Clinical Study With Blinatumomab in Patients With Relapsed/Refractory Diffuse Large B-cell Lymphoma (DLBCL): Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Clinical Study With Blinatumomab in Patients With Relapsed/Refractory Diffuse Large B-cell Lymphoma (DLBCL) (NCT01741792), a na phase 2 study. The primary outcome is Overall Objective Response Rate During Treatment Cycle 1.

2. Clinical Question

The study asked whether blinatumomab had antitumor activity, and what safety events were observed, in patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL). Its primary endpoint was the percentage of participants whose best overall response during the first treatment cycle was a complete response or partial response, assessed during the first 8 weeks.

3. Trial Design

This was an open-label, multicenter, exploratory Phase 2 study of blinatumomab in patients with relapsed/refractory DLBCL. The registry lists the study as completed, with enrollment of 25. The recorded start was 2012-07 and the primary completion was 2014-07. Amgen Research (Munich) GmbH is listed as the sponsor.

The design is classified as single-group, with allocation recorded as NA and masking recorded as NONE. There was no independent untreated or active-control arm. The registry describes two dose regimens. Stage 1, Cohort 1 used a stepwise regimen: 9 µg/day during the first week, followed by 28 µg/day during the second week, then 112 µg/day for the remaining 6 weeks of treatment during cycle 1. Cohort 2 is identified as receiving 112 µg/day. The available description of the regimen for Cohort 3 is incomplete in the registry record, so further dosing details are not reported in the registry record.

Because treatment was not randomized against a control, comparisons among the listed cohorts should not be read as controlled treatment comparisons. Differences between cohorts could reflect factors other than dose regimen, and the record does not provide enough detail to assess such factors. The study's exploratory Phase 2 designation describes its stated development stage, but the registry record does not report a formal sample-size justification or a protocol-based statistical plan.

The listed secondary outcomes include complete and partial response, duration of objective response, duration of complete and partial response, progression-free survival, overall survival, and adverse events. Their presence identifies additional outcomes of interest; numerical results for these endpoints 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.

Before assignment: The study was conducted sequentially in 2 stages and 3 cohorts: In Stage 1, Cohort 1 received an escalating dose of 9/28/112 µg/day blinatumomab and Cohort 2 received a constant dose of 112 µg/day for 8 weeks. In Stage 2, the Cohort 3 dose regimen was determined from the outcome of Cohorts 1 and 2.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Efficacy Set includes all participants who completed at least 7 days of infusion on the highest intended dose level.

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 Objective Response Rate During Treatment Cycle 1, measured over During the first 8 weeks.

The primary endpoint is the overall objective response rate during treatment cycle 1. It is defined as the percentage of participants whose best overall response was complete response (CR) or partial response (PR), with evaluation during the first 8 weeks. A complete response means disappearance of all evidence of disease. A partial response means regression of measurable disease with no new sites.

Response was assessed according to Cheson criteria by a central reader. The registry describes use of computerized tomography (CT) and positron emission tomography (PET) to assess nodal disease or organ enlargement due to nodal or diffuse infiltration, and bone marrow biopsy to assess bone marrow infiltration. Central review provides an assessment method distinct from an individual treating clinician's judgment, although the record does not describe reviewer blinding.

As a general statistical concept, an objective response endpoint reduces a complex clinical course to a defined binary outcome for each participant: response or no response under the stated criteria. The resulting proportion describes how often the defined outcome occurred in the analysis population. It does not by itself describe how long a response lasted, whether disease later progressed, or survival. Those topics appear as separate secondary outcomes in the registry.

The registry record gives the endpoint definition and its 95% confidence interval as the stated measure of precision, but does not report the numerical response estimate or confidence interval bounds. The observed response proportion and its precision therefore cannot be interpreted from the endpoint description alone.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The main outcome is a proportion: participants are classified according to whether they met the response definition, and the percentage meeting it is the overall objective response rate. The endpoint combines complete response and partial response, while the registry also lists those response categories separately as secondary outcomes. A binary endpoint is straightforward to describe, but the definition of the eligible analysis population and the response-assessment rules are essential to interpreting the resulting proportion.

What does the confidence interval add?

In general, a confidence interval expresses the statistical uncertainty around an estimate. It gives a range of values compatible with the data and the method used, rather than a guarantee that the underlying value lies within that range. Intervals are commonly wider when the information available is less precise. The registry identifies a 95% confidence interval for the primary endpoint, but its bounds are not reported in the registry record. No statement about the width or precision of the study's response estimate can therefore be made.

How was response defined?

The best overall response during the first treatment cycle was assessed within the first 8 weeks, using Cheson criteria and central review. Complete response requires disappearance of all evidence of disease; partial response requires regression of measurable disease with no new sites. CT and PET were used to assess nodal disease or organ enlargement due to nodal or diffuse infiltration, while bone marrow biopsy was used to assess bone marrow infiltration. These criteria make the endpoint more specific than an undefined judgment of improvement. The registry does not report additional operational details, such as how unevaluable assessments were handled.

What is the role of the analysis population?

