This page provides an independent statistical analysis and educational interpretation of publicly reported results. ClinicalTrials.gov provides the official trial registry record. Numerical trial results on this page are restricted to the results posted in the ClinicalTrials.gov record; calculations added by Clinical Biostats are labelled as such.
1. Trial at a Glance
This page covers the registry results for A Phase II Trial of Combined Weekly Bortezomib and Tositumomab I-131 in Patients With Relapsed or Refractory Follicular Non-Hodgkin's Lymphoma (NCT00479167), a non-randomized phase 2 study. The primary outcome is The Primary Objective of This Study is to Determine the Maximum Tolerated Dose (up to 1.6 mg/m2) of Bortezomib Combined With Tositumomab and Iodine I 131 Tositumomab.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT00479167 |
| Phase | Phase 2 |
| Condition | Follicular Lymphoma |
| Allocation | Non-Randomized |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 1 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Rush University Medical Center |
| Results posted | Yes |
2. Clinical Question
The study asked whether a tolerable dose of bortezomib could be identified when it was combined with tositumomab and iodine I 131 tositumomab in people with relapsed or refractory follicular non-Hodgkin's lymphoma. Its primary objective was to determine the maximum tolerated dose of bortezomib, up to 1.6 mg/m2. The registry summary also describes an interest in whether the combination was effective, and the secondary outcome concerns further exploration of toxicity and efficacy and tolerability of bortezomib after tositumomab.
The intended clinical question is therefore principally a dose-tolerability question, not a comparison of the combination against a control treatment. The record lists one intervention, Bortezomib and Tositumomab I-131, and a single-group model. It does not identify a separate control group or a randomized comparison. The registry's summary gives a proposed rationale that combining the agents might sensitize cells to radiation from tositumomab I-131; this is a rationale for the study, not a result established by the posted data.
The record reports enrollment of 1, status as terminated, and the primary outcome population as “Subject withdrew.” It provides no numerical maximum tolerated dose, efficacy estimate, or statistical analysis. Consequently, the posted information does not answer whether a tolerable dose was established or whether the combination had an effect on lymphoma outcomes. Those questions remain unresolved by the registry record.
Population
Patients with relapsed or refractory follicular non-Hodgkin's lymphoma; the primary outcome record identifies the population as “Subject withdrew.”
Intervention
Bortezomib combined with tositumomab and iodine I 131 tositumomab.
Comparator
No separate comparator is listed. The study is recorded as non-randomized and single-group.
Primary question
What is the maximum tolerated dose of bortezomib in the combination, up to 1.6 mg/m2?
3. Trial Design
The registry classifies this study as Phase II, non-randomized, unmasked, and single-group. The listed intervention is Bortezomib and Tositumomab I-131. No like-for-like control arm is identified, so the design does not support a randomized comparison of the combination with another treatment. The study is listed under follicular lymphoma.
The record gives a planned primary objective of determining the maximum tolerated dose of bortezomib combined with tositumomab and iodine I 131 tositumomab, with an upper dose stated as 1.6 mg/m2. The primary outcome timeframe is recorded as “Study terminated.” The primary outcome population is recorded as “Subject withdrew.” The record does not describe a dose-escalation schedule, dose-limiting toxicity definition, assessment window, stopping rule, or method for selecting a final dose. Those protocol details are not reported in the registry record.
Enrollment is listed as 1. The registry lists a start date of 2007-05 and a primary completion date of 2008-09, and the study status is terminated. These dates describe the registered study timeline; they do not establish when or why the participant withdrew. A reason for termination and a detailed account of trial conduct are not reported in the registry record.
A dose-finding study generally needs observations of toxicity at the tested doses, together with an explicit rule for how those observations guide dose selection. That is a general description, not a claim about this protocol. With no dose-level results or dose-selection rule posted, the registered objective cannot be evaluated from the available outcome information. The single-group structure also means there is no control-group estimate to distinguish treatment-related changes from other influences. The registry record does not report a planned sample-size justification, interim analyses, or a detailed statistical analysis plan.
