Combination Chemotherapy and Rituximab With Pegfilgrastim Followed by Rituximab, in Large B-Cell Non-Hodgkin's Lymphoma: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Combination Chemotherapy and Rituximab With Pegfilgrastim Followed by Rituximab, in Large B-Cell Non-Hodgkin's Lymphoma (NCT00193479), a na phase 2 study. The primary outcome is Overall Response Rate (ORR), the Percentage of Patients Who Experience an Objective Benefit From Treatment.

2. Clinical Question

3. Trial Design

This is a phase II, single-group clinical trial of brief combination chemotherapy and rituximab with prophylactic pegfilgrastim, followed by maintenance rituximab. The official title describes the intended population as elderly or poor-performance-status patients with large B-cell non-Hodgkin's lymphoma. The registry lists Non-Hodgkins Lymphoma as the condition and reports enrollment of 51 participants.

The described regimen includes cyclophosphamide, mitoxantrone, vincristine, and prednisone with rituximab. The arm description says that all patients receive three courses of combination chemotherapy and rituximab followed by pegfilgrastim, administered at 21-day intervals. The available description is incomplete: the listed prednisone dose ends before the administration details are finished. More complete dosing, eligibility, and treatment-delivery information is not reported in the registry record.

The trial has no randomized allocation and no masking. Its design is classified as single-group, so there is no concurrent control arm described for estimating a relative treatment effect. The registry record marks the study as completed. The recorded start is 2003-04 and the primary completion is 2008-07.

The registry describes one primary outcome measure: overall response rate (ORR), the percentage of patients who experience an objective benefit from treatment, assessed at 18 Months. It reports no analysis entries and does not give the ORR result. The record also does not report a statistical analysis plan, a sample-size justification for the trial itself, or details of planned interim analyses. These gaps limit interpretation of how the primary outcome was to be analyzed and how the planned study size was chosen.

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: Forty-eight of 51 patients (94%) completed the initial three courses of rituximab/chemotherapy. Forty-four of the 48 patients (92%) received the Rituximab maintenance therapy.

Induction Chemotherapy

Reasons for not completing this period:

Maintenance Rituximab

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 Overall Response Rate (ORR), the Percentage of Patients Who Experience an Objective Benefit From Treatment, measured over 18 Months.

The primary endpoint is overall response rate (ORR), expressed as the percentage of patients who experience an objective benefit from treatment. The registry describes response using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions assessed by MRI or CT. Complete response is defined as disappearance of all target lesions. Partial response is defined as a >=30% decrease in the sum of the longest diameter of target lesions. Overall response is the combination of complete and partial responses.

As a response endpoint, ORR records whether a patient meets the stated criteria for an objective response during the assessment period. In general, such endpoints can provide a direct summary of tumor response, but they do not by themselves describe how long a response lasts, whether symptoms or function change, or how treatment compares with an alternative. Those questions require additional outcomes and an appropriate comparison design.

The registry gives the outcome timeframe as 18 Months. It does not report the number or percentage of participants who achieved an overall response, the number evaluated, or an uncertainty interval. Consequently, the endpoint definition is available, but its observed result and precision cannot be assessed from the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What can a single-group estimate tell us?

In general, a single-group trial can describe outcomes among participants who receive a regimen under the study conditions. For a binary outcome such as whether a participant meets a response definition, the main summary is often a proportion or percentage. Its precision depends on how many participants contribute evaluable outcome information and how the responses are distributed. A confidence interval, when reported, communicates a range of estimates compatible with the data under the method's assumptions. It does not guarantee that the true value lies within the interval.

For this trial, the registry names ORR as a percentage outcome but does not report the observed value, denominator, or confidence interval. The response rate therefore cannot be reconstructed from the record. Enrollment alone does not establish how many participants had outcome assessments available or met the analysis definition. No recalculated outcome estimate is available from the registry information.

Why does the absence of a control group matter?

In general, a treatment comparison aims to distinguish differences associated with treatment assignment from differences that may arise from patient characteristics, disease course, or other care. Random allocation can help balance such factors between groups, on average. A single-group design has no internal randomized control, so it can estimate outcomes in the treated group but cannot isolate the effect of treatment relative to a comparator. Comparisons with other studies may be informative context, but differences in eligibility, assessment, follow-up, and analysis can make those comparisons unreliable as causal estimates.

The registry classifies this study as single-group, with allocation recorded as NA and masking as NONE. No like-for-like randomized comparison is reported. Accordingly, a response percentage, if available, would not by itself quantify an effect relative to another strategy.

What does the endpoint definition contribute?

In general, a prespecified endpoint definition determines which observations count as outcomes and how they are summarized. The registry defines complete response as disappearance of all target lesions, partial response as a >=30% decrease in the sum of the longest diameter of target lesions, and overall response as complete response plus partial response. It identifies RECIST v1.0 and MRI or CT assessment. Consistent application of these rules is important for making response classifications interpretable. The record does not describe assessor blinding, review procedures, or handling of equivocal or unavailable scans.

