Rituximab and GM-CSF in Treating Patients With Newly Diagnosed Follicular B-Cell Lymphoma: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Rituximab and GM-CSF in Treating Patients With Newly Diagnosed Follicular B-Cell Lymphoma (NCT00411086), a na phase 2 study. The primary outcome is Complete Response Rate.

2. Clinical Question

3. Trial Design

This was a completed, open-label, phase II, single-group trial sponsored by M.D. Anderson Cancer Center. The registry lists enrollment of 60 and gives the study dates as 2006-11 for study start and 2016-11 for primary completion. The title describes treatment of adults with newly diagnosed follicular B-cell lymphoma using rituximab plus sargramostim, or GM-CSF.

All participants in the treatment group received the combination regimen. Rituximab was administered by vein at 375 mg/m^2 on Days 1, 8, 15, and 22. Sargramostim was administered subcutaneously at 250 mcg three times weekly for 8 weeks, beginning at least 1 hour before the first rituximab dose. The study was open-label, and masking was listed as none. Allocation was not applicable because no randomized allocation between groups is described.

The trial's stated purpose included assessing side effects and how well the regimen worked. The primary outcome was complete response at 12 weeks (3 months). Secondary outcomes were median progression-free survival and overall response rate. The record describes the response and progression criteria as those proposed by the International Workshop to Standardize Response Criteria for Non-Hodgkin's Lymphomas; complete response includes unconfirmed CRs.

A single-group design can describe what was observed among people receiving the regimen, but it cannot provide a like-for-like estimate of how those outcomes would compare with an alternative treatment. The registry does not report a comparator arm, randomization, a masking procedure, or a numerical primary endpoint result. It also does not report the detailed statistical analysis plan, the rationale for enrollment, or an explanation of the gap between the enrollment figure and the safety denominators. These omissions limit interpretation of both the trial's design choices and the posted 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

Analysis population for the primary outcome, as defined in the registry: Response includes unconfirmed CRs.

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 Complete Response Rate, measured over 12 weeks (3 months).

The primary endpoint was the complete response rate, expressed as a percentage of participants, assessed at 12 weeks (3 months). The registry defines complete response as complete disappearance of detectable clinical and radiographic evidence of disease, disappearance of disease-related symptoms that were present before therapy, and normalization of biochemical abnormalities such as LDH when definitely assignable to NHL. The endpoint includes unconfirmed CRs.

A complete-response endpoint is used to describe whether participants meet a specified clinical and radiographic response standard at an assessment time. Stating the criteria matters because response rates depend on what counts as a response, which findings are assessed, and when assessment occurs. The registry says response and progression were evaluated using the International Criteria proposed in the Report of an International Workshop to Standardize Response Criteria for Non-Hodgkin's Lymphomas.

The registry lists the endpoint and its definition, but the numerical complete-response rate and its uncertainty are not reported in the registry record. Consequently, the endpoint definition can be interpreted, but the observed response frequency cannot be assessed from the posted information. No confidence interval or analysis result for this primary outcome is reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does a single-group design estimate?

A single-group study records outcomes after participants receive a specified regimen. It can describe response and adverse events observed in that group, subject to the quality and completeness of measurement. It does not create a concurrent control group. Randomized comparisons are useful because allocation can make treatment groups more comparable with respect to both measured and unmeasured factors. Without that comparison, observed outcomes cannot establish what would have occurred under another treatment or without the regimen.

Here, the registry identifies a phase II, single-group, open-label study. Allocation is listed as not applicable, and masking as none. These design labels do not reveal whether other safeguards were used in conducting assessments; such details are not reported in the registry record. Open-label treatment can matter when outcomes involve clinical judgment or participant-reported symptoms, because knowledge of treatment may affect assessment or reporting. The record specifies response criteria, but it does not describe blinded endpoint review.

What does the primary endpoint represent?

The primary endpoint is a percentage of participants meeting the complete-response definition at 12 weeks (3 months). The definition combines clinical and radiographic evidence with symptoms and relevant biochemical abnormalities. It also expressly includes unconfirmed CRs. A response percentage condenses these classifications into a group-level summary. It does not show how long a response lasts, and it is not interchangeable with progression-free survival or overall response rate.

The measurement time is part of the endpoint: the record's primary assessment is at 12 weeks (3 months). Responses assessed at different times may answer different questions, so interpretation should retain the stated timeframe. The registry names median progression-free survival and overall response rate as secondary outcomes, but does not report their numerical results. Neither should be inferred from the primary endpoint definition.

How should uncertainty be understood?

In general, a confidence interval describes a range of values compatible with the observed data under a specified statistical procedure. It communicates uncertainty around an estimate; it does not guarantee that the true value lies within a particular interval. A narrow interval generally indicates more precision than a wide interval, while the interpretation also depends on the method and assumptions used.

