This page separates reported registry information from statistical interpretation. The ClinicalTrials.gov record reports that results are posted, but the ClinicalTrials.gov record contains no formal statistical analyses, estimates, confidence intervals, or p-values for the primary endpoint.
1. Trial at a Glance
ECHELON-2 was a randomized, double-blind, parallel phase 3 treatment trial evaluating brentuximab vedotin with CHP versus standard-of-care CHOP in patients with CD30-positive mature T-cell lymphomas.
| Feature | ECHELON-2 |
|---|---|
| Trial name | ECHELON-2 |
| NCT identifier | NCT01777152 |
| Therapeutic area | Hematology |
| Phase | Phase 3 |
| Status | Completed |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | Double |
| Primary purpose | Treatment |
| Enrollment | 452.0 |
| Arms | 2 |
| Primary endpoint | Progression-free Survival Per Independent Review Facility (IRF) |
| Primary endpoint type | Time-to-event |
| Results posted | Yes |
| Outcome measures posted | 7 |
| Lead sponsor | Seagen Inc. |
| Sponsor type | Industry |
2. Clinical Question
The central statistical question is whether the randomized treatment comparison in patients with CD30-positive mature T-cell lymphomas differs with respect to the registered primary time-to-event endpoint, Progression-free Survival Per Independent Review Facility (IRF).
Population
Patients with the registered conditions of anaplastic large-cell lymphoma, non-Hodgkin lymphoma, and T-cell lymphoma, within the trial's stated population of patients with CD30-positive mature T-cell lymphomas.
Intervention
Brentuximab vedotin with CHP. The registered interventions also include doxorubicin, prednisone, and cyclophosphamide.
Comparator
Standard-of-care CHOP.
Primary question
How does the randomized comparison of brentuximab vedotin with CHP versus standard-of-care CHOP relate to progression-free survival as defined by the independent review facility?
3. Trial Design
Randomization is a core design feature for comparing outcomes between the two treatment groups while reducing systematic differences attributable to treatment assignment.
The registry identifies the trial as double-masked. Blinding can reduce the influence of knowledge of treatment assignment on trial conduct and assessment.
The trial uses a parallel design, meaning the randomized treatment groups are followed as separate groups rather than being assigned sequential treatment periods.
The registered primary purpose is treatment.
Brentuximab vedotin + CHP
- Brentuximab vedotin
- Doxorubicin
- Prednisone
- Cyclophosphamide
Standard-of-care CHOP
- Standard-of-care CHOP
- The ClinicalTrials.gov record identifies vincristine among the trial interventions.
the ClinicalTrials.gov record identifies the study as a two-arm randomized, double-blind, parallel phase 3 trial with 452.0 enrolled participants. The available data do not provide a randomization ratio, treatment-group enrollment counts, stratification factors, or treatment schedules, so those quantities are not reconstructed here.
4. Endpoints
| Endpoint | Registered definition | Time frame | Endpoint type |
|---|---|---|---|
| Progression-free Survival Per Independent Review Facility (IRF) | The time from the date of randomization to the date of first documentation of progressive disease (PD), death due to any cause, or receipt of subsequent anticancer chemotherapy to treat residual or progressive disease whichever occurred first. | Up to 60 months | Time-to-event |
Why the endpoint is time-to-event
The primary endpoint is not simply a binary response measure. It records when the first qualifying event occurs after randomization. That distinction is important because patients can have different lengths of follow-up, and some participants may not have experienced the endpoint by the time their observed follow-up ends.
The registry definition includes three possible events: progressive disease, death from any cause, or receipt of subsequent anticancer chemotherapy to treat residual or progressive disease. Whichever qualifying event occurs first determines the event time under the registered definition.
5. Statistical Methodology
The registry-reported ECHELON-2 trial data classify the primary endpoint as a time-to-event outcome, but they do not provide a formal statistical analysis record for it. The appropriate statistical framework for an endpoint of this type would ordinarily account for both the event time and right-censored observations.
