Rituximab in Treating Patients Undergoing Donor Peripheral Blood Stem Cell Transplant for Relapsed or Refractory B-cell Lymphoma: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Rituximab in Treating Patients Undergoing Donor Peripheral Blood Stem Cell Transplant for Relapsed or Refractory B-cell Lymphoma (NCT00867529), a na phase 2 study. The primary outcome is Disease Relapse Rate.

2. Clinical Question

In statistical terms, the study asks how often relapse or progression was recorded in this treated group by the stated follow-up point. A single-group result can describe outcomes among participants receiving the regimen, but it cannot by itself distinguish the contribution of rituximab from the contribution of transplantation, disease characteristics, or other influences. The registry lists overall survival, progression-free survival, graft outcomes, engraftment, and graft-versus-host disease among secondary outcomes, but does not report their results in the posted information.

3. Trial Design

This completed phase II trial enrolled 63 participants and evaluated a treatment strategy combining rituximab with donor peripheral blood stem cell transplantation. The registry identifies the model as single group, allocation as NA, and masking as none. Those features matter for interpretation: the posted design has no randomized comparison arm and does not mask treatment assignment. The enrollment figure describes the number enrolled, not necessarily the number with evaluable data for every endpoint.

The intervention was planned around the transplant. Participants received intravenous rituximab on days -3, 10, 24, and 38, while donor peripheral blood stem cell transplantation occurred on day 0. The treatment description says therapy continued unless disease progression or unacceptable toxicity occurred. The record also lists nonmyeloablative allogeneic hematopoietic stem cell transplantation, pharmacological study, and laboratory biomarker analysis among the interventions. Further details of the transplant protocol or biomarker procedures are not reported in the registry record.

The registry gives a start of 2009-02 and a primary completion of 2015-03, and lists the study status as completed. Fred Hutchinson Cancer Center is named as sponsor. The primary endpoint was a participant count for disease relapse at 18 months. Secondary outcomes included acute and chronic graft-versus-host disease, overall and progression-free survival, graft rejection and failure, and time to engraftment.

The record does not report a sample-size justification, a statistical analysis plan, or the criteria used to define the analysis population for each endpoint. It also does not describe an interim analysis. These omissions limit the ability to assess whether the enrolled group was expected to provide a particular level of precision, how endpoints were to be analyzed, or how incomplete follow-up was handled.

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

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 Disease Relapse Rate, measured over At 18 months.

The primary endpoint is the number of participants with relapsed or progressive disease after transplantation, assessed at 18 months. It is a count of participants experiencing the specified disease event, rather than a measure of how many separate relapse episodes occurred. The registry describes the endpoint as a way to evaluate the relapse rate following pre- and post-transplant rituximab.

Relapse is relevant to the stated study question because the treatment strategy was intended to be evaluated in patients whose B-cell malignancy had relapsed or was refractory. In general, defining a follow-up point makes the time horizon of an outcome explicit: the endpoint concerns disease status by the specified assessment time, not an unrestricted claim about later outcomes. The registry record does not explain how relapse or progression was adjudicated, whether assessments followed a specified schedule, or how a participant without an assessment at 18 months was classified.

The posted results do not give the observed relapse count, the number assessed for this endpoint, or an estimated rate and its uncertainty. Without those details, the primary endpoint cannot be quantitatively interpreted from the registry record. The enrollment figure alone cannot serve as the endpoint denominator, because the record does not establish that every enrolled participant had complete endpoint follow-up.

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 observes outcomes among participants receiving the study regimen. For a binary outcome such as whether relapse or progression was recorded by a specified follow-up point, a basic descriptive summary would be the number of participants with the event and the number included in the endpoint analysis. The registry identifies the primary endpoint as a participant count at 18 months, but does not post either the event count or the endpoint analysis denominator. No relapse proportion can therefore be stated from the posted results.

