Bortezomib and Rituximab in Treating Patients With Post-Transplant Lymphoproliferative Disorders: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Bortezomib and Rituximab in Treating Patients With Post-Transplant Lymphoproliferative Disorders (NCT00869323), a na phase 2 study. The primary outcome is Number of Patients With Overall (Complete and Partial) Response Rates.

2. Clinical Question

In statistical terms, the question is whether responses were recorded among participants treated with the combination during the stated timeframe. Without a control group, this design cannot directly compare response outcomes against another treatment or against no treatment. It also cannot separate the contribution of either study agent from the effect of the combination as a whole. The registry record identifies the study as phase II and reports enrollment of 3. That small enrollment means any observed count would describe only the participants in this trial; it would not by itself establish how frequently response would occur in a broader patient population.

The registry record also lists remission duration among patients who respond, time to treatment failure, relapse-free survival, and overall survival as secondary outcomes. Their names indicate additional questions the study intended to address, but their results are not reported in the registry record. The central interpretation is therefore limited to the design and the endpoints that were registered, rather than an estimate of treatment effect.

3. Trial Design

The registry record describes NCT00869323 as a phase II trial of bortezomib and rituximab for patients with PTLD. It lists Masonic Cancer Center, University of Minnesota as the sponsor. The study uses a single-group model: the treated group received bortezomib and rituximab, and there is no separate control arm described. Allocation is listed as not applicable, and masking is listed as none. This was therefore not a randomized, masked comparison between treatment groups.

Enrollment is reported as 3. The study started in 2009-03, and primary completion is recorded as 2013-03. Its status is terminated. The registry record does not report why the trial was terminated, so the status alone does not explain whether or how it affected the planned analyses or follow-up.

The primary outcome is the number of patients with overall response, including complete and partial response, with a timeframe of Day 1 to 2 Years Post Treatment. Secondary outcomes listed are remission duration among patients who respond, time to treatment failure, relapse-free survival, and overall survival. The registry record lists five outcome measures and no analysis entries. It does not report a statistical analysis plan, an allocation schedule, or details of treatment administration.

The design matters when interpreting outcomes. A single-group study can describe what was observed among treated participants, but it does not provide a randomized comparison that can estimate a difference between treatment strategies. Any response count would need to be read as a result for this group, not as a comparative treatment effect. Because the registry record does not report the primary response count, it does not support even a descriptive estimate of observed response from the endpoint information alone.

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.

Induction Therapy

Maintenance Therapy

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 Number of Patients With Overall (Complete and Partial) Response Rates, measured over Day 1 to 2 Years Post Treatment.

The primary endpoint is the number of patients with an overall response, with overall response specified as complete and partial responses. The registered timeframe is Day 1 to 2 Years Post Treatment. This is a binary outcome at the participant level: each participant would be classified according to whether a qualifying response was recorded during the defined period. That is a general description of how a count endpoint is interpreted; the registry record does not report the response criteria used to classify participants.

A response endpoint is used to describe whether participants experienced a defined change in disease status during treatment or follow-up. Combining complete and partial responses into an overall response measure gives a single count for those two categories, but it does not show their separate counts. The endpoint title identifies the outcome as a number of participants, not a comparison between groups or a time-to-event measure.

The registry record does not report the observed number with overall response, the separate complete and partial response counts, or an uncertainty interval for the primary result. It also does not report how participants with incomplete follow-up or unevaluable response status were handled. Therefore, the endpoint definition can be described, but its observed value and precision cannot be assessed from the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

Statistical interpretation begins with the design. This was a single-group phase II trial, not a randomized comparison. The treated participants received bortezomib and rituximab, and the registry lists no separate comparator. The primary endpoint is a count of participants with overall response, including complete and partial responses. For a binary endpoint, a participant is generally classified into one of two categories, such as response recorded or response not recorded. That is a general explanation of the endpoint type; the registry record does not give the detailed response criteria or the rules used to classify participants.

What a count can establish

A count records how many participants met a defined endpoint. A count alone is not the same as a rate, and the registry record does not report the observed primary count. It therefore cannot be used to determine the proportion of the enrolled group with response without adding a calculation that is not reported. The endpoint title describes what was intended to be counted, not the result. It also does not specify whether every participant had sufficient follow-up for assessment through the registered timeframe.

In general, uncertainty intervals around a binary outcome communicate how much imprecision is associated with an estimate. Wider intervals indicate greater uncertainty, while narrower intervals indicate greater precision. The registry record does not report a primary response estimate or its interval, so there is no reported precision measure to interpret. The small enrollment of 3 is relevant context: a count from a very small group can change substantially in meaning when only a few participant outcomes differ. This general point does not substitute for an actual interval or analysis.

