Study of High-Dose Rituximab With Temozolomide as Treatment for Primary Central Nervous System (CNS) Lymphoma: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Study of High-Dose Rituximab With Temozolomide as Treatment for Primary Central Nervous System (CNS) Lymphoma (NCT02113007), a na phase 2 study. The primary outcome is Overall Response Rate.

2. Clinical Question

3. Trial Design

This was a phase II study of high-dose rituximab combined with temozolomide for primary CNS lymphoma. It was registered as a single-group study, with allocation listed as not applicable and masking listed as none. There was no randomized allocation and no separate control arm. The design therefore describes experience with the combination in the enrolled group, rather than a randomized estimate of how outcomes differ between treatments.

The registry record lists enrollment as 2 and the study status as terminated. The study start is recorded as 2014-07, and primary completion as 2016-02. The brief summary says the study closed early due to slow accrual. The record does not explain further why accrual was slow, or give a separate detailed account of the decision to terminate.

The intervention description specifies rituximab at 375 mg/m2 intravenously on days 1, 3, and 5, and temozolomide at 150 mg/m2 orally on days 1-5. The stated population was patients with primary CNS lymphoma who were 60 years of age or older, or patients 18 years or older who refused methotrexate-based treatment. The registry record does not provide further information about how many enrolled participants met each part of that description.

The primary outcome was overall response rate, assessed at approximately 32 weeks. The listed assessment procedure used MRI of the brain and/or spine after 4 cycles (8 weeks) of treatment. Patients with stable disease or better (CR or PR) were described as continuing treatment for 12 cycles (24 weeks). The registry record also lists progression-free survival and adverse events as secondary outcomes. It does not report the study’s detailed statistical analysis plan, sample-size justification, interim analyses, or the criteria used to define analysis populations.

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: The study closed early due to slow accrual. This outcome measure was not reached.

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 Overall Response Rate, measured over approximately 32 weeks.

The primary endpoint was overall response rate, with an assessment timeframe of approximately 32 weeks. In general, response rate is used to describe the proportion of an assessed group meeting a prespecified definition of tumor response. It can provide a direct measure of whether tumor findings meet response criteria, but interpretation depends on the exact response categories, assessment schedule, and rules for handling participants without an evaluable assessment.

The registry record describes MRI of the brain and/or spine after 4 cycles (8 weeks) of treatment, according to Response Criteria for Primary CNS Lymphoma. It defines complete response as no contrast enhancement with a normal eye exam; partial response as a 50 percent decrease in tumor enhancement with a minor retinal pigment epithelium abnormality in the eye exam; and stable disease as a lesion-size change that meets neither the specified shrinkage for partial response nor the increase for progressive disease. Patients with stable disease or better (CR or PR) were described as continuing treatment for 12 cycles (24 weeks).

The record says the study closed early due to slow accrual and that this outcome measure was not reached. It therefore supplies no observed primary response-rate estimate. The record does not report a response numerator, denominator, confidence interval, or further rules for handling missing or unevaluable assessments.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

This study’s design is central to understanding what its statistics can and cannot show. It is registered as a single-group study with no masking and allocation listed as not applicable. In general, a single-group design can describe outcomes among participants who receive an intervention. It does not create a concurrent control group, so it cannot directly estimate a between-group treatment contrast. Random allocation, when used, helps make comparison groups comparable on average; that feature is absent from this record.

What does a response-rate estimate represent?

In general, a response rate is a proportion: the number of participants meeting a stated response definition divided by the number included in the analysis. The exact numerator and denominator depend on the protocol and analysis rules. For example, the analysis could count only participants with an evaluable scan or could treat participants without a documented response as not having responded. Those choices can lead to different estimates. The registry record identifies overall response rate as the primary outcome but does not report the numerator, denominator, analysis rules, or estimate. It says the outcome was not reached.

The listed response assessment used MRI of the brain and/or spine after 4 cycles (8 weeks) of treatment according to Response Criteria for Primary CNS Lymphoma. The record describes CR, PR, and SD criteria and says patients with stable disease or better (CR or PR) would continue treatment for 12 cycles (24 weeks). These details describe the intended assessment and treatment path; they do not supply an observed response result. The primary timeframe is approximately 32 weeks.

Why does precision matter?

In general, an estimate should be read together with its uncertainty. A confidence interval gives a range of values compatible with the data under the model and method used. A narrow interval indicates greater statistical precision than a wide interval, though neither interval alone establishes that a result is clinically important. With a small amount of information, estimates of proportions can be especially imprecise. Here, the record does not report a response estimate or confidence interval, so response precision cannot be assessed from the posted record.

For a single-group study, a response-rate confidence interval would describe uncertainty around the group’s response proportion, not uncertainty around a comparison with another treatment. In general, a confidence interval around a single-group estimate cannot correct for the lack of a control arm. It also cannot remove bias from participant selection, incomplete assessments, or other design limitations.

