Safety and Efficacy of 90Y Zevalin in Nonmyeloablative Transplantation for Lymphoid Malignancies: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Safety and Efficacy of 90Y Zevalin in Nonmyeloablative Transplantation for Lymphoid Malignancies (NCT00048737), a na phase 1, phase 2 study. The primary outcome is Number of Participants With Graft Failure.

2. Clinical Question

In broad terms, the study asked whether this transplant regimen could be administered and what outcomes and safety events would be observed in patients with leukemia or lymphoma. Its single-group structure supports description of outcomes in the treated group, but does not isolate the effect of 90Y Zevalin from the other drugs, the transplant, or other influences. The registry record does not state a comparative treatment-effect question.

3. Trial Design

This completed study is recorded as phase 1 and phase 2, with a single-group model and no masking. Allocation is listed as not applicable. Enrollment was 70. The sponsor was M.D. Anderson Cancer Center. The recorded start was 2002-10, and primary completion was 2011-12.

The sole arm was labelled “90Y Zevalin in ASCT.” Its description specifies allogeneic stem cell transplantation with 90Y Zevalin, cyclophosphamide, and fludarabine as a preparative regimen. The interventions list also includes rituximab. The registry record does not explain the difference in wording between the arm label and its description, or provide further details on the treatment schedule, doses, or supportive care.

With one group, the study can describe what happened among participants treated under this regimen. It cannot estimate a randomized contrast against a concurrent control group. There is no like-for-like comparator in the registry record, and differences from outcomes in other populations or studies would not establish a treatment effect.

The record lists one primary outcome measure: number of participants with graft failure, assessed at 100 days. It defines graft failure as lack of hematologic recovery or lack of, or loss of, detectable donor cells. Although the study summary mentions remission duration and safety as interests, those statements do not substitute for posted outcome results or analyses. No statistical analysis of the primary outcome is reported in the registry record.

The record status is completed, but completion status by itself does not indicate that outcome data or a full analysis have been posted. Details of the protocol, recruitment flow, participant follow-up, and analysis populations are not reported in the registry record.

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 Number of Participants With Graft Failure, measured over 100 days.

The primary endpoint is the number of participants with graft failure within 100 days. The registry defines graft failure as either lack of hematologic recovery or lack of, or loss of, detectable donor cells. This is a binary outcome at the participant level: each participant either meets the definition during the stated assessment period or does not. The endpoint is reported as a count of participants, rather than as a continuous measurement.

This type of endpoint is used to capture whether a specified event occurs after treatment. A clear definition matters because it determines which participants count as having the event. In this record, the definition combines hematologic recovery and detectable donor cells; the record does not give operational details about how those criteria were assessed or adjudicated.

The assessment timeframe is 100 days. A fixed timeframe makes the intended observation window explicit, but interpretation also depends on whether participants were followed and assessed consistently for that period. Follow-up completeness and handling of participants without an evaluable assessment are not reported in the registry record.

The registry record identifies the endpoint but does not post its observed count, an estimate of uncertainty, or an analysis. Consequently, the endpoint definition can be described, but the frequency of graft failure and the precision of any estimate cannot be evaluated from the posted results.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

Statistical interpretation depends first on the study structure and outcome definition. This record describes a single group, with no masking and allocation listed as not applicable. The endpoint is the number of participants with graft failure by 100 days. Those details identify what the study intended to count and the broad design context, but they do not reveal the analysis actually performed. A statistical analysis plan is not reported in the registry record.

What a binary endpoint represents

For a binary endpoint, each participant is classified according to whether the event definition is met within the specified observation period. A count of participants with the event can be accompanied by a proportion and an interval estimate to describe uncertainty. These are general statistical concepts; the registry record does not post a graft-failure count, a proportion, or an interval estimate. No result should be inferred from the enrollment count alone.

The endpoint definition is particularly important when it combines criteria. Here, graft failure includes lack of hematologic recovery or lack of, or loss of, detectable donor cells. A study analysis would need to apply that definition consistently. The record does not explain assessment procedures, the timing of assessments within the 100-day timeframe, or how uncertain or incomplete evaluations were classified.

What a single-group design can establish

A single-group study can report outcomes observed among participants receiving the regimen. It does not create a concurrent counterfactual: the outcome those same participants might have experienced under another treatment. Randomized comparisons can support a more direct estimate of differences between assigned groups because randomization is intended to balance factors on average. That design is absent. Accordingly, even if a group outcome count were posted, it would not by itself establish that the regimen caused the observed outcome or that it performed better or worse than an alternative.

The intervention itself combines multiple components: 90Y Zevalin, rituximab, fludarabine, cyclophosphamide, and allogeneic stem cell transplantation. A single-group result would concern the overall treatment approach as administered, not the isolated effect of one listed component. The registry record does not report a component-specific comparison.