The endpoint is specified at 18 Months. A timepoint label does not, by itself, explain when scans occurred, what assessment window was allowed, or how response over follow-up was summarized. Those operational details are not reported in the registry record. Nor does the record provide an outcome value that could be evaluated against the stated definition.

How should uncertainty and planning be understood?

In general, statistical uncertainty reflects the fact that a study observes a sample rather than every patient in the target population. Confidence intervals can communicate uncertainty around an estimate; a p-value, when used, addresses compatibility with a specified null model under assumptions. Neither is a measure of clinical importance on its own. The registry does not report an ORR confidence interval, p-value, or statistical test for the primary outcome.

A separate sample-size planning illustration is described using a two-sided significance level of 0.05, equal allocation between two arms, a normal approximation, and an effect defined as a stated fraction of the observed effect. Such planning values are design illustrations, not observed evidence and not observed power. The record's trial itself is single-group; the planning assumptions do not convert it into a randomized two-arm comparison. The registry does not report the trial's own sample-size justification, so the illustration should not be treated as the documented basis for enrollment.

General sample-size planning asks how much information a future study might need to detect a prespecified effect under stated assumptions. It depends on the assumed effect and outcome variability, the target error rates, and the design. A planning illustration based on an observed effect is conditional on that effect and its uncertainty; it is not evidence that the trial had a particular probability of detecting an effect. No numeric planning outputs are included in the registry entries described for this trial.

What can the safety counts establish?

For a binary safety summary, the count affected and the count at risk give a basic description of how many participants had a recorded event under the registry's reporting rules. In general, such a summary does not describe event duration, recurrence, clinical seriousness beyond the classification used, or the contribution of treatment exposure time. It also does not establish causation. Comparative safety conclusions require a suitable comparator and consistent event ascertainment.

The registry lists serious adverse events for 51 participants at risk and 24 affected, along with selected serious event terms. It lists other adverse events for 51 at risk and 51 affected. These are registry summaries, not a complete account of event timing, severity, attribution, or exposure. The record does not report enough detail to determine how individual events overlap across terms.

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("CNOP (CVP)/Rituximab/Pegfilgrastim Followed by Rit")
n      <- c(48)
events <- c(39)
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  CNOP (CVP)/Rituximab/Pegfilgrastim Followed by Rit  48  39  81.2  67.4  91.1  68.1  89.8  68.0  89.8

11. Multiplicity, Missing Data and Analysis Populations

The registry record lists one primary outcome measure, overall response rate, and reports no analysis entries. It does not report whether additional outcomes were prespecified in a protocol, whether any subgroup analyses were planned, or whether multiple statistical tests were conducted. A multiplicity strategy—such as an adjustment to account for several formal comparisons—is not reported in the registry record. Without the full analysis plan, it is not possible to determine whether multiplicity was a concern or how it was handled.

The observed primary outcome value, its denominator, and an uncertainty interval are not reported. The record also does not state how participants with missing response assessments were treated, whether anyone was excluded from the analysis, or whether the analysis used an intention-to-treat or evaluable-patient population. These omissions prevent assessment of missing-data assumptions and of how closely the analyzed population may correspond to all enrolled participants.

In general, missing outcome data can affect an estimate if participants without assessments differ systematically from those with assessments. Analysis choices may include assumptions about the unobserved outcomes, but no such choices are described in this record. It is therefore not appropriate to infer how missingness was handled or to reconstruct an analysis from enrollment alone.

Likewise, the record does not report interim analyses, stopping rules, or a statistical analysis plan. Their absence from the registry record does not establish whether such procedures existed elsewhere; it means their methods and consequences cannot be assessed from this 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 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: cva (7.8%), atrial fibrillation (5.9%), pneumonia (3.9%), fractured hip (3.9%), urinary tract infection (3.9%).

The registry lists serious adverse events for a group with 51 participants at risk and 24 affected. It also lists other adverse events with 51 participants at risk and 51 affected. These are counts of participants recorded in each category, not a comparison between treatment groups. Because the trial is single-group, the figures do not show how event frequency would differ under another regimen.

The serious adverse event terms listed are CVA (7.8%), atrial fibrillation (5.9%), pneumonia (3.9%), fractured hip (3.9%), urinary tract infection (3.9%), and diverticulosis (3.9%). The registry does not explain whether participants could appear under more than one term, so the terms should not be added together or treated as separate, mutually exclusive groups. It also does not provide event timing, duration, exposure-adjusted rates, or attribution to treatment.

In general, adverse event counts describe events recorded under a study's reporting process. They do not, by themselves, establish that treatment caused an event or characterize its full clinical course. The registry does not report the details needed to assess those questions or to make a comparative safety estimate.

