Ibrutinib and Blinatumomab in Treating Patients With Relapsed or Refractory B Acute Lymphoblastic Leukemia: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Ibrutinib and Blinatumomab in Treating Patients With Relapsed or Refractory B Acute Lymphoblastic Leukemia (NCT02997761), a na phase 2 study. The primary outcome is Rate of Complete Remission (CR)..

2. Clinical Question

In statistical terms, the primary question is about an observed count of participants meeting a defined response criterion in a single treated group. It is not a randomized comparison of the combination against another treatment or against no treatment. A count from a single group can describe the experience recorded for participants in that group, but without a concurrent comparator it cannot by itself estimate a between-group treatment effect.

The registry also lists outcomes concerning adverse events, minimal residual disease-negative CR/CRi, overall response, overall survival, and bridging to allogeneic hematopoietic cell transplant or CAR-T. Their listing indicates the questions named in the record, not that results for each are available. Detailed definitions and result values for these outcomes are not reported in the registry record.

3. Trial Design

The registry identifies this as a Phase 2 study of ibrutinib and blinatumomab in relapsed or refractory B-cell acute lymphoblastic leukemia. It lists University of California, Davis as the sponsor, an enrollment of 19, and a completed status. The listed start date is 2017-06-27, and the primary completion date is 2025-07-17.

The design is single-group, with no masking and allocation recorded as NA. These features describe a study without a listed randomized allocation between treatment groups and without masking. The intervention arm is titled Treatment (ibrutinib, blinatumomab). Because no separate control group is listed, the study record does not support a like-for-like comparison between participants receiving the combination and participants receiving a different intervention.

The arm description specifies induction therapy. During course 1, ibrutinib is scheduled by mouth once daily on days 1-49, while blinatumomab is scheduled intravenously on days 8-35. During course 2, the description schedules ibrutinib on days 1-42 and blinatumomab on days 1-28. Treatment is described as continuing in the absence of disease progression or unacceptable toxicity. The description begins a consolidation statement for patients with CR/CRi after induction, but further consolidation details are not reported in the registry record. Drug doses are also not reported in the registry record.

The registry lists 19 participants as enrolled, but enrollment alone does not establish how many participants received treatment, completed each course, or contributed data to each outcome. Those counts and the analysis populations are not reported in the registry record. The record also does not report a statistical analysis plan, a sample-size justification, or whether interim analyses were planned. The absence of a listed comparator and the missing outcome count are central when interpreting what can be learned from the posted information.

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

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 Rate of Complete Remission (CR)., measured over Up to about 3 months from start of study treatment..

The primary endpoint is the rate of complete remission, expressed in the registry description as the number of participants who achieve CR. The definition refers to the National Comprehensive Cancer Network Guidelines for Acute Lymphoblastic Leukemia, Version 2.201. The stated timeframe is up to about 3 months from the start of study treatment.

This is a binary outcome at the participant level: a participant either meets the stated CR definition within the outcome timeframe or does not. Reporting the count can describe how many participants in the treated group met that criterion. A proportion or an uncertainty interval can help convey how precisely a group response rate is estimated, but the CR count and such estimates are not reported in the registry record.

CR is used as a defined response endpoint because it records whether participants meet a specified disease-response criterion during the stated period. The meaning depends on applying the cited definition consistently and establishing how response was assessed. The registry gives the definition and timeframe, but does not report details such as assessment procedures, confirmation requirements, or handling of participants whose response status could not be determined.

The endpoint is not equivalent to overall survival, duration of remission, or a comparison of treatments. Those are different questions, and the registry lists overall survival separately among secondary outcomes. Since the primary result is not reported in the registry record, the endpoint definition alone does not establish how many participants achieved CR or how uncertain that count may be.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does a single-group design estimate?

In a single-group study, outcomes are observed among participants receiving the listed intervention. For a binary endpoint such as CR, the basic descriptive result is a count of participants meeting the endpoint definition, together with a denominator identifying the participants whose outcomes were assessed or analyzed. A proportion may also be reported. The registry gives an enrollment of 19, but it does not report the primary CR count or the outcome-specific denominator. Therefore, no response proportion or uncertainty interval can be interpreted from the registry information.

A single-group estimate answers a descriptive question about the participants included in that analysis. It does not, by itself, separate the intervention's effects from other explanations for the observed outcomes. A control group can help establish a comparison under the same study conditions; this record lists no separate control group. Comparing a single-group result with an external benchmark would require careful attention to whether the populations, eligibility rules, outcome definitions, and follow-up are comparable. Such a benchmark or comparison is not reported in the registry record.

What does a confidence interval convey?

In general, a confidence interval expresses the statistical uncertainty around an estimate under the assumptions of the method used. A narrower interval indicates greater precision for that estimate under those assumptions; it does not remove possible bias from selection, measurement, missing data, or study design. For a binary response outcome, an interval around a response proportion can show how compatible the data are with a range of underlying response rates. No confidence interval or analysis method for the primary CR outcome is reported in the registry record.

