Combination Therapy Using Lenalidomide (Revlimid)- Low Dose Dexamethasone and Rituximab for Treatment of Rituximab-Resistant, Non-Aggressive B-Cell Lymphomas: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Combination Therapy Using Lenalidomide (Revlimid)- Low Dose Dexamethasone and Rituximab for Treatment of Rituximab-Resistant, Non-Aggressive B-Cell Lymphomas (NCT00783367), a na phase 2 study. The primary outcome is Response Rate to Lenalidomide-dexamethasone + Rituximab Therapy in Relapsed Small B-cell Lymphoma With Rituximab Resistance.

2. Clinical Question

3. Trial Design

This completed phase 2 study is registered as a single-group, unmasked trial. The registry lists allocation as not applicable, consistent with the absence of a randomized assignment or a stated control group. Its enrollment entry is 50; that entry does not establish how many participants contributed to each outcome analysis. The safety record reports two cohorts, but does not define their relationship to the protocol parts or establish that they represent separate treatment comparisons.

The population of interest had recurrent small B-cell non-Hodgkin lymphoma and recent progression following rituximab treatment. The registry lists conditions including follicular lymphoma, marginal zone B-cell lymphoma, MALT lymphoma, small lymphocytic lymphoma, Waldenstrom macroglobulinemia, and mantle-cell lymphoma. It describes an initial treatment period with lenalidomide-dexamethasone, followed by response assessment after two 28-day cycles. Participants would then enter Part II and receive lenalidomide-dexamethasone with rituximab, with response and progression-free survival used to evaluate the potential reversal of rituximab resistance.

The record lists a start date of 2008-07, primary completion on 2012-11-14, and status as completed. It does not report the detailed schedule for each drug, adherence, treatment modifications, or the operational definitions used to assign participants to the safety cohorts. The planned enrollment and the reported safety denominators should not be assumed to describe the same analysis population. The registry record also does not report a trial-specific sample-size justification or the reasoning for the study design.

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

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 Response Rate to Lenalidomide-dexamethasone + Rituximab Therapy in Relapsed Small B-cell Lymphoma With Rituximab Resistance, measured over 3 months.

The primary endpoint is titled as the response rate to lenalidomide-dexamethasone plus rituximab in relapsed small B-cell lymphoma with rituximab resistance. It is defined as a complete response or partial response assessed at 3 months using anatomic criteria from the International Workshop Response Criteria (Cheson, 1999). The registry records the outcome measure as a count of participants, but does not report the count, an analysis denominator, or a response rate.

Response is used in clinical research to describe whether disease has met prespecified criteria for improvement. Combining complete and partial responses into a response endpoint can capture more than one degree of response while keeping the outcome tied to explicit assessment criteria. The precise interpretation depends on how assessments are performed, how missing assessments are handled, and which participants are included in the analysis. Those details are not reported in the registry record.

Because the study has no randomized comparator, the endpoint can describe response within the treated study population if results are available, but it cannot by itself establish how response compares with another treatment or with the course participants would have had without the study regimen. The registry record does not provide the primary endpoint result.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registered primary outcome is binary in concept: each assessed participant either meets the response definition or does not. The definition includes complete response and partial response under the stated anatomic criteria. Although the registry labels the outcome as a response rate, the recorded measure is a count of participants. Without a response count and a corresponding denominator, a rate cannot be interpreted. Neither is reported in the registry record.

What does a response estimate represent?

General statistical explanation: a response proportion is the number of participants meeting the response definition divided by the number of participants included in the relevant analysis. It describes the observed frequency in that analysis population. It is not automatically the probability of response for every person with the condition, because the study population, eligibility requirements, follow-up, and missing assessments affect how broadly the estimate can be applied. In this study, the analysis population and response result are not reported in the registry record.

General statistical explanation: an uncertainty interval around a proportion describes the range of values compatible with the observed data under the interval’s statistical assumptions. Wider intervals indicate less precision, while narrower intervals indicate greater precision. An interval does not resolve bias from participant selection, outcome assessment, or lack of a comparator. No confidence interval for the primary outcome is reported in the registry record.

Why does the single-group design matter?

General statistical explanation: random assignment can help make groups comparable with respect to measured and unmeasured baseline characteristics, on average. A single-group study has no such concurrent randomized contrast. The observed outcome can be described, but a causal treatment effect cannot be isolated from other explanations using a within-study control comparison. This is particularly relevant when the research question concerns overcoming resistance: a response after treatment is not by itself evidence that the regimen reversed resistance.

The study is described as unmasked. General statistical explanation: when participants or investigators know which treatment is being given, expectations or knowledge of treatment can influence subjective aspects of care, reporting, or assessment. The primary endpoint is defined using anatomic criteria, but the registry record does not describe masking of assessors or procedures intended to reduce assessment bias. The status of those procedures is not reported in the registry record.

