Lenalidomide (Revlimid®, CC-5013) in Subjects With Relapsed or Refractory Indolent Non-Hodgkin's Lymphoma: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Lenalidomide (Revlimid®, CC-5013) in Subjects With Relapsed or Refractory Indolent Non-Hodgkin's Lymphoma (NCT00179673), a na phase 2 study. The primary outcome is Percentage of Participants With Response.

2. Clinical Question

3. Trial Design

This was a phase II, multicenter, single-arm, open-label study of lenalidomide in subjects with relapsed or refractory indolent non-Hodgkin's lymphoma. The registry lists an enrollment of 43 and identifies Celgene as the sponsor. The study is marked completed. Its listed start was 2005-06 and its primary completion was 2008-04.

All participants received single-agent lenalidomide; the record lists no comparator arm. The regimen was 25 mg orally once daily on Days 1 to 21 of each 28-day cycle, continuing for up to 52 weeks or until disease progression. The brief summary says participants who achieved a complete response received an additional 2 cycles before stopping treatment. Participants were to be followed for progression-free survival after leaving the treatment phase.

Open-label means that masking was not used, as reflected in the registry. The response assessment was based on the investigator's determination of best response using the International Workshop Lymphoma Response Criteria. Since treatment assignment was not randomized and no control group is listed, the design can describe outcomes observed during treatment but cannot isolate a treatment effect from other explanations through a controlled comparison.

The registry lists five outcome measures, including tumor control, duration of response, progression-free survival, and adverse events in addition to the primary response endpoint. It does not report statistical analyses for these outcomes in the record details available. The protocol's statistical plan, sample-size justification, and any interim analyses are not reported in the registry record.

4. Participant Flow and Accounting

The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Intent-to-treat (ITT) population, which included all enrolled patients who received at least 1 dose of study drug. Patients who dropped out without having a response assessment or who had a response after they had received other anti-cancer treatments were considered non-responders.

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 Percentage of Participants With Response, measured over From enrollment through study completion. Median duration on study was 4.4 months with a maximum of 32 months.

The primary endpoint was the percentage of participants with a response from enrollment through study completion. Response meant the best investigator-assessed result was a complete response, unconfirmed complete response, or partial response under the International Workshop Lymphoma Response Criteria. These categories distinguish degrees of change in disease findings rather than measuring time until an event.

In the criteria described in the registry, complete response requires disappearance of detectable clinical and radiographic disease and disease-related symptoms, along with normalization of biochemical abnormalities. An unconfirmed complete response meets the complete-response criteria but allows specified residual findings. Partial response is based on a reduction in the sum of the products of diameters of the six largest dominant nodes or nodal masses, with additional conditions concerning other nodes, the liver, and the spleen.

A response proportion is used to describe how many participants in the defined analysis population met the response criteria at some point during the stated assessment period. It is a binary outcome at the participant level: each participant is classified as having met the response definition or not. The registry's population rule counts participants without a response assessment as non-responders, and also counts a response observed only after other anti-cancer treatment as a non-response.

The endpoint is accompanied in the registry by a stated 95% confidence interval, but the interval's numerical limits and the response percentage are not reported in the record details available. Therefore, neither the estimated response proportion nor its precision can be evaluated from those details.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does a response proportion describe?

In general, a response proportion counts participants classified as responders and expresses that count relative to the analysis population. It is a summary of participant-level classification over a specified assessment period. Unlike a time-to-event measure, it does not directly describe when a response occurred or how long it lasted. The primary endpoint was the percentage of participants whose best investigator-assessed response was complete response, unconfirmed complete response, or partial response.

The population rule matters because it determines which participants contribute to the denominator and how missing assessments are treated. The registry defines the primary population as enrolled patients who received at least one dose. Patients who dropped out without an assessment and patients whose response came after other anti-cancer treatment were classified as non-responders. That rule is part of the endpoint interpretation, not a detail that can be separated from the result.

What does a confidence interval add?

In general, a confidence interval expresses uncertainty around an estimate. For a response proportion, it gives a range of values compatible with the data under the interval's statistical assumptions. A narrower interval indicates greater precision than a wider interval, but an interval does not correct design limitations or turn an uncontrolled comparison into a controlled one. The registry specifies a 95% confidence interval for the primary endpoint, but its numerical limits and the corresponding response percentage are not reported in the record details available. The actual precision therefore cannot be described.

General statistical interpretation also distinguishes the estimate from its uncertainty. A point estimate gives one summary of the observed data; the interval indicates how uncertain that summary may be. Neither alone establishes a causal effect. In a single-group study, uncertainty around the response proportion concerns the estimate for the study population under the stated model, not the difference between lenalidomide and a comparator.

Why does the single-group design matter?

In general, a comparator helps distinguish outcomes associated with treatment from outcomes that might also occur under another treatment or in the absence of the study treatment. Random allocation can help make groups comparable with respect to measured and unmeasured characteristics on average. This study is listed as single-group, with allocation marked not applicable and no masking. There is therefore no concurrent control estimate in the registry record for a between-group treatment contrast.