The registry record does not report a numerical estimate or confidence interval for complete response. It also does not report the method used to estimate uncertainty. Consequently, the precision of the primary outcome cannot be evaluated from the posted information. Enrollment alone is not enough to reconstruct an interval or a response rate: the outcome count and analysis population would also be needed, and neither is numerically reported for the primary endpoint.

Why does the comparison structure matter?

With no concurrent comparator group, a response rate would describe the treated group, but it would not by itself quantify a treatment contrast. Differences between a study result and an external figure can reflect differences in eligibility, assessment, follow-up, or other features, as well as treatment. The registry record does not identify an external control or present an adjusted comparison. The safety information likewise has no comparison group in the record, so the listed event frequencies should not be read as relative risks or evidence that the regimen caused or prevented an event.

In general, over-dispersion refers to variability greater than a statistical model expects. When present, it can make standard errors too small if a model assumes less variability than the data contain. That concept is relevant to analyses whose data structure and model call for it; the registry record does not report an analysis model for the primary endpoint, so it is not possible to say whether over-dispersion was assessed or relevant to the sponsor's analysis.

What can the planning assumptions tell a reader?

The registry's planning-illustration description refers to a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation, with the effect to detect defined as a stated fraction of the observed effect. These are assumptions for an illustration, not evidence that the trial used that design or those assumptions. The actual study is listed as single-group, and the registry does not report a comparator arm or the trial's own sample-size justification. Any sample-size figure derived under those illustration assumptions is a planning aid, not observed power and not a retrospective test of whether the trial succeeded.

More generally, power is a design quantity under specified assumptions about the effect, variability, significance threshold, allocation and analysis. It is not a probability that a finding is true, nor a measure of the credibility of an observed result. Because the record does not report a primary outcome result or the trial's own statistical plan, a trial-specific power interpretation cannot be recovered from the registry information.

What does the registry analysis listing mean?

The record lists zero analysis records. This indicates that no analysis entries are posted in that registry listing; it does not establish that the investigators performed no analyses. The sponsor's statistical methods, model specifications, handling of incomplete data, and any deviations from a prespecified plan are not reported in the registry record. A careful reading separates information that is absent from a registry listing from evidence that an analysis was not conducted.

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 + GM-CSF")
n      <- c(52)
events <- c(12)
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 + GM-CSF  52  12  23.1  12.5  36.8  13.7  36.1  13.8  36.2

11. Multiplicity, Missing Data and Analysis Populations

The registry identifies complete response at 12 weeks (3 months) as the primary outcome and lists median progression-free survival and overall response rate as secondary outcomes. It does not report how the testing of multiple outcomes was handled. Whether the analyses were formally adjusted for multiplicity, whether secondary outcomes were descriptive or confirmatory, and whether any testing sequence was prespecified are not reported in the registry record. Without that information, statistical significance across multiple outcomes should not be inferred.

The record does not describe missing-data procedures for the primary or secondary outcomes. It does not state how participants without an assessment at the specified time were treated, whether any imputation was used, or whether sensitivity analyses were performed. The complete-response population is described as including unconfirmed CRs, but the analysis population and rules for incomplete assessments are not reported.

Enrollment is listed as 60, whereas the safety group lists 52 at risk for serious and other adverse events. The registry does not explain the difference. It should not be assumed that the safety denominator represents the primary endpoint population or that the difference is due to a particular reason.

The registry lists zero analysis records, but this is not equivalent to a report that no analyses were conducted. The statistical analysis plan, analysis populations, multiplicity strategy and missing-data methods are not reported in the registry record. These gaps limit assessment of how the reported outcomes, if available elsewhere, would have been selected and analyzed.

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: neutropenia (15.4%), pain (5.8%), fatigue/weakness (3.8%), blurred vision (1.9%), leukopenia (1.9%).

The registry records serious adverse events in the Rituximab + GM-CSF group for 10 of 52 participants at risk. For other adverse events, it records 52 affected among 52 at risk. These are separate registry categories and denominators; the figures should not be combined or treated as counts of different people. The record lists no death count for the group.

The leading serious adverse-event terms are reported as neutropenia, 15.4%; pain, 5.8%; fatigue/weakness, 3.8%; blurred vision, 1.9%; leukopenia, 1.9%; and infusion reaction, 1.9%. The percentages are the registry's posted values. The record does not explain the event-coding rules or provide details about severity grading, duration, attribution to treatment, or follow-up for these entries.

These are descriptive safety data from a single-group study, not a comparison of event rates against another treatment. The figures alone do not establish that the regimen caused an event, nor do they establish how rates would differ under another treatment. Enrollment is listed as 60, while the safety denominators are 52; the registry does not report why the denominators differ. The extent of safety-event ascertainment and the handling of incomplete safety follow-up are also not reported in the registry record.

