Rituximab in Treating Patients With Refractory or Relapsed Primary CNS Lymphoma: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Rituximab in Treating Patients With Refractory or Relapsed Primary CNS Lymphoma (NCT00072449), a na phase 2 study. The primary outcome is Radiographic Response.

2. Clinical Question

The clinical question is therefore about whether radiographic response was observed in a group receiving rituximab, not about a randomized comparison with another treatment or control. Without a reported response count, the posted record does not establish the observed response frequency. Nor does it provide an estimate of how response compares with another approach. The question is clinically focused on a defined disease state and a specified treatment, but the available result information is insufficient to quantify the primary outcome. The registry also lists progression-free survival, overall survival, and toxicity as secondary outcomes; numerical results for those outcomes are not reported in the registry record.

3. Trial Design

The registry identifies this as a phase II study of rituximab for patients with refractory or relapsed primary CNS lymphoma. Its design is recorded as single group, with allocation marked NA and masking marked NONE. Thus the registry does not describe random assignment or a masked comparison. The intervention arm is titled Rituximab monotherapy.

The regimen is described as rituximab at a dose of 375mg/m2, administered as a single IV infusion every week for up to 8 weeks. The record does not report additional treatment details such as criteria for changing or stopping treatment beyond the stated schedule. It records enrollment of 12 participants. The start is listed as 2004-05, primary completion as 2009-03, and overall status as TERMINATED. The reason for termination is not reported in the registry record.

The primary outcome is Radiographic Response, measured in participants. Its stated assessment timeframe is “1 month, 2 months and then q3months.” The outcome description says that if a patient progresses at any time point, no more scans are required and the patient is off study. The registry lists Progression-free Survival, Overall Survival, and Toxicity as secondary outcomes. It records four outcome measures, but the result details and analysis records are not reported in a way that gives an interpretable primary response estimate. The record does not report a control arm, a statistical analysis plan, or an explanation of the enrollment target.

Because this is a single-group study, the treatment experience can be described within the enrolled group, but the design does not provide a concurrent control for separating treatment effects from other explanations for observed outcomes. This is a design limitation, not a calculation about the study’s results.

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 Radiographic Response, measured over 1 month, 2 months and then q3months.

The primary endpoint is Radiographic Response, expressed as a number of participants. It is intended to capture whether imaging showed a response to treatment. The registry specifies assessment at “1 month, 2 months and then q3months.” It also states that if a patient progresses at any time point, further scans are not required and the patient is off study.

Radiographic response is used in oncology studies as an observable measure of disease status on imaging. In general, an imaging endpoint can provide a structured way to assess whether a tumor has changed according to prespecified criteria. The registry record does not name the response criteria, define response categories, or explain how scans were reviewed. Those details are not reported in the registry record, so the precise operational definition of response cannot be evaluated from this information.

The outcome is listed as a count of participants, but the registry does not report how many participants met the response definition. It also does not report a proportion, confidence interval, or an analysis comparing response across groups. Consequently, the endpoint’s intended role is clear, while its observed result and precision are not available in the registry record. The timing description identifies when scans were planned, but does not itself establish that all planned scans occurred or that all participants were assessed at each time point.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The statistical information should be read in light of the single-group design and the limited results recorded. The registry lists the study model as single group, allocation as NA, and masking as NONE. No randomized control group is described. The primary outcome is a count of participants with radiographic response, but the count itself and a corresponding analysis are not reported in the registry record.

What does a participant count tell us?

A count reports how many participants meet an outcome definition. For a binary outcome such as response or no response, the count can be paired with the number assessed to estimate a response proportion. That proportion would describe the observed group, not automatically a treatment effect. In this record, the primary endpoint is described as a participant count, but the response count and the number assessed for response are not reported. No proportion can therefore be read from the posted results.

In general, an estimate should be interpreted alongside its uncertainty. A confidence interval conveys a range of values compatible with the data and the statistical method, rather than guaranteeing that a true value lies within a particular interval. The registry does not report a confidence interval for radiographic response. It also does not identify the response criteria or the analysis method, so there is no basis in the record for evaluating how an interval would have been constructed.

Why does the design affect interpretation?

A single-group study measures outcomes among participants receiving the intervention. In general, it can describe what happened in that group, but it does not estimate a randomized contrast against a control group. Without a concurrent comparator, natural disease course, participant selection, other care, and measurement processes can all be relevant when interpreting an observed outcome. These are general considerations, not claims that any specific factor affected this study.