How should the treatment sequence be understood?

The registered description separates treatment into Part I and Part II. Part I uses lenalidomide-dexamethasone for two 28-day cycles and then assesses response; Part II adds rituximab to lenalidomide-dexamethasone. General statistical explanation: outcomes measured at different points in a treatment sequence answer different questions. A response assessment before a treatment change cannot be treated as an outcome of the later regimen. To estimate the contribution of adding a drug, an analysis needs a clearly defined contrast and a suitable strategy for handling changes in treatment and follow-up. The registry record does not report such an analysis.

What can the safety counts tell a reader?

General statistical explanation: a count of participants with at least one event is different from a count of all event episodes. Participant-level counts are useful for describing how many people were affected, but do not convey how often events recurred or how long participants were at risk. The registry safety entries are expressed as numbers at risk and affected. The record does not explain whether repeated events were counted once per participant, provide event-level detail, or report the follow-up basis for each cohort.

General statistical explanation: over-dispersion matters when event counts vary more than a statistical model expects. For a binary participant-level outcome, over-dispersion is not the main concern in the same way it may be for repeated event counts; repeated events, unequal follow-up, or clustering can require methods that account for dependence and variation. The registry record does not describe an event-count model or a repeated-event analysis, and the posted safety figures should be read as descriptive counts rather than model-based comparisons.

What do planning calculations mean?

General statistical explanation: sample-size planning calculations describe the amount of information a hypothetical design might need under stated assumptions. They are not observed power and do not show that a completed trial had a particular probability of detecting an effect. The planning assumptions associated with this record specify a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation, with the target effect expressed as a fraction of the observed effect. These are planning assumptions, not evidence that this single-group study used a two-arm design. The trial’s own sample-size justification is not reported in the registry record.

The statistical analysis plan, including any adjusted analyses, handling of repeated assessments, and approach to uncertainty, is not reported in the registry record. Without the analysis population, endpoint results, and analysis details, a numerical estimate cannot be independently interpreted or checked against a stated statistical model.

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("Cohort 1", "Cohort 2")
n      <- c(24, 19)
events <- c(14, 13)
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  Cohort 1  24  14  58.3  36.6  77.9  38.8  75.5  38.7  75.6
ARM  Cohort 2  19  13  68.4  43.4  87.4  46.0  84.6  45.7  84.6

11. Multiplicity, Missing Data and Analysis Populations

The study lists a primary response outcome and a secondary outcome of time until progression after lenalidomide-dexamethasone plus rituximab. Reporting multiple outcomes raises a general statistical issue: if many hypotheses are tested, the chance of at least one apparently unusual result can increase unless the analysis plan accounts for multiplicity. The registry record does not report a multiplicity strategy, a hierarchy of tests, or whether any outcomes were designated as supportive rather than confirmatory.

The registry record does not report interim analyses, stopping rules, or a detailed statistical analysis plan. These items should not be assumed. It also does not report the numbers assessed for each outcome, analysis populations, or how participants were handled if they did not complete treatment or outcome assessment.

Missing outcome data can affect interpretation when the people without assessments differ from those with observed outcomes. General statistical explanation: an analysis may use assumptions or sensitivity analyses to examine how missing results could change an estimate. The registry record does not report a missing-data method, reasons for missing assessments, or sensitivity analyses. It is therefore not possible to evaluate the extent or possible influence of missing primary outcome data.

The record gives an enrollment entry of 50 and separate safety denominators for two cohorts. These entries do not establish which participants were eligible for, or included in, each outcome analysis. The number contributing to the primary endpoint and the definition of each analysis population are not reported in the registry record.

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: neutrophil count decreased (17.4%), fever (8.7%), thromboembolic event (7.4%), neoplasms benign, malignant, and unspecified, other: unrelated second malignancies (7.4%), general disorders and administration site conditions, other: tumor flare (4.3%).

The safety record lists serious adverse events by cohort. For Cohort 1, 27 participants were at risk and 12 were affected; for Cohort 2, 23 participants were at risk and 9 were affected. The record also lists other adverse events: 27 at risk and 27 affected in Cohort 1, and 23 at risk and 22 affected in Cohort 2. Deaths are listed as 3 for Cohort 1 and 0 for Cohort 2.

These figures are descriptive. They do not establish that an event or death was caused by study treatment, and the cohorts are not a randomized comparison. The registry record does not report the cohort definitions, follow-up duration for these safety summaries, event severity breakdown beyond the serious-event classification, or how repeated events were counted.

The listed serious-event terms include neutrophil count decreased (17.4%), fever (8.7%), thromboembolic event (7.4%), unrelated second malignancies (7.4%), tumor flare (4.3%), and pelvic infection (4.3%). The denominator and method used to calculate these percentages are not reported in the registry record. These percentages should therefore be read as the registry’s descriptions, not recalculated or interpreted as comparative risks.