A p-value, when appropriate, addresses how compatible observed data are with a specified statistical model or null hypothesis. Its interpretation depends on the question, analysis plan, and assumptions; it does not measure the size or clinical importance of an effect. The registry entries described for this study list no analyses, and no primary-outcome p-value is reported in the registry record. A p-value cannot be reconstructed from the endpoint definition or enrollment alone.

How should the planning assumptions be understood?

The record's planning illustration assumptions describe a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. They also describe the effect to detect as a stated fraction of the observed effect. These are assumptions for a planning illustration, not a description of the registered single-group design, which lists no allocation to separate study arms. Planning sample sizes indicate hypothetical requirements under chosen assumptions; they are not observed power and do not show that the completed study had a particular probability of detecting an effect. The sample-size justification used for the trial itself is not reported in the registry record.

In general, the normal approximation is a simplifying method for estimating sampling variability. Its suitability depends on the endpoint, event frequency, and sample size. For binary outcomes with limited counts, the approximation may be less reliable than methods designed for sparse data. Which method would be appropriate depends on the actual result and analysis question; the primary outcome count and the trial's analysis method are not reported in the registry record.

Why do analysis populations matter?

An analysis population defines who contributes to a particular result. For example, a study may distinguish participants enrolled, treated, or assessed for an outcome. These groups can differ, and exclusions after enrollment can affect the estimated response. A clear report identifies the population, its denominator, the reasons participants were excluded, and how any deviations from the planned treatment were handled. The registry gives enrollment of 19, but the analysis populations and outcome-specific denominators are not reported in the registry record.

Missing outcome data also need a stated approach. In general, excluding participants with missing assessments can change the group represented by the estimate, especially if missingness is associated with disease status, adverse events, or treatment discontinuation. Alternative assumptions about missing responses can produce different estimates. The registry does not report the amount or pattern of missing primary-outcome data, or the method used to handle it. No particular missing-data method should be inferred.

What does multiplicity mean for listed outcomes?

When a study considers several endpoints or statistical tests, the chance of at least one apparently unusual result can increase if each test is interpreted without accounting for the others. Statistical plans may identify a primary endpoint, specify which other outcomes are exploratory, and describe any adjustment or hierarchy for formal testing. The registry identifies CR as primary and lists several secondary outcomes, but adjustment methods, testing hierarchy, and multiplicity procedures are not reported in the registry record. The outcome list alone cannot show whether or how multiple testing was addressed.

The registry does not report interim analyses or stopping rules, and no such procedures should be assumed. For a complete statistical interpretation, readers would need outcome counts and denominators, estimates and uncertainty measures, definitions and assessment details, analysis populations, missing-data handling, and the prespecified analysis approach. The registry entries establish the study structure and the primary endpoint definition, but not these results or methods.

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("Treatment (Ibrutinib, Blinatumomab)")
n      <- c(18)
events <- c(9)
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  Treatment (Ibrutinib, Blinatumomab)  18  9  50.0  26.0  74.0  29.0  71.0  28.9  71.1

11. Multiplicity, Missing Data and Analysis Populations

The registry names a primary CR outcome and lists secondary outcomes covering adverse events, MRD-negative CR/CRi, overall response, overall survival, and bridging to allogeneic hematopoietic cell transplant or CAR-T. Considering multiple outcomes raises a general multiplicity issue: if many statistical tests are performed, interpreting each without a plan can increase the chance of false-positive findings. A prespecified hierarchy or adjustment can address this concern, but the testing hierarchy and multiplicity procedures are not reported in the registry record.

The primary CR outcome is defined, but its participant count is not reported in the registry record. The record also does not report outcome-specific denominators, missing response assessments, or the approach to missing data. In general, missing outcome information can affect a binary response estimate, and the direction of any effect depends on why the data are missing and how the analysis handles them. No missing-data approach can be inferred from the endpoint description.

Enrollment is listed as 19, but the analysis populations are not reported in the registry record. The record does not specify how many participants were treated or assessed for each outcome, or whether participants were analyzed according to a particular treatment or eligibility definition. Interim analyses and the statistical analysis plan are not reported in the registry record. These omissions limit assessment of analysis choices and the completeness of outcome reporting.

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: back pain (26.3%), febrile neutropenia (10.5%), arthralgia (5.3%), gum infection (5.3%), myalgia (5.3%).

The registry safety summary lists 19 participants at risk for serious adverse events, with serious adverse events affecting 8 participants. It also lists 19 participants at risk for other adverse events, with other adverse events affecting 19 participants, and records 1 death. These are the safety figures in the registry record; they should be read as reported counts, not as estimates from a comparison with a control group.

The serious adverse event terms listed with percentages are back pain, 26.3%; febrile neutropenia, 10.5%; arthralgia, 5.3%; gum infection, 5.3%; myalgia, 5.3%; and neurotoxicity, 5.3%. These percentages are reported as event-term figures. They do not show, by themselves, whether events were attributed to treatment, how long they lasted, or whether a participant experienced more than one event. The record does not report detailed event-level timing or causal attribution.

