A Study to Determine the Efficacy and Safety of Lenalidomide in Patients With Mantle Cell NHL Who Have Relapsed or Progressed After Treatment With Bortezomib or Are Refractory to Bortezomib. The "EMERGE" Trial: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Study to Determine the Efficacy and Safety of Lenalidomide in Patients With Mantle Cell NHL Who Have Relapsed or Progressed After Treatment With Bortezomib or Are Refractory to Bortezomib. The "EMERGE" Trial (NCT00737529), a na phase 2 study. The primary outcome is Percentage of Participants Who Achieved an Overall Response According to the Independent Review Committee (IRC).

2. Clinical Question

The clinical question is therefore descriptive: among the enrolled participants meeting the study’s treatment-history criteria and receiving study drug, how often did the IRC classify the best observed tumor response as complete, complete unconfirmed, or partial? The endpoint was assessed from Day 1 of study treatment through progression or early treatment discontinuation, with the reported data cutoff on 06 April 2016. The record also reports a median treatment duration of 94.5 days.

Because the study had one treatment group and no masking, its response endpoint cannot establish how outcomes would have differed under another treatment. The registry record describes the endpoint and the criteria used to define response, but not the numerical primary outcome result. That missing estimate limits interpretation of the trial’s central efficacy question from this record alone.

3. Trial Design

EMERGE was a Phase 2, multicenter, single-arm, open-label study of lenalidomide in participants with mantle cell lymphoma who had relapsed, progressed after bortezomib, or were refractory to bortezomib. The registry lists the allocation as not applicable and the model as a single group. There was no control arm and no masking.

The record reports enrollment of 134 participants. Its primary endpoint population is described as all enrolled participants who received at least one dose of study drug. Lenalidomide was administered as a single agent. The recorded regimen was 10mg or 25 mg oral capsules on days 1 to 21 of each 28 day cycle, with dose dependent on renal function. For participants with normal renal function, defined as creatinine clearance of at least 60 mL/min, the record specifies 25 mg daily. The available regimen description does not provide complete dosing details for every renal-function category.

The study began on 2008-12-22, reached primary completion on 2016-04-06, and is listed as completed. The primary endpoint timeframe runs from Day 1 of study treatment to progression or early treatment discontinuation, with a data cutoff of 06 April 2016. Median duration of treatment was 94.5 days.

This design can describe outcomes observed in the treated study group, but it cannot estimate a randomized treatment contrast. Without a concurrent comparison group, changes in outcomes cannot be separated from other influences through randomization. Open-label status also means the study was not masked, although the primary endpoint was assessed according to the IRC. The registry record does not report the protocol’s sample-size justification, interim-analysis plan, or a detailed 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: All participants were required to have local histologic confirmation of Mantle Cell Lymphoma (MCL) for entry into the study.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: ITT population defined as all enrolled participants who received at least one 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: The baseline characteristics are from the participants assesed within the intent to treat population (ITT), which included all enrolled participants who received at least one dose of study drug.

6. Primary Endpoint

The registry lists the primary outcome as Percentage of Participants Who Achieved an Overall Response According to the Independent Review Committee (IRC), measured over From Day 1 of study treatment to progession or early treatment discontinuation; up to data cut-off date of 06 April 2016; median duration of treatment was 94.5 days..

The primary endpoint was the percentage of participants who achieved an overall response according to the Independent Review Committee. Overall response was defined as the best response of complete response (CR), complete response unconfirmed (CRu), or partial response (PR). The response criteria were described as a modification of the International Lymphoma Workshop Response Criteria. In broad terms, CR represents disappearance of clinical and radiographic evidence of disease; CRu allows specified residual or indeterminate findings; and PR requires a specified reduction in measured disease.

A response percentage is a binary-outcome summary: each participant is classified as having met the response definition or not, and the result expresses the frequency of response in the defined population. This endpoint is used to describe antitumor activity in the study group. Independent review provides an assessment by a committee distinct from the study treatment itself, as identified in the registry record; the record does not give further details about the review procedures.