Kaplan-Meier estimation
A Kaplan-Meier analysis is commonly used to estimate the distribution of time to a specified event. Patients who have not experienced the endpoint by their last evaluable follow-up can contribute information up to that time without being treated as if the event had occurred.
Here, di represents the number of events at time ti, while ni represents the number of participants at risk immediately before that time.
Hazard ratios
For a randomized comparison with a time-to-event endpoint, a Cox proportional-hazards model is a standard method for estimating a hazard ratio between treatment groups. The hazard ratio is a relative measure of the instantaneous event rate under the model; it is not the same as an absolute difference in event probability.
A hazard ratio must be interpreted together with its confidence interval, analysis population, follow-up, censoring rules, and model assumptions.
Log-rank comparison
A log-rank test is commonly used to compare time-to-event distributions between randomized groups. Unlike a simple comparison of proportions at a single time point, it uses information from event times throughout follow-up while accounting for censoring.
Independent review facility assessment
The registered endpoint specifically identifies the Independent Review Facility (IRF). Independent assessment is relevant because progression determination can be subject to assessment procedures and interpretation. The registry definition reported here does not provide additional operational details about the review process, so no further assumptions are made.
6. Planned Analysis
ClinicalTrials.gov reports that results have been posted for the primary endpoint, but the ClinicalTrials.gov record contains no formal statistical analyses. In particular, no hazard ratio, confidence interval, p-value, event count, median progression-free survival, or treatment-group estimate is provided for the primary endpoint in the ClinicalTrials.gov record.
How this endpoint would normally be analysed
- Define the analysis population according to the prespecified statistical analysis plan.
- Determine each participant's time from randomization to the first qualifying primary endpoint event.
- Apply the registered event definition consistently, including progressive disease, death from any cause, and the specified subsequent anticancer chemotherapy event.
- Censor observations according to prespecified rules when the endpoint has not occurred by the relevant end of observation.
- Estimate the time-to-event distributions using Kaplan-Meier methods.
- Compare randomized treatment groups using an appropriate time-to-event test, commonly a log-rank framework.
- Estimate a relative treatment effect, commonly using a Cox proportional-hazards model, together with a confidence interval.
These are methodological explanations rather than reported ECHELON-2 results. The ClinicalTrials.gov record does not provide the numerical output needed to populate a formal treatment-effect result.
7. Safety Results
The ClinicalTrials.gov record reports serious adverse events by randomized arm. These figures are the only arm-specific safety counts provided in the trial data.
| Safety measure | Brentuximab vedotin + CHP | CHOP |
|---|---|---|
| Serious adverse events, affected / at risk | 89 / 223 | 90 / 226 |
The registry reports affected participants together with the corresponding at-risk counts. These figures should be read as counts within the registry-reported safety populations; they should not be treated as efficacy results or used to infer a causal safety difference without the complete prespecified safety analysis.
8. Statistical Methods Explained
Why is progression-free survival a time-to-event endpoint?
Because the endpoint incorporates the time from randomization until the first qualifying event, participants can contribute different amounts of follow-up. This makes methods designed for censored time-to-event data more appropriate than simply comparing the proportion of patients with an event.
Why does the IRF designation matter?
The endpoint is explicitly defined as progression-free survival per an Independent Review Facility. That designation identifies the source of the progression assessment used for the registered endpoint and is therefore part of the endpoint definition itself.
Why is death included in progression-free survival?
Death is explicitly one of the qualifying events in the registry definition. A patient therefore does not remain event-free merely because progressive disease was not documented before death.
Why does subsequent anticancer chemotherapy appear in the endpoint definition?
The registered definition specifies receipt of subsequent anticancer chemotherapy to treat residual or progressive disease as one of the qualifying events. Including it changes the precise statistical definition of the endpoint compared with a simpler definition based only on documented progression or death.
Why is censoring important?
A patient who has not experienced the endpoint during the observed period does not necessarily have an event-free lifetime. Time-to-event methods preserve the information available up to the last relevant observation rather than assigning an artificial event date.
