High-Dose Y-90-Ibritumomab Tiuxetan Added to Reduced-Intensity Allogeneic Stem Cell Transplant Regimen for Relapsed or Refractory Aggressive B-Cell Lymphoma: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for High-Dose Y-90-Ibritumomab Tiuxetan Added to Reduced-Intensity Allogeneic Stem Cell Transplant Regimen for Relapsed or Refractory Aggressive B-Cell Lymphoma (NCT01434472), a na phase 2 study. The primary outcome is Progression-free Survival.

2. Clinical Question

The study was registered as a phase II trial sponsored by Fred Hutchinson Cancer Center. Its stated purpose was to study side effects and how well the treatment sequence worked in patients whose aggressive B-cell lymphoma had returned or had not responded to earlier treatment. The registry does not report a control group, so the primary question is framed around an outcome threshold rather than a direct comparison between assigned treatments.

The intended treatment sequence makes the clinical question about a combined regimen, not about the isolated contribution of any one component. The registry lists several accompanying interventions, including allogeneic hematopoietic stem cell transplantation, fludarabine phosphate, total-body irradiation, rituximab, cyclosporine, and mycophenolate mofetil. The record does not allow the effect of the radiolabeled antibody to be separated from the other parts of the regimen.

3. Trial Design

This was a phase II, single-group study with an enrollment of 20. The registry lists allocation as not applicable and masking as none. Participants were assigned to the treatment regimen described in the record; there was no listed concurrent control arm. The study status is terminated. The start date is 2011-11-16, and the primary completion date is 2020-05-06.

The planned treatment approach used high-dose Y-90-ibritumomab tiuxetan, followed by fludarabine phosphate and low-dose total body irradiation before donor peripheral blood stem cell transplantation. The registry’s arm description says rituximab was given intravenously before the therapy infusion and places the radiolabeled antibody on day -14 relative to transplant. It also describes fludarabine phosphate on days -4 to -2. The arm description ends before the full treatment details are given, so the complete sequence and all administration details are not reported in the registry record.

The primary endpoint was progression-free survival at one year, expressed in the record as a count of participants. The stated decision rule used a one-sample chi-square test at a one-sided significance level of five percent and set 54% or greater as the success threshold for the highest-risk group. The detailed statistical analysis plan, including the exact null hypothesis and endpoint assessment rules, is not reported in the registry record.

The registry lists seven secondary outcomes, including overall survival, response rates, treatment-related mortality, engraftment outcomes, and hematopoietic toxicity. It reports no analyses for these outcomes. The registry does not report the number of participants included in the primary analysis, how participants were followed after treatment, or whether all enrolled participants received the full regimen. These gaps limit what can be inferred from the design entry 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.

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 Progression-free Survival, measured over 1 year.

Progression-free survival is intended to describe whether participants remain alive without disease progression over a specified follow-up period. In this study, the primary assessment period was one year. The registry records the outcome as a count of participants and states that the one-year value in the highest-risk group would be used to judge whether the study met its success criterion of 54% or greater.

General: a time-to-event endpoint such as progression-free survival combines information about the timing of disease progression and death, rather than recording only whether an event ever occurred. It is often used to summarize disease control over follow-up. Interpretation depends on how progression and death are defined, how disease is assessed, how censoring is handled, and which participants are included in the analysis.

The registry record does not specify the operational definition of progression-free survival, assessment schedule, censoring rules, or analysis population. It also does not report the observed one-year result, its uncertainty interval, or the test result. Therefore, the stated threshold describes the planned decision criterion, not a finding that the study achieved that criterion.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does a one-sample test ask?

The primary endpoint description names a one-sample chi-square test. General: a one-sample test assesses whether an observed result in one group is compatible with a specified benchmark or hypothesis. It does not compare two randomized groups. In this study, the stated decision rule connects the test to a one-year progression-free survival threshold of 54% or greater and specifies a one-sided significance level of five percent.

The registry record does not report the complete null and alternative hypotheses, the precise test implementation, or any assumptions used for that analysis. The threshold and significance level describe the intended decision framework, but they are not enough to reconstruct the analysis. The observed result, test statistic, and p-value are also not reported. As a result, the planned test cannot be independently interpreted from the registry entry.

What does a one-sided significance level mean?

General: a one-sided test evaluates evidence in a prespecified direction. A significance level sets a criterion for how unusual data would need to be under the null hypothesis to count as statistically significant, assuming the test’s model and assumptions are appropriate. It does not give the probability that the null hypothesis is true, and it does not measure the probability that a result is due to chance. The direction and benchmark must be defined in the analysis plan. The registry gives a one-sided level of five percent but does not report the full hypothesis statement or the outcome of the test.

The success threshold is not itself an observed estimate. It is a rule for interpreting a future or completed analysis. Whether the observed one-year outcome met that rule cannot be determined because the registry record does not report the result. Nor can statistical precision be judged without an estimate and an uncertainty interval. A threshold-based decision and an estimate of the magnitude and uncertainty of the endpoint answer related but different questions.