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

The record establishes that a completed, open-label phase II study evaluated rituximab plus sargramostim in adults with newly diagnosed follicular B-cell lymphoma. It specifies the regimen, the primary complete-response endpoint, the assessment timeframe and the response criteria. It also provides safety counts and a list of serious adverse-event terms with percentages. Those details describe the study and the information the registry makes available.

The most important interpretive limit is that the numerical result for the primary endpoint is not reported in the registry record. There is no posted complete-response percentage or confidence interval to assess. The registry also names median progression-free survival and overall response rate as secondary outcomes but does not report their results. The available information therefore does not establish the frequency of complete response or the precision of an efficacy estimate.

The study's single-group design does not include a randomized comparator. As a result, the registry information cannot show how outcomes under this regimen compare with outcomes under another treatment or a control condition. A description of outcomes in a treated group is not the same as an estimate of a comparative treatment effect.

The safety figures are also descriptive. They report adverse-event information within the treatment group, but there is no comparison arm in the record. The enrollment figure and safety denominators differ, and the registry does not explain that difference. Details about missing outcome data, analysis populations, statistical methods and the sponsor's analysis are not reported in the registry record.

These limitations do not negate the fact that the registry documents a clinical study and its planned outcomes. They define what can be concluded from the posted record: the treatment regimen and endpoint are described, and some safety counts are available, while the primary efficacy result and important analysis details are not. No claim about comparative benefit or harm can be made from this information alone.

14. Why This Trial Matters Statistically

This trial is statistically informative as an example of the distinction between a clearly defined endpoint and a reported endpoint result. The record specifies complete response, the clinical and radiographic criteria, the inclusion of unconfirmed CRs, and the assessment at 12 weeks (3 months). Those details support understanding what the investigators intended to measure. Yet without a numerical result, the endpoint's observed frequency and precision remain unknown in the registry record.

The single-group design also illustrates the difference between describing an outcome and estimating a comparative effect. The study documents a regimen and has safety observations, but no concurrent control group is listed. A comparison with an alternative treatment cannot be recovered from the design labels or from the safety counts. This matters when interpreting any response or event frequency as evidence about treatment effects.

There is also a practical lesson in denominator transparency. The record lists enrollment of 60, while the safety group uses 52 as the number at risk. The record does not explain the difference. Clear population definitions are important because readers need to know which participants contributed to each outcome and whether missing assessments or eligibility changes affected the analysis.

Finally, the registry lists secondary endpoints and safety details, while analysis methods and the primary numerical result are not reported. A registry record can therefore provide useful design and outcome definitions without supplying all the information needed for statistical evaluation. Recognizing both the information available and the gaps is essential to avoid turning a study description into a comparative conclusion the design and posted results do not support.

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.

Several limitations specific to this trial constrain interpretation of its registry record. It is a single-group, open-label phase II study with no comparator listed. The record therefore does not support a randomized comparison of the combination regimen with another treatment. Allocation is marked not applicable, and masking is listed as none.

The primary endpoint is defined, but its numerical result is not reported in the registry record. No confidence interval or analysis result is posted for complete response at 12 weeks (3 months). The record also names median progression-free survival and overall response rate as secondary outcomes without reporting their numerical results. Thus, the available record does not permit assessment of the efficacy outcomes' magnitude or precision.

The registry lists enrollment of 60, while the safety denominator is 52 at risk for both serious and other adverse events. No explanation for this difference is reported. The record does not state how many participants contributed to the primary endpoint, how missing assessments were handled, or whether the efficacy and safety analysis populations differed.

Further limitations include the absence of a reported statistical analysis plan, sample-size justification for the trial, multiplicity strategy, and methods for handling missing data. The registry lists zero analysis records, which indicates that analysis entries are absent from the listing, not that investigators necessarily conducted no analyses. The safety entries do not include information about event attribution, duration or grading beyond the serious-event categorization and listed terms. These details are not reported in the registry record.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Rituximab and GM-CSF in Treating Patients With Newly Diagnosed Follicular B-Cell Lymphoma — NCT00411086.
• Registry record last updated 2017-12-05; status last verified 2017-11.
• Results first posted 2017-12-05.
• 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

NCT00411086 is a completed phase II, open-label, single-group study sponsored by M.D. Anderson Cancer Center. The registry lists enrollment of 60, a start date of 2006-11, and primary completion in 2016-11. The study evaluated rituximab plus sargramostim in adults with newly diagnosed follicular B-cell lymphoma.

The primary endpoint was complete response at 12 weeks (3 months), using the stated response criteria and including unconfirmed CRs. Median progression-free survival and overall response rate were listed as secondary outcomes. Numerical results for these efficacy outcomes are not reported in the registry record.

Safety information includes serious adverse events in 10 of 52 participants at risk and other adverse events in 52 of 52 at risk. The record does not explain why the safety denominators differ from enrollment. The single-group design, absent numerical primary result, and unreported analysis details limit statistical interpretation of the posted record.