What over-dispersion means

General statistical note: over-dispersion occurs when observed variation is greater than a statistical model assumes. It can make model-based uncertainty estimates too small if the model does not account for that extra variation. This concept can arise in count data, but the registry record does not report an over-dispersion assessment, a count model, or a statistical method for the primary endpoint. No claim can therefore be made that over-dispersion was evaluated or that a particular adjustment was used.

What the design permits

Because the trial has one treated group, a descriptive summary could characterize outcomes among those participants. A controlled design would be needed to directly compare outcomes between treatment strategies. General statistical adjustment cannot, by itself, create the randomized comparison that is absent from this design. The registry record does not report adjusted analyses, covariates, or a formal method for estimating treatment effect. It also contains no analysis entries. These omissions mean the statistical method behind any unreported result cannot be reconstructed from the record.

Planning illustrations and observed evidence

The registry record describes planning illustrations based on the observed effect, using a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. The effect to detect is described as a stated fraction of the observed effect. These are planning assumptions, not a description of the trial's single-group design. A hypothetical two-arm calculation does not mean the trial enrolled two arms or randomized participants. Planning sample sizes are illustrations of how a future study might be sized under specified assumptions; they are not observed outcomes and must not be interpreted as observed power.

For time-to-event planning, the record describes total events using the Schoenfeld method; other planning results are described as participants per arm. The registry record does not give a sample-size justification for the trial itself. It does not report the target enrollment rationale, assumptions used to choose the trial enrollment, or an actual power calculation as part of its analysis plan. Any generated planning illustration should therefore be kept separate from what was observed in this trial.

Analysis and reporting

A statistical analysis plan would ordinarily clarify which participants are included in each endpoint analysis, how missing or unevaluable outcomes are treated, and which methods are used to estimate outcomes and uncertainty. Those details are not reported in the registry record. The record also does not report an interim-analysis plan or multiplicity adjustment. Without these details and without reported primary and secondary outcome results, readers cannot assess whether the stated analyses followed a prespecified plan or determine the precision of the endpoint findings.

General note: an analysis should be interpreted in the context of its design, endpoint definition, participant set, and missing-data handling. Here, the design and endpoint titles are available, while key analysis details and the primary result are not reported in the registry record. The defensible statistical reading is consequently descriptive: the trial was small and single-group, and the registered result cannot be quantified from the 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("Treated Study Participants")
n      <- c(3)
events <- c(2)
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  Treated Study Participants  3  2  66.7  9.4  99.2  20.8  93.9  19.4  93.2

11. Multiplicity, Missing Data and Analysis Populations

The registry record lists the primary outcome and secondary outcomes covering remission duration among responders, time to treatment failure, relapse-free survival, and overall survival. It lists five outcome measures and no analysis entries. The record does not state whether statistical testing was planned for these outcomes, which outcomes would be considered confirmatory, or whether any adjustment for multiple comparisons was planned. It is therefore not possible to determine how the risk of false-positive findings across multiple tests would have been addressed. This is a general concern when several outcomes are examined, not evidence that a particular adjustment was omitted from the trial's actual analysis.

Missing-data handling is not reported in the registry record. In particular, it does not state how incomplete follow-up, missing response assessments, or participants whose response could not be classified would be handled. It also does not report the analysis population for the primary endpoint or for the secondary outcomes. Without those definitions, the number enrolled cannot automatically be treated as the number assessed for every outcome.

The record does not report a statistical analysis plan, interim-analysis procedures, or a reason for the terminated status. Those details should not be inferred from the lack of analysis entries. These omissions limit the ability to assess whether outcomes were analyzed as planned, how multiplicity and missingness were addressed, and whether the analysis population matched the intended population.

12. Safety Results

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

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 0% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: fever (33.3%), urinary tract infection (33.3%), renal failure (33.3%), pain in extremity (33.3%), hypertension (33.3%).

The registry safety record lists 3 treated study participants at risk for serious adverse events, with 2 affected. For other adverse events, it lists 3 participants at risk and 3 affected. These are participant counts, not a comparison between treatment groups. The record also lists Fever, Urinary tract infection, Renal failure, Pain in extremity, Hypertension, and Myoclonus among the serious adverse event terms, each at 33.3%.

General note: event terms and participant counts are not necessarily interchangeable. A participant may experience more than one event, so the listed terms should not be added together to infer a count of unique participants. The registry record does not report event timing, severity details beyond the serious-event classification, or an attribution assessment. It therefore does not establish whether a listed event was judged related to treatment. The number of deaths is not reported in the registry record.

These safety entries describe what the registry records for the treated group. They do not estimate excess risk relative to another group, and they do not by themselves establish the overall safety profile of the combination.

