Rituximab, Cyclophosphamide, and Pegfilgrastim in Treating Patients With Leukemia or Non-Hodgkin's Lymphoma: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Rituximab, Cyclophosphamide, and Pegfilgrastim in Treating Patients With Leukemia or Non-Hodgkin's Lymphoma (NCT00278161), a na phase 2 study. The primary outcome is Engraftment.

2. Clinical Question

In plain terms, this study was designed to describe blood-cell recovery following the treatment regimen in a group of patients with selected B-cell cancers. It was a phase II study, not a randomized trial comparing two groups. That distinction shapes what can be learned: a single-group result can describe outcomes among enrolled participants, but by itself it cannot distinguish the regimen's contribution from other influences on recovery.

The clinical question is therefore narrower than whether the regimen is better than another option. It concerns the observed time to the registry-defined recovery thresholds in the study group. Because the primary numerical outcome is not reported in the registry record, the available record does not permit an estimate of that recovery time or its precision.

3. Trial Design

This was a phase II, single-group study listed as completed. The registry record gives an enrollment of 94 and identifies one treatment group, R-HiCy, receiving rituximab and high-dose cyclophosphamide with pegfilgrastim support. The interventions are listed as rituximab, cyclophosphamide and pegfilgrastim. The study's official title refers to high-dose cyclophosphamide and rituximab in low-grade and mantle cell lymphoma; the brief summary also names B-cell leukemia.

Allocation is recorded as NA, and the model is single group. Masking is listed as none. There is no randomized control arm described in the record, so comparisons with an alternative treatment are not part of the design reported. The registry record does not describe a control group, a blinding procedure, or a prespecified comparative treatment contrast.

The record lists a start date of 2005-01 and primary completion of 2009-12. These dates place the study's recorded conduct and primary completion in context, but they do not supply information about recruitment pace, follow-up completeness, or the timing of individual participant outcomes. The status is completed.

The primary outcome is median time to neutrophil and platelet recovery, with a timeframe of up to 43 days and dispersion described as the full range. The registry lists three outcome measures, but details for the other outcomes are not reported in the registry record. It lists zero analyses. Statistical-analysis methods, a protocol-based sample-size justification, and any interim analysis plan are not reported in the registry record.

As a general design principle, a single-group phase II study can characterize outcomes and safety observations in the enrolled group. It does not, without a suitable comparison, establish how those outcomes would differ under another treatment or under no study treatment. This limitation applies even when a study is completed and the outcome is clinically interpretable. Here, the absence of the primary numerical result further limits what can be said about the observed recovery times.

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: 16 participants were screen failures. IRB allowed 3 of those participants to be analyzed along with the 78 who were treated as part of the study. Because the 3 additional participants received the exact same protocol intervention, the total population for analysis purposes is 81.

Overall Study

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 Engraftment, measured over Up to 43 days.

The primary endpoint is engraftment, expressed as the median number of days to neutrophil and platelet recovery. The registry defines neutrophil recovery as an absolute neutrophil count >= 500 cells per microliter and platelet recovery as an untransfused platelet count >= 20 * 10^9 cells per liter. The timeframe is up to 43 days, and the stated dispersion is the full range.

These thresholds turn the broad idea of blood-cell recovery into operational outcome criteria. Measuring time to a defined threshold can describe how long participants take to reach a clinically interpretable state, rather than merely whether a laboratory value changed. Using both neutrophil and platelet criteria also means that the endpoint refers to recovery in two blood-cell measures. The registry record does not state whether the endpoint's reported time required both thresholds to be met at the same visit or how timing was handled if one threshold was reached before the other.

The median is a measure of the center of a distribution: it identifies the point at which half of observed times are at or below it and half are at or above it, when the data allow that interpretation. The full range describes the lowest and highest observed times. As a general statistical point, medians and ranges can be informative when times are skewed or when extreme values make the mean less representative, but a range is sensitive to the observations at its boundaries.

The registry record does not report the median or the full range for this outcome. It also does not report a confidence interval or other measure of uncertainty for the primary endpoint. Accordingly, the endpoint definition is available, but its observed value and precision are not 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?

