complete account of the allocation process.

The registry lists eight outcome measures and zero analyses. It identifies complete response rate in Part B as the primary outcome, while explicitly marking it as not assessed because the study did not reach Part B. Several secondary outcomes are also specified for Part B, including survival, response, and response-duration outcomes. Their presence in the registry describes planned measurement, not available results. The protocol details behind the study's termination and its design choices are not reported in the registry record.

4. Participant Flow and Accounting

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

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Endpoint not assessed; study did not progress to Part B.

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 Part B Outcome Measure: Complete Response Rate (CR), measured over N/A - Endpoint not assessed.

The primary outcome is identified as the Part B complete response (CR) rate. A response rate is generally the proportion of an assessed group that meets a defined response category under the study's evaluation criteria. Complete response is generally a stringent response category, but the specific assessment criteria and timing rules for CR are not reported in the registry record.

Response outcomes are used in clinical trials to describe whether participants meet prespecified criteria for improvement or disappearance of assessable disease. A complete response rate can be useful for comparing groups when the endpoint is measured consistently, the assessment population is defined, and the results are available for each group. The registry record does not report these group results for this endpoint.

Here, the outcome is explicitly marked “N/A - Endpoint not assessed,” and the description says the study did not progress to Part B. Therefore there is no reported CR rate to interpret, no group contrast, and no estimate of precision for the primary endpoint. The registry does not state a reason for the endpoint being unassessed beyond the study's failure to progress to Part B. Without an assessed endpoint, the intended complete response comparison cannot be reconstructed from the record.

CR rate should also be distinguished from the listed secondary outcomes. Event-free survival, progression-free survival, overall survival, objective response rate, and response duration describe different outcomes and require their own definitions and analysis. Their inclusion in the registry does not substitute for the unassessed primary endpoint or establish results for any Part B outcome.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What can randomization tell readers when the endpoint was not assessed?

Randomization is a method for assigning participants to study groups. In general, it is intended to make groups comparable with respect to measured and unmeasured characteristics on average, so that a properly conducted comparison can estimate the effect of assignment to the study regimens. It does not guarantee that every group characteristic will match, and it does not supply an outcome estimate by itself. For an estimate, the endpoint must be assessed and the results must be analyzed.

This registry describes the study as randomized, but it does not provide an assessed Part B complete response endpoint. Thus the randomization description cannot be used to infer a CR difference. Details such as allocation procedures and the analysis plan are not reported in the registry record. The open-label designation indicates that masking was not used; it does not tell readers whether outcome assessments were blinded, or how assessments were conducted. Those details are also not reported.

What does a response-rate comparison require?

In general, a response-rate analysis needs a defined response criterion, an assessment time, a population whose response status can be classified, and the outcome counts for the groups being compared. A comparison may then be expressed using a difference or another effect measure, with uncertainty described by a confidence interval and, where planned, a hypothesis test. The registry identifies CR rate as the primary Part B outcome but gives no CR counts, rates, effect estimate, confidence interval, or p-value. The endpoint is marked not assessed, so no response-rate comparison can be interpreted.

The registry also does not report the detailed CR criteria, response review procedures, or rules for handling participants whose response status could not be determined. These items matter because response classification and analysis choices affect the population and result being estimated. They cannot be reconstructed from the outcome title alone.

How should survival outcomes be understood?

In general, time-to-event outcomes measure the time until a defined event, such as progression or death, and often account for participants whose event has not occurred by the end of follow-up. Event-free survival, progression-free survival, and overall survival are distinct outcomes because their event definitions differ. A valid interpretation depends on the precise definitions, follow-up duration, censoring rules, and analysis method. The registry lists these outcomes for Part B but does not report their definitions or comparative analyses. No survival effect estimate can therefore be read from this record.

For time-to-event outcomes, statistical methods may use event counts and account for censored observations. In general, censoring occurs when a participant's event status is not observed through the end of the relevant follow-up, while some follow-up information remains available. The registry does not report the Part B follow-up or censoring details. It also does not report whether any survival analyses were performed.

What does the planning illustration represent?

The stated planning assumptions describe an illustration based on an observed effect, not the trial's own design justification. The assumptions use a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation; the effect to detect is a stated fraction of the observed effect. For time-to-event outcomes, the stated method gives the total number of events using the Schoenfeld approach; for other outcomes, it gives participants per arm.

These are planning assumptions, not observed trial findings and not observed power. A planning calculation asks what sample size may be needed under selected assumptions. It does not show that a trial with a particular enrollment had a given probability of detecting an effect, and it does not establish that an effect exists. Because the primary endpoint was not assessed and the registry record does not include an observed CR effect, no CR-based planning value can be interpreted as a study result. The trial's own sample-size justification is not reported in the registry record.

