Feasibility Study to Evaluate Outpatient Blinatumomab in Subjects With Minimal Residual Disease (MRD) of B-precursor Acute Lymphoblastic Leukemia (ALL): Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Feasibility Study to Evaluate Outpatient Blinatumomab in Subjects With Minimal Residual Disease (MRD) of B-precursor Acute Lymphoblastic Leukemia (ALL) (NCT04506086), a na phase 4 study. The primary outcome is Number of Participants With Grade 3 and/or 4 Cytokine Release Syndrome (CRS), Neurotoxicity (NT) or Any Adverse Events Resulting in Hospitalization During MDMP.

2. Clinical Question

The study is titled as a feasibility study of outpatient blinatumomab for adults with minimal residual disease of B-precursor ALL in complete hematologic remission. It is a phase 4, multicenter, open-label study sponsored by Amgen. The stated goal was to determine safety and feasibility, rather than to establish a comparative effect against another treatment or setting. The registry record lists five outcome measures, including the primary safety count and secondary measures concerning therapeutic intervention, adverse events, quality of life, and consequences of treatment-emergent adverse events. Their presence in the record identifies topics of interest, but does not establish that results for those measures are available.

3. Trial Design

This was a phase 4, multicenter, open-label, single-group feasibility study. The registry record lists 10 participants enrolled. It records a start date of 2021-08-26 and a primary completion date of 2024-07-04, and the study status is terminated. A reason for termination is not reported in the registry record. The record does not state how many participants completed treatment or follow-up.

The intervention was blinatumomab, with a Current Wearable Health Monitoring System also listed as a device. The study aim was to assess safety and feasibility of complete outpatient blinatumomab administration in subjects with minimal/measurable residual disease of B-precursor ALL. Further details about treatment delivery, monitoring procedures, or the operational definition of feasibility are not reported in the registry record. The arm description contains no additional details.

There was no randomized allocation and no masking. The registry identifies a single group, so the study is not a like-for-like comparison between outpatient treatment and a control regimen or setting. Its descriptive safety observations can characterize what was recorded among participants at risk, but they cannot by themselves establish what would have occurred under an alternative approach.

The primary endpoint is a count of participants meeting a specified safety-event definition during Cycle 1: Day 1 to Day 3 and Cycle 2: Day 1 and Day 2. The Safety Analysis Set includes enrolled participants who received at least 1 dose of blinatumomab. Whether the reported enrollment of 10 matches the number in that analysis set is not reported separately. The registry record does not describe a sample-size justification, detailed statistical analysis plan, interim analyses, or a reason for terminating the study. Those omissions limit assessment of how the study was planned and how its results were intended to be interpreted.

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: Participants were administered blinatumomab as a continuous intravenous infusion (CiVI) in 2 mandatory cycles. Each cycle lasted 6 weeks (4 weeks of CiVI and 2-week treatment-free). Participants then had the option to continue for 2 additional cycles. Mandatory monitoring period (MDMP) was defined as the first 3 days of Cycle 1 and the first 2 days of Cycle 2. During MDMP, participants wore the current wearable health monitoring system to measure vital signs 24 hours a day.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Safety Analysis Set included all enrolled participants who received at least 1 dose of blinatumomab.

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: Safety Analysis Set: included all enrolled participants who receive at least 1 dose of blinatumomab.

6. Primary Endpoint

The registry lists the primary outcome as Number of Participants With Grade 3 and/or 4 Cytokine Release Syndrome (CRS), Neurotoxicity (NT) or Any Adverse Events Resulting in Hospitalization During MDMP, measured over Cycle 1: Day 1 to Day 3; Cycle 2: Day 1 and Day 2.

The primary endpoint counts participants with grade 3 and/or 4 cytokine release syndrome, neurotoxicity, or any adverse event resulting in hospitalization during specified portions of Cycle 1 and Cycle 2. Events were graded using the Common Terminology Criteria for Adverse Events, CTCAE v5.0. The record defines grade 3 events as severe or medically significant but not immediately life-threatening, and grade 4 events as having life-threatening consequences for which urgent intervention is indicated. It describes CRS as heightened T-cell activation and release of pro-inflammatory cytokines. Listed signs of neurotoxicity include encephalopathy, delirium, aphasia, lethargy, difficulty concentrating, agitation, tremor, seizures, and, rarely, cerebral edema.

