Rituximab and Combination Chemotherapy in Treating Patients With Primary Central Nervous System Lymphoma: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Rituximab and Combination Chemotherapy in Treating Patients With Primary Central Nervous System Lymphoma (NCT00335140), a na phase 2 study. The primary outcome is Complete Response Rate - Locally Reviewed.

2. Clinical Question

This is a response-rate question within one treated group, not a direct comparison of the combination with another treatment or with no treatment. A response percentage can describe the observed outcomes in the analyzed group, but, without a concurrent comparator, it cannot isolate the contribution of rituximab from the effects of chemotherapy, patient characteristics, or other factors.

The registry record identifies the study as phase II and names the Eastern Cooperative Oncology Group as sponsor. The status is terminated. A reason for termination is not reported in the registry record. The registry record does not report a response estimate, the number of participants who achieved complete response, or an interval around a response estimate. Consequently, the stated research question is clear, but its numerical answer cannot be assessed from the posted results.

3. Trial Design

The registry describes an interventional phase II study with a single-group model. Allocation is listed as not applicable, and masking is listed as none. There is no separate control arm or randomized allocation described in the record. The study enrolled 26 participants, and the primary outcome population is specified as eligible, treated patients.

The treatment group combined rituximab with high-dose methotrexate, leucovorin, vincristine, procarbazine, dexamethasone, and cytarabine. Participants with meningeal involvement were to receive additional methotrexate and leucovorin. The record lists these agents as interventions, but does not give a complete dosing schedule or details of treatment delivery in the outcome information.

The primary outcome was complete response based on disease status three weeks after the end of therapy, at week 17. Assessment used local site images and data, with the ECOG-ACRIN data manager assessing the material based on local review. The response definition used contrast-enhancing tumor measurements on CT or MRI and included clinical and disease-status requirements. The same imaging modality was to be used throughout assessment.

The registry lists one outcome measure and zero analyses. It does not post the complete-response count or rate, confidence interval limits, or an analysis result. The study's sample-size justification, any interim analyses, and a fuller statistical analysis plan are not reported in the registry record. The status is terminated, but the reason and its implications for recruitment, treatment, or follow-up are not reported. These omissions limit evaluation of how the trial was conducted and how its primary question was answered.

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: Eligible, treated patients

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.

Population: Eligible patients who began protocol therapy

6. Primary Endpoint

The registry lists the primary outcome as Complete Response Rate - Locally Reviewed, measured over For the primary endpoint, complete response will be based on disease status at three weeks post the end of therapy (week 17)..

The primary endpoint was the complete-response rate among eligible, treated patients. It was defined as a percentage of participants and was assessed using disease status three weeks after the end of therapy, at week 17. The registry states that response was assessed by the ECOG-ACRIN data manager based on images and information from local sites.

Response assessment used the sum of maximal cross sections in two separate axes for enhancing lesions on CT or MRI. The same imaging modality was to be used throughout the assessment. Complete response required disappearance of all contrast-enhancing tumor on CT or MRI, being off all glucocorticoids, and resolution of meningeal and vitreous involvement when present. The response also had to last at least 4 weeks.

A binary response endpoint classifies each participant as meeting or not meeting the stated complete-response definition. General statistical context: a response rate expresses how common that defined outcome was in the analysis population; it does not describe the time until response or how long participants remained free of disease. The registry lists a 95% confidence interval as the endpoint's dispersion measure, but the interval limits and the response estimate are not reported in the registry record. The posted results therefore do not quantify the primary endpoint.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry identifies the primary outcome as a percentage of participants with complete response and names a 95% confidence interval as its dispersion measure. It does not post the response estimate, interval limits, or an analysis result. The statistical concepts below are general explanations; the registry record does not establish that any particular calculation beyond the listed endpoint was performed.

What does a response rate represent?

General: a binary endpoint assigns each participant to one of two outcome categories, such as meeting or not meeting the complete-response definition. A response rate summarizes the proportion of the analysis population meeting the specified definition. It depends on both the definition and the population used as the denominator. Here, the registry names eligible, treated patients as the population, but does not report the number analyzed or the response count. A rate cannot be reconstructed from the enrollment figure alone.

The outcome definition is more specific than a radiology-only finding. It includes disappearance of all contrast-enhancing tumor, being off glucocorticoids, and resolution of meningeal and vitreous involvement if present. It also requires the response to last at least 4 weeks. These criteria determine which participants qualify as complete responders. The registry does not report participant-level outcome data, so it is not possible to verify how the criteria were applied in individual cases.

How should the confidence interval be understood?

