A Phase 1b Open-Label Study Investigating the Safety and Pharmacokinetics of Administration of Subcutaneous Blinatumomab for the Treatment of Relapsed/Refractory Indolent Non-Hodgkin's Lymphoma: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Phase 1b Open-Label Study Investigating the Safety and Pharmacokinetics of Administration of Subcutaneous Blinatumomab for the Treatment of Relapsed/Refractory Indolent Non-Hodgkin's Lymphoma (NCT02961881), a na phase 1 study. The primary outcome is Number of Participants With Dose Limiting-Toxicities (DLTs) After SC Administration.

2. Clinical Question

3. Trial Design

This was a Phase 1b, open-label, single-group study investigating the safety and pharmacokinetics of SC blinatumomab for relapsed or refractory indolent non-Hodgkin's lymphoma. The registry records 35 participants enrolled, a start date of 2017-09-18, primary completion on 2021-09-02 and a completed status. Amgen is listed as the sponsor. No masking was used, and allocation is listed as not applicable.

The study included SC cohorts and cIV treatment periods before and after SC treatment. The registry's adverse-event group labels include cIV before SC Week 1, Week 2 and Week 3; SC Cohorts 1 through 5; cIV after SC; and totals for SC, cIV and SC plus cIV. These labels describe the posted safety groups, but the record does not establish that they were randomized groups or comparable arms. The study's single-group design does not support interpreting differences between these labels as causal treatment effects.

The primary objective was evaluation of SC safety and tolerability. Secondary objectives included pharmacokinetics for cIV and SC administration, estimation of the maximum tolerated dose tested for SC administration, anti-blinatumomab antibody incidence after SC administration and efficacy response. Exploratory objectives included pharmacodynamic time profiles for B- and T-lymphocytes and cytokines, as well as response evaluation using Lugano criteria if PET/CT was used.

The registry lists 17 outcome measures, including pharmacokinetic measures such as steady-state serum concentration and clearance after cIV administration, and concentration, exposure and apparent disposition measures after SC administration. The primary endpoint result and registry analyses are not reported in the registry record. Details such as the full protocol, treatment dose levels, eligibility criteria and statistical analysis plan are also not reported in the registry record.

4. Participant Flow and Accounting

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

Before assignment: The participants underwent an initial continuous intravenous (cIV) blinatumomab run-in period (Weeks 1 to 3). The participants received subcutaneous (SC) administration at Week 4 followed by a treatment free period of 2 to 3 days. After the SC administration period, participants received cIV treatment to complete 6 weeks of therapy (Weeks 5 to 6).

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: DLT analysis set included DLT-evaluable participants who received all (q48h dosing), \>/= 4/5 (q24h dosing) or \>/= 8/9 (q12h dosing) doses of SC blinatumomab or experienced a DLT during the DLT evaluable period.

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 enrolled participants.

6. Primary Endpoint

The registry lists the primary outcome as Number of Participants With Dose Limiting-Toxicities (DLTs) After SC Administration, measured over Day 1 to Day 7 of Week 4.

The primary endpoint counts participants with dose-limiting toxicities after SC blinatumomab administration. The specified evaluation window is Day 1 to Day 7 of Week 4. A DLT was defined through a set of qualifying toxicities judged by the investigator to be related to blinatumomab administration. The listed criteria include death, toxicity leading to removal from the study, persistent intolerable grade 2 non-hematologic adverse events that did not respond to appropriate management within 5 days and led to treatment discontinuation, recurrent grade 2 seizures, and grade 3 or 4 adverse events or laboratory abnormalities, subject to protocol exceptions.

This endpoint is used in early-phase safety evaluation because counting participants with qualifying toxicities gives a direct summary of how many DLT-evaluable participants experienced events that meet the study definition during the specified period. It can inform evaluation of tolerability and the maximum tolerated dose tested, both stated study objectives. It does not capture every aspect of safety: the endpoint is limited by its definition, evaluation window and analysis population.