How should the safety counts be interpreted?

Safety summaries often distinguish the number of participants with an event from the number of events. A participant can experience more than one event, and one event term can be reported for more than one participant. The registry record reports participants at risk and affected for serious and non-serious adverse events in the rituximab plus temozolomide group. It also lists hyponatraemia and hypoglycemia among the top serious terms, each at 50.0%. These are descriptive summaries; they are not a comparison against an untreated or alternative-treatment group.

In general, a small denominator makes a reported proportion sensitive to the outcome of each participant. It also leaves limited information for estimating uncommon events. The registry record does not give event-level narratives, timing, duration, or detail about how events were attributed to treatment. The reported counts therefore need to be interpreted narrowly, as the safety figures recorded for this group.

What can be learned from the secondary outcomes?

Progression-free survival is listed as a secondary outcome. In general, time-to-event analyses consider the time until a defined event and may account for participants whose event status is not known by the end of follow-up through censoring. Interpreting such an analysis requires a defined event, follow-up information, and an analysis method. Those results and details are not reported in the registry record. The other listed secondary outcome concerns participants with serious and non-serious adverse events as a measure of safety.

The record reports 0 analyses. It does not report an analysis plan specifying models, uncertainty intervals, handling of missing outcome data, or a population for analysis. Those omissions mean the posted information does not support a reconstruction of the trial’s intended inferential methods. They also prevent assessment of whether analysis choices were prespecified or how departures from the intended study conduct were handled.

What do planning calculations mean?

In general, a sample-size calculation is a planning tool: it describes how much information might be needed under stated assumptions to detect a specified effect using a chosen method. Such a calculation is not evidence that a study had that amount of information, and it is not observed power. The record says any planning illustration uses a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation, with the effect to detect expressed as a fraction of an observed effect. It also states that the illustration is not the trial’s own design. Those assumptions do not change the fact that this was a single-group study, and no trial-specific sample-size justification is reported in the registry record.

10. Multiplicity, Missing Data and Analysis Populations

The registry record identifies overall response rate as the primary outcome and lists progression-free survival and the number of participants with serious and non-serious adverse events as secondary outcomes. It reports 3 outcome measures and 0 analyses. The record does not provide a statistical analysis plan describing how these outcomes were to be tested or summarized.

Multiplicity arises when several outcomes or hypotheses are assessed. In general, making multiple statistical tests can increase the chance of obtaining at least one apparently notable result by chance. A prespecified strategy may define which outcome is primary, whether secondary outcomes are exploratory, and whether any adjustment is used. The registry record does not report a multiplicity strategy, so it is not possible to determine whether or how multiple outcomes were to be handled inferentially.

The record also does not describe missing-data rules or analysis populations. In general, a trial may define a population based on treatment received, eligibility, or availability of outcome measurements; the chosen population affects the meaning of an estimate. Rules for participants who discontinue, lack a scan, or have incomplete follow-up are also important. Such rules are not reported in the registry record. The primary outcome was not reached, and no primary response estimate or analysis population is posted.

These gaps should not be filled by assumptions about what would usually be done in a phase II study. The record does not report the protocol’s planned statistical methods, interim analyses, or sample-size justification. As a result, readers cannot verify whether the posted summaries correspond to a prespecified analysis or establish how missing outcomes and multiple endpoints were intended to affect conclusions.

11. 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: hyponatraemia (50.0%), hypoglycemia (50.0%).

The registry reports a safety group titled Rituximab Plus Temozolomide. Serious adverse events were recorded for 1 participant among 2 at risk, and non-serious adverse events for 2 participants among 2 at risk. The top serious terms are hyponatraemia and hypoglycemia, each reported as 50.0%.

These figures are counts of affected participants, not necessarily counts of all event episodes. In general, a participant can experience more than one event, and summaries by event term do not establish whether terms occurred in the same or different participants. The registry record does not report that overlap or provide event-level timing, duration, severity beyond the serious/non-serious classification, or attribution details. Deaths are not reported in the registry record.

Because the study has no control group, these safety summaries do not estimate how event occurrence compares with another treatment or with no treatment. The counts describe what was recorded for the enrolled group; they should not be treated as a complete profile of risk or as a precise estimate of event frequency in a broader population.

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

The primary efficacy outcome cannot be interpreted as a treatment result because the registry record says overall response rate was not reached. There is no posted response proportion, response numerator or denominator, or uncertainty interval. The record therefore does not show how many enrolled participants met the stated response criteria, nor how precisely a response rate could be estimated.

The record does establish features of the study: it was a phase II, single-group trial of rituximab plus temozolomide for primary CNS lymphoma; enrollment was 2; and the study was terminated after closing early due to slow accrual. Those details describe trial conduct and scale. They do not provide an efficacy estimate, and they do not indicate what the result would have been if the planned outcome had been reached.