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
| Stage | Bortezomib in Combination With Tositumomab |
|---|---|
| STARTED | 1 |
| COMPLETED | 0 |
| NOT COMPLETED | 1 |
Reasons for not completing this period:
| Reason | Bortezomib in Combination With Tositumomab |
|---|---|
| Withdrawal by Subject | 1 |
Analysis population for the primary outcome, as defined in the registry: Subject withdrew
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.
Population: only subject withdrew
| Characteristic | Unit | Bortezomib in Combination With Tositumomab |
|---|---|---|
| Participants analysed | 0 | |
| Age, Categorical: <=18 years | — | |
| Age, Categorical: Between 18 and 65 years | — | |
| Age, Categorical: >=65 years | — | |
| Sex: Female, Male: Female | — | |
| Sex: Female, Male: Male | — | |
| Region of Enrollment: United States | participants | — |
6. Primary Endpoint
The registry lists the primary outcome as The Primary Objective of This Study is to Determine the Maximum Tolerated Dose (up to 1.6 mg/m2) of Bortezomib Combined With Tositumomab and Iodine I 131 Tositumomab, measured over Study terminated..
| Element | Registry entry |
|---|---|
| Result type | N/A |
| Measure of spread | not applicable |
| Unit | not stated |
| Endpoint classification | not reduced to a single comparison |
The primary endpoint is framed as the maximum tolerated dose of bortezomib when combined with tositumomab and iodine I 131 tositumomab, up to 1.6 mg/m2. In general, a maximum tolerated dose is a dose-finding endpoint: it aims to identify a dose that meets a prespecified tolerability criterion under a defined observation process. The criterion, toxicity grading rules, observation period, and dose-selection procedure are not reported in the registry record, so the precise operational meaning of “maximum tolerated” cannot be reconstructed from the posted entry.
This kind of endpoint is used in early-phase research to guide selection of a dose for further study. It does not, by itself, measure comparative efficacy. Although the registry's summary describes efficacy as an interest of the study, no efficacy result is posted as the primary endpoint result. The secondary outcome refers to further exploration of toxicity and efficacy and to assessing tolerability of bortezomib after tositumomab, but no corresponding result is reported in the registry record.
The primary outcome timeframe is listed as “Study terminated,” and the population is listed as “Subject withdrew.” No maximum tolerated dose, dose-specific toxicity counts, or endpoint estimate is reported. Therefore, the endpoint's intended role is clear at a broad level, but the registry record does not show that it was determined.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The central statistical fact is that the registry reports enrollment of 1, while the primary outcome population is recorded as “Subject withdrew.” The study status is terminated. The registry record reports no numerical primary endpoint result and no analyses. It therefore does not provide an estimate of the maximum tolerated dose or an inferential result about toxicity or efficacy. The missing result should not be interpreted as evidence that a particular dose was tolerable or intolerable.
The trial was single-group and non-randomized. There is no separate control arm in the record, so there is no randomized treatment contrast to interpret. Even if an outcome change had been posted, a single-group observation would not by itself show how outcomes would have differed under another treatment or no treatment. In this record, the problem is more basic: there is no posted efficacy estimate to describe, and the small enrollment and withdrawal information do not supply an endpoint result.
The posted safety counts list 1 participant at risk for serious adverse events and 0 participants affected by serious adverse events. The record also lists 1 participant at risk for other adverse events and 0 affected, with 0 deaths. These are descriptive registry counts. They do not show a comparative safety effect, and the number of participants observed is too limited to characterize uncommon or variable harms. The record does not supply event-level detail that would explain the observation period, ascertainment, or reasons for withdrawal.
The entry includes a secondary outcome statement about further exploring toxicity and efficacy, but the registry does not report its results. A stated objective is not an observed finding. Similarly, the summary's proposed biological rationale is not evidence that the combination produced a clinical benefit. The distinction matters because study objectives, treatment rationale, and outcome results answer different questions.
The registry record does not report the analysis population beyond the primary outcome's “Subject withdrew” entry, nor does it specify a missing-data method. It does not report a formal statistical plan, an interim analysis, or a sample-size justification. With no posted endpoint analysis, a confidence interval, p-value, or estimate of precision is unavailable. The appropriate interpretation is limited to what is explicitly recorded: this was a terminated, single-group Phase II study with enrollment of 1, and the registry does not provide the primary outcome result needed to answer its dose-finding question.
