Bortezomib and Lenalidomide in Treating Patients With Relapsed or Refractory Mantle Cell Lymphoma: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Bortezomib and Lenalidomide in Treating Patients With Relapsed or Refractory Mantle Cell Lymphoma (NCT00553644), a na phase 2 study. The primary outcome is Number of Participants With an Overall Response Defined as Complete Response and Partial Response.

2. Clinical Question

3. Trial Design

This was a phase II, single-group study sponsored by the National Cancer Institute. The registry lists the trial as completed, with enrollment of 53. It names recurrent mantle cell lymphoma as the condition and describes the intended population as patients with relapsed or refractory mantle cell lymphoma. The recorded start date is 2007-11-15, and the primary completion date is 2012-12-31.

All participants were assigned to the treatment arm comprising bortezomib and lenalidomide; there was no separate control arm. Allocation is listed as NA and masking as none. The study therefore provides a record of outcomes within a treated group, not a randomized comparison between treatment and control. The registry does not report a comparator treatment or placebo.

The arm description specifies bortezomib given intravenously over 3-5 seconds on days 1, 4, 8, and 11, together with lenalidomide taken by mouth once daily on days 1-14. Treatment was repeated every 21 days for up to 8 courses unless disease progression or unacceptable toxicity occurred. The remaining description of treatment after response is truncated, so its further details are not reported in the registry record.

The primary outcome was the number of participants with an overall response, assessed by an investigator using International Working Group criteria. Secondary outcomes listed are incidence of adverse events, time to progression, and overall survival. The registry lists four outcome measures in total, but the primary response result and analysis results are not reported in the registry record. Participant characteristics, eligibility details, and the statistical analysis plan are also 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.

Before assignment: One participant was deemed ineligible and removed for all analyses; therefore, 53 participants were analyzed.

Overall Study

Reasons for not completing this period:

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 an Overall Response Defined as Complete Response and Partial Response, measured over Duration of treatment (assessed up to 6 years).

The primary endpoint is the number of participants with an overall response, where response combines complete response and partial response. A complete response requires disappearance of all evidence of disease. A partial response requires a decrease of at least 50% in the sum of products of 6 largest dominant nodes or nodal masses, and in splenic and hepatic nodules, with no increase in the size of nodes, liver, or spleen and no new sites of disease. Response was assessed by the investigator according to International Working Group criteria.

In general, a response endpoint describes whether a participant meets a prespecified definition of improvement at assessment; it does not, by itself, describe how long that response lasts or whether it changes survival. Reporting a count makes clear how many participants met the definition, while a proportion can help readers understand that count in relation to the group assessed. The registry outcome is expressed as a number of participants, and its timeframe is the duration of treatment, assessed up to 6 years.

The primary response count is not reported in the registry record. Therefore, the endpoint definition can be explained, but the number of participants meeting it and the precision of any estimated response rate cannot be evaluated from the recorded result. The registry does not report an endpoint-specific analysis or confidence interval.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary outcome is a binary participant-level status: a participant either meets the overall-response definition or does not. The registry records the intended outcome as a number of participants rather than a continuous measurement. In general, binary outcomes are often summarized with a count and, when the relevant denominator is available, a proportion. The count communicates the observed number meeting the definition; a proportion places that count in the context of the group assessed. Neither can be interpreted reliably without knowing which participants were included in the outcome assessment and how incomplete assessments were treated.

What does the response definition capture?

The endpoint combines complete response and partial response. The registry defines complete response as disappearance of all evidence of disease. Partial response requires at least a 50% decrease in the specified sum of products of dominant nodes or nodal masses and splenic and hepatic nodules, with no increase in the size of nodes, liver, or spleen and no new disease sites. Using stated criteria helps make the classification more consistent than an undefined judgment of improvement. The registry identifies investigator assessment under International Working Group criteria, but does not report additional procedures for independent review or resolving disagreements.

A response count is a snapshot of whether the criteria were met at assessment; it does not alone describe time to response, durability, progression, or survival. The listed timeframe is duration of treatment, assessed up to 6 years. The registry does not specify the timing or schedule of response assessments beyond that timeframe, nor does it report a response result. Accordingly, an estimate of the response frequency or its precision cannot be evaluated from this record.

How should uncertainty be understood?

In general, a confidence interval describes the range of values compatible with the observed data under a statistical model and communicates uncertainty in an estimate. A narrow interval indicates greater precision than a wide interval, but interval width depends on both the data and the analysis assumptions. No confidence interval for the primary response outcome is reported in the registry record. No p-value or endpoint-specific statistical analysis is reported either. Without an estimate and uncertainty measure, the strength and precision of the response evidence cannot be judged numerically.