The endpoint rules explicitly treated participants who discontinued before a response had been observed, or who changed to other anti-lymphoma treatments before a response had been observed, as non-responders. That rule affects the interpretation of the percentage because it defines how some participants enter the outcome classification. The numerical percentage and its 95% confidence interval are not reported in the registry record, so the magnitude and precision of the observed response cannot be assessed from the recorded endpoint information.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary outcome is a binary response measure. Each participant is classified according to whether the best observed response meets the definition of overall response. The registry definition combines CR, CRu, and PR into one outcome category. In general, a percentage for a binary endpoint is a way to summarize how frequently an event or status occurs in the defined population. Here, the event is achieving an IRC-classified overall response.

The endpoint population is defined in the registry as enrolled participants who received at least one dose of study drug. This definition identifies who is intended to contribute to the primary endpoint. It is not the same as a treatment-comparison population, because the trial has no control arm. The record reports enrollment of 134 participants, but it does not report the response count or numerical response percentage for the primary endpoint.

The endpoint also specifies how certain cases were classified. Participants who discontinued before a response had been observed, or changed to other anti-lymphoma treatments before a response had been observed, were considered non-responders. This is part of the outcome definition and should be kept in mind when interpreting any response percentage. It does not tell the reader how every possible missing assessment, incomplete follow-up, or other unobserved outcome was handled. Those details are not reported in the registry record.

The registry names a 95% confidence interval as the measure of dispersion for the primary percentage. In general, a confidence interval presents a range reflecting sampling uncertainty around an estimate, under the assumptions of the method used. It is not a guarantee that the true value lies in that interval, and it does not address systematic limitations such as the absence of a comparison group. The numerical limits are not reported in the registry record. The method used to calculate them is also not reported.

For a binary outcome, statistical precision depends on the amount of information in the observed outcome data and on how common the outcome is. General statistical principle: fewer observations usually provide less precision, and estimates near the extremes can have different uncertainty properties from estimates near the middle. These concepts help explain why both the estimate and its interval matter. They cannot be applied to quantify precision for this trial without the missing response count and interval.

The study is single-arm, so there is no treatment-effect contrast to estimate against a randomized control. In a comparative trial, the analysis could focus on a difference or ratio between treatment groups, depending on the outcome and statistical plan. That is not the question answered by this design. The recorded primary outcome is a percentage within the lenalidomide group. There is no basis in this design for a randomized estimate of the effect of lenalidomide relative to another treatment.

The registry record lists secondary time-to-event outcomes, including progression-free survival, time to progression, time to treatment failure, duration of response, and overall survival. General statistical principle: time-to-event methods are used when the timing of an event matters and participants may have different lengths of follow-up. Such methods can account for incomplete event observation under their assumptions. The registry record does not provide numerical results or analysis details for those outcomes in the registry record recorded for this study, so no estimates or method-specific conclusions can be stated.

Sample-size calculations can be used during planning to estimate the number of participants needed for a specified design and target power, under stated assumptions. The planning illustrations associated with this study are based on the observed effect, use a two-sided significance level of 0.05, assume equal allocation between two arms, and use a normal approximation. For time-to-event outcomes, the illustrations concern total events; other illustrations concern participants per arm. The effect to detect is expressed as a stated fraction of the observed effect.

Those planning assumptions do not describe the actual trial design: EMERGE was single-arm, not an equally allocated two-arm study. The illustrations are planning calculations, not observed power and not the trial’s original design justification. The registry record does not report the protocol’s sample-size justification or the numerical primary response result needed to evaluate the observed effect. No specific calculation method for the primary confidence interval or other endpoint analysis is reported in the registry record.

General statistical principle: over-dispersion arises when outcome variation is greater than a model assumes, potentially making standard errors and confidence intervals too small if the model is not appropriate. It is relevant when a chosen model assumes less variability than the data contain. The registry record does not report an analysis model or a specific over-dispersion assessment for this endpoint, so there is no basis to say whether this issue arose in the trial analysis.

