Lenalidomide (Revlimid®) as Second Line Therapy in Patients With Chronic Graft-Vs-Host Disease (GVHD): Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Lenalidomide (Revlimid®) as Second Line Therapy in Patients With Chronic Graft-Vs-Host Disease (GVHD) (NCT00675441), a na phase 2 study. The primary outcome is Number of Participants' With Treatment Response of Complete or Partial Response.

2. Clinical Question

The study also listed secondary aims involving steroid discontinuation, quality of life, survival, and relapse or second malignancies at specified follow-up points. Results for those aims are not reported in the registry record. The clinical question is therefore broader than the response count alone, but the posted information does not establish results for the secondary outcomes.

3. Trial Design

This was a Phase II study sponsored by M.D. Anderson Cancer Center. The registry lists a single-group model, allocation as not applicable, and no masking. Five participants were enrolled. Lenalidomide was given with standard-of-care steroid treatment, with a planned regimen of 10 mg orally on days 1–21 of each 28-day cycle for 6 cycles. The study status is listed as terminated. The registry records a start of 2008-04 and a primary completion of 2011-08; it does not state why the study was terminated.

Because the design had no control group, the study can describe outcomes among those enrolled but cannot make a direct comparison with an alternative treatment or a concurrent untreated group. The single-group structure also means that any observed outcome could not, from this design alone, be separated from other influences on participants’ disease course or care. The study was unmasked, so participants and study personnel were not kept unaware of the assigned treatment; there was no assigned comparison treatment.

The registry describes response assessment after each 28-day cycle, repeated with each cycle for 6 cycles, approximately 180 days. Response classification involved complete or partial organ response. The listed assessment tools included skin assessment and functional assessment, including minute walk and grip strength. The registry does not report the specific numerical response result, the assessment results by cycle, or a separate analysis population beyond noting that three participants were not evaluable for response.

The record lists one primary outcome measure and no analyses. A statistical analysis plan, sample-size justification, interim analysis approach, and method for handling missing outcome data are not reported in the registry record. The fact that a sample-size planning illustration may accompany the statistical presentation does not make it part of this trial’s design or establish that the trial was planned using those assumptions. The trial’s own design rationale is 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: Of the five (5) participants enrolled, two participants were taken off study after only a few days of therapy and one participant expired, all three of which were not evaluable for response.

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 Number of Participants' With Treatment Response of Complete or Partial Response, measured over Response assessed after completing 28 day cycle, repeated with each cycle for 6 cycles, approximately 180 days..

The primary endpoint was the number of participants with a complete or partial treatment response of cGVHD to lenalidomide. Complete response was defined as resolution of all reversible manifestations related to cGVHD in a specific organ. Partial response required at least 50% improvement on the scale used to measure cGVHD manifestations. Skin assessment and functional assessment, including minute walk and grip strength, were listed as response-evaluation tools.

A response endpoint is used to describe whether the targeted disease manifestations improved according to the study’s defined criteria. Combining complete and partial response gives a count of participants meeting either category, rather than a measure of the size of change for each participant. The registry indicates that assessments were made after completing a 28-day cycle and repeated for each cycle over 6 cycles, approximately 180 days.

The registry’s endpoint description is not itself a reported response result. Although five participants enrolled, two were taken off study after only a few days of therapy and one expired; all three were identified as not evaluable for response. The number who achieved complete response, partial response, or either response is not reported in the registry record. Nor does the record report response results by organ, cycle, or assessment tool. The endpoint’s definition can therefore be described, but its observed outcome cannot be reconstructed from the posted information.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

Statistical methods help translate observed participant outcomes into estimates and clarify the uncertainty around those estimates. In this study, the registry identifies a count-based primary endpoint: the number of participants with complete or partial response. It does not report a numerical endpoint result or an inferential analysis. The general concepts below explain how such outcomes are commonly interpreted without implying that any particular method was used in this trial.

What does a response count describe?

A count records how many participants meet a prespecified outcome definition. For this trial, that definition combines complete and partial organ response. A count can be informative as a direct description, but it does not by itself show how stable the result is likely to be in a broader population. The denominator and analysis population matter: enrollment, treatment exposure, and evaluability are not necessarily identical. The registry identifies five enrolled participants and three who were not evaluable for response, but does not report a response analysis population or the response count.

What would a confidence interval add?

In general, a confidence interval describes the uncertainty around an estimated quantity, such as a response proportion. It gives a range of values compatible with the data under the method’s assumptions; it does not guarantee that the true value lies in that range. For a small study, estimates can be imprecise, so a range is often more informative than a point estimate alone. No confidence interval for the response outcome is reported in the registry record. No response estimate is available from which to interpret one.

Why does the design affect interpretation?

A single-group study estimates outcomes in the participants who received the intervention, subject to its outcome definitions and follow-up. A concurrent control group can support a direct between-group comparison when the design and analysis are appropriate. Without such a group, the observed course cannot be directly contrasted with the course under another treatment within this trial. This is a design limitation rather than a statistical adjustment that can be repaired from the reported counts.