9. Statistical Methods Explained
Statistical methods need to be interpreted in relation to the question a study was designed to answer. This trial's primary objective is dose finding: determining the maximum tolerated dose of bortezomib in a combination, up to 1.6 mg/m2. That is different from estimating the effect of treatment relative to a control. The registry classifies the study as non-randomized and single-group, and it lists no separate comparator. A treatment contrast between randomized arms is therefore not part of the posted design.
What would a dose-finding analysis require?
In general, a dose-finding analysis uses toxicity observations at the doses participants receive and applies a prespecified rule to decide which dose is acceptable for further evaluation. A transparent account would ordinarily identify what counts as a dose-limiting event, the period in which such events are assessed, how dose changes are decided, and how the final dose is selected. These details are important because different rules can lead to different dose recommendations even when the observed toxicities are the same. The registry record does not report those protocol details or any dose-specific toxicity observations. No dose-selection method or maximum tolerated dose result is reported.
The registry lists a primary endpoint and gives “Study terminated” as its timeframe, with “Subject withdrew” as the outcome population. These entries do not provide an endpoint value. Without a reported dose estimate, toxicity criterion, or analysis, there is no numerical result whose uncertainty can be evaluated. A point estimate without uncertainty can be misleading in general; a confidence interval communicates the range of estimates compatible with the data and the method used. No confidence interval is reported in this record.
What does the design imply for comparisons?
In general, randomization helps balance both measured and unmeasured characteristics between treatment groups, supporting a causal comparison when the trial is appropriately conducted and analyzed. Here, the study is identified as non-randomized and single-group, with no control arm listed. It cannot provide a randomized between-group estimate. This does not mean that a single-group study has no useful role: dose and safety observations can inform early research. It does mean that results should not be described as a comparative treatment effect.
The record also indicates that allocation is non-randomized and masking is absent. The registry does not report additional procedures that might have affected assessment, nor does it describe how outcomes were adjudicated. In general, lack of masking can matter when outcome assessment involves judgment, while objective measures may be less susceptible to that influence. The registry does not give enough detail to determine how this issue applies to each outcome in this trial.
What can be said about significance and precision?
No analyses are listed in the registry, and no primary endpoint estimate, standard error, confidence interval, or p-value is reported. Statistical significance cannot be assessed from the available result record. A p-value, in general, describes how incompatible data are with a specified statistical model or null hypothesis; it does not measure the size or clinical importance of an effect. A confidence interval addresses estimation precision under its assumptions. Neither kind of inferential result is available.
The registry includes a description of planning illustrations that use a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation, with the effect to detect expressed as a stated fraction of an observed effect. Those are planning assumptions, not a description of the actual single-group design. The trial record does not report an observed effect from which to assess such illustrations, and it does not report its own sample-size justification. In general, sample-size calculations are conditional on assumptions about the effect, variability, allocation, and analysis. They do not show what a completed study observed, and they are not observed power.
Over-dispersion is a general concern when count outcomes vary more than a chosen statistical model allows; ignoring it can make uncertainty appear smaller than it is. This trial's registry entry does not report a count model or an outcome analysis to which such a concern can be applied. Likewise, no time-to-event analysis or event-time result is reported. These concepts should not be mistaken for methods actually used in the trial.
What is the role of the posted safety counts?
Counts of participants affected by an event are descriptive. In general, a count paired with the number at risk gives a basic account of how many participants were observed to have the event, but interpretation also depends on event definitions, ascertainment, exposure, and follow-up. The record lists 1 at risk and 0 affected for serious adverse events, and 1 at risk and 0 affected for other adverse events. Those counts do not estimate comparative risk, establish absence of risk, or describe the frequency of events in a broader population. The record lists 0 deaths; it does not report a comparative mortality analysis.
Overall, the registry supports a description of the study's design, objective, enrollment, termination status, and limited safety counts. It does not support reconstruction of an analysis plan, calculation of an endpoint estimate, or conclusions about efficacy. Any further statistical interpretation would require results and methods not reported in the registry record.