General: a confidence interval communicates uncertainty around an estimated quantity. For a response rate, it gives a range of values compatible with the observed data under the method's assumptions. It is not a guarantee that the underlying response rate lies within that particular interval, and its width depends on the amount of information and the interval method. The registry names a 95% confidence interval but does not post its limits or identify the calculation method. Thus, neither the magnitude of the response estimate nor its precision can be read from the posted results.

The registry's choice to describe a percentage and confidence interval does not itself establish that a particular interval calculation was used or that the endpoint was analyzed as planned. The calculation method, any adjustment, and any handling of missing response assessments are not reported in the registry record. A confidence interval cannot be independently checked without the observed outcome count, analysis denominator, and method.

What does the single-group structure allow?

General: a single-group study can estimate the frequency of an outcome in its analyzed participants. It does not create a randomized contrast. Without a concurrent comparator, a rate cannot show how outcomes would have differed under another treatment strategy, and it cannot isolate the effect of one component of a combination regimen. This study included rituximab and multiple chemotherapy agents, so a response result, if posted, would describe the combined regimen in the group studied rather than the separate contribution of each agent.

Allocation is listed as not applicable, masking as none, and the model as single group. These design entries should not be interpreted as evidence of randomization or blinded outcome assessment. The registry describes local image review and data assessment by the ECOG-ACRIN data manager; further procedures to reduce assessment bias are not reported.

What statistical plan is documented?

The registry lists one outcome measure and zero analyses. It does not report the statistical plan, sample-size justification, planned handling of missing data, interim analyses, or any multiplicity adjustment. A sample-size calculation or power claim cannot be inferred from enrollment alone. General: planning calculations depend on assumptions about the outcome and the effect the study is designed to detect; they do not describe observed results. The reason the trial was terminated is also not reported.

There is no posted primary analysis to interpret or independently recalculate. In particular, no estimate can be compared with a confidence interval, and no significance test or model can be attributed to the study on the basis of the registry record. The appropriate statistical reading is limited to describing the endpoint, the single-group design, and the absence of a posted estimate. Any claim about a response magnitude, statistical significance, or comparative effect would go beyond the information recorded.

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 + Standard Chemotherapy")
n      <- c(25)
events <- c(16)
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 + Standard Chemotherapy  25  16  64.0  42.5  82.0  44.5  79.8  44.3  79.8

11. Multiplicity, Missing Data and Analysis Populations

The registry lists one outcome measure, the locally reviewed complete-response rate, and zero analyses. A single listed primary outcome narrows the interpretation to that endpoint, but the record does not establish whether other outcomes or analyses were planned outside the posted information. A multiplicity strategy, such as adjustment for testing more than one outcome or analysis, is not reported in the registry record. It is not possible to determine whether multiplicity was relevant to the full study plan.

The primary population is described as eligible, treated patients, while enrollment is 26. The number who were eligible and treated, and the number included in the endpoint analysis, are not reported. Handling of participants without an evaluable response assessment, missing images, or incomplete follow-up is also not reported. As a result, the denominator for the primary endpoint and the potential influence of missing outcome data cannot be assessed.

The registry does not report whether the analysis followed an intention-to-treat approach, a per-protocol approach, or another analysis-population rule. It also does not provide a statistical analysis plan, interim-analysis details, or a sample-size justification. These omissions do not prove that such procedures were absent; they mean that they are not documented in the registry record. Without the planned and analyzed populations, missing-data rules, and outcome counts, readers cannot evaluate possible selection effects or reproduce the primary result.

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: neutrophils decreased (76.9%), leukocytes decreased (65.4%), lymphopenia (38.5%), hypokalemia (30.8%), alanine aminotransferase increased (26.9%).

The registry reports a group of 26 participants at risk for serious adverse events, with 24 affected. For other adverse events, it reports 26 participants at risk and 26 affected. The record lists the following serious adverse-event terms and percentages: neutrophils decreased, 76.9%; leukocytes decreased, 65.4%; lymphopenia, 38.5%; hypokalemia, 30.8%; alanine aminotransferase increased, 26.9%; and anemia, 23.1%. These are registry-reported figures, not an independent assessment of causality.

General: a participant count affected is different from a count of individual events; one participant may experience more than one event. A percentage attached to a term describes the posted frequency for that term, but the registry information does not explain additional details such as event severity grading or attribution. The figures should be read as safety summaries for this treatment group, not as comparative risk estimates, because there is no control group.

Deaths are not reported in the registry record. The record does not provide enough information to infer a death count from that missing entry. The serious-event and other-event summaries do not replace the absent primary efficacy result, and they do not establish whether an event was caused by a particular treatment component.

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

The record documents a phase II, single-group study of rituximab with combination chemotherapy for primary central nervous system lymphoma. It specifies a complete-response endpoint, its assessment time, and its operational criteria. It also gives safety summaries for the treatment group. These are useful descriptions of what the study was designed to evaluate and of selected posted safety data.