A single-group trial can describe outcomes among its participants, but it does not provide a direct concurrent comparison. A response observed after treatment is not, on its own, evidence that the treatment caused the response. A control group can help distinguish differences associated with treatment from changes that might also occur under another course of care. Here, the record lists no comparator arm, and allocation is NA. The results therefore cannot supply a randomized treatment contrast.

What do the planning assumptions mean?

The registry describes a sample-size planning illustration based on the observed effect, with a two-sided significance level of 0.05, equal allocation between two hypothetical arms, and a normal approximation. The intended effect is expressed as a stated fraction of the observed effect. In general, such calculations ask what sample size might be needed to detect a chosen effect under specified assumptions. They are planning exercises, not evidence that a study had a particular probability of finding an effect after it was conducted. They also do not constitute observed power.

The planning setup assumes two arms, whereas this study is single-group. It should therefore not be read as a design description or as a randomized comparison conducted in this trial. The registry does not report the trial's own sample-size justification, and the primary result needed to assess the observed effect is not reported in the registry record. Any planning illustration must be interpreted in light of its stated assumptions rather than as a trial result.

Why can event counts need careful interpretation?

Counts of participants with events are descriptive, and they depend on the event definitions, observation period, and participant population used. In general, adverse events can be summarized by whether a participant experienced at least one event, by event type, or by the number of events. These summaries answer different questions: participant counts do not necessarily equal event counts, because one participant may experience more than one event. The registry provides participant counts affected for serious and other adverse events, along with selected serious-event terms and percentages, but does not report a detailed event-counting method in this information.

Over-dispersion is a general concern when a model assumes event counts vary less than they actually do; ignoring it can make uncertainty appear too small. That concept does not establish that a count model was used in this trial. No such model or analysis method is reported in the registry record. The outcome-analysis methods, handling of repeated assessments, covariate adjustment, and assumptions for time-to-event outcomes are not reported in the registry record.

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("Treatment (Antiangiogenesis Therapy, Enzyme Inhibi")
n      <- c(53)
events <- c(21)
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  Treatment (Antiangiogenesis Therapy, Enzyme Inhibi  53  21  39.6  26.5  54.0  27.6  53.1  27.6  53.1

11. Multiplicity, Missing Data and Analysis Populations

The registry lists a primary outcome of overall response and secondary outcomes of adverse events, time to progression, and overall survival. It reports four outcome measures in total. Considering several outcomes can raise a multiplicity issue: when many hypotheses are tested, the chance of at least one apparently noteworthy result can increase. In general, a statistical plan may define which outcome is primary and how secondary analyses will be interpreted or adjusted. The registry does not report a multiplicity strategy or an analysis plan, and it does not report analysis results for these outcomes.

Missing-data handling is also important. If some participants lack an evaluable response assessment, the result can depend on whether they are excluded, treated as not responding, or handled under another prespecified rule. The registry record does not report the number of participants assessed for the primary endpoint, the extent or reasons for missing assessments, or the method used to handle missing data. The listed enrollment figure does not establish the analysis denominator.

The primary outcome population is not described beyond the empty population entry. There is no reported analysis-population definition, such as a rule specifying which enrolled or treated participants were included. The registry also does not report whether participants who stopped treatment, progressed, or experienced toxicity remained in the endpoint analysis. These omissions prevent assessment of how closely the analyzed group may have matched the enrolled group and how sensitive the endpoint result might be to analysis choices.

For these reasons, the registered outcome definitions alone are not enough to reproduce or fully evaluate the analyses. Neither an adjustment for multiple outcomes nor a missing-data procedure should be assumed when it is 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 0% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: platelet count decreased (37.7%), hemoglobin decreased (35.8%), fatigue (28.3%), leukocyte count decreased (20.8%), neutrophil count decreased (20.8%).

The registry reports 24 participants affected by serious adverse events among 53 at risk, and 48 participants affected by other adverse events among 53 at risk. These are participant counts in the listed treatment group. They are not counts of every individual event, because a participant may have experienced more than one event. The registry does not report further details about event definitions, timing, duration, or how severity was assessed.

Selected serious adverse-event terms are reported with percentages: platelet count decreased, 37.7%; hemoglobin decreased, 35.8%; fatigue, 28.3%; leukocyte count decreased, 20.8%; neutrophil count decreased, 20.8%; and serum calcium decreased, 20.8%. These percentages are presented as registry safety entries; their exact denominator and event-specific counting rules are not reported in the registry record. They should not be treated as percentages of all events or compared as if the terms were mutually exclusive.

The registry does not report a death count in this safety information. The listed figures describe reported adverse events in a single treatment group; without a control group, they do not establish how event frequency compares with another treatment or with no treatment.

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

The registry record documents a phase II, single-group study of bortezomib plus lenalidomide in relapsed or refractory mantle cell lymphoma. It defines overall response using complete and partial response criteria and lists a timeframe of treatment duration, assessed up to 6 years. It also records adverse-event counts and selected serious adverse-event terms. These details describe the study's question and some of its recorded safety information.