What would a hazard ratio tell us?
A hazard ratio would summarize the estimated relative event rate between the randomized treatment groups under a specified statistical model. It would not directly state the probability that an individual patient benefits, nor would it substitute for absolute event probabilities or survival estimates at clinically relevant time points.
Why should a p-value not be reported when the registry data do not provide one?
A p-value is an output of a particular statistical test under a particular analysis specification. Without a reported analysis, importing or reconstructing a p-value would create a result that is not contained in the ClinicalTrials.gov record. The appropriate approach is to describe the analysis that would normally be used without presenting an unreported numerical result.
9. Analysis Populations and Interpretation
the ClinicalTrials.gov record provides the total enrollment of 452.0 and the serious-adverse-event at-risk counts of 223 and 226, but it does not define the efficacy analysis population, safety population beyond those reported at-risk counts, per-protocol population, or modified intention-to-treat population.
| Population / concept | What can be established from the ClinicalTrials.gov record |
|---|---|
| Total enrollment | 452.0 participants were enrolled. |
| Randomized design | The trial is classified as randomized. |
| Efficacy analysis population | Not specified in the ClinicalTrials.gov record. |
| Safety analysis population | Serious adverse events are reported as 89/223 for A+CHP and 90/226 for CHOP. |
| Per-protocol population | Not specified in the ClinicalTrials.gov record. |
| Modified ITT population | Not specified in the ClinicalTrials.gov record. |
This distinction matters because an effect estimate cannot be interpreted correctly without knowing which participants were included and how deviations, treatment exposure, and missing observations were handled.
10. Missing Data, Censoring, and Time Frame
The primary endpoint has a registered time frame of up to 60 months. Because it is a time-to-event endpoint, the analysis must distinguish an observed qualifying event from an observation that ends before an event occurs.
Censoring
The statistical analysis would normally require prespecified rules for determining when a participant is censored rather than counted as having experienced the endpoint.
Missing assessments
Missing or delayed disease assessments can affect the determination of progression time. The ClinicalTrials.gov record does not specify the missing-assessment or imputation rules.
Administrative follow-up
A participant can reach the end of the defined observation period without experiencing the endpoint. Time-to-event methods can incorporate that incomplete event information through censoring.
Endpoint window
The registry specifies follow-up for the primary endpoint as up to 60 months. No additional time frame is substituted.
11. Blinding and Independent Assessment
The trial is registered as double masked. Blinding is a design feature intended to limit the influence of treatment assignment knowledge on trial conduct, participant management, assessment, or other aspects of the study, depending on the exact implementation.
The primary endpoint is also defined as progression-free survival per an Independent Review Facility. Together, these features make assessment procedures an important statistical-design topic: progression is an observed endpoint, and the mechanism used to determine whether progression has occurred becomes part of the measurement process.
For a time-to-event endpoint, statistical analysis depends not only on the mathematical model but also on how event dates, censoring dates, and qualifying events are operationally determined.
12. Randomization and Causal Interpretation
Randomization is explicitly recorded in the ClinicalTrials.gov record. In a randomized treatment trial, the fundamental statistical comparison is between outcomes according to the assigned treatment groups rather than according to treatment received after randomization.
This distinction is particularly important when interpreting time-to-event outcomes. Treatment discontinuation, deviations from assigned therapy, subsequent therapy, or other post-randomization events can complicate the relationship between assignment and observed exposure. The ClinicalTrials.gov record does not describe crossover or subsequent-treatment rules, so no such effects are assumed here.