Uncertainty and estimates

A confidence interval is a general way to express the statistical uncertainty around an estimate. For an event frequency, it would help readers distinguish a relatively precise estimate from one that is compatible with a broad range of values. No confidence interval or other uncertainty estimate for graft failure is reported in the registry record. There are also no posted primary outcome analyses from which to assess model choice, adjustment, or assumptions.

For binary data, the number of observed events and the number of participants assessed are both important to the estimate and its precision. The record gives enrollment and a serious-adverse-event count, but not the primary endpoint count or the number assessed for that endpoint. Those safety details cannot stand in for the graft-failure result.

Planning calculations and observed results

General sample-size illustrations are planning scenarios, not observed power. The stated illustration assumptions use a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation, with the target effect expressed as a fraction of the observed effect. The trial itself is single group, so those illustration assumptions do not describe its design. The record does not report the trial's own sample-size justification. No planning illustration can replace an observed endpoint result, and planned power is not evidence that a result was detected or that an effect exists.

In general, over-dispersion refers to variability greater than a statistical model expects. It can matter when a model for counts or rates assumes less variability than the data contain, because estimated uncertainty may then be too small. The primary endpoint is described as a participant count for a binary event, and the record reports no model or analysis that would justify discussing over-dispersion as an issue in this trial. No model-based interpretation is reported.

What is and is not documented

The registry lists one outcome measure and no analyses. The absence of posted analyses means there is no reported test statistic, p-value, adjusted estimate, or confidence interval for the primary endpoint to interpret. Statistical methods beyond the broad design and endpoint description are not reported in the registry record. The record also does not report interim analyses, covariate adjustment, missing-data procedures, or a prespecified approach to multiple outcomes. These omissions limit the ability to evaluate whether the eventual analysis, if conducted, followed a prespecified plan.

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("90Y Zevalin in ASCT")
n      <- c(70)
events <- c(1)
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  90Y Zevalin in ASCT  70  1  1.4  0.0  7.7  0.3  7.7  0.3  7.6

11. Multiplicity, Missing Data and Analysis Populations

The registry record lists one outcome measure and does not report analyses. It does not describe a statistical analysis plan, identify a family of hypotheses, or state how multiplicity was handled. Multiplicity arises when several outcomes, time points, or subgroup comparisons are tested; without a stated plan, the reader cannot determine whether any adjustment was intended. The study summary mentions remission duration and safety, but the record does not provide results or analysis details for those aims.

Missing-data methods are not reported in the registry record. The primary endpoint requires an assessment within 100 days, but the record does not state how participants who died, withdrew, were lost to follow-up, or lacked an evaluable assessment were treated. These are general examples of circumstances that can affect outcome ascertainment, not claims that any occurred in this study. Without participant flow and follow-up information, completeness of endpoint measurement cannot be assessed.

Analysis populations are also not described. The record does not say whether analyses used all enrolled participants, only those who began the regimen, or a subset with evaluable endpoint data. No flow of participants through treatment and follow-up is reported. The enrollment count should therefore not be assumed to be the denominator for the primary outcome analysis.

Because no primary analysis is posted, it is not possible to assess whether exclusions, missing observations, or multiple outcomes influenced the findings. These are reporting limitations, not evidence that any particular analysis choice was made.

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: pneumonia (2.9%), neutropenia (1.4%), thrombosis (1.4%), acute renal failure (1.4%), sepsis (1.4%).

The safety information is for the single group labelled “90Y Zevalin in ASCT.” The registry lists 70 participants at risk for serious adverse events and 7 affected participants. It separately lists serious adverse-event terms with percentages: pneumonia, 2.9%; neutropenia, 1.4%; thrombosis, 1.4%; acute renal failure, 1.4%; sepsis, 1.4%; and C-Diff colitis, 1.4%.

These entries should be read as descriptive safety reporting for the study group, not as a comparison with another treatment. The percentages do not establish whether an event was caused by 90Y Zevalin, another drug, the transplant, or another factor. There is no control group in this study to estimate how the listed events compare with a concurrent alternative.

The registry record does not give event-level details such as onset, duration, recurrence, severity grading, or attribution. It also does not provide a full narrative of safety monitoring or specify how overlapping events in the same participant were counted. The reported serious-event information therefore gives a limited account of selected events, rather than a complete basis for comparing safety profiles.

Safety information should be considered alongside the design and reporting limitations: a single group, no posted primary endpoint analysis, and no comparative safety estimate.

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

The registry record documents a completed phase 1 and phase 2, single-group study of a regimen combining 90Y Zevalin and other listed drugs with allogeneic stem cell transplantation. It identifies graft failure within 100 days as the primary endpoint and defines the event. It also records enrollment and selected serious adverse-event information. These details describe the study's intent and some of its reported safety data.

