Ibritumomab Tiuxetan for Treatment of Non-Follicular CD20+ Indolent Lymphomas: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Ibritumomab Tiuxetan for Treatment of Non-Follicular CD20+ Indolent Lymphomas (NCT00493454), a na phase 2 study. The primary outcome is Objective Response Rate.

2. Clinical Question

3. Trial Design

This was a multicenter phase II study of ibritumomab tiuxetan with rituximab in patients with relapsed or refractory indolent lymphoma subtypes. The registry classifies the design as single-group, with allocation not applicable and no masking. No separate control arm is described, so the design can document outcomes among participants receiving the regimen but cannot, by itself, estimate how those outcomes compare with a concurrent alternative.

The registry records enrollment of 6 participants. It also states that one participant did not receive treatment and was excluded from analysis of the primary endpoint. The listed treatment arm is Ibritumomab tiuxetan + Rituximab. Its schedule includes rituximab intravenously on Days 1 and 8, 111In ibritumomab tiuxetan intravenously on Day 1, and 90Y ibritumomab tiuxetan intravenously on Day 8 after rituximab. The described 90Y dose is 0.3 or 0.4 mCi/kg. These details describe the registered regimen; reasons for any dose choice are not reported in the registry record.

The phase is listed as phase II. The recorded study start is 2006-04 and primary completion is 2011-03. The status is terminated, but the reason for termination is not reported in the registry record. The record lists objective response rate as the primary objective and duration of response, time to treatment progression, response categories, and time to next anticancer therapy as secondary objectives. A statistical analysis plan, details of any interim review, and the rationale for the enrollment target 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

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: One participant did not receive treatment and was excluded from analysis.

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 Objective Response Rate, measured over Evaluation 4 weeks after administration of Zevalin up to 3 years.

The primary endpoint is objective response rate, defined as the proportion of participants with a complete response or partial response. Combining these two response categories gives a binary outcome for each participant: a response meeting either category is counted as an objective response, while the endpoint does not distinguish the clinical meaning of complete versus partial response in its overall rate.

The registry describes complete response as disappearance of all target and non-target lesions. A partial response requires at least a 30% decrease in the sum of the longest diameters of target lesions from baseline. Responses were to be assessed with MRI or CT scans, every 3 months for the first year and every 6 months up to 3 years following treatment. The listed timeframe begins with evaluation 4 weeks after administration of Zevalin and extends up to 3 years.

As a general statistical concept, a response proportion is a direct summary of how often a defined response occurs in the analyzed group. Its usefulness depends on a clear response definition, consistent assessment, and an explicit analysis population. The registry record lists the endpoint definition and states that one participant who did not receive treatment was excluded, but it does not report the observed response count or rate. The result and its precision are therefore not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary outcome is a proportion: the number of participants meeting the response definition relative to the analysis population. That makes it a binary endpoint at the participant level, even though the clinical assessment distinguishes complete response and partial response. The registry defines the combined response outcome and describes the imaging schedule, but does not report the observed endpoint result or the statistical method used to analyze it.

What does a confidence interval communicate?

As a general statistical explanation, a confidence interval expresses uncertainty around an estimate under a specified method and its assumptions. For a response proportion, the width depends on the amount of information in the data and on the interval procedure. Different procedures can behave differently, especially with sparse data or proportions near the boundaries. The registry record does not identify an interval method or report an interval for objective response rate, so no particular interval procedure should be attributed to this study.

A point estimate alone would not reveal how precisely the response proportion was estimated. A narrow interval would indicate greater precision under the chosen method, while a wide interval would indicate substantial uncertainty. Neither an interval nor a test result would resolve the limitations of a single-group design: statistical precision about an observed proportion is not the same as evidence of a comparative effect.

How should the response definition be read?

The registry combines complete response and partial response into the primary objective response rate. A complete response requires disappearance of all target and non-target lesions. A partial response requires at least a 30% decrease in the sum of the longest diameters of target lesions from baseline. As a general measurement principle, a clear threshold helps define which observations count as responses, but the resulting classification still depends on the timing, quality, and interpretation of assessments. The record specifies MRI or CT and a follow-up schedule, but does not report details about blinded review, central assessment, or adjudication.

The endpoint timeframe is described as evaluation 4 weeks after Zevalin administration up to 3 years. Assessments were planned every 3 months during the first year and every 6 months thereafter up to 3 years. A response proportion can depend on which assessment time is used and how later responses are handled. The registry description does not report a detailed rule for selecting the response assessment used in the primary analysis.