Eligibility for the DLT analysis set depended on dosing schedule. Participants qualified if they received all doses for q48h dosing, at least 4/5 doses for q24h dosing, or at least 8/9 doses for q12h dosing, or if they experienced a DLT during the DLT-evaluable period. The primary DLT count or result is not reported in the registry record, so the number of participants meeting the endpoint cannot be stated from this record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary endpoint is a count of participants meeting a binary event definition: each DLT-evaluable participant either experienced a qualifying DLT during the specified period or did not. The registry labels the endpoint as the number of participants with DLTs after SC administration. It does not report the primary count or an analysis estimate. No analysis method for the primary endpoint is reported in the registry record.

What does a participant count tell us?

A count communicates how many people in an analysis group experienced an event, but it needs context. The number at risk gives the size of the group being described. The event definition determines what is counted, and the observation window determines when events qualify. Counts from groups of different sizes cannot be compared as if they represented the same amount of information. General statistical explanation: a proportion can express the event count relative to the group at risk, while an interval estimate can describe uncertainty in that proportion. No primary DLT proportion or confidence interval is reported in the registry record, and no new values should be inferred from the counts.

Why is the analysis population important?

The DLT analysis set includes participants who received the required number of doses for their schedule or experienced a DLT during the DLT-evaluable period. The stated requirements differ by schedule: all doses for q48h dosing, at least 4/5 for q24h dosing, or at least 8/9 for q12h dosing. The rule that a participant who experienced a DLT could qualify even without meeting the dose requirement is part of the population definition. This matters because the endpoint result depends on which participants are included. The registry does not report how many participants were in the DLT analysis set.

What does the single-group design allow?

The trial is listed as single-group, with no masking and allocation not applicable. The cIV and SC periods and cohorts in the adverse-event record are not a randomized control comparison. General statistical explanation: random allocation can support a balanced comparison of groups, while a single-group study chiefly describes outcomes in the people treated and observed. Differences across the named periods or cohorts may reflect differences in participants, sequence, exposure or observation. They cannot by themselves isolate an effect of route or establish a causal contrast.

How should pharmacokinetic outcomes be understood?

The listed secondary outcomes include steady-state serum concentration and systemic clearance after cIV administration, and maximum concentration, time to maximum concentration, area under the concentration-time curve for a dosing interval, minimum concentration, apparent clearance and apparent volume of distribution after SC administration. These outcomes describe drug concentration over time and related measures of exposure or disposition. The registry lists these outcomes, but their numerical results and analysis methods are not reported in the registry record. The pharmacokinetic objectives should therefore be distinguished from the primary DLT endpoint and from the adverse-event summaries.

What can be said about planning assumptions?

The record describes a planning illustration based on an observed effect, with a two-sided significance level of 0.05, equal allocation between two arms, a normal approximation and an effect specified as a fraction of the observed effect. It also distinguishes the event total used for time-to-event planning from participants per arm for other outcomes. These assumptions describe a planning exercise, not the design of this single-group trial. The record does not report a trial-specific sample-size justification or a numerical planning result in the information available for this analysis. A planning calculation is not observed power and does not add evidence about the outcomes actually observed.

General statistical explanation: power calculations estimate the sample size needed under stated assumptions to detect a specified effect at a chosen significance level. They depend on the assumed effect and variability, among other factors. They do not demonstrate that a study had a particular probability of finding a true effect after data collection. The record does not report an interim analysis plan, stopping rule or trial-specific power calculation.

The registry lists 17 outcome measures and 0 analyses. This means the record contains no posted inferential analysis results in the information, including no reported p-values or confidence intervals for the primary endpoint. The statistical analysis plan, any adjustment for multiple outcomes and methods for missing data are not reported in the registry record. Without those details and the primary endpoint result, the event summaries cannot be expanded into inferential claims about treatment effects.

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("Blinatumomab SC Cohort 1", "Blinatumomab SC Cohort 2", "Blinatumomab SC Cohort 3", "Blinatumomab SC Cohort 4", "Blinatumomab SC Cohort 5")
n      <- c(6, 6, 7, 6, 5)
events <- c(0, 1, 1, 0, 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  Blinatumomab SC Cohort 1  6  0  0.0  0.0  45.9  0.0  39.0  0.4  41.0
ARM  Blinatumomab SC Cohort 2  6  1  16.7  0.4  64.1  3.0  56.4  3.7  57.9
ARM  Blinatumomab SC Cohort 3  7  1  14.3  0.4  57.9  2.6  51.3  3.2  52.7
ARM  Blinatumomab SC Cohort 4  6  0  0.0  0.0  45.9  0.0  39.0  0.4  41.0
ARM  Blinatumomab SC Cohort 5  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 17 outcome measures spanning the primary DLT endpoint, pharmacokinetic outcomes, antibody formation, response, and exploratory pharmacodynamic measures. The registry record lists 0 analyses. It does not report how the study handled multiplicity across these outcomes, whether a hierarchy of testing was used, or whether any outcomes were considered descriptive only. The statistical analysis plan is not reported in the registry record.

