Bortezomib and Rituximab in Treating Patients With Mantle Cell Lymphoma Who Have Previously Undergone Stem Cell Transplantation: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Bortezomib and Rituximab in Treating Patients With Mantle Cell Lymphoma Who Have Previously Undergone Stem Cell Transplantation (NCT01267812), a na phase 2 study. The primary outcome is Two-year Disease-free Survival.

2. Clinical Question

This is a phase II study of bortezomib together with rituximab in the post-transplant setting. The registry gives an enrollment of 23 and describes follow-up for up to 5 years after initial treatment. The study also lists two-year overall survival and grade 3 or 4 toxicities among its secondary outcomes.

The question is descriptive rather than comparative: it concerns the observed disease-free survival in the treated group, not a difference between treatment and control groups. Without a comparator, the study cannot isolate the regimen's effect from other factors that may influence outcomes after transplantation. The treatment schedule and endpoint are stated, but the registry record does not report the primary outcome result needed to describe the observed two-year estimate.

3. Trial Design

This is a phase II, single-group study registered as NCT01267812. The registry lists an enrollment of 23, identifies City of Hope Medical Center as the sponsor, and marks the study as completed. Allocation is listed as not applicable, consistent with the single-group model, and masking is listed as none. There is no randomized control arm or blinded comparison described in the registry record.

The intervention combines bortezomib and rituximab as maintenance treatment after transplantation. The listed schedule gives bortezomib at 1.3 mg/m2 weekly for four weeks, with those four-week courses repeated every three months for eight cycles. Rituximab is listed at 375 mg/m2 weekly for four weeks, with those courses repeated every six months for four cycles. The record also lists laboratory biomarker analysis, staining, RNA, gene expression and DNA analyses, and a pharmacological study as interventions or study activities.

The primary endpoint is two-year disease-free survival. The registry describes participants as followed for up to 5 years after initial treatment and says Kaplan-Meier survival analysis was used to generate the two-year estimate. The listed secondary outcomes are two-year overall survival and grade 3 or 4 toxicities of treatment. Although the record lists 3 outcome measures, it does not report their numerical results in the information available for this interpretation.

A single-group design can describe outcomes among people who received the regimen, but it does not estimate a treatment contrast against a concurrent control group. The registry record does not report a statistical analysis plan, sample-size justification, interim analyses, or detailed eligibility criteria. Those omissions limit assessment of how design decisions were made and how broadly the findings might apply.

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 Two-year Disease-free Survival, measured over Participants were followed up to 5 years after initial treatment and Kaplan-Meier survival analysis was used to generate the two-year disease-free survival estimate presented..

The primary endpoint is two-year disease-free survival, expressed as a percentage of participants. Disease-free survival is a time-to-event measure: it concerns the time until a defined disease-related event, with participants who have not had an event by their last observation contributing follow-up up to that point. The exact event definition and detailed censoring rules are not reported in the registry record.

The registry states that follow-up continued for up to 5 years after initial treatment and that Kaplan-Meier survival analysis was used to generate the two-year estimate. In general, Kaplan-Meier methods use each participant's observed follow-up time and event status, rather than treating every participant as if follow-up ended at the same time. This approach can accommodate differing follow-up durations, provided the method's assumptions are reasonably met.

The record specifies a 95% confidence interval calculated using Greenwood's formula. In general, a confidence interval communicates the uncertainty around an estimated survival probability; it is not a guarantee that the true value lies within that particular interval. The numerical two-year estimate and its interval are not reported in the registry record, so neither the outcome level nor its precision can be assessed from the posted results.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary endpoint is described as a Kaplan-Meier estimate of two-year disease-free survival, with a 95% confidence interval calculated using Greenwood's formula. Those methods are suited to time-to-event outcomes, where participants can have different lengths of follow-up and some may not have experienced the event by the time their observation ends. The registry record does not give the numerical estimate, interval, event definition, or detailed analysis population.

What does Kaplan-Meier estimation do?

In general, Kaplan-Meier estimation builds a survival curve over time from the sequence of observed event times. At each event time, the method uses the participants still under observation immediately before that time to estimate the conditional probability of continuing without the event. Those conditional probabilities are combined across event times to form an estimated probability of remaining event-free over follow-up.

A participant who has not had an event when their observation ends is commonly treated as censored at that time. Censoring is not the same as an event: it means the later outcome is not observed in the analysis. The method relies on assumptions about censoring, including that censoring does not systematically conceal a different event risk among those censored, after accounting for the analysis. The registry record does not report censoring patterns or describe how censoring assumptions were assessed.

The estimate at two years is read from the estimated survival curve at that time point. The record says participants were followed up to 5 years after initial treatment, but does not report how many had observed follow-up through two years or how many events occurred. Those details would help readers understand how much information supports the estimate, especially at later follow-up times. They are not reported in the registry record.

What does a 95% confidence interval communicate?