What can the planning illustrations tell readers?

Planning illustrations are not observed power and should not be read as proof that the study could detect a particular effect. The stated assumptions for the illustrations include a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. Those are planning assumptions rather than a description of this study’s actual design, which is single-group. The illustrations are therefore not a substitute for a prospective sample-size rationale or an analysis of the observed data. The design rationale and sample-size justification are not reported in the registry record.

In general, calculations based on an observed effect are sensitive to the size and uncertainty of that estimate. If an observed estimate is unstable, a planning calculation based on it can also be unstable. Any such illustration is conditional on its assumptions; it does not mean the trial had a specified probability of finding a result, nor does it show that a null result would be informative. The registry record does not report a prospective statistical plan that would clarify a target effect, analysis method, or decision threshold.

Why does over-dispersion matter?

As a general concept, over-dispersion occurs when variability in observed data exceeds what a statistical model assumes. It can make standard errors too small and intervals too narrow if ignored. It is relevant to some count or clustered-data models, but the registry record does not describe a model for objective response rate or report a variance estimate. There is therefore no basis to claim that a particular over-dispersion adjustment was used or needed for this endpoint.

The registry lists zero analysis entries. No model specification, test, confidence interval method, adjustment for covariates, or missing-data method is reported in the registry record. Interpretation should remain limited to the endpoint and design information that are documented, without assigning unreported statistical methods to the study.

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("Ibritumomab Tiuxetan + Rituximab")
n      <- c(5)
events <- c(0)
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  Ibritumomab Tiuxetan + Rituximab  5  0  0.0  0.0  52.2  0.0  43.4  0.4  45.9

11. Multiplicity, Missing Data and Analysis Populations

The registry identifies objective response rate as the primary objective and lists duration of response, time to treatment progression, complete and partial response categories, and time to next anticancer therapy as secondary objectives. These are multiple questions, and repeated assessments are also described for imaging follow-up. The record does not report a statistical plan explaining how conclusions across the primary and secondary objectives were prioritized or how multiplicity was addressed. No adjustment procedure, testing hierarchy, or rule for interpreting several analyses is reported in the registry record.

The record lists one outcome measure and zero analysis entries. This means the endpoint is described without a corresponding analysis result in the registry record. The record does not report observed response counts, estimates, confidence intervals, or p-values. It also does not report results for the secondary objectives. The absence of those analyses from the registry record does not establish what may have been conducted elsewhere; their results are simply not reported in the registry record.

For the primary endpoint, one participant did not receive treatment and was excluded from analysis. Other analysis-population details are not reported in the registry record. In particular, the record does not state whether the analysis was intended to include all enrolled participants, only treated participants, or another defined population. Missing outcome handling, imputation, and the treatment of participants without evaluable imaging are not reported in the registry record.

As a general statistical point, missing outcomes can affect both the estimate and its uncertainty, especially when the reasons for missingness relate to disease status or treatment experience. Without a documented analysis population and missing-data approach, readers cannot determine how such issues were addressed. The registry record also does not report an interim-analysis plan or stopping rules.

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: neutropenia (20.0%).

The safety summary lists the Ibritumomab Tiuxetan + Rituximab group with 5 participants at risk for serious adverse events and 1 affected participant. Neutropenia is listed among the serious adverse event terms at 20.0%. These are descriptive figures in a small treated group, not a comparison with another regimen. The registry record does not report a death count for this summary.

The same entry lists 5 participants at risk and 5 affected for other adverse events. The “other” category should not be conflated with the serious adverse event count: the registry presents separate serious and other adverse event fields. These counts do not establish severity, timing, duration, or whether an event was judged related to treatment. Details beyond the listed summary are not reported in the registry record.

As a general statistical point, adverse event proportions are sensitive to the number of participants observed and the duration and completeness of safety follow-up. A small denominator can leave considerable uncertainty around the frequency of events, and a single-group summary cannot establish comparative risk. The listed percentages and counts should therefore be read as registry-reported descriptions, not as a precise estimate of risk across a broader population.

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

This record establishes that a phase II, single-group study was registered to evaluate ibritumomab tiuxetan with rituximab in relapsed or refractory indolent lymphoma subtypes. It documents objective response rate as the primary objective, gives a response definition, and describes an imaging schedule. It also records enrollment of 6 participants and notes that one participant who did not receive treatment was excluded from analysis of the primary endpoint.