Why does the single-group design matter?

General: a single-group study can describe outcomes among participants receiving a regimen, but it lacks a concurrent randomized arm to balance prognostic factors and provide a direct treatment contrast. An outcome may be compared with a benchmark if the benchmark is defined, but that comparison depends on the validity and relevance of the benchmark. The registry does not report the benchmark’s source or full statistical specification. The design also cannot isolate the contribution of each regimen component, because the components were given as a combined treatment strategy.

The record lists no masking. Lack of masking can matter when outcomes involve clinical judgments or assessments that may be influenced by knowledge of treatment. The registry does not report whether progression assessments were blinded, how progression was adjudicated, or whether endpoint assessment used prespecified criteria. These details are relevant to understanding how consistently the primary outcome was measured.

How should the outcome and follow-up be understood?

General: progression-free survival is a time-to-event outcome, and its analysis usually depends on the definition of an event, follow-up duration, censoring rules, and the treatment of participants whose status is unknown at the end of observation. The registry specifies a one-year timeframe but does not report these operational details. It also does not state whether the endpoint was estimated as a survival probability or handled in another way before being expressed as a participant count.

For a time-to-event endpoint, participants may have different lengths of observation. Censoring can account for incomplete observation without treating every participant lost to follow-up as having experienced an event, but the validity of the approach depends on assumptions and documented procedures. No censoring rules, follow-up summaries, or missing-data methods are reported in the registry record. Without them, the one-year endpoint cannot be reconstructed.

What can planning calculations tell a reader?

General: sample-size planning uses assumptions about the target effect, significance level, allocation, and statistical model to illustrate how much information a study might need. Such calculations are not a measure of the probability that a completed study will find a statistically significant result. They are not observed power. The planning assumptions described in the record use two-sided significance, equal allocation between two arms, a normal approximation, and an effect defined as a fraction of an observed effect. These are hypothetical planning assumptions and do not match the listed single-group trial design.

The record does not report numeric planning results or the trial’s own sample-size justification. It therefore does not establish that the enrollment of 20 was selected using those planning assumptions. Because the observed primary outcome is also absent, a reader cannot assess the observed effect or use it to interpret any planning illustration. Planning calculations should remain distinct from the study’s actual enrollment, analysis, and results.

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 (Radiolabeled Antibody, TBI, Allogeneic ")
n      <- c(20)
events <- c(11)
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 (Radiolabeled Antibody, TBI, Allogeneic   20  11  55.0  31.5  76.9  34.2  74.2  34.0  74.3

11. Multiplicity, Missing Data and Analysis Populations

The registry lists seven secondary outcomes: absolute neutrophil count engraftment, overall survival, response rates, treatment-related mortality, platelet engraftment, hematopoietic toxicity, and one additional listed outcome category in the record. It reports zero analyses. No secondary outcome estimates, uncertainty intervals, or test results are reported in the registry record.

Multiplicity arises when a study evaluates several outcomes or performs several tests: the chance of at least one nominally significant finding can increase as the number of analyses grows. General: investigators may address this through a prespecified hierarchy, adjustment procedure, or clear distinction between confirmatory and exploratory analyses. The registry does not report whether any multiplicity strategy was planned, which outcomes were considered confirmatory, or whether analyses were performed outside the posted record. The listed outcome names alone do not establish that results were tested or that any adjustment was used.

Missing-data methods and analysis populations are not reported in the registry record. The record does not state how many participants had complete one-year endpoint information, how withdrawals or losses to follow-up were handled, or whether the primary analysis included all enrolled participants or a defined subset. It also does not report an intention-to-treat, per-protocol, or other analysis population. These details are important because incomplete follow-up or exclusions can change both the estimated outcome and its precision.

The registry does not report an interim-analysis plan, stopping boundaries, or a protocol for handling early termination. The terminated status does not reveal whether interim findings informed that status. Without a protocol or analysis report in the registry record, readers cannot determine how missingness, multiplicity, or analysis-population decisions were handled.

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 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: neutropenic fever (15.0%), abdominal pain (10.0%), acute renal injury (10.0%), diarrhea (10.0%), blood infection (10.0%).

The registry reports 20 participants at risk for serious adverse events, with 11 affected, and 20 at risk for other adverse events, also with 11 affected. It lists six deaths. These entries are counts within the study group, not comparisons against a control group. They do not establish that an event was caused by the treatment.

Among the listed serious adverse-event terms, neutropenic fever is reported at 15.0%. Abdominal pain, acute renal injury, diarrhea, and blood infection are each reported at 10.0%. Thromboembolic event - cerebal infarct is reported at 5.0%. These percentages are reproduced as recorded; the registry entry does not provide event-level detail or clarify whether participants could contribute to more than one term.

The record does not report the timing, duration, severity grading, outcome, or treatment attribution for each event. It also does not explain how the six deaths relate to the event counts or provide a cause-of-death breakdown. The safety figures should therefore be read as descriptive registry entries, not as estimates of comparative safety or proof of causation.

