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 Bortezomib to Treat Significant Complication of HSCT (NCT01929980), a na phase 2 study. The primary outcome is Number of Participants With Response.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT01929980 |
| Phase | Phase 2 |
| Condition | Allogeneic Stem Cell Transplantation, Refractory Autoimmune Cytopenia(s) |
| Allocation | Not applicable (single group) |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 4 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Children's Hospital Medical Center, Cincinnati |
| Results posted | Yes |
2. Clinical Question
Population
People with refractory autoimmune cytopenia(s) in the setting of allogeneic stem cell transplantation. The registry record does not report further eligibility details or a fuller description of the participant population.
Intervention
Bortezomib was described as four doses of 1.3mg/m2, administered intravenously or subcutaneously on Days 1, 4, 8, and 11. The arm description also names rituximab and plasmapheresis; the relationship of those details to the bortezomib regimen is not clarified.
Comparator
There was no separate control group. The study is recorded as single-group, with allocation listed as NA, so the response outcome does not represent a randomized comparison against another treatment or a control condition.
Primary question
The primary outcome was the number of participants with response at 6 weeks. Response was defined using different clinical and laboratory criteria for autoimmune hemolytic anemia, autoimmune neutropenia, and autoimmune thrombocytopenia. The numerical response count is not reported in the registry record.
The clinical question is therefore whether participants in this small, uncontrolled study met the specified response criteria during the stated assessment period. The criteria combine changes in blood counts, laboratory findings, antibody status, transfusion frequency, and supportive treatment requirements. Which particular criteria applied depended on the type of autoimmune cytopenia. The record does not report how many participants had each condition, so the outcome definition cannot be mapped to the enrolled group by condition from the registry information alone.
3. Trial Design
This was a completed phase 2, single-group trial sponsored by Children's Hospital Medical Center, Cincinnati. Enrollment was 4 participants. The study start is recorded as 2012-07 and primary completion as 2014-05. Masking was recorded as none, and allocation was listed as NA. With no separate comparison arm, the design cannot distinguish changes associated with the intervention from changes that might occur for other reasons over the same period.
The intervention arm description specifies four doses of bortezomib, 1.3mg/m2, by intravenous or subcutaneous administration on Days 1, 4, 8, and 11. The same arm description also lists rituximab 375 mg/m2 intravenously once on day 1 and says plasmapheresis 2 hours prior. The registry record does not clarify how these details relate to one another, whether they applied to every participant, or how treatment decisions were made. Additional operational details, including adherence and treatment changes, are not reported in the registry record.
The primary outcome was the number of participants with response at 6 weeks. Its response rules differ across autoimmune hemolytic anemia, autoimmune neutropenia, and autoimmune thrombocytopenia. The criteria include measures assessed at 2 weeks, 4 weeks, and 6 weeks, while the overall outcome timeframe is listed as 6 weeks. No separate outcome values or statistical analyses are reported in the registry record. The record also does not report a control-group plan, masking procedures beyond masking being none, or details of how the outcome was adjudicated.
A single-group phase 2 study can describe treatment experience and whether recorded participants met an outcome definition. It does not, by itself, estimate a comparative treatment effect. The very small enrollment also means that the recorded experience represents only a limited number of participants; the registry record does not provide enough outcome detail to quantify response or its precision.
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 |
|---|---|
| STARTED | 4 |
| COMPLETED | 3 |
| NOT COMPLETED | 1 |
Reasons for not completing this period:
| Reason | Bortezomib |
|---|---|
| Physician Decision | 1 |
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.
| Characteristic | Unit | Bortezomib |
|---|---|---|
| Participants analysed | 4 | |
| Age, Categorical: <=18 years | Participants | 4 |
| Age, Categorical: Between 18 and 65 years | Participants | 0 |
| Age, Categorical: >=65 years | Participants | 0 |
| Sex: Female, Male: Female | Participants | 1 |
| Sex: Female, Male: Male | Participants | 3 |
6. Primary Endpoint
The registry lists the primary outcome as Number of Participants With Response, measured over 6 weeks.
| Element | Registry entry |
|---|---|
| Result type | Number |
| Measure of spread | not applicable |
| Unit | participants |
| Endpoint classification | Binary Endpoint |
The primary endpoint is the number of participants with response, assessed at 6 weeks. It is a binary outcome at the participant level: a participant either meets the applicable response definition or does not. The registry record names this endpoint but does not report the number who responded, the number who did not, or a corresponding estimate of uncertainty.