The primary efficacy set includes participants who completed at least 7 days of infusion on the highest intended dose level. This definition ties inclusion to treatment exposure. As a general statistical principle, changing who is included can change the estimated proportion, especially when inclusion depends on events occurring after treatment starts. The record does not state the size of this efficacy set, give a participant flow accounting, or describe how missing or incomplete response assessments were handled. Those matters are not reported in the registry record.

Why does the design affect interpretation?

A single-group study estimates outcomes among participants receiving the study treatment, but it does not directly estimate a treatment contrast against a concurrent control. A treatment contrast requires outcomes under both treatment strategies in groups suitable for comparison. This record has no separate control group, and the cohorts represent blinatumomab regimens. The registry explicitly notes that the arms are not a like-for-like control comparison. Accordingly, cohort differences should not be interpreted as randomized evidence of a dose effect.

General statistical reasoning also distinguishes association from causal effect. In a non-randomized, single-group design, patient characteristics, disease course, assessment timing, or other factors may influence observed outcomes. The record does not provide analyses that adjust for such factors, and the number of registered analyses is 0. That registry entry does not establish what analyses may have been conducted elsewhere; details beyond the record are not reported in the registry record.

How should the planning illustrations be read?

The planning illustrations use stated assumptions of a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. They define the effect to detect as a stated fraction of the observed effect. In general, such calculations describe how much information a hypothetical design might require under specified assumptions; they do not describe the information actually observed in this single-group trial. The record says these are planning illustrations computed from the observed effect, not the trial's own design. They must not be interpreted as observed power or as evidence that the study was designed to achieve a particular power.

The illustrations are based on a two-arm planning setup even though the study is recorded as single-group. The sample-size assumptions therefore describe a hypothetical comparison, not the trial's actual allocation. The record does not report a protocol-based sample-size justification, and no such rationale should be inferred from the illustrations. For time-to-event outcomes, the stated convention is a total number of events; for other outcomes, it is participants per arm. These conventions describe the planning calculations, not observed trial results.

What can be said about over-dispersion?

As a general concept, over-dispersion arises when observed variation is greater than a statistical model expects. It matters because a model that understates variability can produce uncertainty estimates that are too narrow. The primary endpoint is a participant-level binary response proportion, and the registry does not report a model-based analysis or a method for addressing over-dispersion. There is therefore no basis to claim that over-dispersion was assessed or corrected for this endpoint.

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("Cohort 1: Blinatumomab 9/28/112 μg/d", "Cohort 2: Blinatumomab 112 μg/d", "Cohort 3: Blinatumomab 9/28/112 μg/d")
n      <- c(7, 1, 13)
events <- c(4, 1, 4)
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  Cohort 1: Blinatumomab 9/28/112 μg/d  7  4  57.1  18.4  90.1  25.0  84.2  24.5  84.3
ARM  Cohort 2: Blinatumomab 112 μg/d  1  1  100.0  2.5  100.0  20.7  100.0  15.8  98.7
ARM  Cohort 3: Blinatumomab 9/28/112 μg/d  13  4  30.8  9.1  61.4  12.7  57.6  12.8  58.1

11. Multiplicity, Missing Data and Analysis Populations

The registry lists one primary endpoint and multiple secondary outcomes, including complete response, partial response, response duration, progression-free survival, overall survival, and adverse events. When several outcomes or comparisons are tested, the chance of finding at least one apparently notable result can increase. As a general statistical practice, a plan may define which outcome is primary and whether or how testing across outcomes is controlled. The registry record does not report a multiplicity-adjustment procedure, a testing hierarchy, or an analysis plan for the secondary outcomes. No adjustment method should be assumed.

The registry lists 0 analyses. This means numerical analyses are not registered in the record; it does not establish that no analysis was conducted. The numerical primary outcome, its confidence interval, and numerical results for the secondary outcomes are not reported in the registry record.

The primary efficacy population is defined by completing at least 7 days of infusion on the highest intended dose level. The number meeting this definition, participant flow into the analysis set, missing response data, and the method for handling missing assessments are not reported in the registry record. A missing-data strategy matters because excluding participants with unavailable outcomes can affect the interpretation of a response proportion, depending on why outcomes are unavailable.

The record does not report whether interim analyses were planned or conducted, nor does it give details of any missing-data sensitivity analyses. Those details cannot be inferred from the endpoint definition or the completed status.

12. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

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: agranulocytosis (50.0%), bone marrow toxicity (50.0%), neutropenia (50.0%), pyrexia (50.0%), pneumonia (50.0%).

The safety listings distinguish participants at risk from participants affected by serious adverse events and other adverse events. For Cohort 1, the serious-event figures are 9 at risk and 9 affected; for Cohort 2, 2 and 2; for Cohort 3, 14 and 12; for Cohorts 1+3, 23 and 21; and for the overall group, 25 and 23. The corresponding figures for other adverse events are 9 and 9, 2 and 2, 14 and 14, 23 and 23, and 25 and 25.

