Study of Brexucabtagene Autoleucel (KTE-X19) in Participants With Relapsed/Refractory Mantle Cell Lymphoma (Cohort 1 and Cohort 2): Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Study of Brexucabtagene Autoleucel (KTE-X19) in Participants With Relapsed/Refractory Mantle Cell Lymphoma (Cohort 1 and Cohort 2) (NCT02601313), a na phase 2 study. The primary outcome is Percentage of Participants With Objective Response (OR) Per the Lugano Classification According to Independent Radiology Review Committee (IRRC) in Cohort 1.

2. Clinical Question

3. Trial Design

The registry describes NCT02601313 as a phase 2, multicenter study evaluating KTE-X19 in participants with relapsed/refractory mantle cell lymphoma. Its model is single-group, masking is listed as none, and allocation is listed as not applicable. Enrollment is recorded as 105. The study status is completed; the recorded start date is 2015-11-09 and the primary completion date is 2023-09-22.

The study title refers to Cohort 1 and Cohort 2, and the primary endpoint is specifically defined for Cohort 1. The registry also lists secondary outcomes for both cohorts, including duration of response, best objective response, objective response, and progression-free survival. The assessment methods differ by cohort for some of those outcomes: Cohort 1 outcomes are described with International Working Group 2007 criteria, while Cohort 2 outcomes are described with the Lugano Classification. Investigator assessment is specified for those secondary outcomes.

The intervention listing names brexucabtagene autoleucel, cyclophosphamide, fludarabine, and axicabtagene ciloleucel. However, the arm description pairs the study context with conditioning chemotherapy and then names axicabtagene ciloleucel as the infused product. Because that description is not consistent with the study title and intervention listing, the registry wording does not support confidently reconciling the treatment assignment from the information available.

As a single-group study, the record does not describe a randomized control arm. Cohort or retreatment groups in the safety record should not be treated as randomized comparisons. The registry record does not report a sample-size justification, details of any interim analyses, or a fuller statistical analysis plan.

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 from 2 x 10\^6 axicabtagene ciloleucel (AC) didn't contribute to primary and secondary analysis. The process used to manufacture axicabtagene ciloleucel was modified to manufacture brexucabtagene autoleucel (KTE-X19).

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: mITT set included all participants enrolled and treated with anti-CD19 CAR T cells at any dose in Cohort 1. Percentages were rounded off.

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: The Safety Analysis Set included all participants treated with any dose of anti-CD19 CAR T cells.

6. Primary Endpoint

The registry lists the primary outcome as Percentage of Participants With Objective Response (OR) Per the Lugano Classification According to Independent Radiology Review Committee (IRRC) in Cohort 1, measured over Up to 7.8 years.

The primary endpoint is the percentage of participants with an objective response in Cohort 1, assessed by an independent radiology review committee using the Lugano Classification. The registry gives a timeframe of up to 7.8 years. Its response definition includes complete metabolic response, complete radiological response, partial metabolic response, and partial radiological response, with criteria involving imaging findings and changes in measurable disease.

A percentage response endpoint describes the fraction of the defined analysis population meeting the response criteria. It can summarize whether participants met a prespecified disease-response definition, but it does not by itself describe how long a response lasted, how symptoms changed, or how outcomes compare with an untreated or differently treated group. Those are distinct questions, and the registry lists duration of response and other outcomes separately.

In general, response assessment depends on both the criteria used and who evaluates the evidence. Independent radiology review is intended to separate the primary assessment from investigator assessment, while the classification defines what findings count as a response. The record specifies these features, but does not report the numerical endpoint result or its uncertainty. As a result, the primary endpoint’s observed magnitude and precision are not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

For a binary endpoint such as whether a participant meets an objective-response definition, the basic result is a proportion of the defined analysis population. The numerator is the number meeting the response criteria, and the denominator is the number included in the endpoint analysis. The registry describes the Cohort 1 modified intention-to-treat population and says percentages were rounded, but it does not report the primary endpoint numerator, denominator, or percentage in the record information available for this analysis. The result therefore cannot be independently interpreted as a magnitude or precision estimate.