In general, a confidence interval expresses statistical uncertainty around an estimate under the assumptions of the analysis. A narrower interval indicates greater precision than a wider interval, all else equal. The interval does not show the range of individual participant outcomes, nor does it account automatically for every possible source of bias. The registry specifies a 95% confidence interval but gives no endpoints, so its width and the estimate's precision cannot be assessed.

Greenwood's formula is a standard way of estimating the variance of a Kaplan-Meier survival estimate, which is then used to construct a confidence interval. It quantifies sampling uncertainty under the method; it cannot correct for limitations such as an unrepresentative study group, outcome misclassification, or informative loss to follow-up. The registry record does not report whether any alternative interval method or sensitivity analysis was used.

Why does the single-group design matter?

In general, a single-group study estimates outcomes in the participants who received the intervention. It does not directly estimate what would have happened to comparable participants under another treatment or without the intervention. A treatment effect is inherently comparative: it concerns a contrast between outcomes under different conditions. Without a concurrent control group, observed outcomes may reflect the intervention, the underlying disease course, participant selection, other care, or a combination of influences.

The study is listed as having no masking and no allocation procedure. The registry therefore does not describe randomized assignment or blinded outcome assessment. The record does not report whether outcome adjudication was independent, whether particular analyses were adjusted, or whether statistical methods beyond the stated survival analysis were used. These details should not be inferred from the phase designation or from the existence of a named endpoint.

How should planning calculations be understood?

General sample-size calculations use assumptions about a target effect, significance level, allocation, and statistical method to illustrate how much information might be needed for a future comparison. The planning assumptions described for this record specify a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation; they also define the target effect as a stated fraction of an observed effect. These are described as planning illustrations, not as the trial's own design or observed power.

That hypothetical two-arm framework does not match the registry's single-group design. The registry record does not report the study's sample-size justification or the numerical values needed to judge any particular planning scenario. No planning figure should be interpreted as a measure of the probability that this completed study detected an effect. Power is a design concept based on assumptions; it is not a post hoc measure of whether a result is true, and it cannot replace the missing endpoint estimate and confidence interval.

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 (Bortezomib and Rituximab)")
n      <- c(23)
events <- c(21)
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 (Bortezomib and Rituximab)  23  21  91.3  72.0  98.9  73.2  97.6  73.0  97.3

11. Multiplicity, Missing Data and Analysis Populations

The record lists 3 outcome measures, including two-year disease-free survival as the primary endpoint and two secondary outcomes: two-year overall survival and grade 3 or 4 toxicities. The registry record does not report a multiplicity strategy, such as an adjustment for testing several outcomes, nor does it give a detailed statistical analysis plan. It is therefore not possible to determine whether or how the study accounted for multiple outcome assessments.

The analysis count is listed as 0. Numerical results for the primary endpoint and the secondary outcomes are not reported in the registry record. The record does not identify which analysis populations were used, how participants were included in each analysis, or whether any participants were excluded from an outcome analysis.

Missing-data handling is not reported in the registry record. For a time-to-event endpoint, incomplete follow-up may be represented through censoring, but the record does not describe censoring patterns, missing outcome information, or sensitivity analyses. It also does not report the number at risk over time for the primary endpoint. These omissions make it difficult to assess how much information supports the two-year estimate or whether departures from the analysis assumptions might affect it.

In general, multiplicity matters because considering multiple outcomes or analyses can increase the chance of a statistically notable finding occurring by chance. Missingness matters because the observed participants may not represent those whose outcomes are unavailable. These are general statistical considerations, not claims about what occurred in this study; the relevant procedures are not reported in the registry record.

12. 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 0% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: fever (8.7%), neutrophil count decreased (4.3%), skin infection (4.3%), wound infection (4.3%), lung infection (4.3%).

The registry lists one treatment group for safety reporting. For serious adverse events, 23 participants were at risk and 7 were affected. For other adverse events, 23 were at risk and 23 were affected. The record also lists 3 deaths. These are the reported counts; the registry record does not provide a comparative safety group or enough detail to attribute any event or death to treatment.

The listed serious-event terms include Fever at 8.7%, Neutrophil Count Decreased at 4.3%, Skin Infection at 4.3%, Wound Infection at 4.3%, Lung Infection at 4.3%, and Myelodysplastic Syndrome at 4.3%. These percentages should be read as registry-reported values. The record does not provide further detail about event timing, duration, recurrence, severity grading for each term, or the relationship of each event to treatment.

In general, adverse-event counts describe events recorded within the study and do not by themselves establish causation. A single-group safety record also cannot show whether an event frequency is higher or lower than it would have been under a comparator. The reported counts and percentages should therefore be interpreted as descriptive safety information, not as a comparative estimate of treatment-related risk.

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

The registry record establishes that a phase II study evaluated maintenance bortezomib and rituximab after stem cell transplantation in patients with mantle cell lymphoma. It identifies two-year disease-free survival as the primary endpoint and states that Kaplan-Meier analysis was used, with a 95% confidence interval calculated using Greenwood's formula. The numerical endpoint result and interval are not reported in the registry record.