13. Multiplicity and Interim Analysis
The ClinicalTrials.gov record does not provide information about multiplicity adjustment, alpha allocation, interim analyses, stopping boundaries, group-sequential monitoring, or an endpoint hierarchy beyond identifying one registered primary endpoint.
| Design topic | Information in the ClinicalTrials.gov record |
|---|---|
| Primary endpoint count | 1 |
| Multiplicity adjustment | Not reported in the ClinicalTrials.gov record. |
| Interim analysis | Not reported in the ClinicalTrials.gov record. |
| Alpha-spending method | Not reported in the ClinicalTrials.gov record. |
| Stopping boundary | Not reported in the ClinicalTrials.gov record. |
| Bayesian methods | Not reported in the ClinicalTrials.gov record. |
These omissions matter because the interpretation of a p-value depends on the testing strategy that generated it. When multiple looks at the data or multiple hypotheses are formally incorporated into a trial, the nominal significance level may not correspond directly to the overall type I error rate unless the design accounts for that multiplicity.
14. Non-Inferiority, Factorial Design, and Crossover
The ClinicalTrials.gov record does not identify ECHELON-2 as a non-inferiority trial, do not provide a non-inferiority margin, and do not describe a factorial design or crossover scheme.
Non-inferiority margin
No non-inferiority margin is reported in the ClinicalTrials.gov record.
Factorial design
The registered design model is parallel; no factorial structure is reported in the ClinicalTrials.gov record.
Crossover
No crossover procedure is reported in the ClinicalTrials.gov record.
Bayesian analysis
No Bayesian method is reported in the ClinicalTrials.gov record.
These distinctions are important because non-inferiority, factorial, crossover, and Bayesian trials require different statistical interpretations. They should not be inferred simply because a trial has a randomized treatment comparison.
15. Trial Timeline
Trial start
The registered ECHELON-2 trial began on January 31, 2013.
Primary completion
The registered primary completion date was August 15, 2018.
Completed
the ClinicalTrials.gov record lists the study status as completed.
16. Primary Endpoint: Statistical Interpretation Framework
The registered primary endpoint measures time from randomization to the first occurrence of progressive disease, death due to any cause, or receipt of subsequent anticancer chemotherapy to treat residual or progressive disease, whichever occurs first.
No hazard ratio, confidence interval, p-value, event count, median progression-free survival, or arm-specific primary-endpoint estimate is provided in the posted results. Therefore, no numerical treatment effect is reported on this page.
If a hazard ratio and 95% confidence interval were available, the interval would describe statistical uncertainty around the estimated treatment effect under the specified model and analysis framework. It would not describe the range of effects experienced by individual patients.
If a p-value were available, it would describe evidence against a specified null hypothesis under the statistical testing framework. It would not quantify the magnitude of clinical benefit. Effect size, uncertainty, absolute event probabilities, and the testing framework should be interpreted separately.
17. Limitations
- Incomplete numerical analysis record: the ClinicalTrials.gov record states that results are posted but contain no formal statistical analyses. Consequently, formal numerical treatment-effect results cannot be reproduced from the ClinicalTrials.gov recordset.
- No primary-event counts: the number of primary endpoint events by arm is not reported.
- No median progression-free survival: no median time-to-event estimate is reported.
- No confidence intervals: the ClinicalTrials.gov record does not provide uncertainty intervals for the primary endpoint.
- No p-values: no formal hypothesis-test results are posted on ClinicalTrials.gov for the primary endpoint.
- No analysis population definition: the ClinicalTrials.gov record does not identify the exact efficacy analysis population.
- No censoring specification: the registry definition is reported, but detailed censoring rules are not.
- No missing-data procedure: imputation or missing-assessment handling is not described in the ClinicalTrials.gov record.
- No stratification information: randomization is reported, but stratification factors are not provided.
- No multiplicity or interim-analysis details: the ClinicalTrials.gov record does not specify alpha adjustment, interim looks, or stopping boundaries.
- No crossover information: the ClinicalTrials.gov record does not describe crossover or subsequent-treatment rules.
- Safety scope: only serious adverse events by arm are reported; broader safety interpretation would require the complete safety dataset.
