A Study of Brentuximab Vedotin and CHP in Frontline Treatment of PTCL With Less Than 10% CD30 Expression: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Study of Brentuximab Vedotin and CHP in Frontline Treatment of PTCL With Less Than 10% CD30 Expression (NCT04569032), a non-randomized phase 2 study. The primary outcome is Objective Response Rate (ORR) Per Blinded Independent Central Review (BICR) by Revised Response Criteria for Malignant Lymphoma Criteria (Cheson 2007) by Central CD30 Assessment.

2. Clinical Question

3. Trial Design

This was a phase 2, open-label, non-randomized, parallel-cohort study. The registry lists an enrollment of 82 and describes the study as completed. The recorded start date is 2020-11-12 and the primary completion date is 2024-05-09. These record details describe the trial’s status and schedule; they do not provide its primary outcome result.

Participants had PTCL with CD30 expression below 10% and were grouped according to CD30 expression. The CD30-negative cohort was defined as expression less than 1%. The CD30-positive cohort was defined as expression at least 1% and less than 10%. The cohort definitions are not treatment assignments, and the registry identifies no randomized control comparison. Because allocation was non-randomized, differences between cohorts could reflect differences in their participants or other factors as well as CD30 category.

The intervention was brentuximab vedotin with CHP, with CHP consisting of cyclophosphamide, doxorubicin, and prednisone. The study was open-label, meaning the record does not describe masking of treatment assignment. The primary endpoint used blinded independent central review, a separate assessment feature that does not make the overall trial masked.

The primary outcome was ORR by the Cheson 2007 criteria, classified by central CD30 assessment. The listed follow-up point was the end of treatment or the first assessment after the last dose, before long-term follow-up or subsequent anti-cancer therapies; the stated timeframe was up to 41.91 months. Secondary outcomes included response and time-to-event measures, as well as adverse events and laboratory abnormalities. The registry record does not report the primary ORR estimate or analysis results.

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: Results reported are based on the primary completion date (PCD) of the study; data for only those secondary outcome measures are reported for which analyses were complete at PCD. Remaining outcome measures would be reported upon completion of their analyses at study completion.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Full analysis set (FAS) included all participants who received any amount of brentuximab vedotin or any component of cyclophosphamide, doxorubicin, and prednisone (CHP). Analyses as planned was based on the participants classified based on central laboratory assessment for CD30 expression.

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 Objective Response Rate (ORR) Per Blinded Independent Central Review (BICR) by Revised Response Criteria for Malignant Lymphoma Criteria (Cheson 2007) by Central CD30 Assessment, measured over At EOT or the first assessment after the last dose of study treatment (prior to long term follow-up or initiation of subsequent anti-cancer therapies); up to 41.91 months.

Objective response rate is the percentage of participants who meet the specified criteria for complete response or partial response. In this study, response was assessed after completion of study treatment, at end of treatment or at the first assessment after the last dose and before long-term follow-up or subsequent anti-cancer therapies. The stated timeframe was up to 41.91 months.

The registry defines complete response as disappearance of all detectable clinical evidence of disease and disease-related symptoms if present before therapy. Partial response was defined using a reduction of at least 50% in the sum of the product of the diameters of up to six of the largest dominant nodes or nodal masses. These definitions follow the listed Cheson 2007 response criteria. Blinded independent central review (BICR) was used to assess the endpoint, and participants were classified by central CD30 assessment.

In general, a response proportion is a compact summary of how many assessed participants met a prespecified response definition. It does not by itself describe how long a response lasted, whether the disease later progressed, survival, or adverse effects. The registry lists these as separate secondary outcomes. A confidence interval would convey uncertainty around the response proportion, but the primary endpoint result and its interval are not reported in the registry record. The endpoint definition alone cannot establish the observed response rate.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry identifies a binary percentage endpoint: ORR, defined by whether a participant had a complete or partial response. For this kind of endpoint, the basic descriptive statistic is a proportion among participants assessed for the outcome. A 95% confidence interval, when reported, represents uncertainty about the underlying response proportion under the assumptions of the method used. It is not a range containing a guaranteed share of individual participants’ outcomes, and it does not account automatically for every design limitation.

What does central review add?

The primary outcome was assessed by blinded independent central review using the Cheson 2007 criteria. Central review means the response classification was made through the specified independent review process rather than relying only on local assessment. Blinding the reviewers can reduce the influence of knowledge of treatment or other information on outcome classification. This endpoint-level review feature is distinct from the overall trial design: the study itself is listed as open-label. The registry does not report further details about review procedures, disagreement resolution, or the number of assessments available.

Why distinguish central and local CD30 assessment?

The primary outcome and several response-related secondary outcomes were classified by central CD30 assessment. The safety groups, by contrast, are labeled by local laboratory assessment. These are different assessment bases and should not be silently treated as interchangeable. Central assessment was the planned basis for classifying participants in the primary analysis; local assessment was used for the posted safety group labels. The registry record does not report how often the assessments differed or how any discrepancies were handled.

What does non-randomized allocation imply?