Even if an event proportion were available, it would describe the study group under the conditions of this trial. Without a concurrent comparison group, that proportion would not directly estimate the difference between outcomes under rituximab and outcomes under a specified alternative. In general, a treatment effect is a comparison between outcomes under different treatment strategies; a single observed group does not supply that contrast by itself. The registry lists allocation as NA and the model as single group, so it does not describe a randomized treatment contrast.

How should uncertainty be understood?

In general, a confidence interval expresses the range of values reasonably compatible with the observed data under a stated statistical method. It communicates precision as well as the direction or scale of an estimate. A narrow interval indicates greater precision than a wide interval, while neither interval width nor an estimate alone resolves design limitations such as the absence of a control group. No confidence interval for the primary endpoint is reported in the registry record.

When outcomes are counts, the statistical interpretation depends on the unit being counted. The primary endpoint describes participants with relapse or progression, whereas adverse-event reporting may also include event terms. Participant counts and event counts are not interchangeable: one participant can experience more than one event, and a set of event categories need not represent unique individuals unless the reporting rules establish that. The registry’s posted adverse-event figures identify numbers of participants affected, but do not give enough information to determine overlap among the listed terms.

What does the treatment schedule contribute?

The schedule defines the intervention being studied: rituximab was planned before and after transplantation, with administration on days -3, 10, 24, and 38 and transplantation on day 0. This is a combined treatment strategy, rather than a trial of rituximab in isolation. Consequently, outcomes cannot be attributed to rituximab alone based on this design. The record says treatment continued in the absence of progression or unacceptable toxicity, but does not report adherence, dose modifications, or the number of participants who completed each administration.

What can the enrollment figure tell readers?

The trial enrolled 63 participants. Enrollment is a description of study size, not a measure of statistical power and not proof that every participant contributed to every endpoint. For an endpoint assessed at 18 months, the number with an available assessment can differ from the total enrolled. Follow-up completeness and endpoint-specific analysis populations are not reported in the registry record. General statistical planning can use assumptions about event rates, effect sizes, and precision, but the record does not report a sample-size justification or the assumptions used to set enrollment.

Planning illustrations, when presented, answer a hypothetical design question: how many participants might be needed under specified assumptions to detect a chosen effect. Such illustrations are not observed outcomes, do not show the actual probability that this trial detected an effect, and cannot substitute for a reported result. The registry record does not give a trial-specific design justification or a reported statistical plan from which to assess the original planning choices.

Why do analysis details matter?

Interpretation also depends on prespecified definitions and analytic choices. For the primary endpoint, relevant details could include how relapse and progression were defined, how death before relapse was handled, whether all enrolled participants were included, and what happened when 18-month status was unavailable. These details are not reported in the registry record. It also does not report an analysis method, an estimate of uncertainty, or a hypothesis test for the primary endpoint.

Secondary endpoints measure different aspects of outcome. Survival outcomes concern time until an event, graft endpoints concern transplant outcomes, and graft-versus-host disease concerns a complication category. Each requires an outcome definition and an approach to follow-up and censoring appropriate to its form. The registry lists these outcomes but does not post analysis results or enough methods detail to evaluate their estimation. In general, time-to-event analyses must account for participants whose event status is not observed through the full follow-up period; the record does not state how this was handled.

Statistical significance, when reported, would not by itself establish clinical importance or causation. A p-value addresses compatibility of data with a specified statistical model and null hypothesis; it is not the probability that a treatment works or that a finding is true. A confidence interval would help describe precision, while the single-group design would still constrain causal comparison. Neither a p-value nor a confidence interval for the primary endpoint is reported in the registry record.