18. Why This Trial Matters Statistically
ECHELON-2 is a useful teaching example because its registry profile brings several fundamental clinical-trial concepts together: randomization, double masking, parallel-group design, an independent-review time-to-event endpoint, and a defined observation window of up to 60 months.
| Concept | How it appears in ECHELON-2 |
|---|---|
| Randomization | The allocation is explicitly registered as randomized. |
| Blinding | The masking designation is double. |
| Parallel design | The design model is parallel with 2 arms. |
| Time-to-event analysis | The primary endpoint is classified as time-to-event. |
| Independent assessment | The primary endpoint is defined per Independent Review Facility. |
| Composite event definition | Progressive disease, death, or specified subsequent anticancer chemotherapy can define the first endpoint event. |
| Censoring | Time-to-event methodology ordinarily requires rules for observations without a qualifying event during follow-up. |
| Statistical uncertainty | A formal analysis would ordinarily pair an effect estimate with a confidence interval. |
| Hypothesis testing | A formal comparison would ordinarily specify the null hypothesis and testing framework. |
| Safety analysis | Serious adverse events are reported by arm with affected and at-risk counts. |
19. Statistical Methods Explained: A Deeper View
Why not compare only 60-month event rates?
A single time-point comparison discards information about when events occurred. A time-to-event analysis uses the timing of events throughout follow-up and can accommodate participants whose observations end before an event.
Why does randomization matter?
Random assignment provides the design foundation for comparing outcomes between treatment groups without intentionally assigning treatment according to prognostic characteristics.
Why is double masking useful?
Knowledge of treatment assignment can influence behavior and assessment. Masking is designed to reduce such influences where feasible.
Why is an IRF named in the endpoint?
The identity of the assessment mechanism is part of the registered endpoint specification. It helps define how progression is determined for the primary analysis.
20. Results Reporting Status
the ClinicalTrials.gov record states that results are posted and that 7 outcome measures are posted. However, the ClinicalTrials.gov recordset contains zero formal statistical analyses.
| Reported registry feature | Supplied information |
|---|---|
| Results posted | Yes |
| Outcome measures posted | 7 |
| Primary endpoints registered | 1 |
| Results posted for primary endpoint | Yes |
| Formal statistical analyses reported | None |
| Analyses omitted for length | 0 |
This distinction is important for reproducible evidence reporting. A registry can contain outcome-measure information without the particular formal statistical-analysis fields needed to state a hazard ratio, confidence interval, or p-value. A rigorous statistical summary should preserve that distinction rather than fill the gap with estimates from memory or an unrelated source.
21. Sources
- ClinicalTrials.gov: NCT01777152 — ECHELON-2.
- PubMed: PMID 40829107.
- PubMed: PMID 40750774.
- PubMed: PMID 35470385.
- PubMed: PMID 30522922.
- PubMed: PMID 25135998.
The numerical trial content on this page is restricted to the registry-reported ECHELON-2 trial data. The linked PubMed records are provided as source navigation and are not used here to introduce additional numerical trial results.
Continue through the Clinical Biostats statistical methods library
Use the related tutorials and calculators to explore the design concepts that underpin randomized clinical-trial analysis.
22. Record Summary
ECHELON-2 is a completed randomized, double-blind, parallel phase 3 treatment trial with 452.0 enrolled participants and 2 treatment arms. Its registered primary endpoint is progression-free survival per Independent Review Facility, defined as time from randomization to first documentation of progressive disease, death due to any cause, or receipt of subsequent anticancer chemotherapy to treat residual or progressive disease, whichever occurs first, with a time frame of up to 60 months.
The statistical structure of the endpoint naturally leads to time-to-event methods such as Kaplan-Meier estimation, log-rank comparison, and Cox modeling. However, the ClinicalTrials.gov record contains no formal statistical-analysis results for the primary endpoint. The page therefore distinguishes the registered endpoint and appropriate statistical framework from numerical treatment-effect evidence that is not present in the ClinicalTrials.gov record.
The ClinicalTrials.gov record reports serious adverse events in 89 of 223 participants in the A+CHP arm and 90 of 226 participants in the CHOP arm. These figures are presented as reported and are not expanded into unreported safety analyses.