Counts of participants affected are not interchangeable with counts of individual events, and adverse-event summaries do not establish causation. The registry does not provide the contextual detail needed to compare safety with another treatment or to account for duration of exposure. The listed death should likewise be understood as a recorded safety figure; its relationship to treatment is not reported in the registry record.

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

The registry record establishes that a completed Phase 2, single-group study evaluated ibrutinib and blinatumomab in relapsed or refractory B-cell acute lymphoblastic leukemia. It specifies a primary outcome based on complete remission, a timeframe of up to about 3 months from treatment start, and an enrollment of 19. It also lists several secondary outcomes and safety figures.

The primary CR participant count is not reported in the registry record. Without that result, the posted information does not show how many participants met the CR definition, what response estimate was observed, or how precisely it was estimated. It also does not allow a comparison of the combination with another treatment: no separate comparator arm is listed. The record therefore cannot support a conclusion about a difference between treatments or attribute an observed outcome to the intervention.

The safety counts and event-term percentages describe what the registry lists, but they do not establish that the intervention caused those events. A fuller safety assessment would require information such as event timing, treatment relationship, duration, and relevant comparison data; these details are not reported in the registry record.

More generally, a defined endpoint and a completed study status are not substitutes for outcome results. Interpretation depends on knowing who contributed to each analysis, how outcomes were assessed, how missing information was handled, and what statistical methods were prespecified. These details are not reported in the registry record. The appropriate statistical reading is therefore bounded: the record describes the design, intervention schedule, primary endpoint, and selected safety information, while the primary response result and its uncertainty remain unavailable in the registry record.

14. Why This Trial Matters Statistically

This study illustrates why design and result reporting must be considered together. A single-group study can describe outcomes among participants receiving a treatment combination, but it does not provide a concurrent control comparison. That distinction is essential when interpreting any response count: a group outcome is not the same estimand as a difference between treatment groups.

It also illustrates the difference between an outcome definition and an outcome result. The registry defines CR by reference to a guideline and gives a timeframe, but the primary participant count is not reported in the registry record. Without the count, denominator, and an uncertainty estimate, readers cannot assess the observed response rate or its precision. Enrollment alone does not supply those missing quantities.

The registry lists a number of secondary outcomes and safety figures, which raises general questions about outcome definitions, analysis populations, missing data, and multiplicity. These are not merely technical details: they determine what data contribute to an estimate and how confidently findings can be interpreted. The relevant analysis plan and several of these reporting details are not reported in the registry record.

The record's planning assumptions also show why sample-size illustrations must be separated from the actual design and results. Assumptions about equal allocation between two arms do not describe the listed single-group design. Planning calculations are hypothetical and are not observed power. Taken together, these features make the study statistically instructive: readers need to distinguish registry design information, planned outcomes, safety counts, and actual outcome analyses rather than treating them as interchangeable 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.

The principal limitation for interpreting the primary question is that the CR participant count is not reported in the registry record. The outcome-specific denominator, an estimate of the response rate, and an uncertainty interval are also not reported. Although enrollment is listed as 19, it is not possible to assume that every enrolled participant contributed to the primary analysis.

The study is described as single-group, with no separate comparator listed. This limits direct comparative interpretation and does not provide a randomized estimate of the difference between the combination and another treatment. The registry's lack of a listed comparator is not evidence about how the outcome compares with results in other populations.

The intervention description provides induction schedules but not drug doses. It begins a consolidation description for participants with CR/CRi after induction, while further consolidation details are not reported in the registry record. Eligibility criteria beyond the listed conditions, participant characteristics, outcome assessment procedures, and follow-up details are also not reported.

The registry does not report analysis populations, missing-data handling, the statistical analysis plan, multiplicity procedures, or interim analyses. The listed safety counts do not include the detailed context needed to assess timing, attribution, or exposure. These gaps limit assessment of both the primary endpoint and safety results. They do not establish that a particular method was or was not used; those details are simply not reported in the registry record.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Ibrutinib and Blinatumomab in Treating Patients With Relapsed or Refractory B Acute Lymphoblastic Leukemia — NCT02997761.
• Registry record last updated 2026-06-09; status last verified 2026-06.
• Results first posted 2026-06-09.
• 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

The registry describes a completed Phase 2, single-group study of ibrutinib and blinatumomab for relapsed or refractory B-cell acute lymphoblastic leukemia. Enrollment is listed as 19. The primary endpoint is the number of participants achieving CR according to the stated guideline definition, within up to about 3 months from treatment start.

The primary CR count is not reported in the registry record. No separate comparator arm is listed, and the statistical analysis plan, analysis populations, missing-data methods, and multiplicity procedures are not reported. Safety information lists serious adverse events affecting 8 of 19 participants, other adverse events affecting 19 of 19 participants, and 1 death. These figures do not establish causation or a comparative treatment effect.