The record does not report the observed graft-failure count or an analysis of that endpoint. It therefore does not show how often graft failure occurred in the study group, nor how precise an estimate would be. The study summary refers to remission duration, but a remission-duration result is not reported in the registry record. The posted safety information likewise does not support a comparative conclusion about adverse events.

Even if the primary outcome count were available, the one-group design would constrain what it could mean. A count could describe the experience of participants receiving the overall regimen, but without a concurrent comparator it would not establish what would have happened under another approach. It also would not isolate the effects of 90Y Zevalin from the other regimen components or the transplant procedure.

These limitations do not erase the value of clearly defining an endpoint or recording adverse events. They do mean that interpretation must distinguish what the registry states from what would require additional outcome data and a suitable comparison. The completed status indicates the study is recorded as completed; it is not itself evidence of a particular clinical outcome.

The most defensible conclusion is that the available record describes the study design, treatment approach, primary endpoint definition, enrollment, and selected safety counts. It does not provide the primary result or comparative evidence needed to estimate a treatment effect.

14. Why This Trial Matters Statistically

This study is statistically notable because its design and reporting illustrate the distinction between a research question and evidence capable of answering a comparative question. The record describes a phase 1 and phase 2 investigation in lymphoma and leukemia, with an overall regimen that includes multiple drugs and allogeneic transplantation. Its single-group model can document experience in that group, but cannot supply a randomized contrast against an alternative.

The primary endpoint is defined in clinical terms and tied to a stated timeframe of 100 days. That specificity is useful: readers can identify the event the study intended to count. Yet an endpoint definition without the observed result is not an outcome analysis. The absence of a posted count, uncertainty estimate, and analysis makes it impossible to judge the observed graft-failure frequency from this registry record.

The safety entries also demonstrate why event counts need context. The record reports serious adverse events in the study group and lists selected terms and percentages, but without a control group these figures cannot quantify a difference in risk between treatments. Event attribution, timing, and broader follow-up information are not reported.

Finally, enrollment and completion status should not be confused with statistical evidence of efficacy or safety. Sample-size planning illustrations, when present, are planning tools rather than observed power or evidence of an effect. The record does not report its own sample-size justification or the analysis plan needed to connect the study objectives to a prespecified statistical interpretation.

The statistical lesson is that design, endpoint definition, results, and analysis reporting each answer different questions. In this record, design and endpoint information are available, but the primary outcome result and comparative analysis are not.

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 main limitation for interpreting the primary objective is that the registry record does not report the graft-failure result or any analysis of that endpoint. Although the endpoint is defined and its assessment timeframe is stated as 100 days, the observed event count, denominator assessed, and uncertainty estimate are absent. The primary outcome therefore cannot be quantified from the posted results.

The study has one group and no control arm. This prevents direct comparison with another regimen and limits causal interpretation. The intervention combines several drugs and a transplant procedure, so the contribution of an individual component cannot be separated in this design.

Details needed to judge endpoint ascertainment are also not reported in the registry record. These include how the criteria were assessed, how often they were assessed, whether endpoint status was adjudicated, and how incomplete follow-up was handled. The record does not report participant flow, analysis populations, missing-data methods, or a statistical analysis plan.

The study summary refers to remission duration, but no result or analysis for that outcome is posted. The safety information includes selected serious-event counts and terms, but does not report event timing, duration, attribution, or a comparative estimate. The record also does not provide the trial's sample-size justification or describe interim analyses.

These limitations concern what can be concluded from the registry record. They do not establish that unreported procedures or analyses were never conducted; rather, those details are not reported in the registry record.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Safety and Efficacy of 90Y Zevalin in Nonmyeloablative Transplantation for Lymphoid Malignancies — NCT00048737.
• Registry record last updated 2013-06-13; status last verified 2013-06.
• Results first posted 2013-06-13.
• 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

NCT00048737 is recorded as a completed phase 1 and phase 2, single-group study sponsored by M.D. Anderson Cancer Center. It enrolled 70 participants with lymphoma or leukemia. The recorded start was 2002-10, and primary completion was 2011-12.

The study examined 90Y Zevalin with a preparative regimen that included cyclophosphamide and fludarabine, followed by allogeneic stem cell transplantation; rituximab is also listed among the interventions. The primary outcome was the number of participants with graft failure within 100 days. Graft failure was defined as lack of hematologic recovery or lack of, or loss of, detectable donor cells.

The registry record does not report the primary outcome result or an analysis. It lists 7 participants with serious adverse events among 70 at risk, as well as selected serious-event terms and percentages. With no control group, the record does not provide a randomized comparison or a comparative treatment-effect estimate.