The definition is condition-specific. For autoimmune hemolytic anemia, at least 3 of 5 criteria should be met. These cover stabilization of hemoglobin without transfusions by 2 weeks, conversion of DAT from + to - by 6 weeks, normalization of serum haptoglobin and indirect bilirubin by 6 weeks, and a 50% reduction in transfusion frequency by 4 weeks. For autoimmune neutropenia, at least 2 of 3 criteria should be met: stabilization of absolute neutrophil count by 2 weeks, undetectable antineutrophil antibodies by 6 weeks, or a 50% reduction in GCSF dose by 6 weeks. For autoimmune thrombocytopenia, at least 2 of 3 criteria should be met: stabilization of platelet count without platelet transfusions by 2 weeks, undetectable antiplatelet antibodies by 6 weeks, or a 50% reduction in platelet transfusion frequency from pre-bortezomib values by 6 weeks.
General: A composite endpoint can combine multiple features of a condition into a participant-level classification. It can capture different forms of change, but interpretation depends on the exact criteria and how they are applied. Here, the record does not report the condition distribution or participant-level results, limiting assessment of which components drove any response classification.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record describes a study of 4 participants and specifies a primary response endpoint at 6 weeks. It does not report the numerical response count. As a result, the posted information does not establish how many participants met the criteria, and it does not support a numerical estimate of response frequency or its precision. The record lists one primary outcome measure and no analyses; no inferential result or formal treatment-effect estimate is reported.
The endpoint definition is a set of rules rather than a single laboratory threshold. Participants with autoimmune hemolytic anemia, autoimmune neutropenia, or autoimmune thrombocytopenia are assessed using different criteria, and each condition has its own minimum number of criteria to meet. The listed measures include blood-count stabilization, laboratory or antibody findings, and reductions in transfusion frequency or GCSF dose. Because the record does not report which conditions were represented among participants, or the results for individual criteria, it is not possible to determine which elements contributed to any participant's outcome.
The single-group design is important to interpretation. Any changes observed in participants would describe what happened during the study, but without a concurrent control group the record cannot show how those outcomes compare with what would have happened under another treatment or without the study regimen. The absence of masking, as recorded, also means that masking cannot be invoked as a safeguard against awareness of treatment assignment; the record does not describe outcome adjudication procedures.
The small enrollment limits how broadly the experience can characterize outcomes or adverse events. Even if a result were reported, the experience of 4 participants would be imprecise and sensitive to individual outcomes. In this registry record, that limitation is compounded by the absence of the primary response count and analysis results. The appropriate statistical reading is therefore descriptive: the record identifies a treatment regimen, a participant group, and an outcome definition, but it does not provide the numerical primary result needed to quantify the observed response.
Planning illustrations based on fractions of an observed effect are not evidence of observed power or proof that a treatment effect exists. The stated assumptions include a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. Those assumptions describe the illustrations rather than the actual single-group trial design. Since no formal outcome analysis is reported, the illustrations cannot supply the missing primary result or establish comparative evidence.
9. Statistical Methods Explained
The statistical methods that can be described from the registry record are limited. The study is classified as a single-group phase 2 trial with 4 participants, and its primary outcome is a participant count with response at 6 weeks. No analysis results are reported in the registry record. The outcome count, an uncertainty interval, and a formal comparison are not reported. The record does not state a statistical analysis plan, so the method used to summarize or analyze the primary endpoint cannot be established.
What does a participant-count endpoint represent?
General: A binary endpoint classifies each participant according to whether a defined event or response occurred. A count records how many participants met that definition. For interpretation, the definition must be applied consistently, and the number assessed should be clear. A count alone does not describe uncertainty in the underlying response probability; a statistical interval can express the range of values compatible with the observed data under specified assumptions. In this registry record, the response count and any such interval are not reported.
The endpoint is composite and condition-specific. The definition requires a threshold number of criteria to be met for each type of autoimmune cytopenia. This approach can reflect multiple clinical or laboratory features, but it makes the exact rule central to interpretation. A response classification can depend on which criteria were observed, when they were assessed, and how missing measurements were treated. These operational details are not reported in the registry record. The record also does not give the number of participants in each condition group or component-level outcomes.
What can a single-group design estimate?
General: A single-group study can describe outcomes among participants who receive the study intervention. A comparative treatment effect requires a meaningful comparison, typically against a concurrent control group, because outcomes may change over time for reasons unrelated to treatment. Here, the design is recorded as single-group and allocation is NA. The record therefore contains no randomized between-group comparison. A before-and-after contrast, if one were made, would not by itself resolve the absence of a concurrent control. No such contrast is reported.
Masking is recorded as none. General: Masking is intended to reduce the influence of treatment knowledge on care, assessment, or reporting, depending on who is masked. Without masking, outcome assessment may be more vulnerable to awareness of treatment, especially when criteria require judgments about stabilization. The registry record does not describe additional safeguards, independent assessment, or adjudication, so their use cannot be assumed.
What do the planning illustrations mean?