The design can still provide descriptive information about participants treated under the study regimen. Its response endpoint summarizes investigator-assessed best response, and its listed safety outcomes describe adverse events recorded in the treated group. These summaries should not be interpreted as a comparison with a control arm, because no such arm is listed.

How should best response be understood?

Best response selects the most favorable response classification recorded for a participant during the endpoint period. It is not the same as a measure of response duration, and it does not show whether a response was sustained. The registry lists duration of response and progression-free survival as separate secondary outcomes, but numerical results for them are not reported in the record details available.

The criteria combine clinical, radiographic, and biochemical elements for complete response; allow specified residual findings for unconfirmed complete response; and define partial response through reductions in measured disease with conditions concerning other sites. This structured definition supports consistent classification in principle. However, the record does not report the assessment schedule, independent review procedures, or details about how disagreements in investigator assessment were handled.

What can planning calculations say?

In general, sample-size calculations estimate the number of participants needed under stated assumptions to detect a specified effect with a chosen statistical approach. They are planning illustrations, not results observed in a completed trial and not measures of observed power. The record's stated planning assumptions include a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation, with the effect to detect expressed as a fraction of the observed effect. For time-to-event planning, the record says the calculation concerns total events; other planning results are expressed as participants per arm.

Those assumptions describe a planning framework, not this trial's single-group design. The record does not report a trial-specific sample-size justification, and numerical planning results are not stated in the record details available. No planning figure can substitute for a reported primary response estimate or its confidence interval.

For binary outcomes, general methods may model the probability of an event or use an interval based on the observed proportion. For outcomes with event counts, over-dispersion can matter when observed variability exceeds what a simple model expects; accounting for it can affect uncertainty estimates. These are general statistical considerations, not claims that a particular model or adjustment was used in this trial. The registry record does not report the primary endpoint's calculation method or any model details.

Finally, statistical significance and clinical importance are different concepts in general. A significance test evaluates compatibility with a specified null hypothesis under assumptions; it does not determine whether a magnitude is important for patients or whether a treatment caused the result. Here, the numerical primary estimate, interval limits, and analysis details are not reported, so neither a significance assessment nor a precision assessment can be reconstructed from the stated information.

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(43)
events <- c(10)
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  43  10  23.3  11.8  38.6  13.2  37.7  13.2  37.8

11. Multiplicity, Missing Data and Analysis Populations

The registry lists five outcome measures, including the primary percentage of participants with response and secondary measures covering tumor control, duration of response, progression-free survival, and adverse events. When several outcomes or analyses are examined, multiplicity can increase the chance of at least one apparently noteworthy finding by chance. In general, a prespecified hierarchy or adjustment can address that issue, but the registry record does not report a multiplicity strategy or the statistical plan used for these outcomes.

The record indicates no analyses in the reported analysis count, and does not provide numerical results for the primary endpoint in the details available. It is therefore not possible to assess whether results were adjusted for multiple comparisons, whether all planned outcomes were reported, or how any analyses were selected. The protocol's analysis plan and any interim analyses are not reported in the registry record.

The primary population is described as an intent-to-treat population consisting of enrolled patients who received at least one dose. The endpoint rules state that patients who dropped out without a response assessment, or who had a response only after other anti-cancer treatment, were considered non-responders. This is an explicit handling rule for those cases. The record does not report the number of participants in either situation, other missing-data patterns, or any sensitivity analyses addressing missing response assessments.

The term intent-to-treat is used with the population definition in the record; its exact membership is governed by that stated rule. No assumptions about a broader randomized population are appropriate for this single-group study. Additional details about analysis exclusions, protocol deviations, or the handling of missing secondary outcomes are not reported in the registry record.

12. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

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: abdominal pain nos (4.7%), pyrexia (4.7%), asthenia (4.7%), fatigue (4.7%), pneumonia nos (4.7%).

The registry reports safety figures for the lenalidomide group. It lists 18 participants affected by serious adverse events among 43 at risk, and 41 affected by other adverse events among 43 at risk. These are participant counts, not numbers of event episodes, and they do not indicate how many different event types an individual participant experienced.

The listed serious adverse-event terms and percentages are Abdominal Pain NOS at 4.7%, Pyrexia at 4.7%, Asthenia at 4.7%, Fatigue at 4.7%, Pneumonia NOS at 4.7%, and Anemia Not Otherwise Specified (NOS) at 2.3%. The record excerpt does not state the number of events for each term or whether a participant could appear under more than one term. The listed percentages should therefore be read as term-specific reported figures, not added together or treated as mutually exclusive categories.

In general, safety summaries describe events observed during the defined study period and do not by themselves establish that the study treatment caused an event. The registry record does not provide further detail about event timing, severity gradations, exposure-adjusted rates, or a control group. With no comparator arm, the listed figures are descriptive of the treated group and do not support a comparative safety estimate.