A participant count is a direct way to describe how many people met a safety definition in the analysis population and timeframe. Combining specified severe CRS or NT with adverse events resulting in hospitalization focuses the endpoint on clinically consequential events, while the separate components may have different clinical features. A count does not describe the number of events per participant, their duration, or their timing within the assessment window.

The registry record provides the endpoint definition but does not report its observed count. It also does not report component-specific results, so the contribution of CRS, NT, and hospitalization to the primary endpoint cannot be determined from the posted results.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary measure is a binary participant-level outcome: each person either meets the endpoint definition during the stated periods or does not. The endpoint is reported as a count of participants, rather than as a continuous measurement such as a score or laboratory value. Its components are grade 3 and/or 4 CRS, grade 3 and/or 4 NT, or any adverse event resulting in hospitalization. The specified assessment periods are Cycle 1: Day 1 to Day 3; Cycle 2: Day 1 and Day 2. The population is the Safety Analysis Set, defined as enrolled participants who received at least 1 dose of blinatumomab.

What does a participant count convey?

A count conveys how many participants met the endpoint definition, but interpretation also depends on the number of participants assessed. The record reports 10 participants enrolled and defines the safety population, but does not separately report the size of that population or the primary endpoint count. It therefore does not permit a reader to calculate an event proportion or assess its precision. No such calculation is appropriate without the relevant endpoint result and denominator.

General statistical principle: an estimate based on a small group is subject to sampling uncertainty. A confidence interval expresses a range of values reasonably compatible with the observed data under a specified statistical method. Wider intervals indicate less precision; narrower intervals indicate greater precision. No interval estimate for this primary endpoint is reported in the registry record. This concept explains how an interval would be read, but does not supply an estimate for this study.

Why does the endpoint combine event types?

The definition brings together severe CRS or NT and any adverse event resulting in hospitalization. A composite can capture several kinds of serious safety experience in one endpoint, but the overall count does not reveal which component contributed to it. Components can differ in frequency, severity, and clinical meaning. The record does not report component-specific primary endpoint counts, so the combined result cannot be unpacked. Nor does it report the number or duration of individual episodes; its stated unit is participants.

CTCAE v5.0 grading provides the stated framework for classifying event severity. The registry description distinguishes grade 3 events, which are severe or medically significant but not immediately life-threatening, from grade 4 events, which have life-threatening consequences and indicate urgent intervention. The primary definition includes grade 3 and/or 4 CRS and NT, but does not restrict the hospitalization component to a stated grade. The record does not describe adjudication procedures or how overlapping events were handled.

What can the design estimate?

In a single-group study, descriptive safety summaries can characterize outcomes among participants in that group. Without a concurrent control group, the study does not estimate a difference between outpatient blinatumomab and an alternative. General statistical principle: a comparison is needed to distinguish an outcome level under one approach from the outcome that might have occurred under another, while accounting for uncertainty and differences between groups. This design does not supply that contrast.

The study is open-label, and masking is listed as none. This is a design feature, not proof that outcome assessment was biased. The registry record does not describe blinding of assessors, independent event review, or other procedures that might influence assessment. Such procedures should not be assumed.

What analyses are reported?

The registry record lists five outcome measures and zero analyses. It does not report a statistical analysis plan, endpoint estimate, confidence interval, p-value, or adjusted model. The record also does not report interim analyses or a sample-size justification. Without a stated plan, it is not possible to assess prespecified choices about handling incomplete observations, analysis populations beyond the primary definition, or adjustment for multiple outcomes.

General statistical principle: a p-value, when reported, summarizes how compatible data are with a specified null model under its assumptions; it is not a measure of clinical importance or a probability that a hypothesis is true. A confidence interval gives information about estimate precision, while an effect estimate gives the magnitude and direction of a contrast when a comparison exists. None of these inferential results is reported for the primary endpoint in the registry record. There is no basis for inferring statistical significance or a comparative effect.

The registry record also states planning-illustration assumptions elsewhere, including a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. It describes the effect to detect as a stated fraction of the observed effect and says non-time-to-event illustrations are expressed as participants per arm. These are assumptions for a planning illustration, not a reported design rationale for this single-group study. The record does not report the study's own sample-size justification, and a planning illustration is not observed power. No planning results are described in the posted results.