Randomization is a method for creating comparable treatment groups on average. This study is explicitly listed as non-randomized, and the CD30 cohorts are categories of participants rather than assigned treatment arms. General statistical interpretation therefore treats cohort results as descriptive. A difference in response or safety counts between these groups could be related to CD30 category, other participant characteristics, or other factors. Without a randomized treatment comparison and an analysis addressing relevant differences, cohort contrasts do not identify a causal treatment effect.

How should the confidence interval be read?

In general, a confidence interval communicates the precision of an estimate: narrower intervals indicate greater statistical precision under the analysis assumptions, while wider intervals indicate less precision. It does not correct for selection bias, measurement differences, missing outcomes, or confounding. The primary endpoint specifies a 95% confidence interval, but its numerical result is not reported in the registry record. No interval width or level of uncertainty around the observed ORR can therefore be interpreted from the record.

What is the role of the endpoint definition?

A prespecified response definition gives a consistent rule for deciding which observations count as responses. Here, complete response and partial response are defined using the listed Cheson 2007 criteria, and ORR combines the two categories into a percentage. This summary does not preserve all detail about response depth or duration. Duration of response, progression-free survival, and overall survival were listed separately as secondary outcomes. The record does not provide their results in the registry record described for this analysis.

How do planning illustrations differ from observed results?

General sample-size planning asks how many participants per arm might be needed under stated assumptions to detect a chosen effect with a specified power and significance level. The registry’s planning description says its illustration uses the observed effect, 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. Such illustrations are planning calculations, not observed power and not evidence that the study achieved a particular power. For time-to-event outcomes, the description specifies total events; for other outcomes, it specifies participants per arm. The primary ORR result is not reported, so the record does not permit interpretation of an observed effect from that endpoint. The trial’s own sample-size justification is not reported in the registry record.

What can be inferred from the safety counts?

Safety counts are descriptive summaries of participants recorded with events within the listed local-assessment cohorts. A count does not show event timing, duration, severity beyond the stated category, or whether the event was judged treatment-related unless the record explicitly identifies that measure. The secondary outcomes include treatment-emergent adverse events, serious adverse events, treatment-related adverse events, and laboratory abnormalities, but the posted counts do not provide every detail for those outcomes. General statistical practice distinguishes the number of participants with at least one event from the number of event episodes; readers should follow the registry’s outcome wording and not treat the count as a count of episodes without confirmation.

In general, a complete statistical assessment also considers the analysis population, missing observations, endpoint timing, and any multiplicity adjustments. The registry describes the full analysis set and the planned CD30 classification basis, but does not report the primary estimate, the missing-data handling, or multiplicity procedures. Those gaps limit interpretation even when endpoint definitions and design features are available.

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("CD30 <1% [Central Laboratory Assessment]", "CD30 1% to <10% [Central Laboratory Assessment]")
n      <- c(23, 31)
events <- c(14, 25)
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  CD30 <1% [Central Laboratory Assessment]  23  14  60.9  38.5  80.3  40.8  77.8  40.6  77.9
ARM  CD30 1% to <10% [Central Laboratory Assessment]  31  25  80.6  62.5  92.5  63.7  90.8  63.6  90.7

11. Multiplicity, Missing Data and Analysis Populations

The registry lists the primary ORR endpoint and secondary outcomes covering complete response, progression-free survival, overall survival, duration of response, ORR under modified Lugano criteria, adverse events, and laboratory abnormalities. Considering multiple outcomes can increase the chance of obtaining at least one apparently notable result by chance if many statistical tests are performed. In general, multiplicity procedures can control that risk, but the appropriate approach depends on the analysis plan and the intended claims. A multiplicity strategy is not reported in the registry record. The record lists no analysis entries.

The full analysis set included participants who received any amount of brentuximab vedotin or any component of CHP. The planned analyses were based on classification using central laboratory assessment for CD30 expression. This definition identifies who was included in the described analysis population, but it does not tell readers how many participants contributed to the primary endpoint or how missing response assessments were handled.

Missing outcome data can affect a response proportion if participants without an assessment are excluded, counted as nonresponders, or handled by another rule. These approaches can produce different estimates. The handling of missing primary endpoint data, the extent of missingness, and any sensitivity analyses are not reported in the registry record. The record also does not report a sample-size justification or the protocol’s statistical plan. Therefore, the stated endpoint and population definition are not enough to reconstruct the full analysis or assess the impact of unavailable observations.

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: febrile neutropenia (18.8%), pyrexia (11.8%), diarrhoea (5.9%), fatigue (5.9%), anaemia (4.2%).

The registry reports safety counts in cohorts defined by local CD30 assessment. For the cohort with CD30 less than 1%, 34 participants were listed as at risk for serious adverse events, with 15 affected; 34 were listed as at risk for other adverse events, with 31 affected; and deaths were listed as 11. For the cohort with CD30 from 1% to less than 10%, the corresponding at-risk counts were 48 for serious and other adverse events, with 16 and 43 affected, respectively; deaths were listed as 13. These counts are descriptive and do not establish a causal difference between cohorts.