The registry material describes planning illustrations calculated from an observed effect, using a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. The illustrated effect is described as a stated fraction of the observed effect. These are planning assumptions, not evidence about the actual single-group design. The illustrations are not observed power and do not establish that a comparative effect was detected. Sample-size planning calculations ask what enrollment might be needed under specified assumptions; they do not change the number enrolled or substitute for the trial's outcome data.
General: Power is a design property defined relative to a hypothesized effect, variability, sample size, and testing procedure. It is not a measure of how likely a result is to be true after the study. A planning calculation depends on its assumptions, and a calculation based on an effect estimated from a small study may be especially unstable. No new inference can be drawn from a planning illustration when the underlying primary outcome result and analysis are not reported in the registry record.
Why does over-dispersion matter for count outcomes?
General: For count outcomes, a simple model may assume that variation is tied closely to the average count. Over-dispersion means the observed variation is greater than that assumption allows. If it is ignored, standard errors may be too small and confidence intervals or tests may be misleading. This trial's primary endpoint is a participant count with response, not a repeated event count described in the record, and the registry does not report a count model or over-dispersion assessment. The concept is relevant to count analyses generally but cannot be attributed to this trial's analysis.
More broadly, a statistically complete report would ordinarily clarify the analysis population, handling of missing endpoint data, estimation method, and uncertainty around the result. Those details are not reported in the registry record. The absence of reported methods is not evidence that a particular method was or was not used; it means the method cannot be evaluated from the registry entry.
10. Multiplicity, Missing Data and Analysis Populations
The registry record lists one primary outcome measure: number of participants with response at 6 weeks. It does not report a statistical analysis plan, hypothesis-testing procedure, or any analyses. The record therefore does not establish whether multiple hypotheses were tested, whether any multiplicity adjustment was planned, or whether other outcomes were designated as secondary. It would be inappropriate to infer a multiplicity strategy from the listed endpoint alone.
Missing-data methods are not reported in the registry record. In particular, the entry does not state how participants with unavailable measurements, incomplete follow-up, or unassessable criteria were handled in the primary response classification. This matters because the endpoint requires meeting a condition-specific threshold of criteria. Without a stated rule for missing components, the way incomplete information could affect classification cannot be evaluated.
The analysis population is also not reported in the registry record. The enrolled group comprised 4 participants, but the entry does not state whether all enrolled participants were included in the primary endpoint analysis, whether any were excluded, or whether an alternative population was defined. No participant flow or analysis denominator is reported alongside the primary outcome.
General: Multiplicity arises when several outcomes or hypotheses are examined, increasing the chance of at least one apparently notable result if each is assessed separately. Missing-data decisions can also affect estimates when information is incomplete. These are general considerations, not findings about the study's procedures. With no statistical analysis details or endpoint results reported, neither multiplicity control nor the effect of missing data can be assessed for this trial.
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 | 2 | 4 | 50.0% |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 0% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Bortezomib | 1 of 4 |
Most frequent serious adverse event terms
| Event term | Organ system | Bortezomib |
|---|---|---|
| Pneumatosis Coli | Gastrointestinal disorders | 1 of 4 |
| Thrombocytopenia | Blood and lymphatic system disorders | 1 of 4 |
| Neutropenia | Blood and lymphatic system disorders | 1 of 4 |
| C diff colitis | Infections and infestations | 1 of 4 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Bortezomib |
|---|---|---|
| Nausea | Gastrointestinal disorders | 1 of 4 |
| Cellulitis | Skin and subcutaneous tissue disorders | 1 of 4 |
Serious events with the highest arm-level rate: pneumatosis coli (25.0%), thrombocytopenia (25.0%), neutropenia (25.0%), c diff colitis (25.0%).
The adverse-event record lists 4 participants at risk in the bortezomib group. Serious adverse events affected 2 participants, and other adverse events affected 1 participant. These are participant counts, not estimates of comparative risk: the study has no control group, and the registry entry does not provide a comparison with another treatment or condition.
The listed serious terms are Pneumatosis Coli, Thrombocytopenia, Neutropenia, and C diff colitis, each reported as 25.0%. These term-level figures should be read as the registry lists them; they do not show how events were distributed over time or whether the same participant contributed to more than one term. The record does not report event onset, duration, severity details beyond the serious-event classification, or a causal assessment for these terms.
Deaths are not reported in the registry record. That is different from a reported count of zero. The small group size means the adverse-event experience is limited, and the registry information does not support a precise estimate of event frequency beyond the recorded counts. The safety figures describe reported events in this study; they do not establish whether bortezomib caused an event or how the figures compare with another regimen.