The record does not report the observed objective response rate, response categories, or uncertainty around an efficacy estimate. It therefore does not allow readers to determine the frequency of complete or partial responses from the registry entry. The secondary outcomes are listed as objectives, but their results are not reported in the registry record. The safety summary contains descriptive adverse event counts, but those figures do not answer the primary efficacy question.

The single-group design also limits what any response proportion could mean. An observed proportion would describe outcomes in the group studied; without a comparator, it would not establish how outcomes would differ under another treatment or without the regimen. This is a design limitation, separate from the missing result. Even a fully reported estimate and confidence interval would not remove the absence of a concurrent comparison.

Nor does the record explain why the study was terminated. The termination status alone does not show whether the decision was related to safety, recruitment, efficacy, administrative reasons, or another cause. That reason is not reported in the registry record. A reader should distinguish the documented study objectives and design from conclusions that require outcome data or a comparative analysis. The record supports a limited account of what investigators set out to study, not a conclusion about treatment benefit or lack of benefit.

14. Why This Trial Matters Statistically

Statistically, this study illustrates the difference between registering an endpoint and reporting an estimable result. Objective response rate is defined in the record, including the clinical categories and imaging schedule. Yet the registry entry does not report the response count or rate, or an interval describing its precision. A clearly defined endpoint is essential, but it cannot answer the research question without the corresponding results.

The design also matters for interpretation. A single-group study can describe outcomes observed among participants receiving a regimen, but it does not provide a randomized comparison. Any response estimate would remain a description of that group rather than a direct estimate of what the regimen changes relative to a control. This distinction is important when readers encounter a numerical result without a comparison: the outcome’s frequency and a treatment effect are different statistical quantities.

The small enrollment recorded, together with the exclusion of a participant who did not receive treatment, makes transparent reporting of the analysis population particularly important. The registry does not provide the primary outcome result or a full account of how evaluability and missing assessments were handled. It therefore cannot show the degree of precision or the influence of analysis choices.

Finally, the registry distinguishes planned objectives from posted analyses: secondary questions are listed, but no analysis entries are present. This underscores why readers need outcome estimates, uncertainty measures, analysis definitions, and clear accounting of participants to judge what the data support. Without those details, statistical interpretation must remain bounded by the design and information documented in the registry record.

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 immediate limitation is that the registry record does not report the primary endpoint result. It defines objective response rate but gives no observed response count or proportion, and no confidence interval or test. The listed secondary objectives likewise have no reported analyses in the record. Statistical precision and the direction or magnitude of any observed efficacy outcome therefore cannot be evaluated from this entry.

The study is single-group, with no concurrent comparator. This prevents a direct estimate of a between-group treatment difference and leaves observed outcomes open to influences that a controlled design could help address. The record also lists no masking. It does not report whether response assessments were independently reviewed or adjudicated, so such procedures should not be assumed.

Enrollment was 6, and the registry states that one participant did not receive treatment and was excluded from primary endpoint analysis. The record does not detail the analysis population beyond that statement, explain the handling of unavailable imaging or other missing data, or report participant-level outcome accounting. It also does not give a sample-size justification, detailed statistical analysis plan, multiplicity strategy, interim-analysis plan, or stopping rules. Each of these items is not reported in the registry record.

The study status is terminated, but the reason is not reported in the registry record. Without that context, the status should not be used to infer why the study ended. Finally, the registry’s safety summaries are descriptive and lack a comparator; their interpretation is limited by the small number at risk and by the absence of further event details in the record.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Ibritumomab Tiuxetan for Treatment of Non-Follicular CD20+ Indolent Lymphomas — NCT00493454.
• Registry record last updated 2013-05-31; status last verified 2013-05.
• Results first posted 2013-05-31.
• 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

The registry record describes a multicenter phase II, single-group study of ibritumomab tiuxetan with rituximab for relapsed or refractory indolent lymphoma subtypes. It records enrollment of 6 participants, with one participant not treated and excluded from the primary endpoint analysis. The primary objective was objective response rate, defined by complete or partial response using RECIST and imaging follow-up. Secondary objectives included response duration and time-to-event outcomes.

The study status is terminated; the reason is not reported in the registry record. The primary outcome result, secondary analyses, statistical analysis plan, and missing-data methods are also not reported in the registry record. The safety entry lists serious and other adverse event counts for the treatment group, but does not provide a comparative safety analysis.