What does a confidence interval add?

In general, a confidence interval expresses the uncertainty around an estimated effect or proportion under the statistical method used. A narrower interval indicates greater precision under that method; a wider interval indicates less precision. An interval does not remove limitations in the study design, correct measurement problems, or establish that a treatment caused an outcome. No primary endpoint confidence interval is reported in the registry record, so the precision of the response estimate cannot be assessed.

How does the study design affect interpretation?

The registry classifies the study model as single-group and allocation as not applicable. In general, a single-group outcome can describe what happened among participants meeting the analysis definition, but it does not provide a randomized between-group estimate. Randomization helps balance measured and unmeasured factors on average between comparison groups; without that structure, differences across separate groups may reflect differences in participants, follow-up, assessment, or other factors as well as treatment. The registry cautions that the listed arms are not a like-for-like control comparison.

Why do endpoint criteria matter?

The primary endpoint uses the Lugano Classification and independent radiology review. The response categories in the registry include complete metabolic response, complete radiological response, partial metabolic response, and partial radiological response, with imaging and disease-measurement criteria specified in the endpoint description. In general, consistent criteria make an endpoint more reproducible, while the chosen criteria determine which participants count as responders. The record also lists investigator-assessed secondary outcomes and different criteria across cohorts. Those results, if reported elsewhere, would not automatically be interchangeable with the primary endpoint.

What is the role of the planning illustrations?

The registry entries state that the sample-size assumptions are planning illustrations computed from the observed effect, not the trial’s own design. The stated assumptions are a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation; the effect to detect is a stated fraction of the observed effect. For time-to-event planning, the stated quantity is total events using the Schoenfeld approach; other planning quantities are participants per arm. These are hypothetical planning calculations, not observed power and not evidence that the study enrolled enough participants to detect an effect. The registry record does not report the study’s own sample-size justification. No planning values are repeated.

What can be concluded from the posted analysis status?

The record lists zero analyses. The primary outcome information does not include an effect estimate or an uncertainty interval. General statistical principles can explain how such quantities would be read, but cannot substitute for their absence. In particular, neither a planning illustration nor a safety count can supply the missing primary endpoint result.

For the adverse-event summaries, counts describe participants recorded as affected within the listed safety groups. In general, group-specific rates depend on a clear denominator and a consistent event definition; severity, timing, exposure, and follow-up also matter. The record includes at-risk and affected counts for serious and other events, but those figures alone are not a comparative causal analysis. Death counts are listed, but the information does not establish their causes or attribute them to treatment.

The methods information available is therefore limited to the endpoint definition, analysis-population description, design classification, and stated planning assumptions. The registry record does not report the full statistical plan, missing-data methods, multiplicity procedures, or interim-analysis details. Those omissions should remain explicit rather than being filled with conventional assumptions.

10. Exact Estimates for Each Arm

No two-arm comparison is shown for this trial, but each arm's result can still be summarized with exact interval estimates computed from the posted counts. The Clopper-Pearson interval is exact and conservative; the Wilson interval is a common closer-to-nominal alternative; the Bayesian credible interval uses a uniform Beta(1, 1) prior. For small groups the three can differ noticeably.

R code and output

arm    <- c("Cohort 1: 2 x 10^6 Brexucabtagene Autoleucel")
n      <- c(68)
events <- c(62)
for (i in seq_along(n)) {
  ci <- binom.test(events[i], n[i])$conf.int          # Clopper-Pearson exact interval
  cr <- qbeta(c(0.025, 0.975), 1 + events[i], 1 + n[i] - events[i])   # Bayesian, uniform Beta(1,1) prior
  wi <- (function(x, n) { p <- x / n; z <- qnorm(0.975); d <- 1 + z^2 / n
    c((p + z^2 / (2 * n) - z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d, (p + z^2 / (2 * n) + z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d) })(events[i], n[i])
  cat(sprintf("ARM|%s|%d|%d|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f\n", arm[i], n[i], events[i], 100 * events[i] / n[i],
              100 * ci[1], 100 * ci[2], 100 * wi[1], 100 * wi[2], 100 * cr[1], 100 * cr[2]))
}