The trial is listed as a single-group study with allocation recorded as NA. In general, a single-group design measures outcomes among participants who receive the study regimen. The resulting summary can characterize the observed group, subject to how the outcome and analysis population are defined. It does not supply a randomized control estimate. Without a comparison group, the observed outcome cannot be separated from the natural course of illness, differences in participant mix, other care, or other factors that may influence the same outcome.

That distinction is relevant even when the endpoint is measured objectively. A blood-count threshold can be defined in advance and recorded consistently, but an objective measurement does not create a counterfactual comparison. Here, the registry reports a primary endpoint definition, but not its numerical result. Thus neither a group-level recovery-time estimate nor a treatment contrast can be read from the registry record.

What does the median time measure?

The endpoint is the median days to neutrophil and platelet recovery. In general, a median describes the center of observed times and is less influenced by extreme observations than an arithmetic mean. The registry specifies full range as the dispersion measure, which would describe the span from the smallest to the largest reported time. The actual median and range are not reported in the registry record.

Time-to-event methods are often used when an outcome is the time until an event occurs. A key feature of such data is censoring: some participants may not have an observed event within the available follow-up, so their exact event time is unknown. This is a general explanation, not a claim about what occurred in this trial. How censoring, incomplete follow-up, or participants who did not meet recovery criteria were handled is not reported in the registry record. The endpoint's stated timeframe is up to 43 days, but that alone does not identify the analysis method.

What can a confidence interval add?

As a general statistical concept, a confidence interval communicates the uncertainty around an estimated quantity under the assumptions of the analysis. A narrow interval indicates greater statistical precision than a wide interval, while neither interval alone resolves bias or the limits of the study design. A confidence interval for the primary median, or another uncertainty measure, is not reported in the registry record. No numerical precision statement for the endpoint can therefore be described.

A p-value is also not reported in the registry record. In general, a p-value assesses how compatible data are with a specified statistical model and null hypothesis; it is not a direct measure of clinical importance or the probability that a hypothesis is true. Since no comparative hypothesis test is described in the record, an inferential interpretation should not be invented.

How should the planning illustrations be understood?

The planning assumptions described for the separate sample-size illustrations specify 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. For time-to-event illustrations, the assumption is to express the total number of events using the Schoenfeld approach; for other outcomes, the illustration is expressed as participants per arm. These are planning assumptions, not a description of the actual single-group study design.

In general, a sample-size calculation asks how much information would be needed under particular design assumptions to detect a target effect with a chosen error rate and power. Such calculations are conditional on assumptions about the outcome, variance or event pattern, target effect, allocation, and analysis. The registry record does not report the trial's own sample-size justification or its planned target effect. Planning illustrations should therefore not be interpreted as the actual enrollment plan, observed power, or proof that a particular effect was detected.

The trial itself has enrollment of 94 and one listed treatment group. Assumptions about equal allocation between two arms do not transform it into a two-arm study. The illustrations are hypothetical planning scenarios and do not constitute a like-for-like randomized comparison. The observed primary effect used for those illustrations is not reported in the registry record, and no numerical planning output is stated in the registry record.

What is known about the analysis plan?

The record lists three outcome measures and zero analyses. It does not report the statistical-analysis plan, the analysis population, handling of missing data, adjustment for covariates, or multiplicity procedures. It also does not report whether outcomes were analyzed according to a protocol-defined population or whether sensitivity analyses were performed. These omissions prevent assessment of whether analytic decisions were prespecified or how robust results might be to alternative choices.

As a general matter, analysis methods should match the outcome structure and the study question. Time-to-event data may call for methods that account for censoring; a median and full range describe a distribution differently from a hazard ratio. The record's general note that time-to-event illustrations use sponsor-reported hazard ratios does not provide a hazard ratio for this endpoint. No sponsor-reported hazard ratio for the primary outcome is stated in the registry record.

Finally, statistical methods cannot compensate for information that is absent from the record. The endpoint's thresholds and timeframe are identifiable, but the numerical endpoint result, uncertainty, analysis details, and comparison are not reported in the registry record. Interpretation should stay within those boundaries.