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

The record describes a clinical question in a population with recurrent small B-cell non-Hodgkin lymphoma and recent progression after rituximab. It specifies a regimen involving lenalidomide, low-dose dexamethasone, and rituximab, and defines the primary outcome as complete or partial response assessed at 3 months using anatomic criteria. It also reports safety counts for two cohorts.

Those details do not establish the rate of response. The registry record does not report the number of participants who achieved complete or partial response, the denominator used to calculate a rate, or a confidence interval. It also does not report the result for time until progression. Without these results, the magnitude and precision of the outcomes cannot be assessed.

Even if a response result were available, a single-group study would describe outcomes in the treated population rather than provide a randomized comparison. It could not, on its own, determine what would have happened under another treatment or establish that rituximab resistance had been reversed. The treatment sequence further matters: Part I assesses lenalidomide-dexamethasone before the planned Part II regimen that includes rituximab. Results at those distinct points would address different questions.

The safety summaries show recorded affected-participant counts and selected serious-event terms. They do not identify the cause of events, and the two cohorts cannot be treated as control and treatment groups based on the registry record. Differences between their listed counts would not, by themselves, estimate a treatment effect.

The appropriate interpretation is therefore limited to what the record documents: the intended population, treatment sequence, endpoint definition, and descriptive safety information. Claims about treatment benefit, lack of benefit, comparative effectiveness, or precise risks require outcome and analysis information not reported in the registry record.

14. Why This Trial Matters Statistically

This study is statistically informative as an example of the distinction between a clearly stated clinical question and an interpretable estimate. The registry describes a focused population with recent progression after rituximab, a sequential treatment strategy, and a response endpoint tied to stated anatomic criteria. Yet the primary response result and its denominator are not reported. A defined endpoint alone is not enough to evaluate the size or precision of an outcome.

The sequential design also highlights the importance of aligning the analysis with the treatment question. Response after the initial lenalidomide-dexamethasone phase is not interchangeable with response after the later regimen that adds rituximab. To make claims about the contribution of the added treatment, the timing of response assessment and a valid comparison must be explicit. A single-group design does not provide a randomized comparison for that purpose.

The safety entries illustrate another basic issue: participant counts, event counts, and percentages answer different questions. A reader needs the denominator, risk period, cohort definition, and event-counting method to assess what a safety summary means. Several of those details are not reported in the registry record.

Finally, a completed study and an enrollment entry do not guarantee that outcomes and analysis methods are available in the registry. For clinical researchers, this record underscores the value of reporting analysis populations, missing-data handling, uncertainty intervals, and results for prespecified outcomes. Those details are necessary to move from a protocol description to a quantitative 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 registry record does not report the primary response result, response denominator, or confidence interval. It therefore does not support evaluation of the observed response frequency or its precision. The secondary time-until-progression result is also not reported, and no inferential analyses are listed.

The single-group design provides no randomized concurrent comparator. It cannot separate outcomes associated with the regimen from other influences or establish a comparative treatment effect. The unmasked status may also matter for aspects of care and assessment; the registry does not report whether outcome assessors were masked or how assessment consistency was maintained.

The protocol describes a sequential treatment approach, but the record does not provide results separately by treatment stage or an analysis that isolates the contribution of rituximab. It does not report detailed eligibility criteria, baseline characteristics, treatment exposure, adherence, modifications, or the analysis population. The enrollment entry cannot be assumed to be the denominator for an outcome.

Safety interpretation is constrained by missing detail about cohort definitions, follow-up, event ascertainment, repeated events, and the denominators underlying listed percentages. The adverse-event summaries are descriptive and do not establish causality. Handling of missing outcome data, multiplicity, interim monitoring, and the statistical analysis plan are not reported in the registry record. These omissions limit both reproducibility and assessment of potential bias.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Combination Therapy Using Lenalidomide (Revlimid)- Low Dose Dexamethasone and Rituximab for Treatment of Rituximab-Resistant, Non-Aggressive B-Cell Lymphomas — NCT00783367.
• Registry record last updated 2023-03-30; status last verified 2023-03.
• Results first posted 2021-05-07.
• 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 record describes a completed phase 2, single-group, unmasked study of lenalidomide, low-dose dexamethasone, and rituximab in recurrent small B-cell non-Hodgkin lymphoma after recent progression on rituximab. Its protocol description includes an initial lenalidomide-dexamethasone period followed by a period adding rituximab.

The primary endpoint is complete or partial response at 3 months using anatomic criteria from the International Workshop Response Criteria (Cheson, 1999). The registry record does not report the response result, denominator, or an analysis. It also lists time until progression as a secondary outcome without a reported result. Safety counts and selected serious adverse-event terms are recorded for two cohorts, but cohort definitions and key analysis details are not reported.