A Study of Itacitinib (INCB039110) in Combination With Ibrutinib in Subjects With Relapsed or Refractory Diffuse Large B-Cell Lymphoma: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Study of Itacitinib (INCB039110) in Combination With Ibrutinib in Subjects With Relapsed or Refractory Diffuse Large B-Cell Lymphoma (NCT02760485), a na phase 1, phase 2 study. The primary outcome is Phase 1: Number of Participants With Any Treatment-emergent Adverse Event (TEAE).

2. Clinical Question

The study concerns a combination regimen in people whose lymphoma is described as relapsed or refractory. Its primary endpoint is a safety count, not a comparison of tumor response between treatment groups. The record lists response-related outcomes for the study, including objective response rate in Phase 1 and duration of response, durable response rate, and progression-free survival in Phase 2. It does not give results for those outcomes in the record.

The two dose descriptions do not create a controlled comparison. The record describes an open-label, single-group study and does not report random allocation. Differences between the listed groups, including their enrollment periods or participant characteristics, are not described. A between-group contrast would therefore lack the design basis needed to interpret it as a randomized treatment effect. The clinical question supported by the posted information is principally whether adverse events were recorded during study treatment and follow-up, not whether the combination outperformed another regimen.

3. Trial Design

This was an open-label Phase 1/2 study of itacitinib in combination with ibrutinib in participants with relapsed or refractory diffuse large B-cell lymphoma. The study model is single-group, allocation is listed as NA, and masking is listed as none. The registry reports an enrollment of 33 and a completed status. The listed study start date is 2016-12-29, and the primary completion date is 2022-06-06.

The treatment descriptions include Phase 1 Cohort 1, with itacitinib 300 mg QD and ibrutinib 560 mg QD, and a group spanning Phases 1 and 2, with itacitinib 400 mg QD and ibrutinib 560 mg QD. These descriptions identify dose regimens, but do not establish a randomized dose comparison. The record does not report a control arm or a masking procedure.

The primary outcome is a count of participants with any TEAE in Phase 1. Its timeframe is listed as up to 285 days. The safety population is defined as participants enrolled in Phase 1 who received at least 1 dose of study drug. The registry also lists outcomes concerning response, progression-free survival, and adverse events in Phase 2. Although the study status is completed, the listed outcome measures are not accompanied by efficacy estimates or a detailed statistical analysis in the record.

The enrollment figure is 33, while the adverse-event group totals list 32 participants at risk. The record does not explain this difference, so the adverse-event denominators should be read as their own reported safety totals rather than reconciled with the overall enrollment. Details such as the planned sample-size justification, criteria for moving between phases, and the statistical plan 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: This study was conducted at 12 study centers in the United States.

Phase 1

Reasons for not completing this period:

Phase 2

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Safety Run-In Population: all participants enrolled in the Phase 1 portion of the study who received at least 1 dose of study drug

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: In Phase 1, Baseline data were collected for members of the Safety Run-In Population, defined as all participants enrolled in the Phase 1 portion of the study who received at least 1 dose of study drug. In Phase 2, Baseline data were collected for members of the Intent-to-Treat Population, defined as all participants enrolled in the Phase 2 portion of the study.

6. Primary Endpoint

The registry lists the primary outcome as Phase 1: Number of Participants With Any Treatment-emergent Adverse Event (TEAE), measured over up to 285 days.

The primary endpoint counts participants with any treatment-emergent adverse event in the Phase 1 portion. A TEAE is defined as an adverse event first reported, or a pre-existing event that worsened, after the first dose of study drug and through 30 days after the last dose. An adverse event is described as an untoward medical occurrence after informed consent, whether or not it is considered related to study drug. Abnormal laboratory values or test results count as adverse events only under the conditions specified in the registry, including accompanying clinical signs or symptoms, clinical meaningfulness, need for therapy, or a change to study drug.

This endpoint is used to describe the safety experience during treatment and the defined post-treatment window. Counting participants with at least one event gives a straightforward summary of how many people experienced an event, but it does not capture the full pattern of events. The count alone does not show how many events each participant had, how long they lasted, their severity, or whether investigators considered them related to treatment. Those details require separate outcome information.