10. Multiplicity, Missing Data and Analysis Populations

The registry record lists three outcome measures, but identifies only the primary endpoint in the available record: median time to neutrophil and platelet recovery. Details of the other outcome measures are not reported in the registry record. The record lists zero analyses, and it does not describe a statistical-analysis plan, a hierarchy among outcomes, or a procedure for addressing multiple comparisons.

As a general statistical explanation, multiplicity arises when several outcomes or hypotheses are examined. Testing multiple questions can increase the chance of at least one apparently notable result unless the analysis accounts for that structure. It is not possible to judge whether or how that issue was addressed because multiplicity procedures are not reported in the registry record. The existence of three outcome measures alone does not establish that multiple hypothesis tests were conducted.

The analysis population and missing-data methods are also not reported in the registry record. The record does not state how many participants contributed to the primary endpoint, whether all enrolled participants were included, how incomplete follow-up was handled, or how participants who did not reach a recovery threshold were treated analytically. These details matter in general because a summary based on observed outcomes may differ from one that accounts for missing observations or censored times.

No interim analysis plan, covariate adjustment, sensitivity analysis, or protocol-based analysis population is described in the registry record. Those methods should not be inferred from the phase II designation or from the reported enrollment. Consequently, readers cannot assess prespecification, the effect of missing data, or the sensitivity of any endpoint estimate to analysis choices using this record alone.

11. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Deaths

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: febrile neutropenia (7.4%), bacteremia (2.5%), atrial fibrillation with rapid ventricular response (1.2%), constipation (1.2%), dehydration (1.2%).

For the R-HiCy group, the registry lists 81 participants at risk for serious adverse events and 15 affected. It also lists 81 at risk for other adverse events and 64 affected. The record lists 11 deaths. These are safety observations recorded for the study group; the information does not establish that the regimen caused an adverse event or death.

The serious adverse-event terms with the highest listed percentages are febrile neutropenia, 7.4%; bacteremia, 2.5%; atrial fibrillation with rapid ventricular response, 1.2%; constipation, 1.2%; dehydration, 1.2%; and fever, 1.2%. These percentages are registry-recorded descriptions. The record does not provide further information about event timing, duration, recurrence, participant overlap across terms, or the basis for attributing events to treatment.

In general, serious adverse events are a category distinct from other adverse events; the category is not itself a statement of causation. The counts and listed percentages should be read as descriptive safety information, not as a comparison with another group. Since there is no randomized comparator in this study, these figures cannot establish whether the observed event frequency was higher or lower than it would have been under another regimen. The registry record does not report the cause of the 11 deaths.

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

The record establishes that a completed phase II study enrolled 94 participants and evaluated a single R-HiCy group receiving rituximab and high-dose cyclophosphamide with pegfilgrastim support. It defines the primary endpoint as median days to neutrophil and platelet recovery, using explicit blood-count thresholds and a timeframe of up to 43 days. This information helps clarify the study question and the outcome the investigators intended to describe.

It does not, however, report the median recovery time or its full range. The primary result is not reported in the registry record, and neither a confidence interval nor another precision measure is stated. The record also does not give a comparative estimate, which is consistent with the single-group design. These gaps mean that the available information cannot quantify the observed primary outcome or determine how it compares with another treatment group.

The safety record lists participants affected by serious and other adverse events, the most frequently listed serious-event terms and their percentages, and 11 deaths. Such data can describe what was recorded in the study group. They do not establish treatment causation, and they do not provide a controlled estimate of risk relative to another group. The record does not state the relationship of the deaths to treatment.

In general, statistical interpretation distinguishes description from causal comparison. A group-level outcome is descriptive; a randomized comparison can support an estimate of the difference between assigned groups under its design and analysis assumptions. This study's registry record describes a single-group design, so a treatment effect relative to a comparator is not established. Likewise, absence of a numerical result in the registry record should not be mistaken for a particular result or a finding of no effect.

The record therefore supports a bounded conclusion: the endpoint and regimen are identifiable, and some descriptive safety figures are available, but the primary numerical result, detailed analysis methods, and comparative evidence are not reported in the registry record. No statement that the regimen works or does not work follows from these data alone.