The safety summaries report serious and non-serious adverse-event counts and two top serious terms. These figures are descriptive for the recorded group. Without a comparator, they cannot establish whether event occurrence was higher or lower than under another treatment. They also do not provide enough event detail to characterize timing, duration, or the full range of events.

More generally, a single-group study can generate information about outcomes among enrolled participants, but observed outcomes alone do not isolate the effect of an intervention from other influences. A controlled comparison would be needed to make a direct estimate of relative outcomes, subject to its own design and analysis assumptions. No such comparison is part of this record.

The appropriate interpretation is therefore limited: the registry records the intervention, design, early termination, and available safety counts, but not a completed primary response result or secondary outcome analyses. It does not establish benefit or lack of benefit, and it does not support a precise estimate of efficacy or comparative safety.

13. Why This Trial Matters Statistically

This trial is statistically notable for the gap between a clearly stated primary outcome and the outcome information ultimately posted. Overall response rate was the primary endpoint, with MRI-based assessment and response criteria described in the registry. Yet the record says the study closed early due to slow accrual and that this endpoint was not reached. That distinction is important: a planned outcome and an assessment schedule do not amount to an observed result.

The single-group design also frames the questions the study could answer. It could have described response and safety in the enrolled participants, but it did not include a randomized comparator for estimating differences between treatments. This limits interpretation even when outcome data are available, and the limitation is especially consequential when the primary outcome result is absent.

The enrollment of 2 and the termination status further emphasize the narrow scope of the available evidence. Small groups generally yield limited precision, especially for proportions and uncommon events. The registry’s adverse-event summaries should accordingly be read as descriptive counts rather than stable estimates of event frequency in a broader population. The record does not post uncertainty intervals that would quantify precision.

The record also illustrates why transparent reporting of analysis methods matters. It lists three outcome measures but reports 0 analyses, with no posted detailed statistical plan, analysis population, or missing-data rules. Without those details, readers cannot assess the intended handling of multiple outcomes or incomplete follow-up. The statistical significance and clinical importance of an unreported endpoint cannot be inferred from the study’s phase or stated objectives.

For these reasons, the record is most informative as documentation of the study’s design and its early closure, rather than as a completed efficacy evaluation. It shows why enrollment, outcome completion, analysis methods, and uncertainty estimates all matter when interpreting clinical-trial evidence.

14. 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 most direct limitation is that the primary outcome was not reached. The registry states that the study closed early due to slow accrual, and it does not report an overall response-rate result. Consequently, there is no posted efficacy estimate or interval with which to judge its precision.

The study was single-group, with allocation listed as not applicable and masking listed as none. It therefore lacked a separate control group and randomized comparison. This design cannot directly estimate a treatment contrast, and the absence of a response result further restricts what can be concluded from the record.

Enrollment was 2, and the study status is terminated. The record does not report a detailed account of participant flow, reasons for individual discontinuation or missing assessments, or the number included in any endpoint analysis. It also does not specify analysis-population definitions or missing-data procedures. These omissions matter because response and time-to-event estimates depend on how participants with incomplete data are handled.

The safety information is limited to recorded participant counts and the listed serious-event terms. Event timing, duration, participant overlap, and attribution details are not reported in the registry record. The absence of a comparator also means these figures cannot be interpreted as a comparative safety estimate. Deaths are not reported in the registry record.

Finally, the registry does not report a detailed statistical analysis plan, interim analyses, or a trial-specific sample-size justification. Although planning assumptions are described for an illustration, the record says that calculation is not the trial’s own design. The available information therefore does not establish which inferential procedures were planned or how outcome uncertainty was to be quantified.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Study of High-Dose Rituximab With Temozolomide as Treatment for Primary Central Nervous System (CNS) Lymphoma — NCT02113007.
• Registry record last updated 2017-02-07; status last verified 2016-12.
• Results first posted 2017-02-07.
• 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.

18. Record Summary

NCT02113007 was a phase II, single-group study of high-dose rituximab combined with temozolomide for primary CNS lymphoma. The stated population was patients 60 years of age or older, or patients 18 years or older who refused methotrexate-based treatment. The record lists enrollment as 2, a start date of 2014-07, primary completion in 2016-02, and status as terminated.

The primary outcome was overall response rate at approximately 32 weeks. The registry says the study closed early due to slow accrual and the outcome measure was not reached. Progression-free survival and adverse events were listed as secondary outcomes, and the record reports 0 analyses. Safety summaries list serious adverse events for 1 participant among 2 at risk and non-serious adverse events for 2 participants among 2 at risk. The record does not provide a completed primary efficacy estimate or a controlled treatment comparison.