The endpoint is described for the Phase 1 safety population: participants enrolled in that portion who received at least 1 dose. Its timeframe is listed as up to 285 days. The record does not separately report a primary-endpoint result for this measure. The serious and other adverse-event counts listed in the safety information should not automatically be treated as the reported primary TEAE result, because the record does not identify them as a substitute for that endpoint.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does a participant count represent? The primary endpoint is a count: the number of participants with at least one TEAE. A participant-level count treats a participant with one event and a participant with multiple events as having the endpoint. It answers how many participants were affected, not how many total events occurred. It also does not, by itself, describe event severity, duration, or causal attribution. Those questions require additional outcomes or event-level summaries.

The endpoint definition sets a time window for deciding which events qualify. An event must first be reported, or worsen from a pre-existing condition, after the first dose and through 30 days after the last dose. This definition makes the treatment-emergent classification depend on timing, rather than requiring the event to be judged drug-related. The registry separately explains circumstances in which an abnormal laboratory value or test result is counted as an adverse event. That distinction matters: not every abnormal result automatically qualifies under the stated definition.

Why does the denominator matter? A count is interpretable only with its population and denominator. The Phase 1 safety population includes participants enrolled in that portion who received at least 1 dose. The adverse-event information reports 6 participants at risk in the 300 mg QD group, 26 in the 400 mg QD group spanning Phases 1 and 2, and 32 in total. The overall enrollment is 33. Since the record does not explain the discrepancy, the reported group denominators should be retained as stated rather than silently adjusted. A denominator may also vary across outcomes if not all participants are included in every assessment; details of such outcome-specific populations are not reported.

How should adverse-event counts be compared? In general, a difference between two observed counts or proportions can reflect the underlying risk, the amount of observation, or random variation. A fair causal comparison usually depends on a suitable control and a design that makes the groups comparable. This study is identified as single-group, open-label, and not randomized. Its dose groups do not constitute a randomized control comparison on the information reported. Describing their counts separately is possible; interpreting a difference as the effect of dose or treatment is not supported by the design details in the registry record.

In general, a confidence interval communicates the range of effect values compatible with the observed data under a specified statistical model. It helps readers assess precision, which a point estimate alone cannot convey. The registry record does not list confidence intervals for the outcomes. Without an estimate and its uncertainty, the precision of the safety counts cannot be assessed through interval estimates. Sparse counts can also yield substantial uncertainty; that is a general statistical consideration, not a separately reported finding about this study.

What do the planned sample-size illustrations mean? General sample-size illustrations based on an observed effect are planning exercises, not evidence about the actual design or the certainty of the trial’s findings. The stated illustration assumptions are a two-sided significance level of 0.05, equal allocation between two hypothetical arms, and a normal approximation; the target effect is a stated fraction of the observed effect. Those assumptions do not turn this single-group study into a randomized two-arm trial. They do not represent observed power, and they are not the trial’s own sample-size justification. The registry record does not report the protocol’s sample-size rationale.

In general, over-dispersion matters when count data vary more than a statistical model expects. A model that assumes too little variability may produce uncertainty estimates that are too narrow. The primary endpoint is a participant count rather than a reported rate of recurrent events, and the registry record does not identify an over-dispersion model or provide the data needed to assess one. More broadly, the statistical model, covariate adjustment, and estimation procedure are not reported in the registry record.

The listed Phase 2 outcomes have different statistical meanings. Duration of response concerns time from the first overall response contributing to an objective response until the earlier of death or progressive disease, as defined in the record. Progression-free survival concerns time from first dose until the earlier of death from any cause or disease progression determined by objective radiographic assessments. Such outcomes are generally analyzed with methods that account for follow-up time and censoring, but the registry does not report the analysis methods or results for these outcomes. It is therefore not possible to determine how censoring, missing assessments, or follow-up differences were handled.