The registry does not report the numerical complete-response result. Without a response count, rate, confidence interval limits, and analysis denominator, the primary outcome cannot be quantified or judged for precision. The listed 95% confidence interval is a description of the intended or recorded dispersion measure, not a reported interval with interpretable bounds.

Even if a response estimate were available, the single-group design would describe outcomes in treated participants rather than establish a randomized comparison with an alternative. Since the regimen included rituximab and several chemotherapy agents, such a design would not identify the individual contribution of any component. The outcome definition also depends on imaging and clinical criteria, including being off glucocorticoids and the duration requirement; a general notion of tumor response should not be substituted for that defined endpoint.

The safety counts and listed percentages describe events recorded in the treatment group. With no comparison group, they do not estimate how event frequencies differ from another regimen or from untreated participants. They also do not establish that a particular drug caused an event. The listed death value is not reported in the registry record.

The study is marked terminated, but no reason is given. It is therefore not possible to connect the status to recruitment, safety, results, or any other cause. The posted information supports a description of the study design, endpoint definition, and selected safety figures; it does not support a conclusion about comparative benefit, treatment effectiveness, or the size and precision of the primary response result.

14. Why This Trial Matters Statistically

This trial illustrates why an endpoint definition and an endpoint result are different kinds of information. The registry gives a detailed definition of complete response, including imaging findings, steroid status, resolution of specified involvement, timing, and required duration. Those details help clarify what a response would mean. They do not tell readers how many participants met the definition. Since no primary response estimate or interval limits are posted, the most central statistical quantity remains unavailable.

The single-group design also shapes the scope of any statistical conclusion. A response rate from one treated group can describe observed outcomes in that group, but it does not provide a randomized comparison. This distinction matters when a regimen contains multiple active components: a group-level outcome cannot separate their contributions. Statistical summaries should therefore be matched to the design that generated them.

The record further shows why denominators and analysis populations matter. It reports enrollment of 26 and identifies eligible, treated patients as the primary endpoint population, but does not state the number analyzed. Without that denominator and the number meeting the response definition, a response percentage cannot be checked. The same issue applies to evaluating missing assessments or the influence of participant exclusions.

Finally, the safety figures are presented for one treatment group. Counts and listed term percentages can describe recorded events, but without a comparator they do not quantify relative risk. Taken together, these features make the registry record a useful example of how design, endpoint definition, analysis population, precision, and reporting completeness jointly determine what can be concluded statistically.

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 in the posted record is that the primary complete-response result is not reported. The registry lists the endpoint and a 95% confidence interval as its dispersion measure, but gives neither the response estimate nor the interval limits. No analysis is listed. The central outcome therefore cannot be interpreted quantitatively.

The analysis population is identified as eligible, treated patients, but the record does not give the number meeting those criteria or the number with an evaluable endpoint. Enrollment of 26 should not be treated as the response denominator without confirmation. Exclusions, missing assessments, and the handling of incomplete follow-up are not reported.

The single-group design has no randomized comparator, so it cannot establish a comparative treatment effect. Masking is listed as none, and the endpoint uses local image review and data. The record does not give further details that would permit assessment of how outcome assessment was standardized or protected from bias. The study includes a multi-agent regimen, so the individual effects of its components cannot be distinguished from a group response.

The registry does not report a sample-size justification, interim analyses, multiplicity procedures, or a complete statistical analysis plan. The reason for termination is also not reported. These gaps limit assessment of the original design assumptions, analysis choices, and the context for the status. The safety information is likewise limited: the record provides selected serious adverse-event terms and summary counts, but not a comparative group. Deaths are not reported in the registry record.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Rituximab and Combination Chemotherapy in Treating Patients With Primary Central Nervous System Lymphoma — NCT00335140.
• Registry record last updated 2023-07-03; status last verified 2023-06.
• Results first posted 2017-06-28.
• 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

NCT00335140 is a phase II, single-group study sponsored by the Eastern Cooperative Oncology Group. It enrolled 26 participants and evaluated rituximab with combination chemotherapy for primary central nervous system lymphoma. The regimen included high-dose methotrexate, leucovorin, vincristine, procarbazine, dexamethasone, and cytarabine; additional methotrexate and leucovorin were specified for patients with meningeal involvement.

The primary outcome was locally reviewed complete response in eligible, treated patients, assessed three weeks after the end of therapy at week 17. The record defines response using imaging and clinical criteria and lists a 95% confidence interval as the dispersion measure. It does not report a response estimate, confidence interval limits, or analysis result. Safety summaries include 24 participants affected by serious adverse events among 26 at risk, and 26 affected by other adverse events among 26 at risk. The study status is terminated; the reason is not reported in the registry record.