More generally, planning estimates depend on assumptions about the outcome, effect size, variability or event rate, allocation, significance level, and analysis method. If those assumptions differ from the eventual study conditions, the resulting illustration may not match the sample size needed in practice. A sample-size calculation also cannot repair the absence of outcome data or substitute for an analysis.

Why does over-dispersion matter in general?

For outcomes analyzed as counts, a statistical model may assume a particular relationship between the expected count and its variability. Over-dispersion means the observed variation is greater than that assumed by a simpler model. If it is ignored, standard errors may be understated and confidence intervals or tests may appear more precise than warranted. This is a general statistical consideration, not a reported feature of this study. The registry does not report a count-outcome analysis or a model assessment for over-dispersion.

Across all these methods, the key distinction is between a planned outcome and an analyzed outcome. The registry records a planned Part B primary endpoint and planned secondary outcomes, but explicitly says the study did not progress to Part B. The record reports no efficacy analyses. Statistical concepts can explain what an analysis would ordinarily require, but they cannot generate the missing trial estimates.

10. Multiplicity, Missing Data and Analysis Populations

The registry record does not report a statistical analysis plan or a multiplicity adjustment. Multiplicity arises when several outcomes, time points, or statistical tests are considered; in general, interpreting many tests can increase the chance of at least one apparently notable result by chance. Prespecified strategies can address that issue, but no such strategy is reported. The presence of several listed secondary outcomes does not establish how the investigators intended to control or interpret multiple comparisons.

The record lists event-free survival, progression-free survival, overall survival, objective response rate at end of treatment, and duration of objective and complete response as Part B secondary outcomes. It does not provide their analysis populations, missing-data rules, censoring rules, or multiplicity procedures. These methods are not reported in the registry record and should not be inferred from the outcome names.

The primary CR endpoint is marked not assessed because the study did not progress to Part B. That is different from a report that the endpoint was measured but some response values were missing. The registry does not describe Part B outcome data, so the extent or handling of missing endpoint values cannot be assessed. It also does not identify intention-to-treat, per-protocol, or other efficacy analysis populations. The safety group counts do not define the analysis population for the unassessed efficacy endpoint.

Without these details, readers cannot determine how participants would have been included in an efficacy analysis, how unavailable assessments would have been handled, or how multiple planned outcomes would have been interpreted. The absence of those details does not imply that a particular method was used; it means the method is not reported in the registry record.

11. 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: febrile neutropenia (23.1%), hypotension (9.1%), acute kidney injury (9.1%), asthenia (9.1%), cerebrovascular accident (9.1%).

The safety record reports serious adverse event counts for the two listed combination groups. For denintuzumab mafodotin plus RCHP, 11 were at risk and 5 were affected by serious adverse events; for denintuzumab mafodotin plus RCHOP, 13 were at risk and 4 were affected. The record also reports other adverse events in 11 of 11 at risk in the RCHP group and 13 of 13 at risk in the RCHOP group. These are descriptive counts; the registry does not report comparative statistical tests for these safety summaries.

The record lists febrile neutropenia at 23.1% and hypotension, acute kidney injury, asthenia, cerebrovascular accident, and palpitations at 9.1% each among the top serious adverse event terms. The registry record does not identify group-specific percentages for these terms, so they should not be assigned to one group. It also does not report the event-term definitions, follow-up duration, exposure-adjusted rates, or how the listed terms relate to the group-level counts.

Deaths are recorded as 2 in each group. The registry does not report causes, timing, or attribution to study treatment for these deaths. The counts alone cannot establish whether a death was related to treatment or whether the groups differed in risk. Differences in exposure or observation time could also affect crude counts, but those details are not reported. These safety summaries should be read as recorded events, not as a causal comparison or a conclusion about treatment effects.

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

This study record describes a randomized phase 2 investigation of denintuzumab mafodotin combined with RCHOP or RCHP in frontline therapy for DLBCL or FL grade 3b. It also specifies a planned Part B comparison with RCHOP alone. Its primary Part B outcome, complete response rate, was not assessed because the study did not progress to Part B. The record therefore does not provide a comparative efficacy result for that endpoint.

That absence should not be interpreted as evidence of no effect, equivalence, or a difference between regimens. Those conclusions require outcome data and an analysis. The record does not report CR rates, effect estimates, confidence intervals, p-values, or Part B analyses of the listed secondary outcomes. It cannot establish whether the intended groups differed in response or survival, or how precisely any such difference might have been estimated.