ARM  Cohort 1: 2 x 10^6 Brexucabtagene Autoleucel  68  62  91.2  81.8  96.7  82.1  95.9  82.0  95.8

11. Multiplicity, Missing Data and Analysis Populations

The registry lists a primary response endpoint alongside multiple secondary outcomes. These include duration of response, best objective response, objective response, and progression-free survival, with outcomes specified separately for Cohort 1 and Cohort 2. A family of endpoints raises a multiplicity question: when several statistical hypotheses are tested, the chance of at least one apparently positive result can increase unless the analysis plan accounts for that. This is a general statistical concern, not evidence that a particular adjustment was or was not used in this study.

Multiplicity procedures, a hierarchy for testing outcomes, and any allocation of statistical error across endpoints are not reported in the registry record. The record also does not describe interim analyses or identify which secondary outcomes were formally tested. The number of listed outcomes should not be treated as proof that each was tested or that any specific correction was applied.

The primary outcome description defines the Cohort 1 modified intention-to-treat set as enrolled participants treated with anti-CD19 CAR T cells at any dose in Cohort 1. It states that percentages were rounded. Other details about analysis populations, including how participants with missing assessments were handled, are not reported in the registry record. The missing-data assumptions, methods, and sensitivity analyses are also not reported in the registry record.

These gaps affect interpretation because endpoint estimates can depend on who is included and how unavailable assessments are handled. The absence of a reported method does not show that missing data occurred or that a particular method was used. Likewise, the absence of multiplicity information does not establish that the analyses were invalid; it means the registry record does not support a detailed assessment of those choices.

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: encephalopathy (40.0%), hypotension (21.4%), pyrexia (20.6%), disseminated intravascular coagulation (20.0%), corynebacterium infection (20.0%).

The registry reports safety groups with counts at risk and counts affected by serious events and other events, along with deaths. For example, the group titled “Cohort 1: 2 x 10^6 Brexucabtagene Autoleucel” lists 68 at risk for serious events and 49 affected; its other-event counts are 68 at risk and 68 affected, with 42 deaths listed. These are descriptive entries for that group, not a randomized comparison.

Other listed groups include “2 x 10^6 Axicabtagene Ciloleucel,” “Cohort 2: 0.5 x 10^8 Brexucabtagene Autoleucel,” and retreatment groups. Their reported counts differ, and the group definitions and sizes are not alike. The record warns that the arms are not a like-for-like control comparison. The counts therefore should not be read as comparative estimates of treatment risk, and the death counts do not establish cause or treatment attribution.

The registry lists encephalopathy at 40.0%, hypotension at 21.4%, pyrexia at 20.6%, disseminated intravascular coagulation at 20.0%, Corynebacterium infection at 20.0%, and sepsis at 20.0% among top serious terms. The record information does not provide the term-specific denominators or further context needed to compare these percentages across groups. In general, adverse-event summaries describe recorded events; they do not alone establish causation or predict an individual participant’s outcome.

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

The study record addresses objective response in participants with relapsed/refractory mantle cell lymphoma and defines a Cohort 1 primary endpoint using the Lugano Classification and independent radiology review. It also describes secondary outcomes across two cohorts and records safety information for cohort and retreatment groups. These features identify the questions the study was designed to examine and the outcome definitions used.

However, a numerical primary endpoint result is not reported in the registry record. Without that estimate and its precision, the magnitude of the observed response and the uncertainty around it cannot be assessed from the record. The listed enrollment does not substitute for the endpoint denominator, and safety counts do not provide the missing response result.

The design also limits what a response percentage could mean. The study is single-group, and the registry states that the arms are not a like-for-like control comparison. Even if an outcome estimate were available, it would describe the observed study population under its endpoint definition; it would not by itself establish a causal contrast with a control or identify what would have happened under another treatment strategy.

Response, duration of response, and progression-free survival are different outcomes. A response category does not by itself convey how long that response lasted or whether a participant experienced progression. The registry lists such outcomes separately, and their criteria and assessment approaches vary across cohorts. No numerical results for those outcomes are reported in the information used.