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("Lenalidomide")
n      <- c(134)
events <- c(40)
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  Lenalidomide  134  40  29.9  22.3  38.4  22.8  38.1  22.8  38.1

11. Multiplicity, Missing Data and Analysis Populations

The registry lists a primary overall response endpoint and multiple secondary outcomes, including complete response or complete response unconfirmed, duration of response, progression-free survival, time to progression, time to treatment failure, time to response, time to complete response, and overall survival. When several outcomes are examined, the chance of finding at least one apparently notable result can increase. General statistical practice may address this through a prespecified hierarchy, adjustment, or careful interpretation, but the registry record does not report a multiplicity strategy or an ordering of secondary analyses.

The registry record does not provide a numerical primary endpoint result, and its analysis entries are not reported. A detailed analysis plan, including any interim analyses, is not reported in the registry record. Therefore, the approach to statistical testing, confidence-interval construction, and multiplicity cannot be independently assessed from this information.

For the primary response endpoint, the record defines enrolled participants who received at least one dose as the population. It also states that participants who discontinued before a response was observed, or changed to other anti-lymphoma treatment before a response was observed, were counted as non-responders. This rule addresses those specified cases, but does not document every possible missing-data situation. The handling of other missing or unevaluable assessments is not reported in the registry record.

The endpoint timeframe extends from Day 1 of study treatment to progression or early treatment discontinuation, through the data cutoff of 06 April 2016. The registry record does not describe additional censoring rules or sensitivity analyses for the listed time-to-event outcomes. Conclusions about those methods would therefore be speculative.

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: pneumonia (6.0%), febrile neutropenia (5.2%), hypotension (5.2%), pyrexia (4.5%), mantle cell lymphoma (4.5%).

The registry record lists one lenalidomide group, with 134 participants at risk for serious adverse events and 70 listed as affected. For other adverse events, it lists 134 at risk and 125 affected. It also reports 106 deaths. These are separate recorded safety figures; the record excerpt does not establish that deaths were caused by treatment or that every death had a particular relationship to an adverse event.

The most frequently listed serious adverse event terms are pneumonia (6.0%), febrile neutropenia (5.2%), hypotension (5.2%), pyrexia (4.5%), mantle cell lymphoma (4.5%), and squamous cell carcinoma of skin (4.5%). These percentages are registry-reported values and should be read as listed, not as comparative risks. There is no control group for estimating a difference in safety outcomes.

Serious adverse events and other adverse events are distinct registry groupings; the two affected counts should not be added or treated as mutually exclusive. The record does not provide further information about event-level counts, severity grading, timing, recurrence, or causal attribution. The counts describe the safety entries recorded for the study group and do not by themselves establish whether an event was caused by lenalidomide.

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

The study addresses a defined clinical question: the percentage of participants with mantle cell lymphoma and a specified history of relapse, progression, or refractoriness after bortezomib who achieved an IRC-defined overall response while receiving single-agent lenalidomide. The registry describes the population, treatment, response definition, timeframe, and an intended 95% confidence interval.

The numerical response result is not reported in the registry record. Consequently, the record does not allow a quantitative statement about how often the defined response occurred or how precisely that frequency was estimated. This absence should not be interpreted as either a positive or negative response result. The response estimate and its interval are simply not reported in the registry record.

Even if the numerical response percentage were available, this single-arm, open-label study would describe outcomes observed in the lenalidomide group rather than demonstrate a randomized difference from another treatment. Without a comparator, it cannot establish how outcomes would have differed under an alternative treatment or control condition. A response classification is an observed outcome under the study’s criteria, not by itself a causal treatment contrast.

The endpoint definition matters. It combines complete response, complete response unconfirmed, and partial response, and classifies participants who discontinued or changed anti-lymphoma treatment before a response was observed as non-responders. Thus, the endpoint represents a particular study-defined measure of response, not every possible measure of disease control or clinical benefit. The registry record does not report details sufficient to extend the endpoint into claims about other outcomes.