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

The registry record describes a phase II study of a combined treatment strategy for relapsed or refractory aggressive B-cell lymphoma. It gives a one-year progression-free survival success threshold and reports some adverse-event counts. It does not report the observed primary endpoint result, so the record cannot establish whether the stated threshold was reached. It also does not report an endpoint confidence interval or test result, leaving the precision and statistical evidence for the primary question unknown.

The single-group design means that outcomes are not contrasted with a concurrent control group. Any outcome observed in participants who received the regimen would describe their experience in the study, but would not by itself establish what would have happened under a different treatment. The design also cannot identify the separate effects of Y-90-ibritumomab tiuxetan, conditioning, transplantation, or the other listed interventions.

The adverse-event entries document reported counts and selected event terms, but do not establish treatment causation. The absence of detailed timing, grading, attribution, and participant-level overlap limits interpretation. Likewise, the terminated status is a registry status, not an explanation of why the study ended or a result in itself.

General: statistical significance, if reported, would not by itself show that an effect is large, clinically important, or reliably estimated. An effect estimate and its uncertainty are needed to understand magnitude and precision. In this record, the primary estimate and uncertainty are absent. The record is therefore informative about the study’s intended question, design, threshold, and selected safety entries, but does not support a conclusion about whether the regimen met the primary endpoint or how it compared with alternatives.

14. Why This Trial Matters Statistically

This trial illustrates why a stated success criterion and an observed result must be distinguished. The registry gives a specific one-year progression-free survival threshold of 54% or greater and identifies a one-sample testing approach. Without the observed endpoint estimate and its uncertainty, however, readers cannot tell whether the criterion was met or how stable an estimate would be.

It also demonstrates the interpretive limits of a single-group design. A regimen that includes radiolabeled antibody, conditioning treatment, and allogeneic transplantation is a complex strategy. Without a concurrent comparator, the study cannot estimate a randomized contrast or separate the contribution of each component. That limitation matters when interpreting both efficacy and adverse-event counts.

The enrollment of 20 and the list of secondary outcomes provide context for the scale and scope of the registry entry, but do not substitute for outcome data. Counts at risk and affected participants give some descriptive safety information; the lack of event timing, attribution, and detailed outcome reporting restricts conclusions about those counts. The terminated status likewise raises questions about study conduct that the registry entry does not answer.

More broadly, the record shows the value of reporting analysis populations, endpoint definitions, missing-data handling, and uncertainty alongside a decision threshold. Those details allow readers to distinguish the planned question from the evidence generated by the study. Their absence means the registry record can be read as a description of design and selected safety information, but not as a complete statistical account of the primary question.

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 interpreting efficacy is that the registry record does not report the observed one-year progression-free survival result. It also omits the corresponding uncertainty interval, test statistic, and p-value. The stated threshold of 54% or greater is a planned criterion, not evidence that the criterion was reached.

The endpoint description does not provide its operational definition, disease-assessment schedule, censoring rules, or analysis population. The registry also does not report follow-up completeness or how missing endpoint information was handled. As a result, the primary analysis cannot be reconstructed from the registry entry.

The single-group, unmasked design has no concurrent comparator and cannot isolate the effects of individual treatment components. The arm description is incomplete, ending before all regimen details are specified. The record does not report the full protocol, the sample-size justification, interim-analysis procedures, or the reason for termination.

Safety reporting is limited to counts and selected serious-event terms. Timing, duration, severity grading, attribution, outcome, and the relationship between deaths and event categories are not reported. The record lists secondary outcomes but provides no analyses for them. These omissions restrict both efficacy and safety interpretation and prevent a full assessment of the study’s conduct or statistical methods.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: High-Dose Y-90-Ibritumomab Tiuxetan Added to Reduced-Intensity Allogeneic Stem Cell Transplant Regimen for Relapsed or Refractory Aggressive B-Cell Lymphoma — NCT01434472.
• Registry record last updated 2021-07-20; status last verified 2021-07.
• Results first posted 2021-05-25.
• 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

NCT01434472 is a phase II, single-group study sponsored by Fred Hutchinson Cancer Center. It enrolled 20 participants and is listed as terminated. The study investigated high-dose Y-90-ibritumomab tiuxetan followed by fludarabine phosphate, low-dose total body irradiation, and allogeneic stem cell transplantation for relapsed or refractory aggressive B-cell lymphoma.

The primary endpoint was progression-free survival at one year. The stated success criterion was 54% or greater in the highest-risk group, using a one-sample chi-square test with a one-sided significance level of five percent. The observed primary endpoint result and its uncertainty are not reported in the registry record.

The record lists seven secondary outcomes and reports no analyses. Safety entries include 11 participants affected among 20 at risk for serious events, 11 among 20 for other events, and six deaths. The record does not provide the details needed to establish event attribution or compare outcomes with another treatment.