These are descriptive counts for the listed groups, not comparisons against a control group. The registry also lists Agranulocytosis, Bone marrow toxicity, Neutropenia, Pyrexia, Pneumonia, and Drug administration error among the top serious terms, each reported as 50.0%. The denominator or calculation basis for those percentages is not specified in the registry record, so they should not be treated as participant-level rates without further information. Death counts are not reported in the registry record; their absence from the listing does not establish that no deaths occurred.

In general, adverse-event counts describe events recorded under a study's reporting procedures. They do not on their own establish causation or comparative risk. The record does not provide a control group for that purpose.

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

The registry record establishes that this was a completed, open-label, exploratory Phase 2 study of blinatumomab in relapsed/refractory DLBCL, with a single-group design and enrollment of 25. It defines the primary endpoint as the percentage of the efficacy population with complete or partial response during the first treatment cycle, assessed during the first 8 weeks. It also describes central review, the response criteria, and imaging and biopsy methods.

However, the numerical primary response result and its 95% confidence interval are not reported in the registry record. The record therefore does not establish the observed response percentage or its precision. It also does not report numerical results for the listed secondary efficacy outcomes. The safety listings provide counts for affected participants and report several serious adverse-event terms as 50.0%, but the basis for those term percentages is not specified.

The single-group design is important: the study's recorded outcomes cannot be contrasted with a concurrent control group, and the cohorts are not a like-for-like control comparison. The record alone cannot establish that any observed outcome was caused by blinatumomab or determine how it compares with another treatment. Nor can it establish outcomes for patients outside the defined efficacy population.

In general, an endpoint definition, an observed estimate, and a comparison answer different questions. The definition explains what was measured; the estimate describes what was observed; and a suitable comparative design is needed to estimate a treatment contrast. The registry record gives the first, but not the numerical primary result or a controlled comparison. Conclusions should remain limited to those details.

14. Why This Trial Matters Statistically

This trial illustrates why design and outcome reporting must be read together. The primary endpoint is defined in operational terms: response was assessed by central review using Cheson criteria, with CT, PET, and bone marrow biopsy contributing to disease assessment. That definition clarifies what the study intended to count as a response, but without the numerical estimate and confidence interval it does not reveal how often the endpoint occurred or how precisely it was estimated.

The study also illustrates the limits of single-group evidence. A response proportion can describe the treated study population, but it is not a comparative effect. The absence of a control group means the registry cannot support a direct contrast with another treatment, and the dose cohorts are not a like-for-like control comparison. This distinction remains important even when a study has a clearly defined endpoint and safety listings.

Finally, the efficacy-population definition and incomplete reporting of analysis details matter to interpretation. The primary population is restricted to participants who completed at least 7 days of infusion on the highest intended dose level, while its size and the handling of missing assessments are not reported in the registry record. The listed planning assumptions concern a hypothetical two-arm design, not the actual single-group trial. These features show why design descriptions, analysis populations, uncertainty estimates, and numerical results are all needed to assess the strength and scope of clinical evidence.

15. Limitations

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

Several limitations are specific to the information recorded for this study. The primary endpoint is defined, but its numerical response estimate and 95% confidence interval are not reported in the registry record. The size of the primary efficacy population is also not reported, so enrollment of 25 should not be mistaken for the number included in that analysis.

The study is classified as single-group, with no control arm. Its listed cohorts represent blinatumomab regimens and do not provide a like-for-like control comparison. The study is open-label, and the registry record does not describe reviewer blinding. These design features limit comparative interpretation.

The available description of Cohort 3's dosing is incomplete. The record does not report the handling of missing response assessments, participant flow into the efficacy set, or a numerical sample-size justification. It lists no registered analyses, but does not provide enough information to determine what analyses may have been performed outside the registry record. Multiplicity procedures, interim analyses, and statistical details for the secondary outcomes are not reported in the registry record.

Safety data are presented as affected and at-risk counts by group, alongside serious-event terms with percentages. The denominator or calculation basis for those term percentages is not specified, and death counts are not reported. These omissions limit interpretation of the safety listings and prevent an assessment of comparative safety.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Clinical Study With Blinatumomab in Patients With Relapsed/Refractory Diffuse Large B-cell Lymphoma (DLBCL) — NCT01741792.
• Registry record last updated 2017-01-06; status last verified 2016-11.
• Results first posted 2015-07-27.
• 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

NCT01741792 is a completed, open-label, multicenter, exploratory Phase 2 single-group study of blinatumomab in relapsed/refractory DLBCL. Enrollment was 25; the recorded start was 2012-07 and primary completion was 2014-07. Amgen Research (Munich) GmbH is listed as sponsor.

The primary endpoint was overall objective response rate during the first treatment cycle, assessed during the first 8 weeks. The efficacy set included participants who completed at least 7 days of infusion on the highest intended dose level. The registry defines response using complete or partial response under Cheson criteria and specifies central review with imaging and bone marrow assessment.

The numerical primary result and confidence interval, secondary outcome results, efficacy-set size, missing-data methods, and death counts are not reported in the registry record. Safety listings include adverse-event counts by group and several serious-event terms reported as 50.0%, without a stated denominator for those percentages. The single-group design does not provide a concurrent control comparison.