The most frequent serious adverse event terms listed with percentages were febrile neutropenia at 18.8% and pyrexia at 11.8%. Diarrhoea and fatigue were each listed at 5.9%; anaemia and hypoxia were each listed at 4.2%. The record does not give further detail alongside these terms about event duration or timing. The percentages should be read as the registry’s reported values, not recalculated from the cohort counts.

Serious adverse events, other adverse events, and deaths are distinct summaries. Counts alone do not indicate whether each event was considered related to treatment, and they do not provide a comparison with an untreated or randomized control group.

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

The record establishes that this was a completed, open-label, non-randomized phase 2 study of brentuximab vedotin with CHP in PTCL with CD30 expression below 10%. It defines two CD30 cohorts, specifies the primary response criteria and assessment process, and reports selected safety counts. These features allow readers to understand what the study set out to assess and how the primary endpoint was defined.

They do not establish the observed primary response rate. The primary ORR estimate and its 95% confidence interval are not reported in the registry record. Without those results, the magnitude of response and its precision cannot be evaluated from this record. The presence of a defined endpoint is not itself evidence of an outcome.

The two CD30 cohorts also do not provide a randomized comparison. They differ by a biomarker category and were not assigned as treatment and control groups. Any observed difference between them would require cautious descriptive interpretation and could not, on its own, show that the category caused the difference. The record does not provide an untreated or randomized control comparison for estimating the effect of the combination against another treatment.

The safety counts show the numbers listed for adverse events and deaths in each local-assessment cohort. They are useful as descriptive information, but they do not alone establish treatment causation, relative risk, or a complete safety profile. The registry also lists additional safety and laboratory outcomes, while detailed results for those measures are not reported in the record details.

Accordingly, the defensible reading is limited: the registry describes the trial design, planned response assessment, cohort definitions, and selected safety observations. It does not permit an efficacy conclusion, a causal comparison between CD30 cohorts, or a judgment about the precision of the primary endpoint estimate.

14. Why This Trial Matters Statistically

This trial is statistically notable for separating a planned response assessment from the biomarker grouping used to describe participants. The primary endpoint relied on blinded independent central review and central CD30 assessment, whereas the reported safety groups are labeled by local CD30 assessment. Keeping these assessment bases distinct is important when reading endpoint definitions and group-level safety counts.

The design also illustrates why cohort comparisons are not automatically treatment comparisons. The study was non-randomized and organized in parallel cohorts defined by CD30 expression. Those categories can support descriptive reporting, but they do not provide the balance created by random assignment. A difference between cohorts should not be interpreted as a causal effect of CD30 status or of treatment without an appropriate analysis and supporting design.

The endpoint definition is another important statistical feature. ORR combines complete and partial response into a percentage under specified criteria, while other outcomes such as duration of response, progression-free survival, and overall survival answer different questions. Treating these endpoints as interchangeable would obscure what each measures.

Finally, the distinction between a planned endpoint and a posted result matters. The registry describes the primary outcome and its confidence interval as the measure of interest, but the primary numerical estimate and interval are not reported in the registry record. Statistical interpretation must therefore stop short of an efficacy conclusion. The available material supports examination of the design and selected safety counts, while leaving the principal response estimate unavailable.

15. Limitations

• The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
• Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.

The primary limitation for interpreting the study’s main question is that the registry record does not report the primary ORR estimate or its 95% confidence interval. Without these values, neither the observed response proportion nor its precision can be described. Endpoint definitions and an assessment timeframe do not substitute for outcome results.

The study was non-randomized, and the CD30 categories were cohorts rather than randomized treatment arms. This limits causal interpretation of any differences between cohorts. The registry does not describe a like-for-like control comparison. The open-label design is also relevant to the overall study context, although the primary endpoint was assessed by blinded independent central review.

The primary endpoint used central CD30 assessment, while safety groups were labeled by local CD30 assessment. The registry record does not report agreement between the assessment methods or how discrepancies were managed. It also does not report the handling or extent of missing primary outcome data, sensitivity analyses, or a multiplicity procedure across the listed outcomes.

The safety information described in the record is limited to selected counts and serious adverse event terms with percentages. These summaries do not give full event timing, duration, or attribution detail, and counts alone cannot establish causality. The trial’s own sample-size justification and statistical plan are not reported in the registry record. These limitations constrain conclusions about both the main response question and the broader pattern of outcomes.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: A Study of Brentuximab Vedotin and CHP in Frontline Treatment of PTCL With Less Than 10% CD30 Expression — NCT04569032.
• Registry record last updated 2026-08-13; status last verified 2026-07.
• Results first posted 2025-05-15.
• 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 describes a completed phase 2, open-label, non-randomized, parallel-cohort study of brentuximab vedotin with cyclophosphamide, doxorubicin, and prednisone in PTCL with CD30 expression below 10%. Enrollment was 82. Participants were grouped as CD30 less than 1% or CD30 at least 1% and less than 10%.

The primary outcome was ORR by blinded independent central review using Cheson 2007 criteria and central CD30 assessment. The primary response estimate and confidence interval are not reported in the registry record. Selected adverse event counts are reported by local CD30 assessment, but they do not constitute a randomized comparison. The record lists secondary response, survival, adverse event, and laboratory outcomes; the analyses and statistical details needed for fuller interpretation are not reported.