The primary response count and proportion are not reported in the registry record. As a result, the primary outcome cannot be translated into a numerical estimate of how often participants met the response definition. There is also no reported confidence interval or analysis result to indicate precision. The registry's enrollment figure does not substitute for an endpoint result or tell readers how many participants had an evaluable assessment.

Even if a response result were available, the single-group design would remain an important constraint on interpretation. Without a concurrent comparator, differences between observed outcomes and what might have happened under another treatment cannot be estimated directly. The design does not isolate treatment effects from other possible explanations for the outcomes. Masking is listed as none, and response was investigator-assessed, which are relevant features when interpreting a criteria-based endpoint.

The adverse-event entries indicate that serious and other adverse events were recorded in the treatment group, and identify several reported serious-event terms. They do not establish a comparative safety profile. The registry does not report details needed to interpret event timing, overlap among event categories, or the exact denominator underlying each listed term percentage.

Thus, the record supports a description of the trial design, endpoint definitions, and recorded safety counts, but not a quantified conclusion about primary response or a causal claim that the regimen changed clinical outcomes. Missing analysis methods, outcome results, and details about missing data further limit the strength of statistical interpretation.

14. Why This Trial Matters Statistically

This trial illustrates how a clearly defined endpoint and a study design determine what conclusions can be drawn. The response outcome is not an unstructured impression: it uses stated complete- and partial-response criteria, including requirements about disease measurements and the absence of new sites. Such definitions make the target outcome more explicit and help readers understand what a reported response count would represent.

At the same time, the single-group structure limits comparative inference. An observed outcome in participants receiving a regimen is not a direct estimate of the difference between that regimen and an alternative. This distinction is important when reading phase II evidence: descriptive outcomes and randomized comparisons answer different statistical questions. The registry lists no concurrent control group, so the design cannot provide a controlled treatment contrast.

The record also demonstrates that endpoint definitions do not replace endpoint results. The primary outcome is described, but its result is not reported in the registry record. Without the count, denominator, and an uncertainty measure, readers cannot judge the magnitude or precision of the response finding. This separates what can be learned about a trial's intended measurement from what can be learned about its observed outcomes.

Safety reporting adds another statistical lesson. Counts of participants affected and percentages for selected event terms are not interchangeable with counts of every event, and event categories may overlap. A careful interpretation keeps the reported denominators and definitions in view and avoids treating descriptive single-group figures as comparative evidence.

Overall, this study is useful for understanding the limits that arise when outcome results and analysis details are absent from a registry record. The design, endpoint criteria, and safety entries remain informative, while the unreported response result and lack of a comparator restrict what can be concluded.

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 single-group design. There is no concurrent control arm, and allocation is listed as NA. Outcomes in the treatment group therefore cannot establish a comparative treatment effect. Masking is listed as none, and the primary response assessment was made by an investigator; the registry does not report independent response review or additional safeguards against assessment bias.

The primary outcome result is not reported in the registry record. Although the endpoint definition and timeframe are stated, the response count, assessed denominator, and uncertainty estimate are not available. Enrollment of 53 does not establish how many participants contributed to the primary analysis. The registry does not report missing-data methods, analysis-population rules, or the statistical plan.

Participant characteristics and detailed eligibility criteria are not reported in the registry information described. This limits assessment of how the enrolled group represents the broader population of people with relapsed or refractory mantle cell lymphoma. The treatment description is also truncated after the initial treatment account, so further details about management after response are not reported in the registry record.

Safety information includes affected-participant counts and selected serious-event terms, but detailed event definitions, timing, counting rules, and the denominator for the term-specific percentages are not reported. A death count is not reported in the registry safety information. Secondary outcome results for adverse events, time to progression, and overall survival are not reported in the registry record, and no analysis methods for those outcomes are available.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Bortezomib and Lenalidomide in Treating Patients With Relapsed or Refractory Mantle Cell Lymphoma — NCT00553644.
• Registry record last updated 2018-10-30; status last verified 2018-10.
• Results first posted 2014-02-20.
• 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, single-group trial sponsored by the National Cancer Institute, with enrollment of 53 and no masking. The study examined bortezomib with lenalidomide in relapsed or refractory mantle cell lymphoma. Treatment was specified as repeated 21-day courses, with bortezomib on days 1, 4, 8, and 11 and lenalidomide on days 1-14, for up to 8 courses in the absence of progression or unacceptable toxicity.

The primary endpoint was the number of participants with complete or partial response by investigator assessment using International Working Group criteria, assessed during treatment up to 6 years. The primary response result is not reported in the registry record. The registry reports 24 participants affected by serious adverse events and 48 affected by other adverse events, each among 53 at risk, and lists selected serious-event terms with percentages. A comparator, analysis results, analysis-population definition, missing-data approach, and statistical plan are not reported in the registry record.