Unmasked treatment assignment is another design feature. In general, knowledge of treatment can influence care, reporting, or assessment, depending on the outcome and procedures. The registry states that masking was none, but it does not describe safeguards for response assessment or whether assessments were independently reviewed. Those details are not reported in the registry record.

How should the planning illustration be understood?

The planning assumptions described for the accompanying sample-size illustration use a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. The illustration is based on fractions of an observed effect, and the assumptions state that figures for non-time-to-event outcomes are participants per arm. These are planning assumptions for an illustration, not the design of this single-group trial. They are not evidence that the trial enrolled enough participants, and they are not observed power. The registry record does not report the trial’s own sample-size justification or its intended effect size.

In general, sample-size planning asks how much information a proposed design might need to detect a target effect under stated assumptions. It depends on the outcome, the anticipated effect, variability or event frequency, the significance threshold, and the planned comparison. If an observed effect is used as the starting point for a later planning illustration, the resulting figures remain hypothetical. They do not increase the precision of the study that produced that observed effect, and they do not substitute for a reported analysis.

For a binary outcome, a statistical model or interval method may be selected to reflect the data structure and study design. However, the registry does not identify a test, model, confidence-interval method, covariate adjustment, or analysis procedure for the primary endpoint. No unreported method should be attributed to the investigators. The record also contains no primary analysis results to recalculate or compare with a sponsor analysis.

What do missing outcomes and adverse-event counts require?

In general, missing outcome information can affect both the denominator and interpretation of an estimate. A complete-case approach uses participants with observed outcomes, while other approaches may make assumptions about missing outcomes. Those approaches can produce different results, and their suitability depends on why information is missing and what was planned. The registry’s evaluability note does not provide enough information to identify an analysis approach, and missing-data handling is not reported in the registry record.

Safety counts are descriptive counts of participants affected, not estimates of treatment causality. A serious adverse event is a classification of seriousness, while an event term names the recorded event. Those concepts should not be conflated. The posted figures give an affected count and a leading serious-event term but do not supply event narratives, timing, relatedness assessments, or exposure-adjusted rates. These details are not reported in the registry record.

Because the trial record reports no analyses, no confidence intervals, and no response count, there is no basis to describe statistical significance or precision for the primary endpoint. General methods explain what such statistics can mean; they do not fill gaps in the trial’s reported results.

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(2)
events <- c(2)
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  2  2  100.0  15.8  100.0  34.2  100.0  29.2  99.2

11. Multiplicity, Missing Data and Analysis Populations

The registry lists one primary outcome measure and several secondary objectives: steroid-sparing capacity, quality-of-life changes, survival at 6 and 12 months, and relapse or second malignancies at 6 and 12 months. Results for these secondary objectives are not reported in the registry record. The record does not state whether the investigators planned adjustments for multiple outcomes or repeated assessments, or whether any outcome was designated as exploratory beyond the primary and secondary labels. A multiplicity strategy is not reported in the registry record.

Multiplicity arises when several outcomes, time points, or statistical tests are considered. In general, the more analyses considered, the greater the chance that at least one result may appear notable by chance if no adjustment or interpretive plan is used. Whether adjustment is appropriate depends on the objectives and analysis plan. No such plan is available in the registry record, so the handling of multiplicity cannot be assessed.

The registry identifies three participants as not evaluable for the primary response outcome: two were taken off study after only a few days of therapy and one expired. It does not give response results for the other participants or state whether an intention-to-treat, evaluable-participant, or other analysis population was used. The reasons and timing are only partly described, and the treatment of these participants in any analysis is not reported in the registry record.

In general, missing outcomes can change an estimate if participants with missing results differ systematically from those with observed results. Methods for handling missingness require assumptions and should be described alongside the analysis. Here, no missing-data method, sensitivity analysis, or imputation approach is reported. The available evaluability note should therefore be read as a limitation on interpreting the endpoint, not as a substitute for a complete outcome analysis.

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

Serious events with the highest arm-level rate: sudden cardiac arrest (20.0%).

The registry reports five participants at risk for serious adverse events and one participant affected. For other adverse events, five were at risk and none were affected in the posted count. Sudden Cardiac Arrest is listed as the top serious adverse-event term, at 20.0%. The record’s deaths field is not reported.

These figures describe reported participant counts and the leading listed serious-event term. They do not show how many total event episodes occurred, when events happened, or whether an event was considered related to lenalidomide. The registry does not report those details. The term “serious” identifies an event category; it does not by itself establish cause or severity beyond the applicable classification.

The registry separately notes that one participant expired and that this participant was not evaluable for response. It does not report a cause of death or connect the expiration to the listed serious-event term. The information should therefore be read as descriptive safety reporting for a small enrolled group, not as evidence that lenalidomide caused or did not cause an event. The limited counts also do not establish how frequently such events would occur in a larger population.