The registry does provide descriptive safety counts for the two combination groups and records deaths in both. These observations are relevant to understanding what the safety record contains, but they do not establish treatment causality or a comparative safety effect. The record does not report causes of death, attribution, follow-up duration, or a statistical comparison of safety outcomes.

The study's termination is recorded, but the reason is not reported. It should not be assumed that termination reflected efficacy, harm, recruitment, or any other specific cause. The enrollment and safety summaries do not explain why the study stopped or what decisions were made during conduct.

In general, a registry can document a study's intended question, design, and planned endpoints even when outcome results are unavailable. Here, it records the planned clinical comparison but also makes clear that the primary Part B endpoint was not assessed. The sound interpretation is therefore limited: the proposed efficacy comparison remains unanswered by the results reported in the registry record.

13. Why This Trial Matters Statistically

This study is statistically informative because it illustrates the distinction between a registered clinical question and an answered clinical question. The record names a randomized, open-label phase 2 design and a primary Part B endpoint, but it also states that the study did not reach Part B. Without an assessed primary endpoint, the intended treatment comparison cannot yield a reported efficacy estimate.

That distinction matters when readers encounter planned endpoints alongside safety counts or enrollment information. Design labels and endpoint listings describe how a study was intended to proceed. They do not by themselves demonstrate that an outcome was collected, that a comparison was performed, or that an effect was estimated. The record's explicit “not assessed” status is essential to interpreting the study accurately.

The study also makes clear why results need more than a point estimate. A comparative analysis ordinarily requires a defined analysis population, an outcome estimate, and information about uncertainty. For survival outcomes, definitions and follow-up methods are also important; for response outcomes, assessment criteria and handling of unavailable assessments matter. These details are not reported for Part B in this registry record. General statistical methods can explain their role, but cannot replace missing trial results.

Finally, the safety summaries have a different role from efficacy analyses. They document counts and selected serious adverse event terms, but they do not explain the unassessed primary endpoint or establish why the trial terminated. Keeping these strands separate helps prevent descriptive safety data from being mistaken for a comparative efficacy result. The main statistical lesson is not a treatment conclusion, but a careful boundary on what can be inferred from the available record.

14. 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 that the study did not progress to Part B, so its primary CR endpoint was not assessed. The registry does not report comparative efficacy results for the planned Part B groups. The reason for termination is not reported, which prevents interpretation of why the study ended or whether any particular consideration influenced that decision.

The registry describes a randomized, open-label, parallel phase 2 study, but does not report allocation procedures, group assignment details, or the study's own sample-size justification. It lists enrollment of 24, but this does not establish how many participants would have contributed to any particular efficacy analysis. The record lists zero analyses and does not identify an efficacy analysis population.

Outcome details are limited. The specific CR criteria and assessment procedures are not reported, nor are the definitions and analysis methods for the listed Part B secondary outcomes. The registry does not report confidence intervals, p-values, or effect estimates for efficacy. It also does not report missing-data rules, censoring methods, or a multiplicity strategy.

The safety information is descriptive and does not include reported group-specific attribution for the listed serious adverse event terms. The record does not provide the timing or cause of deaths, treatment attribution, follow-up duration, or exposure-adjusted event rates. These gaps limit interpretation of the safety counts and do not support causal or comparative conclusions. All of these limitations concern information not reported in the registry record; they should not be filled with assumptions.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Denintuzumab Mafodotin (SGN-CD19A) Combined With RCHOP or RCHP Versus RCHOP Alone in Diffuse Large B-Cell Lymphoma or Follicular Lymphoma — NCT02855359.
• Registry record last updated 2019-03-11; status last verified 2019-02.
• Results first posted 2019-01-08.
• 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.

18. Record Summary

The registry describes NCT02855359 as a randomized, open-label, parallel phase 2 study of denintuzumab mafodotin combined with RCHOP or RCHP for frontline therapy in DLBCL or FL grade 3b. RCHOP alone was the planned Part B comparator. The record lists enrollment of 24 and status as terminated.

The primary Part B outcome was complete response rate, but it was not assessed because the study did not progress to Part B. The registry lists eight outcome measures and zero analyses. Part B secondary outcomes include event-free survival, progression-free survival, overall survival, objective response rate, and response duration, without reported comparative results.

Safety information includes group-level counts for serious and other adverse events, selected serious adverse event terms, and deaths. The reason for termination, efficacy analysis methods, and the trial's sample-size justification are not reported in the registry record. The record documents the intended study question but does not provide an answer to its planned Part B efficacy comparison.