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

The record establishes that a completed phase II, single-group trial evaluated a regimen combining chemotherapy with rituximab and pegfilgrastim, followed by maintenance rituximab, in a population described as elderly or poor-performance-status patients with large B-cell non-Hodgkin's lymphoma. It also establishes that ORR, assessed using RECIST v1.0 criteria and MRI or CT at 18 Months, was the primary outcome.

The record does not provide the observed ORR. It therefore does not show what percentage of participants met the response definition, how precise that estimate was, or how many participants contributed evaluable outcome information. A missing result is not evidence of either a high or low response rate. The available registry information cannot establish that the regimen did or did not improve outcomes.

Even if the response result were available, this single-group design would describe outcomes in the treated group rather than estimate a randomized treatment contrast. It could not on its own establish how outcomes would differ under another regimen. The design also cannot separate outcomes associated with the regimen from other influences on response.

The adverse event summaries describe recorded safety information in the study group, including the serious event counts and selected event terms. They do not establish treatment causation or comparative risk. Interpretation is further limited because the registry does not report the event assessment details, outcome analysis population, missing-data handling, or full statistical plan.

The appropriate statistical reading is therefore narrow: the registry documents a trial design, an endpoint definition, enrollment, and selected safety summaries, but not the primary efficacy result. Conclusions about response magnitude, comparative benefit, precision, or causal effect are not supported by the registry record.

14. Why This Trial Matters Statistically

This trial is statistically instructive because the primary question concerns an objectively defined binary response outcome, while the study design is single-group. In general, a response proportion can describe outcomes among treated participants, but a comparative treatment effect requires a comparator. Recognizing that distinction prevents a descriptive outcome from being interpreted as proof of superiority over another treatment.

The registry's endpoint definition also illustrates why outcome rules matter. Complete response, partial response, and overall response are specified using target-lesion criteria, a measurement threshold, and imaging assessment. Those definitions create a framework for classification, but an endpoint definition is not itself an outcome result. Without the observed response estimate, its denominator, and an uncertainty interval, neither magnitude nor precision can be evaluated.

The record also demonstrates the difference between a study's design justification and a planning illustration. The described sample-size illustration uses stated assumptions and an effect based on an observed effect. In general, planning calculations depend on assumptions and should not be mistaken for observed power or for evidence that a study detected a treatment effect. The registry does not report the trial's own sample-size justification or analysis plan.

Finally, safety counts need context. Counts and listed terms can summarize reported events, but without a comparator, timing, exposure, and attribution information they do not quantify comparative risk or causation. Together, these points show why statistical interpretation depends not only on endpoint labels and counts, but also on design, analysis details, and transparent reporting of estimates and uncertainty.

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 most consequential limitation of the registry record is that it does not report the primary ORR result. The endpoint definition and timeframe are stated, but there is no observed percentage, denominator, or uncertainty interval with which to assess the response estimate.

The single-group design provides no concurrent randomized comparator. Consequently, the study cannot directly estimate a treatment contrast or distinguish outcomes associated with the regimen from other influences. Allocation is recorded as NA and masking as NONE. The record does not describe assessor blinding or independent outcome review.

Important details about the analysis are not reported in the registry record. These include the analysis population, handling of missing imaging or response assessments, treatment of participants who did not complete the regimen, and the statistical analysis plan. The full eligibility criteria, participant characteristics, assessment schedule, and follow-up procedures are also not described in the available record.

The treatment description is incomplete: it states the chemotherapy and pegfilgrastim schedule, but the listed prednisone administration details are truncated. The registry does not provide enough information to assess variation in treatment delivery or exposure.

The safety summaries provide counts and selected serious adverse event terms, but not event timing, recurrence, duration, attribution, or exposure-adjusted information. The record does not clarify whether terms overlap. These limitations constrain both safety interpretation and any comparison with other studies.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Combination Chemotherapy and Rituximab With Pegfilgrastim Followed by Rituximab, in Large B-Cell Non-Hodgkin's Lymphoma — NCT00193479.
• Registry record last updated 2022-03-03; status last verified 2022-02.
• Results first posted 2014-02-21.
• 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 NCT00193479 as a completed phase II, single-group trial sponsored by SCRI Development Innovations, LLC. It records enrollment of 51 participants, a start of 2003-04, and primary completion of 2008-07. The intended population is described as elderly or poor-performance-status patients with large B-cell non-Hodgkin's lymphoma.

The regimen included cyclophosphamide, mitoxantrone, vincristine, prednisone, and rituximab with prophylactic pegfilgrastim, followed by maintenance rituximab. The primary outcome was overall response rate at 18 Months, assessed using RECIST v1.0 and MRI or CT. The registry does not report the primary outcome result or its uncertainty.

The record lists serious adverse events for 24 affected participants among 51 at risk, selected serious event terms, and other adverse events for 51 affected participants among 51 at risk. These are descriptive summaries without a control-group comparison. Analysis populations, missing-data methods, and the statistical analysis plan are not reported in the registry record.