General statistical explanation: when many outcomes are tested, the chance of at least one apparently notable result can rise if each is judged separately. Prespecified outcome ordering or adjustment methods can address that issue, but the registry record does not identify such methods. No p-values or inferential results are reported in the record for evaluating this question.

The DLT analysis set is defined by dosing requirements or by experiencing a DLT during the DLT-evaluable period. The number of participants in that set and the primary endpoint result are not reported in the registry record. The analysis populations for the other outcomes are not reported in the registry record.

Missing-data methods, the amount of missing outcome data, and any sensitivity analyses for missingness are not reported in the registry record. General statistical explanation: missing-data handling can affect which participants contribute to an estimate, especially when outcome availability is related to health status or treatment exposure. Without the analysis population, missingness information and analysis method, the extent to which incomplete data could affect the posted findings cannot be assessed. The record also does not report an interim analysis plan or a statistical strategy for stopping or selecting outcomes.

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: erosive oesophagitis (14.3%), aphasia (14.3%), seizure (14.3%), hallucination (14.3%), nervous system disorder (11.4%).

The safety groups include counts of participants at risk and participants affected by serious adverse events or other adverse events. For the SC total, 31 participants were at risk; 2 were affected by serious adverse events and 24 by other adverse events. For the cIV total, 35 were at risk; 18 were affected by serious adverse events and 34 by other adverse events. For the SC plus cIV total, 35 were at risk; 19 were affected by serious adverse events and 35 by other adverse events. These are the registry's descriptive group counts.

The cIV and SC total groups are not randomized arms. Participants may contribute across treatment periods, so the totals are not independent samples and should not be used as a direct comparison of route-specific risk. The record lists 2 deaths in the cIV total and 2 in the SC plus cIV total; the cIV-before-SC Week 1 and cIV-after-SC groups each list 1 death. The SC total lists 0 deaths. The registry counts do not by themselves establish cause or treatment relatedness.

The listed serious-event terms include erosive oesophagitis, aphasia, seizure and hallucination at 14.3% each; nervous system disorder at 11.4%; and cytokine release syndrome at 7.1%. The denominator and event-term calculation details are not reported in the registry record. These percentages should not be interpreted as treatment-specific risks without that information. Serious adverse events are not interchangeable with DLTs: the DLT endpoint has its own definition, attribution criterion and evaluation window.

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

The registry record establishes that this completed Phase 1b study evaluated SC blinatumomab in a single-group, open-label design, with safety and pharmacokinetics among its objectives. It records enrollment of 35 participants and describes a DLT endpoint for Day 1 to Day 7 of Week 4. It also reports adverse-event counts across cIV periods, SC cohorts and combined totals. Those are descriptive details about the study and the posted safety groups.

The primary DLT count is not reported in the registry record. Consequently, the record does not show how many DLT-evaluable participants experienced a DLT. Nor does it provide a numerical result for the stated secondary objectives concerning pharmacokinetics, maximum tolerated dose, anti-blinatumomab antibodies or efficacy response. The listed efficacy objective does not itself establish that a response occurred.

Because the study was single-group and open-label, the reported adverse-event groups cannot be treated as randomized treatment arms. Differences among cIV and SC group counts do not demonstrate that one route caused more or fewer events. The counts also do not establish whether any event was related to treatment unless the applicable assessment is stated; the registry's DLT definition specifically required investigator judgment of relatedness, but the DLT result itself is absent.

General statistical explanation: descriptive findings characterize the participants and events observed, whereas an estimate of a comparative treatment effect requires a suitable comparison and a defined analysis. Precision also matters; a point estimate without an uncertainty interval cannot show how uncertain the estimate is. The registry record does not report the primary endpoint estimate, its precision or an inferential comparison.