That absence limits what can be concluded about the primary question. The record does not allow readers to quantify the estimated probability of remaining disease-free at two years or assess the estimate's precision. The listed follow-up of up to 5 years does not itself establish an outcome; an analysis result is needed to describe what was observed.

The single-group design also limits interpretation. Any observed outcomes would describe the study group, rather than a contrast against a control group receiving another treatment or no maintenance treatment. Even if numerical outcomes were available, differences from other studies or historical experience would not create the same controlled comparison. Differences in eligibility, care, follow-up, and outcome assessment could contribute to any apparent contrast.

The safety record reports affected-participant counts and serious-event terms, but these are descriptive. Without a comparator, they cannot establish whether the regimen raises or lowers event risk relative to another approach. The listed 3 deaths are not accompanied by details that would allow attribution or a cause-specific interpretation.

Overall, the registry supports understanding the study's design, regimen, intended endpoint, and selected safety reporting. It does not support a numerical claim about disease-free survival, a conclusion about comparative effectiveness, or a causal safety claim. These distinctions are important when interpreting registry records: methods and outcomes are different kinds of information, and a stated analysis method cannot substitute for a reported result.

14. Why This Trial Matters Statistically

This study is statistically notable for asking a time-to-event question in a single-group post-transplant setting. Disease-free survival is not simply a count at one visit: the Kaplan-Meier method is intended to use event times and differing follow-up durations to estimate the probability of remaining event-free at a specified time. The registry identifies the two-year point and the confidence-interval method, making the intended estimand and approach partly clear.

The design also illustrates an important distinction between describing outcomes and estimating treatment effects. A single-group study can document outcomes among participants receiving a regimen, but a comparator is needed for a direct treatment contrast. This is particularly relevant when outcomes can be influenced by disease history, patient selection, transplant-related factors, and other care. The registry record does not provide a control group for separating these influences from the intervention.

Reporting precision is central to interpreting a survival estimate. A point estimate alone would not show how uncertain it is, while a confidence interval helps readers judge the range of values compatible with the analysis. In this record, the method for the interval is named, but neither the estimate nor the interval is reported. The absence of these numerical results prevents assessment of both outcome level and precision.

The record also offers a useful reminder that planning calculations and observed findings answer different questions. Illustrative sample-size assumptions do not constitute an analysis of the completed study and do not establish its power. For readers evaluating clinical evidence, attention to the design, analysis, reporting completeness, and limits on comparison is as important as recognizing the endpoint name.

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 primary limitation for interpretation is that the two-year disease-free survival estimate and its 95% confidence interval are not reported in the registry record. The number of events, the number at risk over time, the event definition, and censoring details are also not reported. Without them, readers cannot assess the magnitude or precision of the primary outcome.

The study is single-group and has no concurrent comparator. This prevents direct estimation of a treatment contrast and limits causal interpretation. The registry also lists masking as none. It does not report whether outcomes were independently adjudicated or whether any safeguards were used to limit assessment bias.

The enrollment is 23, but the registry record does not report the primary analysis population or the number contributing to the endpoint analysis. It does not describe missing-data methods, loss to follow-up, protocol deviations, or sensitivity analyses. The record lists secondary outcomes but does not report their numerical results or a multiplicity plan.

Further design details are not reported in the registry record, including a statistical analysis plan, sample-size justification, interim analyses, and detailed eligibility criteria. The treatment schedule is described, but the registry information does not provide enough detail to evaluate adherence or treatment exposure for individual participants. Safety information is descriptive and lacks a comparator and event-level context sufficient for attribution. These limitations do not establish that a particular bias occurred; they define what cannot be evaluated from the registry record.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Bortezomib and Rituximab in Treating Patients With Mantle Cell Lymphoma Who Have Previously Undergone Stem Cell Transplantation — NCT01267812.
• Registry record last updated 2023-07-27; status last verified 2023-07.
• Results first posted 2022-02-04.
• 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

NCT01267812 is a completed phase II, single-group study sponsored by City of Hope Medical Center. It enrolled 23 participants with mantle cell lymphoma who had previously undergone stem cell transplantation. The intervention was maintenance bortezomib and rituximab, with the registry describing separate schedules for the two treatments.

The primary outcome is two-year disease-free survival, assessed using Kaplan-Meier analysis, with a 95% confidence interval described as calculated using Greenwood's formula. Follow-up was reported as up to 5 years after initial treatment. The numerical primary outcome and interval are not reported in the registry record. Secondary outcomes include two-year overall survival and grade 3 or 4 toxicities.

The study has no separate comparator group. The record lists serious adverse events affecting 7 participants among 23 at risk, other adverse events affecting 23 among 23 at risk, and 3 deaths. These are descriptive registry figures and do not establish comparative treatment effects or causation.