The study is recorded as phase II, but the registry record does not report the statistical plan or explain the intended role of the phase II design in setting a decision threshold. It does not report a sample-size justification, target effect, interim analyses, or stopping rules. Those aspects should not be inferred from the phase label or from the enrollment count.

How should the planning illustrations be read?

The planning assumptions describe an illustration based on an observed effect, using a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. The stated effect to detect is a fraction of the observed effect. Such calculations are hypothetical planning exercises; they are not observed power and do not describe what happened to participants in the trial. The stated equal allocation between two arms is a planning assumption, not a description of this single-group study’s allocation.

The record does not report the primary response result needed to evaluate the observed effect used by such an illustration. Any planning estimate should therefore be understood as conditional on its stated assumptions, not as evidence of efficacy or as a feature of the trial’s original design. The registry record does not report that these assumptions were used to plan enrollment.

What is not available for re-analysis?

The registry records no analysis entries. It does not provide the primary response count, assessed population, missing response information, or an effect estimate with uncertainty. A recalculation from summary statistics is therefore not available for the primary endpoint. No alternative analysis should be treated as the sponsor’s analysis, since an analysis result is not reported. The record does not include enough detail to assess whether outcomes were analyzed as originally intended or whether any adjustments were used.

For time-to-event outcomes such as progression-free survival and overall survival, interpretation generally depends on event and follow-up information and on the analysis method. The registry lists these as secondary outcomes but does not report the corresponding numerical results or analyses. Their status as named outcomes is not evidence that an estimate was produced or that follow-up was complete.

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("Rituximab Monotherapy")
n      <- c(11)
events <- c(4)
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  Rituximab Monotherapy  11  4  36.4  10.9  69.2  15.2  64.6  15.2  65.1

11. Multiplicity, Missing Data and Analysis Populations

The registry lists Radiographic Response as the primary outcome and Progression-free Survival, Overall Survival, and Toxicity as secondary outcomes. It records four outcome measures, while the number of analysis records is zero. The registry record does not report a multiplicity strategy, such as a prespecified adjustment or a hierarchy for interpreting several outcomes. It also does not report whether any analyses were designated exploratory.

In general, evaluating several outcomes can increase the chance of finding an apparently notable result by chance if each is interpreted as an independent confirmatory test. Statistical methods can address that issue, but the record does not identify a method used in this study. The absence of reported analyses means that the effects of any multiplicity approach cannot be assessed. It would be inappropriate to assume that no adjustment was planned merely because none is described, or to assume that an adjustment was performed.

Missing data are also not described. The primary endpoint schedule includes scans at “1 month, 2 months and then q3months,” and the endpoint description says that no further scans are required after progression. The record does not report how many participants had scans at each time point, whether any assessments were missing, how missing assessments were handled, or which participants were included in an endpoint analysis. The enrollment count alone does not establish the analysis population for response.

The registry does not state whether analyses followed an intention-to-treat principle, used an evaluable-patient population, or applied another population definition. It does not provide a participant flow accounting for exclusions, withdrawals, or endpoint availability. These details are not reported in the registry record, so the extent and possible influence of missing outcome information cannot be evaluated.

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: infection-sepsis (8.3%).

The registry safety entry lists the Rituximab Monotherapy group with 12 participants at risk for serious adverse events and 1 affected. For other adverse events, it lists 12 at risk and 12 affected. These are counts of participants with an event, as indicated by the registry’s event-count definition; they should not be read as a complete accounting of the number of individual event episodes.

In general, an “at risk” count is the group used as the denominator for a reported safety measure. The registry’s top serious terms list infection-sepsis at 8.3%. The record does not provide enough detail to determine event timing, recurrence, severity beyond the serious classification, or the relationship of each event to treatment. It also does not establish from these entries whether the listed term accounts for all serious events.

The deaths entry is null, so deaths are not reported in the registry record. A missing death count should not be interpreted as evidence that no deaths occurred. Likewise, the affected counts do not by themselves establish causation. The registry reports adverse events during the study but does not provide an assessment attributing them to rituximab.

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

The record establishes that a phase II, single-group study evaluated rituximab monotherapy in patients with refractory or relapsed PCNSL. It specifies the dosing schedule and names radiographic response as the primary outcome. It also records enrollment of 12 participants and provides limited adverse-event counts. These are useful details about the study’s design and registry reporting.