General statistical principle: over-dispersion matters when count data vary more than a chosen model expects; in that setting, uncertainty estimates based on a restrictive model can be too small. The primary endpoint is a participant count, not a reported event-rate model, and no such model or dispersion estimate is reported. This general consideration does not imply that over-dispersion was present or that a particular model was used.

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")
n      <- c(10)
events <- c(2)
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  10  2  20.0  2.5  55.6  5.7  51.0  6.0  51.8

11. Multiplicity, Missing Data and Analysis Populations

The registry lists five outcome measures: the primary safety count and secondary outcomes concerning time to therapeutic intervention during MDMP, treatment-emergent adverse events and events of interest, change in the EORTC QLQ-C30 global health status/quality of life score, and treatment-emergent adverse events resulting in hospitalization, surgeries, concomitant medications, or device/procedure intervention. The registry record does not report analyses for these outcomes. It does not state whether a hierarchy, multiplicity adjustment, or other procedure was planned to address the interpretation of multiple outcomes.

General statistical principle: when several outcomes are tested, the chance of at least one apparently unusual result can increase if each is assessed separately without accounting for multiplicity. A prespecified hierarchy or adjustment can help control how evidence is interpreted. Since no analysis plan or inferential results are reported, it is not possible to determine how multiplicity was handled or whether any outcome was designated for confirmatory inference beyond the primary label.

Missing-data methods, reasons for missing observations, and completion rates are not reported in the registry record. The primary analysis population is defined as enrolled participants who received at least 1 dose of blinatumomab, but the record does not separately state how many participants met that definition. It also does not report whether any participant had incomplete assessment during the specified endpoint windows or how incomplete observations were treated. No assumptions about missingness or imputation should be inferred.

The registry record gives enrollment of 10 and identifies the Safety Analysis Set definition. It does not report additional analysis populations or explain whether all enrolled participants contributed to each secondary outcome. Thus the analysis denominator and handling of missing data cannot be reconstructed for those measures.

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 (10.0%), cytokine release syndrome (10.0%), sepsis (10.0%), encephalopathy (10.0%).

The adverse event summary lists 4 participants affected by serious adverse events among 10 at risk, and 10 participants affected by other adverse events among 10 at risk. It reports 0 deaths. These are distinct categories in the registry display; the record does not explain the detailed classification rules or whether participants could appear in both categories. The serious adverse event terms listed are pyrexia, cytokine release syndrome, sepsis, and encephalopathy, each reported as 10.0%.

The listed percentages are event-term summaries, not the primary endpoint result. The registry record does not state whether these terms occurred in the same or different participants, nor does it provide timing, duration, grade, or participant-level overlap for the term listings. It is therefore not possible to add the terms together to infer a number of affected participants. The reported serious adverse event count also should not be equated with the primary endpoint count: the endpoint has specified severity and hospitalization criteria and a defined timeframe, while the serious-event listing is a separate summary.

These figures describe observations in this study and do not establish a comparative risk. The record does not report a control group, adjusted comparison, or confidence interval for the serious adverse event figures. The listed count of deaths is 0; it does not describe other dimensions of safety or substitute for the endpoint result.

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

The registry record identifies a study of outpatient blinatumomab administration intended to assess safety and feasibility among adults with B-precursor ALL and minimal residual disease. It gives the design, enrollment, endpoint definition, and selected adverse event summaries. In the serious adverse event summary, 4 participants were affected among 10 at risk; the other adverse event summary lists 10 affected among 10 at risk; deaths are reported as 0. Four serious adverse event terms are each listed at 10.0%.

Those observations do not answer the primary endpoint question because the endpoint's observed participant count is not reported in the registry record. The serious adverse event summaries cannot be treated as a substitute: their definitions and assessment windows are not shown to be identical to the primary endpoint definition. The record also does not provide results for the listed secondary outcomes, so changes in quality of life, time to therapeutic intervention, and other specified outcomes cannot be described from the posted results.

The study has no control group, and its open-label, single-group design does not support a comparative estimate. The observed safety figures cannot show whether outpatient administration changes risk relative to another setting, nor can they establish that an event was caused by the intervention. The record does not report a reason for termination, so termination itself should not be interpreted as evidence of benefit, harm, or operational failure.