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

The registry record establishes that a phase II study of bortezomib and rituximab for PTLD was registered as a single-group trial, with enrollment of 3 and a status of terminated. It identifies an overall response endpoint covering complete and partial response over Day 1 to 2 Years Post Treatment. It does not report the observed response count. The registry information therefore cannot show how many participants responded or how precise any response estimate would be.

The design also limits what could be inferred from a response count, even if one were available. With no comparator group, the trial cannot directly estimate a difference between the combination and another strategy. The contribution of each study agent cannot be separated. A result from a single group would be descriptive of the participants assessed, not a randomized estimate of comparative effect.

The listed secondary outcomes and safety counts provide additional context, but the record does not report secondary outcome results or the number of deaths. Serious adverse events affected 2 participants out of 3 at risk; other adverse events affected 3 out of 3 at risk. Each listed serious adverse event term is recorded at 33.3%. These entries are not a comparative safety assessment, and the registry record does not report attribution to treatment.

The terminated status does not explain why the study ended, and no reason is reported. It should not be interpreted as evidence for or against the intervention. Overall, the registry record documents the study question and some design and safety details, but it does not report enough outcome information to quantify response or draw a treatment-effect conclusion.

14. Why This Trial Matters Statistically

This trial matters statistically because it illustrates the distinction between a registered research question and a reportable result. The registry identifies an overall response endpoint and a follow-up timeframe, but does not report the observed response count. An endpoint definition alone cannot establish an outcome. Readers need the observed result and an account of how it was analyzed to evaluate both the direction and precision of the evidence.

The single-group design is another central consideration. It can describe outcomes in the treated group, but cannot provide a randomized comparison with another treatment. That distinction remains important regardless of the endpoint or the statistical method used. When a trial has no comparator, a reported outcome should not be read as a causal contrast between strategies.

Enrollment of 3 also underscores why precision matters. General statistical principle: estimates based on very small groups are often uncertain, and each participant's classification can have substantial influence on the group summary. Here, no primary response estimate or uncertainty interval is reported, so the magnitude of that uncertainty cannot be quantified from the registry record.

The record lists several secondary outcomes and safety information, but it does not report results for the secondary outcomes or details of the analysis plan, missing-data approach, or multiplicity handling. These gaps show why registry status and endpoint listings should be read separately from completed outcome reporting. The statistical value of the record is in documenting the design and intended questions, while its limits prevent a reliable estimate of treatment effect or comparative safety.

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 principal trial-specific limitation is the absence of a reported primary response result. The registry record names the endpoint and timeframe but does not state the observed number with overall response or give separate counts for complete and partial response. It also does not report an uncertainty interval for that outcome.

The trial enrolled 3 and used a single treated group. There is no separate comparator, so a comparative treatment effect cannot be estimated from the design as registered. The registry record does not report response criteria, dose or schedule details, eligibility criteria beyond the PTLD population, or how the analysis population was defined.

Secondary outcomes are listed, but their results are not reported in the registry record. Missing-data procedures, endpoint-specific participant counts, statistical methods, and any multiplicity strategy are also not reported. The record lists no analysis entries, but does not explain that absence. It reports a terminated status without a reason for termination, so the reason and its implications for follow-up or outcome assessment are unknown.

Safety reporting is limited to participant counts and selected serious adverse event terms. The record does not report a death count, event timing, or treatment attribution. These limitations mean the registry record can support a description of the registered design and selected safety entries, but not a full assessment of efficacy, precision, or comparative safety.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Bortezomib and Rituximab in Treating Patients With Post-Transplant Lymphoproliferative Disorders — NCT00869323.
• Registry record last updated 2017-12-05; status last verified 2017-12.
• Results first posted 2017-04-05.
• Data retrieved from ClinicalTrials.gov on 2026-11-09.
• Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.

19. Record Summary

NCT00869323 is a phase II, single-group trial of bortezomib and rituximab for PTLD, sponsored by Masonic Cancer Center, University of Minnesota. Enrollment was 3. The study began in 2009-03, primary completion is listed as 2013-03, and status is terminated. Allocation is not applicable, and masking is none.

The primary endpoint is the number of participants with overall response, including complete and partial responses, from Day 1 to 2 Years Post Treatment. Secondary outcomes include remission duration among responders, time to treatment failure, relapse-free survival, and overall survival. The primary response result and secondary outcome results are not reported in the registry record.

Serious adverse events affected 2 of 3 participants at risk, while other adverse events affected 3 of 3. Six serious adverse event terms are listed, each at 33.3%. No comparator is registered, and the record does not report a reason for termination, statistical analysis plan, or missing-data approach.