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

The registry record documents a Phase II, single-group study of lenalidomide for cGVHD after steroid failure. It specifies the oral regimen, the response definitions, and the schedule of repeated response assessment. It also reports that five participants enrolled and that three were not evaluable for response: two left study after only a few days of therapy, and one expired.

What the record does not provide is the primary response result. It does not say how many participants achieved complete response, partial response, or either type of response. It also does not report an estimate of response frequency, a confidence interval, or a statistical test. Consequently, the posted information cannot quantify the response outcome or its precision.

The design has no control group, so it cannot provide a direct comparison with another treatment. The intervention was given alongside standard-of-care steroids already being received, and the record does not provide a comparison that separates the effects of lenalidomide from concurrent treatment or other influences. Even a reported response in a single group would be descriptive rather than a controlled estimate of comparative effect.

The safety figures report one participant with a serious adverse event among five at risk and no participants with other adverse events in the listed count. Sudden Cardiac Arrest is the top serious term, recorded as 20.0%. These figures do not establish causality, and the registry does not report the deaths field or the relationship of events to study treatment.

In general, a small study may be useful for describing feasibility, outcome definitions, and observed events, but precision and broader applicability depend on the number of evaluable participants, outcome completeness, and design. The registry’s terminated status does not explain why the study ended. The available record supports a cautious description of what was planned and which limited counts were posted; it does not support a conclusion about treatment benefit or comparative safety.

14. Why This Trial Matters Statistically

This study illustrates why a clearly defined endpoint and a reported endpoint result are both necessary for statistical interpretation. The registry defines complete and partial cGVHD response, describes tools used for assessment, and gives an assessment schedule. Those details establish what the investigators intended to measure. However, the number meeting the response definition is not reported, so readers cannot estimate the primary outcome from the registry entry.

It also illustrates the difference between enrollment and evaluability. Five participants entered the study, while the registry identifies three as not evaluable for response. That distinction matters because an outcome count must be interpreted in relation to who was assessed and how missing outcomes were handled. Those analysis details are not reported in the registry record.

The single-group, unmasked design is important when considering what any result could establish. Without a comparator, the study cannot directly estimate a difference between lenalidomide and another treatment. The concurrent use of standard-of-care steroids is part of the stated treatment context, but the record offers no design-based way to isolate the contribution of each component.

The safety record likewise shows why counts need context. It lists a serious-event count and a leading event term, but does not report causality, timing, or the deaths field. Such information should not be stretched into a claim about risk attributable to treatment.

Statistically, the central lesson is that methods cannot recover results that are not reported. Planning illustrations, general statistical principles, and outcome definitions can clarify how a study might be evaluated, but they do not replace an observed response count, a documented analysis population, or uncertainty estimates. The registry record’s omissions therefore set the boundaries of 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 main trial-specific limitation is the absence of the primary response result. Although the endpoint is defined in detail, the registry does not report the count of participants with complete or partial response. It also does not report an uncertainty interval, a statistical test, or a detailed analysis population.

The enrolled group was small, with five participants. The registry identifies three as not evaluable for response: two were taken off study after only a few days of therapy, and one expired. It does not state how those participants were handled in an analysis, or report response outcomes for the remaining participants. The reasons for early study removal and the timing or cause of the expiration are not reported in the registry record.

The study was single-group and unmasked, with no like-for-like control comparison. Participants also received standard-of-care steroid treatment they were already receiving. These features limit what could be concluded about comparative outcomes or the contribution of lenalidomide alone, even if a response count were available.

The registry lists the study as terminated but does not give the reason. It does not report the statistical analysis plan, sample-size justification, interim analyses, multiplicity approach, or missing-data methods. Results for the listed secondary aims are also not reported in the registry record. The safety information is limited to participant counts and a leading serious-event term; details such as timing, relatedness, and cause of death are not reported.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Lenalidomide (Revlimid®) as Second Line Therapy in Patients With Chronic Graft-Vs-Host Disease (GVHD) — NCT00675441.
• Registry record last updated 2013-12-11; status last verified 2013-10.
• Results first posted 2013-12-11.
• 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 NCT00675441 as a Phase II, single-group study of lenalidomide for chronic graft-versus-host disease after steroid failure. M.D. Anderson Cancer Center is listed as sponsor. Five participants were enrolled; the status is terminated, with a start of 2008-04 and primary completion of 2011-08.

The planned regimen was lenalidomide 10 mg by mouth on days 1–21 of a 28-day cycle for 6 cycles, alongside standard-of-care steroids. The primary outcome was the number of participants with complete or partial response, assessed repeatedly over approximately 180 days. Three participants were not evaluable for response. The primary response result and analyses are not reported in the registry record.

The posted safety counts list one participant with a serious adverse event among five at risk and none with other adverse events among five at risk. Sudden Cardiac Arrest is the top listed serious term at 20.0%. The deaths field and the reason for termination are not reported.