12. What the Result Does, and Does Not, Mean
The registry record establishes that a completed phase 2, single-group study enrolled 4 participants with refractory autoimmune cytopenia(s) after allogeneic stem cell transplantation and assessed a response outcome at 6 weeks. It also records an intervention description and condition-specific response criteria. Those details define the intended clinical and statistical question, but they are not a numerical answer to that question.
The primary response count is not reported in the registry record. Consequently, the posted results do not establish how many participants met the response definition, and they do not permit a numerical estimate of the response rate or its precision. No statistical analysis results are reported. The listed adverse-event counts describe the recorded safety experience, but cannot determine whether the intervention caused the events or how its safety compares with another treatment.
The trial also cannot establish a comparative treatment effect from its design. There is no separate control group, and allocation is listed as NA. Outcomes in a single group may reflect multiple influences, so the study record cannot show what would have happened to a comparable group under a different approach. The absence of masking and the lack of reported assessment details add uncertainty about how outcome judgments were protected from awareness of treatment.
General: A study can be informative about feasibility, observed experience, and the operation of an outcome definition without providing definitive comparative evidence. The strength of any conclusion depends on the actual results, design, precision, and methods. In this case, the registry entry gives the design and endpoint framework, but omits the primary numerical result and analysis details. The conclusion must therefore remain limited to what the record documents: the study was completed, the outcome was defined, and a small participant group was enrolled. It does not report enough information to quantify the primary response outcome.
13. Why This Trial Matters Statistically
This trial is statistically notable because it applies a participant-level response definition to refractory autoimmune cytopenia(s) after allogeneic stem cell transplantation, a setting represented in the registry by a single-group study with 4 participants. The endpoint combines several kinds of evidence, including blood-count stabilization, laboratory and antibody findings, transfusion frequency, and GCSF dose. The condition-specific rules make the endpoint definition important to any interpretation of response.
The entry also illustrates why an outcome definition and an outcome result are not interchangeable. A detailed criterion can explain what would count as a response, but without the number of participants meeting that criterion it cannot answer how often response occurred. No numerical primary result or inferential analysis is reported in the registry record. This prevents assessment of both the observed result and its statistical precision.
The single-group design is another key statistical feature. It can record experience among treated participants, but it does not provide a randomized control comparison. Therefore, even a reported change in the group would not alone identify the change attributable to the treatment. The small enrollment further limits the amount of information the study can contribute about outcome variability and safety.
Finally, the registry's planning illustrations use assumptions for a hypothetical two-arm calculation, including equal allocation and a normal approximation. Their presence does not change the trial's single-group design and does not constitute observed power. Separating design assumptions, observed outcomes, and comparative evidence is essential when reading the record. Here, the design and measurement framework are described, while the primary result needed to quantify the study's outcome is not reported.
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 most direct limitation of the registry entry is that the numerical primary response result is not reported. The endpoint is clearly described, but no response count, nonresponse count, analysis denominator, or uncertainty estimate is available in the record. This prevents readers from quantifying the primary outcome.
Enrollment was 4 participants, and there was no separate control group. The study therefore offers a limited descriptive experience and cannot make a randomized comparison. The record does not report participant characteristics beyond the condition context, the distribution across the autoimmune cytopenia types, or further eligibility details. Those omissions constrain assessment of how the enrolled group relates to the population addressed by the study question.
The response definition depends on different criteria for autoimmune hemolytic anemia, autoimmune neutropenia, and autoimmune thrombocytopenia. The registry does not report which criteria applied to each participant, component-level results, missing-measurement handling, or adjudication procedures. The arm description also names rituximab and plasmapheresis alongside bortezomib, without clarifying how those details relate to the regimen or whether they applied uniformly.
The record does not report a statistical analysis plan, analysis population, or methods for handling missing data. It also does not report event attribution or deaths. These are limits of what can be established from the registry record, not evidence that procedures were absent or that unreported events did not occur. Taken together, the missing outcome and methods details prevent a full statistical appraisal of efficacy, precision, and safety.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Bortezomib to Treat Significant Complication of HSCT — NCT01929980.
- Registry record last updated 2016-10-24; status last verified 2016-10.
- Results first posted 2016-10-24.
- 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
NCT01929980, titled Bortezomib to Treat Significant Complication of HSCT, is recorded as a completed phase 2, single-group study sponsored by Children's Hospital Medical Center, Cincinnati. The study enrolled 4 participants and lists a start of 2012-07 and primary completion of 2014-05. Masking is recorded as none, with allocation listed as NA.
The intervention description specifies bortezomib dosing and also mentions rituximab and plasmapheresis. The primary outcome is number of participants with response at 6 weeks, defined through condition-specific criteria. The numerical primary response result and statistical analyses are not reported in the registry record. Adverse-event listings include serious and other affected-participant counts, while deaths are not reported in the registry record.