The study lists 10 outcome measures and 0 analyses. This indicates that the registry information summarized contains outcome definitions but no listed analysis records; it does not supply estimates for the efficacy outcomes. Statistical interpretation should distinguish an endpoint definition from its result. Naming an outcome, even with a detailed definition, does not reveal the observed estimate, its uncertainty, or the analysis population 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("Phase 1; Cohort 1: Itacitinib 300 mg QD + Ibrutini", "Phase 1; Cohort 2: Itacitinib 400 mg QD + Ibrutini")
n      <- c(6, 7)
events <- c(6, 7)
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  Phase 1; Cohort 1: Itacitinib 300 mg QD + Ibrutini  6  6  100.0  54.1  100.0  61.0  100.0  59.0  99.6
ARM  Phase 1; Cohort 2: Itacitinib 400 mg QD + Ibrutini  7  7  100.0  59.0  100.0  64.6  100.0  63.1  99.7

11. Multiplicity, Missing Data and Analysis Populations

The registry record lists multiple outcomes across Phase 1 and Phase 2, including safety measures and response-related outcomes. It does not report how statistical multiplicity was handled. When multiple outcomes are examined, the chance of finding at least one apparently notable result can depend on how many tests are performed and how they are selected. General strategies include prespecifying a primary outcome, adjusting significance thresholds, or treating secondary analyses as exploratory. Which approach was planned or used in this study is not reported in the registry record.

There are 0 listed analyses in the record summarized. This means no analysis results or analysis-specific populations are available there for assessing multiplicity, adjustment, or robustness. It does not establish what analyses may have been performed outside the registry record. The study’s primary outcome is defined as a Phase 1 participant count, but a numeric result for that endpoint is not separately reported.

Missing-data handling is not reported in the registry record. The record does not describe how participants without a recorded endpoint assessment, incomplete follow-up, or missing response evaluations were treated. It also does not report whether participants were excluded from specific analyses or whether any imputation procedure was used. Those details matter because missingness can change which participants contribute to a result and can affect interpretation.

The Phase 1 safety population is described as those enrolled in that portion who received at least 1 dose. The analysis populations for the listed Phase 2 outcomes are not reported in the registry record. The record also does not specify an intention-to-treat population or a per-protocol population. These omissions prevent a full assessment of who was included in any endpoint analysis and whether the analysis set followed a prespecified plan.

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: mental status changes (33.3%), impetigo (16.7%), pneumonia (16.7%), pneumonia aspiration (16.7%), fatigue (15.4%).

The safety record reports participants affected by serious adverse events as 4 of 6 in the 300 mg QD itacitinib plus 560 mg QD ibrutinib cohort, 18 of 26 in the 400 mg QD itacitinib plus 560 mg QD ibrutinib group, and 22 of 32 in total. It also lists other adverse events in 6 of 6, 26 of 26, and 32 of 32 participants. These are participant counts, not counts of every event episode, and the record does not report event duration or recurrence in this summary.

The deaths listed are 2, 19, and 21, respectively. The registry information does not identify these as treatment-related deaths or give causes. Seriousness and treatment relatedness are distinct concepts: a serious event is not necessarily caused by the study drug, and the data do not support assigning causality.

Selected serious-event terms and percentages are also reported: Mental status changes (33.3%), Impetigo (16.7%), Pneumonia (16.7%), Pneumonia aspiration (16.7%), Fatigue (15.4%), and Dehydration (11.5%). The associated counts and denominators are not reported alongside these percentages in the record summarized, so they should not be converted into inferred participant counts. The terms do not establish a treatment effect or represent a complete account of all safety events. The total safety denominator of 32 is distinct from the overall enrollment of 33; the reason is not reported in the registry record.

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

The posted information supports a descriptive account of study design and selected safety counts. It identifies an open-label, single-group Phase 1/2 study of itacitinib with ibrutinib and reports serious adverse-event counts, other adverse-event counts, and deaths for the listed safety groups. These counts describe participants recorded as affected in the registry. They do not, by themselves, estimate how the combination compares with another treatment or with no treatment.

The record’s stated purpose includes evaluating safety, tolerability, and efficacy. However, the outcome definitions for objective response, duration of response, durable response, and progression-free survival are not accompanied by results in the information summarized. The record therefore does not support a numerical conclusion about tumor response or disease control. A completed study status is not a substitute for posted outcome estimates.

The safety counts also do not establish whether events were caused by either study drug. The registry’s TEAE definition is based on when an event occurred, not necessarily on whether it was judged related to treatment. The death counts are not identified as treatment-related deaths. The serious-event term percentages likewise do not establish causality, and their supporting denominators are not given alongside the terms.