Safety entries likewise describe events recorded in named groups, not proof that treatment caused them. Group counts, affected counts, and death counts should not be interpreted as comparative risks when the groups are not randomized, and the listed death counts do not establish cause. Thus the record supports a description of study design and intended outcome measurement, but not a quantified conclusion about the primary response result or a causal treatment effect.

14. Why This Trial Matters Statistically

This trial is statistically notable for the gap between a clearly specified primary endpoint and the lack of a numerical primary result in the registry record. The endpoint identifies the population, response classification, reviewer, and timeframe, which are central elements for interpreting a clinical outcome. Yet the response percentage and its precision are not reported. A well-defined endpoint cannot answer the outcome question without an estimate and adequate context for its uncertainty.

The single-group model is also important. It can support description of outcomes within a defined cohort, but it does not provide the randomized comparison needed to distinguish treatment effects from other explanations for observed outcomes. The record itself cautions against treating the listed arms as like-for-like controls. This is a design limitation on causal interpretation, not a reason to treat safety or response entries as comparative evidence.

Further, the registry contains cohort-specific outcomes with different assessment criteria and both investigator and independent review approaches. Keeping endpoint definitions and assessment methods separate is essential: results from different criteria or cohorts may not represent the same estimand. The record’s description of the modified intention-to-treat population also illustrates why the denominator must be understood before reading a response percentage.

Finally, planning illustrations should not be confused with the study’s design rationale or observed statistical power. The record describes assumptions for hypothetical planning based on an observed effect, while its own sample-size justification and fuller statistical plan are not reported. Together, these features make the record useful for understanding the statistical questions and constraints, while leaving the principal numerical efficacy result 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 most direct limitation is that the registry record does not report the numerical primary objective-response result or its precision. It therefore does not support an assessment of the observed response magnitude from the primary endpoint. The Cohort 1 analysis-population definition is available, but the primary endpoint numerator and denominator are not reported in the information used.

The single-group design has no randomized control comparison, and the registry explicitly cautions that the listed arms are not like-for-like controls. Outcomes across cohorts or retreatment groups cannot be interpreted as randomized treatment contrasts. The record also contains an intervention-description inconsistency: the study title and intervention listing identify brexucabtagene autoleucel, while the arm description names axicabtagene ciloleucel after conditioning chemotherapy. The record information does not resolve that discrepancy.

The endpoint information specifies independent review for the primary outcome, whereas several secondary outcomes are investigator assessed and use different response criteria across cohorts. Such differences can complicate comparisons between outcomes. The record does not report the statistical analysis plan, missing-data procedures, multiplicity strategy, interim analyses, or sample-size justification.

Safety counts and listed serious-event percentages are descriptive, with no basis in the record information for causal attribution or a like-for-like comparison. The term-specific denominators and additional context are not reported. These limitations concern what can be concluded from the registry record; they do not establish that omitted analyses or information were absent from other study materials.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Study of Brexucabtagene Autoleucel (KTE-X19) in Participants With Relapsed/Refractory Mantle Cell Lymphoma (Cohort 1 and Cohort 2) — NCT02601313.
• Registry record last updated 2026-03-18; status last verified 2026-03.
• Results first posted 2020-09-10.
• 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

NCT02601313 is a completed phase 2, multicenter, single-group study of KTE-X19 in relapsed/refractory mantle cell lymphoma. The registry records enrollment of 105, no masking, and allocation as not applicable. The primary endpoint is the percentage of Cohort 1 participants with objective response under the Lugano Classification according to independent radiology review, with a timeframe of up to 7.8 years.

The primary endpoint population is described as enrolled participants treated with anti-CD19 CAR T cells at any dose in Cohort 1. The registry lists secondary response, duration-of-response, and progression-free-survival outcomes for Cohort 1 and Cohort 2. Safety groups and serious-event terms are also recorded.

The registry record does not report a numerical primary endpoint result, confidence interval, or full statistical analysis plan. Its intervention and arm wording also contains a discrepancy regarding the infused product. These limitations prevent a quantified interpretation of the primary response outcome and caution against treating listed groups as comparative controls.