10. Multiplicity, Missing Data and Analysis Populations
Multiplicity arises when several outcomes, time points, subgroups, or statistical tests are assessed. In general, conducting many tests can increase the chance of at least one apparently notable result, so a study may prespecify a primary outcome and explain how additional analyses will be interpreted or adjusted. The registry identifies a primary objective concerning maximum tolerated dose and lists a secondary outcome concerning further exploration of toxicity and efficacy and tolerability after tositumomab. It does not report a multiplicity procedure, a hierarchy for interpreting outcomes, or results for the secondary outcome. The registry record does not report an analysis plan that would clarify how multiple outcomes were handled.
Missing data also affect interpretation. The primary outcome population is recorded as “Subject withdrew,” and enrollment is listed as 1. The record does not state why the participant withdrew, when withdrawal occurred relative to treatment or endpoint assessment, what data were collected before withdrawal, or whether any replacement or follow-up procedures were used. A missing-data method, imputation approach, or sensitivity analysis is not reported in the registry record. It is therefore not possible to determine from the entry whether the endpoint was unobserved, partially observed, or evaluated but not posted.
The registry does not define an intention-to-treat, treated, evaluable, or safety analysis population. The safety counts list 1 participant at risk, but the record does not explain how that population was defined or how long participants were followed for those outcomes. No analysis population beyond the primary outcome's withdrawal notation is reported.
These omissions do not establish that the investigators failed to conduct analyses or manage missing data; they mean those methods and results are not reported in the registry record. Given the absence of a posted endpoint result and analysis, it is not possible to assess multiplicity control, missing-data assumptions, or robustness to alternative analysis populations.
11. Safety Results
The registry reports serious adverse events as affected participants divided by participants at risk.
| Arm | Participants with serious adverse events | Participants at risk | Percentage |
|---|---|---|---|
| Bortezomib in Combination With Tositumomab | 0 | 1 | 0.0% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Bortezomib in Combination With Tositumomab | 0 of 1 |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 1% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Bortezomib in Combination With Tositumomab | 0 of 1 |
The registry lists a safety group titled Bortezomib in Combination With Tositumomab. It reports 1 participant at risk for serious adverse events and 0 affected by serious adverse events. For other adverse events, it reports 1 at risk and 0 affected. Deaths are listed as 0. No serious adverse event terms are listed among the top serious terms.
These counts are descriptive entries, not comparative estimates. In general, observing no events in a small group does not establish that an event cannot occur or that the treatment is free of risk. The count also does not communicate how long participants were observed, how events were collected, or whether the participant's withdrawal limited follow-up; those details are not reported in the registry record.
The “at risk” count should be read as the registry's denominator for the listed safety outcome, not as evidence that every possible event was assessed over a common or complete period. No event rate comparison, confidence interval, or adjusted safety analysis is reported. With enrollment of 1 and terminated status, these data provide only a narrow description of the recorded observations and cannot characterize safety more broadly.
12. What the Result Does, and Does Not, Mean
The result that can be described is a registry record of a Phase II, single-group, non-randomized study of combined bortezomib and tositumomab I-131, with enrollment of 1 and status listed as terminated. The primary objective was to determine the maximum tolerated dose of bortezomib, up to 1.6 mg/m2. The primary outcome population is recorded as “Subject withdrew,” and no numerical endpoint result is posted. Safety counts list 0 serious adverse events among 1 participant at risk, 0 other adverse events among 1 at risk, and 0 deaths.
These entries do not establish a maximum tolerated dose. They do not show whether the treatment combination was effective, whether a particular dose was tolerable under the protocol's intended criteria, or how outcomes compare with another treatment. The record includes an efficacy interest and a proposed treatment rationale, but those statements are not findings. No efficacy estimate or inferential analysis is reported.
In general, statistical conclusions depend on both the observed data and the methods used to collect and analyze them. Here, key details such as the toxicity criterion, dose-selection procedure, follow-up period, analysis population, and missing-data method are not reported in the registry record. Without those details and a posted endpoint analysis, precision and potential sources of bias cannot be assessed. The safety counts should not be treated as evidence that adverse effects are absent, especially because the registry's enrollment is limited and the participant withdrew.