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("Treatment (Rituximab Pre- and Post-transplant)")
n      <- c(63)
events <- c(18)
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  Treatment (Rituximab Pre- and Post-transplant)  63  18  28.6  17.9  41.3  18.9  40.7  18.9  40.8

11. Multiplicity, Missing Data and Analysis Populations

The registry names a primary endpoint and several secondary outcome areas: acute and chronic graft-versus-host disease, overall and progression-free survival, graft rejection and graft failure, and time to engraftment. Considering multiple outcomes creates a multiplicity issue in general, because examining many outcomes can increase the chance of at least one apparently notable result. Methods such as prespecifying a hierarchy or adjusting for multiple testing can address particular multiplicity concerns. The registry record does not report whether such methods were planned or used.

The record does not provide a statistical analysis plan, hypothesis-testing strategy, or account of which outcomes were intended to be confirmatory versus descriptive. It also does not report whether interim analyses were conducted. These details are not reported in the registry record; their absence from the posted information should not be interpreted as proof that they did not occur.

Missing data are important for an endpoint assessed at 18 months. Participants may not have an observed status at the assessment time, and the way those cases are handled can affect an estimate. The registry does not report the endpoint denominator, completeness of follow-up, reasons for missing assessments, or any method for handling missing values. It is therefore not possible to assess whether the primary outcome represents all enrolled participants or a subset with available data.

Analysis populations are also not described. The record does not state whether the primary analysis included all enrolled participants, only those who received transplantation, or another defined group. Nor does it report how participants who stopped treatment, changed treatment, or did not complete follow-up were handled. These omissions limit reproducibility and make it difficult to compare an endpoint result with results from another study, even if such a result were posted.

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: death due to infection (3.2%), multiple pulmonary emboli (1.6%), suspected pulmonary embolism (1.6%), sepsis and tachycardia (1.6%), sepsis, respiratory failure, mental status change (1.6%).

For the treatment group, the registry reports 5 participants with serious adverse events among 63 at risk, and 15 participants with other adverse events among 63 at risk. These figures describe participants affected, not the total number of separate events. The record lists “Death Due to Infection” at 3.2%, “Multiple Pulmonary Emboli” at 1.6%, “Suspected Pulmonary Embolism” at 1.6%, “Sepsis and Tachycardia” at 1.6%, and “Sepsis, Respiratory Failure, Mental Status Change” at 1.6% among the top serious event terms.

Event-term percentages should be read as registry-reported figures. The record does not state whether participants can appear in more than one term, how terms were grouped, or whether each listed term represents a unique participant. It also does not report a count for deaths as a separate overall category. The serious-event count and the other-event count should not be added to infer a total number of distinct participants, because overlap between categories is not described.

These safety counts are descriptive. In a single-group trial, they do not establish how often the same events would occur under a different treatment strategy. The registry does not report a safety comparison group or event attribution details sufficient to assign outcomes to rituximab rather than transplantation or other aspects of care.

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

The record describes a completed phase II study of a combined regimen: rituximab administered before and after donor peripheral blood stem cell transplantation in patients with relapsed or refractory B-cell malignancies. Its primary question concerned the number of participants with relapse or progression at 18 months. The reported enrollment was 63, and the registry lists several additional outcome areas related to survival, transplant outcomes, engraftment, and graft-versus-host disease.

The posted information does not report the primary endpoint result. There is no relapse count, endpoint denominator, estimated rate, or measure of uncertainty in the registry record. It is therefore not possible to say from this record how many participants had relapse or progression by 18 months, or how precisely that outcome was estimated. This is an absence of a reported result, not a result showing that relapse did not occur.

The design also determines the scope of interpretation. Because the study was single group and did not report a concurrent comparator, it can describe outcomes in participants receiving the regimen but cannot establish what their outcomes would have been under another strategy. The intervention combines rituximab with transplantation, so the study cannot isolate the contribution of rituximab alone. In general, observed outcomes may reflect the treatment components together with participant characteristics, disease course, follow-up, and other influences.

The safety information provides participant counts for serious and other adverse events and lists several serious event terms. Those figures are useful as descriptive registry reports, but the record does not establish comparative risk or explain overlap among event categories. The listed figures should not be interpreted as a complete causal assessment of the regimen.