13. Why This Trial Matters Statistically

Statistically, this trial illustrates why design and reporting must be read together. The study is identified as phase II and completed, with enrollment of 94, but its model is single group and allocation is listed as NA. Those design details determine the kind of inference the study can support. It can be understood as an investigation of outcomes in a treated cohort, not as a randomized comparison that estimates a difference between treatment groups.

The primary endpoint is defined in a concrete way: time to neutrophil and platelet recovery under stated thresholds. That definition makes the intended outcome interpretable. At the same time, the median and full range are not reported in the registry record. This contrast highlights a basic reporting principle: an endpoint definition answers what is to be measured, whereas a numerical result is needed to describe what was observed and how precisely it was estimated.

The safety figures also show why denominators and event categories matter. The registry records 81 at risk in each of the serious and other adverse-event categories, along with affected counts and listed serious-event terms. Those observations are descriptive and do not supply a causal comparison. Without a control group, the figures should not be read as evidence of a difference in risk attributable to the regimen.

Finally, the sample-size assumptions are planning illustrations based on hypothetical two-arm assumptions, whereas the registry design is single group. Keeping planning scenarios separate from the actual trial design prevents a mistaken reading of those calculations as the trial's own design or as observed power. The record does not report the study's own sample-size justification or statistical-analysis plan.

Together, these features make the trial statistically informative as an example of the difference between an outcome definition, an outcome estimate, and a comparative treatment effect. The registry provides the first and some descriptive safety information, but does not report the primary estimate or a comparative result.

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 primary limitation for interpreting the principal outcome is that the registry record does not report its numerical result. Although the endpoint is defined as median days to neutrophil and platelet recovery and the dispersion is described as the full range, neither value is reported. No confidence interval or other uncertainty measure is reported in the registry record. Thus, the outcome's magnitude and precision cannot be evaluated.

The single-group design has no randomized comparator described. It therefore cannot provide a like-for-like comparison against another treatment within this study. The record also lists masking as none. Any influence of unblinded care or assessment cannot be evaluated from the available information, and the record does not describe additional safeguards or procedures relevant to outcome assessment.

The registry lists an enrollment of 94, while 81 participants are listed at risk in the R-HiCy safety group. The record does not explain the relationship between those figures or identify the analysis population for the primary endpoint. No conclusions should be drawn about why the counts differ. The numbers contributing to the endpoint, missing observations, censoring, and follow-up completeness are not reported in the registry record.

Further limitations include the absence of details for two of the three listed outcome measures, no listed analyses, and no reported statistical-analysis plan, multiplicity procedure, interim-analysis plan, or protocol-based sample-size justification. The record does not describe participant characteristics in detail, eligibility criteria, treatment schedule, or the relationship of deaths and adverse events to treatment. These missing details limit assessment of applicability, analytic choices, and safety attribution.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Rituximab, Cyclophosphamide, and Pegfilgrastim in Treating Patients With Leukemia or Non-Hodgkin's Lymphoma — NCT00278161.
• Registry record last updated 2018-11-05; status last verified 2018-10.
• Results first posted 2018-11-05.
• 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.

18. Record Summary

This completed phase II study is recorded as a single-group trial with enrollment of 94. The R-HiCy group received rituximab and high-dose cyclophosphamide with pegfilgrastim support. The registry lists allocation as NA and masking as none; no randomized comparator is described.

The primary endpoint was median time to neutrophil and platelet recovery, with defined blood-count thresholds, a timeframe of up to 43 days, and full range as the dispersion measure. The median and range are not reported in the registry record. The record lists three outcome measures and zero analyses.

For the R-HiCy group, 81 participants are listed at risk for serious and other adverse events; 15 are listed as affected by serious events, 64 by other events, and 11 deaths are recorded. The listed serious-event terms include febrile neutropenia at 7.4%, bacteremia at 2.5%, and four terms at 1.2% each. These are descriptive registry observations and do not establish causation. Comparative results and detailed analysis methods are not reported in the registry record.