The study's design can still be distinguished from a comparative trial: it was recorded as a single-group study, with no randomized control arm. Accordingly, no treatment-versus-control effect is available to interpret. The most defensible conclusion is descriptive and bounded: the registry documents a terminated study with minimal enrollment, withdrawal noted for the primary outcome, and no posted primary endpoint result. It leaves the central dose-finding and efficacy questions unanswered.
13. Why This Trial Matters Statistically
This trial illustrates why registered objectives and reported results need to be read separately. The primary objective is specific in broad terms: determine a maximum tolerated dose of bortezomib in combination with tositumomab and iodine I 131 tositumomab, up to 1.6 mg/m2. But the objective alone does not provide the evidence needed to identify a dose. That requires toxicity observations and an interpretable dose-selection method, neither of which is reported in the registry record.
The entry also shows how study design sets limits on the conclusions available. A single-group, non-randomized design can address early questions about administration and observed toxicity, but it does not create a randomized comparison. The record lists no comparator, and no comparative effect is reported. Keeping that distinction clear prevents a proposed rationale or an outcome objective from being mistaken for evidence of benefit.
The safety counts provide another statistical lesson: zero recorded events in a very small group are not equivalent to proof that no risk exists. Counts depend on who was observed, what was counted, and for how long. The record reports enrollment of 1 and withdrawal in the primary outcome population, while key details about follow-up and event ascertainment are not reported. The resulting counts have a narrow descriptive scope.
Finally, a terminated study with no posted endpoint analysis cannot answer the question its primary objective posed. That is not a negative estimate; it is an absence of a reported estimate. Recognizing the difference between an unavailable result and a result showing no effect is essential for accurate evidence synthesis. This registry entry demonstrates how design information, outcome reporting, and uncertainty must be considered together before drawing statistical conclusions.
14. 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 registry record leaves important trial-specific limitations unresolved. It reports enrollment of 1, status as terminated, and a primary outcome population of “Subject withdrew.” It does not state the reason for withdrawal, the point in the study when it occurred, or whether the participant received treatment or completed any outcome assessments. The effect of withdrawal on endpoint ascertainment therefore cannot be determined.
The record does not report a dose-escalation plan, the operational definition of maximum tolerated dose, dose-limiting toxicity criteria, the observation window for toxicity, or a dose-selection rule. Without these details, the endpoint cannot be independently interpreted or reproduced. No dose-specific outcomes or maximum tolerated dose estimate are posted.
The trial is recorded as single-group, non-randomized, and unmasked. There is no separate control group for comparison. The record does not describe outcome-assessment procedures or any steps used to reduce possible assessment bias. A detailed statistical analysis plan, sample-size justification, interim analysis plan, and missing-data approach are not reported in the registry record.
The posted safety information is limited to counts: 1 participant at risk and 0 affected for serious adverse events, 1 at risk and 0 affected for other adverse events, and 0 deaths. Event definitions, duration of observation, and detailed event information are not reported. The record lists a secondary toxicity and efficacy objective but does not provide its outcome results. Taken together, these limitations prevent estimation of dose tolerability, efficacy, or the precision of any clinical effect from the posted information.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: A Phase II Trial of Combined Weekly Bortezomib and Tositumomab I-131 in Patients With Relapsed or Refractory Follicular Non-Hodgkin's Lymphoma — NCT00479167.
- Registry record last updated 2021-11-04; status last verified 2021-10.
- Results first posted 2021-11-04.
- 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.
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18. Record Summary
NCT00479167 is listed as a Phase II study of combined weekly bortezomib and tositumomab I-131 in patients with relapsed or refractory follicular non-Hodgkin's lymphoma. Rush University Medical Center is listed as sponsor. The study is recorded as non-randomized, unmasked, and single-group, with one intervention and enrollment of 1. The registry lists a start date of 2007-05, a primary completion date of 2008-09, and status as terminated.
The primary objective was to determine the maximum tolerated dose of bortezomib in combination with tositumomab and iodine I 131 tositumomab, up to 1.6 mg/m2. The primary outcome timeframe is “Study terminated,” and its population is “Subject withdrew.” No primary endpoint estimate or analysis is reported in the registry record. Safety counts list 0 serious adverse events among 1 participant at risk, 0 other adverse events among 1 at risk, and 0 deaths. The registry does not report the protocol details or outcome results needed to answer the dose-finding or efficacy questions.