The record does not report the primary response count, an estimate of response, or a confidence interval. It therefore cannot establish the observed frequency of radiographic response or how precise that frequency was. The study’s single-group design also does not provide a randomized comparison. Even if an outcome estimate were available, the design would not by itself show what would have happened under a control condition.

The listed secondary outcomes do not substitute for missing primary results. Progression-free survival, overall survival, and toxicity are named, but their numerical analyses are not reported in the registry record. Likewise, the safety counts are descriptive entries and should not be interpreted as proving that treatment caused or did not cause an event. Deaths and further event details are not reported in the registry record.

In general, a trial result is most informative when the outcome definition, analysis population, estimate, uncertainty, missingness, and comparison are all clear. Here, several of those elements are absent. The appropriate interpretation is consequently limited to what the registry records: the study design and regimen, the planned endpoint and assessment schedule, the enrollment entry, and the posted safety counts. Claims about treatment efficacy, comparative effectiveness, or the size of any benefit are not supported by the reported results.

14. Why This Trial Matters Statistically

This study illustrates an important distinction between a clinical question and the evidence available to answer it. The registry identifies a focused question about radiographic response to rituximab in refractory or relapsed PCNSL. It also specifies a treatment schedule and an imaging-assessment timeframe. Yet the primary response result is not reported. A clearly named endpoint is not a substitute for the estimate needed to interpret it.

The single-group design is also central to statistical interpretation. It can describe outcomes among participants receiving rituximab, but it does not offer a randomized control comparison. This limitation should shape any reading of an observed result, even when outcome data are available. In this record, the absence of the primary result means the descriptive question cannot be quantified either.

The registry entry further demonstrates why safety counts need context. It records participants affected and participants at risk, and identifies infection-sepsis at 8.3% among the top serious terms. But it does not report the event narratives, timing, treatment attribution, or death count. Counts are informative, but their interpretation depends on definitions and supporting detail.

Finally, the record distinguishes study design from later planning illustrations. The planning assumptions describe a hypothetical two-arm calculation, whereas the trial itself is recorded as single group. Planning estimates do not recover missing trial results and are not observed power. Keeping these categories separate helps prevent a hypothetical calculation from being mistaken for evidence generated by participants in the study.

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 principal limitation for interpreting efficacy is that the registry record does not report the primary radiographic-response count or analysis. It does not give a response estimate, confidence interval, or endpoint-specific assessment population. As a result, the primary outcome cannot be quantified from the posted results.

The single-group design provides no concurrent randomized comparator. It can describe outcomes in the treated group, but cannot support a randomized treatment contrast. The record also does not report a statistical analysis plan, sample-size justification, interim analyses, or stopping rules. The study status is TERMINATED, but the reason for termination is not reported in the registry record.

The response criteria and scan-review procedures are not reported. Although the record gives assessment times and says that scanning can stop after progression, it does not report how many participants were assessed at each time or how missing assessments were handled. The analysis population and participant flow are also not reported.

For safety, the record provides affected and at-risk counts and a serious-term listing, but not fuller event descriptions, timing, attribution, or a reported death count. These omissions limit interpretation of both efficacy and safety. They do not establish that an outcome or event did not occur; they indicate that the relevant information is not reported in the registry record.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Rituximab in Treating Patients With Refractory or Relapsed Primary CNS Lymphoma — NCT00072449.
• Registry record last updated 2013-08-28; status last verified 2013-06.
• Results first posted 2013-08-28.
• 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 identifies NCT00072449 as a phase II study of rituximab in patients with refractory or relapsed primary CNS lymphoma. It records a single-group design, allocation NA, masking NONE, enrollment of 12, and status TERMINATED. The study start is listed as 2004-05 and primary completion as 2009-03.

The intervention is rituximab monotherapy, described as a 375mg/m2 single IV infusion every week for up to 8 weeks. The primary outcome is Radiographic Response, assessed at “1 month, 2 months and then q3months.” Progression-free Survival, Overall Survival, and Toxicity are listed as secondary outcomes.

The registry does not report the primary response result or an analysis. Safety entries list 1 participant affected by a serious adverse event and 12 affected by other adverse events, each with 12 at risk. Infection-sepsis is listed among the top serious terms at 8.3%. Further analysis details, missing-data handling, and the reason for termination are not reported in the registry record.