The study therefore contributes a description of its design, endpoints and posted safety counts, but the registry record does not support a conclusion about the primary DLT outcome, comparative safety, efficacy or the effect of SC rather than cIV administration. Absence of a result in the registry record is not evidence that no events occurred or that an outcome was favorable or unfavorable.

14. Why This Trial Matters Statistically

This study is statistically notable for the distinction between an early-phase safety question and a controlled treatment comparison. Its primary endpoint is a count of participants with qualifying DLTs after SC administration during a defined evaluation period. That kind of endpoint is suited to describing safety and tolerability in an early-phase setting, but interpretation depends on the DLT definition, the evaluation window and the DLT-evaluable population.

The DLT population rule makes the analysis set especially relevant. Participants qualified based on schedule-specific dose completion or experiencing a DLT. The registry does not report the size of that set or the DLT count, so readers cannot assess the observed endpoint or its precision from the record. This illustrates why an endpoint definition alone is not a result.

The study also includes cIV and SC periods and several SC cohorts. Their presence may be useful for organizing the safety and pharmacokinetic observations, but the single-group, open-label design does not make them randomized comparisons. Statistical interpretation must keep descriptive safety summaries separate from causal claims. The adverse-event counts are informative as posted observations, while differences across groups are not isolated treatment effects.

Finally, the objectives span safety, pharmacokinetics, antibodies, efficacy and exploratory pharmacodynamics. The registry lists 17 outcome measures but reports 0 analyses. Without the analysis plan, multiplicity approach, missing-data methods and outcome results, it is not possible to evaluate a full inferential evidence package. The record's value lies in clarifying the study structure and stated questions, while also making clear which results are not reported.

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 primary endpoint result is not reported in the registry record. The number of participants in the DLT analysis set is also not reported, limiting interpretation of the stated safety question. Although the record defines the DLT evaluation window and qualifying toxicities, it does not provide the observed DLT count or a measure of its precision.

The design was single-group and open-label, with allocation listed as not applicable and masking as none. There is no randomized control group. The cIV periods and SC cohorts in the safety summaries should therefore not be treated as comparable arms. Their counts may reflect different treatment periods or group composition, and the registry information does not support causal comparisons among them.

The registry record does not report detailed eligibility criteria, dose levels, the full protocol, a statistical analysis plan, interim analyses, missing-data methods or multiplicity handling. It also does not report numerical findings for the listed pharmacokinetic, antibody, efficacy or exploratory outcomes. The listed percentages for serious-event terms lack a reported denominator in the information available for this analysis, so their population basis cannot be assessed.

Enrollment was 35, and the adverse-event summaries include groups of varying sizes. General statistical explanation: estimates based on smaller groups are often less precise, and counts alone do not quantify that uncertainty. No confidence intervals for the primary result are reported in the registry record. These limitations mean the posted safety counts should be interpreted descriptively and should not be extended to conclusions about comparative treatment effects or efficacy.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: A Phase 1b Open-Label Study Investigating the Safety and Pharmacokinetics of Administration of Subcutaneous Blinatumomab for the Treatment of Relapsed/Refractory Indolent Non-Hodgkin's Lymphoma — NCT02961881.
• Registry record last updated 2024-02-02; status last verified 2023-05.
• Results first posted 2024-02-02.
• Data retrieved from ClinicalTrials.gov on 2026-11-09.
• Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.

19. Record Summary

This completed Phase 1b study evaluated SC blinatumomab for relapsed or refractory indolent non-Hodgkin's lymphoma. It was open-label and single-group, enrolled 35 participants, and listed Amgen as the sponsor. The primary endpoint was the number of participants with DLTs after SC administration during Day 1 to Day 7 of Week 4. The DLT result is not reported in the registry record.

The registry lists 17 outcome measures and 0 analyses. It includes descriptive adverse-event counts for cIV periods, SC cohorts and combined totals, alongside objectives covering pharmacokinetics, antibodies, efficacy and pharmacodynamics. These data do not constitute a randomized comparison. The statistical analysis plan, missing-data methods and multiplicity approach are not reported in the registry record.