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

The study record describes a phase II, open-label, single-group evaluation of lenalidomide in subjects with relapsed or refractory indolent non-Hodgkin's lymphoma. It specifies the treatment regimen and defines a primary response endpoint based on investigator-assessed best response. It also gives a response-population rule that classifies participants without an assessment, and those responding only after other anti-cancer treatment, as non-responders.

However, the primary response percentage and its 95% confidence interval are not reported in the registry record details available. Without them, the central efficacy summary and its precision cannot be described. The endpoint definition tells readers what was intended to count as a response; it does not reveal how many participants met that definition. Numerical results for the listed secondary outcomes are also not reported in the details available.

The safety record lists serious and other adverse-event counts for the lenalidomide group, as well as selected serious-event terms and percentages. Those figures describe events recorded among participants in the study. Since there is no comparator group, they do not establish how safety outcomes compare with another treatment or what would have occurred without study treatment.

In general, an uncontrolled study can provide descriptive evidence about outcomes observed in its participants, but it cannot by itself separate treatment effects from other influences. Open-label assessment and investigator-determined best response are also relevant context. The registry does not report blinded response review or the statistical procedures used to calculate the primary estimate.

Accordingly, the record supports a description of the question, design, endpoint rules, and selected safety figures, but not a conclusion about the size or precision of the response result. The study's reported design should not be mistaken for a randomized comparative test, and planning calculations should not be mistaken for observed outcomes or observed power.

14. Why This Trial Matters Statistically

This trial is statistically notable because its primary endpoint is a participant-level response proportion in a single-group design. That setup makes the endpoint relatively direct to describe: participants are classified according to their best response during the stated assessment period. At the same time, the absence of a comparator limits what can be inferred about treatment effects. Descriptive outcome estimates and comparative causal estimates answer different questions.

The registry's response definition also illustrates that an endpoint depends on operational rules. Complete response, unconfirmed complete response, and partial response are grouped together, and the analysis population has explicit rules for participants without an assessment or with a response after other anti-cancer treatment. These choices shape the meaning of any reported percentage. A reader interpreting a response result would need both the numerical estimate and these classification rules.

Precision is another central issue. The registry specifies a 95% confidence interval, which would help convey uncertainty around the response estimate, but the estimate and interval limits are not reported in the record details available. Without them, statistical uncertainty cannot be quantified. This is a reminder that an endpoint definition and a confidence-interval label do not substitute for the actual numerical result.

The listed adverse-event counts add a descriptive safety dimension, while the absence of a control group again constrains comparison. Finally, planning calculations based on an observed effect are design illustrations rather than evidence that a study had a particular observed power. The registry does not report its own sample-size justification or statistical plan. Together, these features make clear why study design, analysis population, endpoint definition, numerical results, and uncertainty all need to be read as distinct parts of 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 immediate limitation in interpreting the registry record is that it does not report the primary response percentage or the numerical limits of its 95% confidence interval. The primary endpoint is defined, but the observed estimate and its precision cannot be evaluated. Numerical results for the listed secondary outcomes are also not reported in the record details available.

The study is single-group, open-label, and has no comparator. Its design therefore does not provide a direct between-group estimate. Response was assessed by the investigator, and the record does not report blinded or independent review. These features matter when interpreting a best-response endpoint, although the record does not provide information to quantify their influence.

Participants could remain on study for different lengths of time: the record reports a median duration on study of 4.4 months and a maximum of 32 months. The endpoint period ran from enrollment through study completion, but the assessment schedule and details on differing observation time are not reported in the registry record. Best response also does not describe response duration; duration of response is listed separately as a secondary outcome, without a numerical result in the details available.

The stated population rules address patients without a response assessment and responses occurring only after other anti-cancer treatment, but the record does not report how many participants were affected or provide sensitivity analyses. The statistical analysis method, multiplicity approach, interim analyses, and trial-specific sample-size justification are not reported. The listed safety figures are descriptive and have no control-group comparison in this single-arm design.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Lenalidomide (Revlimid®, CC-5013) in Subjects With Relapsed or Refractory Indolent Non-Hodgkin's Lymphoma — NCT00179673.
• Registry record last updated 2025-05-13; status last verified 2025-05.
• Results first posted 2013-10-14.
• 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 II, multicenter, single-arm, open-label study of lenalidomide for subjects with relapsed or refractory indolent non-Hodgkin's lymphoma. Enrollment is listed as 43. Participants received 25 mg orally once daily on Days 1 to 21 of every 28-day cycle, for up to 52 weeks or until disease progression.

The primary endpoint was the percentage of participants with complete response, unconfirmed complete response, or partial response, assessed by the investigator using the International Workshop Lymphoma Response Criteria. The primary population included enrolled patients who received at least one dose, with specified cases counted as non-responders. The registry record details available do not report the primary response percentage or its 95% confidence interval.

The record lists 18 participants affected by serious adverse events among 43 at risk and 41 affected by other adverse events among 43 at risk. It also lists selected serious-event terms and percentages. No comparator arm is listed, and the statistical plan and trial-specific sample-size justification are not reported in the registry record.