In general, a single-group study can describe what happened among enrolled participants, but it cannot separate treatment effects from other explanations as effectively as a suitable controlled comparison. Here, the groups are not reported as randomized controls, and the design is listed as single-group. The record also lacks confidence intervals, detailed analysis methods, missing-data handling, and efficacy results. These omissions limit assessment of precision and bias. The appropriate reading is therefore narrow: the registry records a safety experience in the listed groups, while comparative efficacy and causal conclusions are not established by the reported information.

14. Why This Trial Matters Statistically

This trial is statistically notable because the registry combines a Phase 1 safety endpoint with a Phase 1/2 development program while identifying the overall model as single-group. That makes it important to distinguish descriptive safety evidence from comparative treatment-effect evidence. Counts can document what was observed among participants, but without a concurrent control and an appropriate analysis they cannot isolate the contribution of the study drugs from other causes.

The record also illustrates why endpoint definitions and endpoint results must be kept separate. The primary outcome is carefully defined as a count of participants with any TEAE, including a specified event window and a description of the safety population. Yet the registry information summarized does not provide a separate numeric primary-endpoint result or efficacy estimates. A detailed definition improves clarity about what should be measured, but it cannot answer how often the endpoint occurred unless the result is reported.

Denominator transparency is another key issue. The overall enrollment is 33, while the adverse-event group total is 32. The record does not explain that discrepancy. Reporting both figures allows readers to notice the difference, but not to determine its reason. This matters because safety findings are interpreted relative to the population at risk and the analysis set.

Finally, the listed response and time-to-event outcomes are not accompanied by analysis details. Without results, uncertainty estimates, missing-data procedures, and multiplicity information, readers cannot assess precision or the strength of evidence for those outcomes. The trial’s statistical record is therefore most useful as a description of design and selected safety observations, while leaving important inferential questions unresolved.

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 registry information has several limitations for interpreting this specific study. It gives no efficacy estimates for the listed response and progression outcomes, and no confidence intervals or analysis results. Although the study is marked completed, that status does not resolve the absence of those results in the record summarized. The primary Phase 1 endpoint is defined, but a separate result for the number of participants with any TEAE is not reported.

The study is open-label and single-group, with allocation listed as NA. The listed dose groups are not identified as randomized comparison groups, so their event counts should not be interpreted as a causal contrast between doses or as a comparison with another treatment. The record does not describe baseline characteristics, treatment exposure by participant, follow-up duration distributions, or factors that might affect observed event counts. These details are not reported in the registry record.

There is a difference between the enrollment of 33 and the total adverse-event denominator of 32, which the record does not explain. The serious-event terms are accompanied by percentages but not their supporting counts and denominators in the information summarized. The deaths are reported without causal attribution or causes. The registry also does not report missing-data procedures, analysis populations for Phase 2 outcomes, multiplicity handling, interim analyses, or a statistical plan.

These limitations mean that the posted safety counts are descriptive and that their precision cannot be fully assessed from the record. They also prevent conclusions about comparative efficacy, treatment causality, or the robustness of analyses that are not reported. The record does not provide enough detail to reconcile these gaps.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: A Study of Itacitinib (INCB039110) in Combination With Ibrutinib in Subjects With Relapsed or Refractory Diffuse Large B-Cell Lymphoma — NCT02760485.
• Registry record last updated 2023-06-15; status last verified 2023-06.
• Results first posted 2023-06-15.
• 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 record describes a completed, open-label, single-group Phase 1/2 study of itacitinib with ibrutinib in relapsed or refractory diffuse large B-cell lymphoma. Enrollment is 33. The listed regimens include itacitinib 300 mg QD with ibrutinib 560 mg QD and itacitinib 400 mg QD with ibrutinib 560 mg QD.

The primary Phase 1 endpoint is the number of participants with any TEAE, in a safety population defined by receipt of at least 1 dose. The record lists serious adverse events, other adverse events, and deaths for a total safety group of 32, but does not explain the difference from overall enrollment. It lists efficacy outcomes without reporting their results in the information summarized. Statistical analyses, missing-data handling, and the study’s statistical plan are not reported in the registry record.