The safety entries similarly describe recorded events in the study group. They do not establish causation, and the death count cannot be interpreted as a count of treatment-related deaths from the information reported. In practical statistical terms, the record supports understanding what was studied and how outcomes were defined, but not a quantitative efficacy conclusion or a comparative safety conclusion.

14. Why This Trial Matters Statistically

This trial is statistically notable for the difference between a clearly specified endpoint and an unavailable numerical endpoint result in the registry record. The primary measure is defined as a percentage, with a named assessment committee, a stated response definition, a specified population, and a 95% confidence interval as the intended measure of uncertainty. Yet the actual percentage and interval are not reported in the registry record. Statistical interpretation requires both the outcome definition and the result.

The design also illustrates the distinction between estimation within one group and comparison between groups. A single-arm study can record the frequency of an outcome among treated participants. It cannot, through randomization, estimate a treatment contrast against an alternative. The allocation is listed as not applicable, and the model as single group. Those design features determine which questions the data can address.

Outcome rules are another important statistical feature. The record explicitly classifies participants who discontinued before a response was observed, or changed treatment before response was observed, as non-responders. Such rules shape the estimated response percentage and make the definition of the analysis population and missing-outcome handling central to interpretation. The record gives some of these rules, while other missing-data procedures are not reported.

Finally, planning calculations should not be confused with evidence from the completed study. The stated planning assumptions describe hypothetical two-arm calculations, despite the actual single-arm design. They are not observed power and do not replace a reported outcome estimate. The registry’s missing numerical primary result therefore remains a key constraint on statistical interpretation.

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 for interpreting the primary endpoint is that its numerical result and 95% confidence interval are not reported in the registry record. The response estimate, its precision, and the number of participants classified as responders therefore cannot be described. The record defines the endpoint but does not supply the result needed to answer the primary quantitative question.

The single-arm design has no concurrent comparator, and the study was open-label. Consequently, the study does not provide a randomized treatment comparison. IRC assessment is part of the endpoint description, but it does not overcome the absence of a control group. The registry record does not provide further details about the review procedures.

The endpoint includes a specific non-responder rule for participants who discontinued or changed anti-lymphoma treatment before response was observed. How other missing or unevaluable response assessments were handled is not reported in the registry record. The analysis method for the response percentage and confidence interval is also not reported.

The registry lists secondary outcomes but does not report their numerical results in the registry record recorded for this study. It does not report a multiplicity plan, interim-analysis plan, or detailed statistical analysis plan. The sample-size assumptions described are planning illustrations for a hypothetical two-arm setting, not the actual single-arm design, and the protocol’s original sample-size justification is not reported in the registry record.

The safety information gives affected counts, a death count, and selected serious adverse event terms, but does not state causal attribution in the information available. These limitations restrict conclusions about comparative efficacy and safety and about the precision of the primary outcome.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: A Study to Determine the Efficacy and Safety of Lenalidomide in Patients With Mantle Cell NHL Who Have Relapsed or Progressed After Treatment With Bortezomib or Are Refractory to Bortezomib. The "EMERGE" Trial — NCT00737529.
• Registry record last updated 2018-12-13; status last verified 2018-12.
• Results first posted 2013-09-09.
• Data retrieved from ClinicalTrials.gov on 2026-11-09.
• Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.

19. Record Summary

NCT00737529 is the completed Phase 2 EMERGE study of single-agent lenalidomide in participants with mantle cell lymphoma who had relapsed, progressed after bortezomib, or were refractory to bortezomib. It was multicenter, open-label, and single-arm, with enrollment of 134 participants. The primary endpoint was the percentage with an IRC-defined overall response, including complete response, complete response unconfirmed, or partial response.

The registry reports the endpoint definition, its assessment timeframe, and a 95% confidence interval as the dispersion measure. The numerical primary response estimate and interval are not reported in the registry record. The study began on 2008-12-22, had primary completion on 2016-04-06, and is listed as completed. Safety entries include 70 participants listed as affected by serious adverse events, 125 affected by other adverse events, and 106 deaths. The study has no randomized comparator.