Accordingly, the registry supports a clear account of the trial’s intended question, design, intervention schedule, enrollment, and selected safety reporting. It does not support a numerical conclusion about the primary endpoint or a causal comparison of treatments. No claim that the regimen reduced relapse, increased relapse, or had no effect can be drawn from the absence of a posted primary result.

14. Why This Trial Matters Statistically

This trial illustrates why a clearly stated clinical question and a reported endpoint result are both necessary for statistical interpretation. The registry identifies relapse or progression by 18 months as the primary endpoint and explains why the outcome was of interest. Yet the observed count and endpoint denominator are not reported. Without those values, the primary question remains quantitatively unanswered in the posted record, regardless of the enrollment figure.

The study also highlights the distinction between describing an outcome and estimating a treatment contrast. A single-group design can report what occurred among participants receiving a regimen, but it lacks a concurrent comparison for estimating how outcomes differ under another strategy. That distinction is especially relevant when the intervention includes both rituximab and transplantation: results from the combined approach would not isolate the effect of one component.

Reporting denominators and uncertainty is part of making results interpretable. An enrollment total does not show how many participants had complete follow-up for an endpoint. A count without its analysis population or follow-up context may not tell readers how representative the result is of everyone enrolled. Confidence intervals, when available, help describe precision, but they do not remove limitations imposed by study design.

Finally, the registry illustrates the value of transparent analysis details. Information about endpoint definitions, missing observations, analysis populations, and multiplicity would help readers evaluate the reliability and scope of findings. Those methods are not reported in the registry record. Statistical interpretation therefore depends not only on the planned question and design, but also on complete outcome and methods reporting.

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 direct limitation for interpreting efficacy is that the primary endpoint result is not reported. The registry names relapse or progressive disease at 18 months as the endpoint but does not give the observed count, denominator, estimate, or uncertainty. Secondary outcome results are also not included in the posted information, despite being identified in the record.

The single-group design means there is no reported concurrent comparator for distinguishing the outcomes under this regimen from outcomes under another treatment strategy. Since rituximab was combined with transplantation, the design also cannot separate the contribution of rituximab from the transplant or other care. No masking was used, according to the registry, and the record does not describe outcome adjudication procedures.

The record lists a broad set of disease conditions, including adult and childhood diagnoses, but does not report the enrolled participants’ diagnostic composition or other baseline characteristics. It is not possible to determine from the listed eligibility-related conditions how many participants had each disease or how representative the enrolled group was of any one diagnosis. The registry also does not report adherence, treatment completion, or dose modifications.

Follow-up and analysis details are limited. The endpoint-specific denominator, missing-data methods, analysis populations, relapse definition, and approach to participants without an 18-month assessment are not reported in the registry record. A sample-size justification, statistical analysis plan, and interim-analysis information are also not reported. These omissions restrict assessment of precision, reproducibility, and the possible effects of incomplete follow-up.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Rituximab in Treating Patients Undergoing Donor Peripheral Blood Stem Cell Transplant for Relapsed or Refractory B-cell Lymphoma — NCT00867529.
• Registry record last updated 2018-01-02; status last verified 2017-12.
• Results first posted 2017-05-22.
• 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

NCT00867529 is a completed phase II, single-group trial sponsored by Fred Hutchinson Cancer Center. It enrolled 63 participants and studied rituximab before and after donor peripheral blood stem cell transplantation for relapsed or refractory B-cell malignancies. The planned rituximab schedule was days -3, 10, 24, and 38, with transplantation on day 0.

The primary endpoint was the number of participants with relapse or progressive disease at 18 months. The registry record does not report that endpoint’s observed count or denominator, or a statistical analysis of it. Safety reporting lists 5 participants with serious adverse events and 15 with other adverse events among 63 at risk. The single-group design does not provide a like-for-like treatment comparison, and the posted information does not establish a causal effect of rituximab.