General statistical principle: descriptive findings in a small study can be informative about what was observed but are usually limited in precision and generalizability. An absent result is not evidence that the event did not occur; it is a limit on what can be concluded from the registry record. No confidence interval or uncertainty estimate is reported for the primary endpoint.

Accordingly, the posted information supports a description of selected safety counts and the study's design, but not a conclusion about comparative safety, efficacy, or feasibility. The registry record does not report a formal feasibility result or criteria by which feasibility was judged.

14. Why This Trial Matters Statistically

This study is statistically notable because its stated aim concerns complete outpatient administration, while its design is a single-group feasibility study. Such a design can document outcomes observed during a study and help describe operational experience, but it cannot directly estimate a contrast with inpatient administration or another treatment strategy. That distinction matters when reading safety counts: they are descriptive observations, not comparative evidence.

The primary endpoint is framed around participant-level safety events with defined severity and assessment periods. Clear definitions and time windows are important because they determine which observations count toward an endpoint. The registry record states CTCAE v5.0 grading and specifies the periods for assessment, but does not report the resulting primary count. Without that result, readers cannot evaluate the primary endpoint using the registry record.

The record also illustrates why an adverse event summary and a prespecified endpoint should not be conflated. Serious event terms are listed, along with counts for serious events, other events, and deaths. Those figures provide some descriptive context, but do not establish how many participants met the composite primary definition. Keeping outcome definitions separate avoids drawing conclusions from a related but nonidentical safety summary.

Finally, the record highlights the importance of transparent reporting. It identifies the analysis population and lists secondary outcomes, but does not report analysis results, missing-data handling, multiplicity procedures, or a statistical analysis plan. These details are needed to judge precision, completeness, and the interpretation of multiple outcomes. The absence of a comparator and the small enrollment also constrain what the results could establish, even if all planned outcomes were 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 record reports enrollment of 10, but does not separately report the number who received at least 1 dose, despite defining the Safety Analysis Set by treatment receipt. This leaves uncertainty about the denominator for the primary safety analysis. The primary endpoint count and its component-specific counts are not reported, preventing direct assessment of the main safety measure.

The study is single-group, open-label, and has no randomized comparator. It therefore cannot separate the observed event experience from background risks or establish how outcomes would differ under another approach. The record does not report event adjudication procedures, assessor masking, or how multiple or overlapping events were counted. Details about the operational definition of feasibility and its result are also absent.

Although the registry lists secondary outcomes, it does not report their results or analyses. Missing-data extent and handling, outcome completion, analysis populations beyond the primary definition, and a statistical analysis plan are not reported in the registry record. Multiplicity procedures, interim analyses, and the sample-size justification are also not reported. These omissions make it difficult to assess precision, selective availability of outcomes, or the intended inferential framework.

The study status is terminated, but the reason is not reported. The record does not indicate whether termination affected follow-up, planned enrollment, or outcome availability. The listed serious adverse event terms do not include participant-level overlap or the details needed to connect them to the primary endpoint. These limitations call for a descriptive, cautious reading of the posted figures rather than a comparative or causal interpretation.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Feasibility Study to Evaluate Outpatient Blinatumomab in Subjects With Minimal Residual Disease (MRD) of B-precursor Acute Lymphoblastic Leukemia (ALL) — NCT04506086.
• Registry record last updated 2025-05-18; status last verified 2025-04.
• Results first posted 2025-05-18.
• 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

NCT04506086 is a phase 4, multicenter, open-label, single-group feasibility study of outpatient blinatumomab administration for adults with B-precursor ALL and minimal residual disease in complete hematologic remission. The registry record lists Amgen as sponsor, enrollment of 10, a start date of 2021-08-26, a primary completion date of 2024-07-04, and status terminated. Blinatumomab and a Current Wearable Health Monitoring System are listed as interventions.

The primary endpoint counts participants with grade 3 and/or 4 CRS, NT, or any adverse event resulting in hospitalization during specified periods in Cycle 1 and Cycle 2. Its result is not reported in the registry record. Safety summaries list 4 participants with serious adverse events among 10 at risk, 10 with other adverse events among 10 at risk, and 0 deaths. The record lists four serious adverse event terms at 10.0% each. It does not report inferential analyses, secondary outcome results, or the reason for termination.