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 Thymoglobulin and Total Lymphoid Irradiation for Hematologic Malignancies (NCT00476229), a non-randomized na study. The primary outcome is Composite Success Rate.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT00476229 |
| Phase | NA |
| Condition | Lymphoma, Leukemia |
| Allocation | Non-Randomized |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 20 |
| Arms in the primary outcome | n/a |
| Lead sponsor | M.D. Anderson Cancer Center |
| Results posted | Yes |
2. Clinical Question
Population
Participants with lymphoma or leukemia undergoing allogeneic transplantation for lymphoid malignancies. The registry record does not report further eligibility details or participant characteristics.
Intervention
The recorded regimen combined total lymphoid irradiation, Thymoglobulin, Rituximab, and blood stem cell transplant (BSCT). The arm description specifies the regimen’s listed schedule and doses.
Comparator
There was no separate comparator group: the allocation is nonrandomized and the model is single-group. The registry record does not describe a control arm.
Primary question
Was the composite success rate likely to be at least 40%? Success required being alive at day 100, having no Grade 3–4 graft-versus-host disease (GVHD), having no Grade 4 toxicity unrelated to infection, and having engrafted.
The study record frames the primary question as whether a particular combination of outcomes could meet a stated threshold. It does not ask for a randomized comparison between the regimen and another treatment. Because there is only one study group, the primary endpoint describes the proportion meeting all of the listed conditions within that group; it cannot, by itself, isolate the effect of any one component of the regimen.
The registry identifies lymphoma and leukemia as the conditions and describes the transplant context in the official title. It does not report further details about the participants’ disease status, prior treatments, or other clinical characteristics. Those omissions limit how specifically the study population can be characterized from the registry record.
The secondary objectives concern chronic GVHD, overall survival, and disease-free survival. The record does not report results for those objectives. It also does not report the observed value of the primary composite success rate, so the threshold question cannot be answered from the posted results.
3. Trial Design
This was a completed, nonrandomized, single-group study sponsored by M.D. Anderson Cancer Center. The registry lists the phase as NA and describes enrollment as 20. The record gives a start date of 2006-06 and a primary completion date of 2009-05. It does not report a separate comparator group, and masking is listed as none.
The study combined total lymphoid irradiation, Thymoglobulin, Rituximab, and peripheral blood stem cell infusion. The arm description names the group “Radiation + Chemotherapy + BSCT” and describes total lymphoid irradiation (2 times) at 80 cGy daily for five days, Thymoglobulin 1.5 mg/kg intravenously for 5 days, Rituximab 375 mg/m^2 intravenously on 4 different days, and blood stem cell transplant (BSCT). These are descriptions of the recorded regimen, not evidence about how each component contributed to outcomes.
The primary endpoint was assessed at day 100 and defined as a composite of survival, GVHD, toxicity, and engraftment criteria. The primary objective was to determine whether the composite success rate was likely to be at least 40%. Secondary objectives were the cumulative incidence of chronic GVHD, overall survival, and disease-free survival.
The registry describes the primary endpoint analysis as per protocol and notes that one participant was inevaluable. It does not report a randomized allocation process, an allocation ratio, a masking procedure, or a statistical analysis plan. It also does not report a rationale for the enrollment target or a sample-size justification. Because the design has no control group, the study can describe outcomes in this group but cannot provide a direct between-group treatment contrast.
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 | Radiation + Chemotherapy + BSCT |
|---|---|
| STARTED | 20 |
| COMPLETED | 19 |
| NOT COMPLETED | 1 |
Reasons for not completing this period:
| Reason | Radiation + Chemotherapy + BSCT |
|---|---|
| Progressive shortness of breath | 1 |
Analysis population for the primary outcome, as defined in the registry: Analysis was per protocol. One participant was inevaluable.
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 | Radiation + Chemotherapy + BSCT |
|---|---|---|
| Participants analysed | 20 | |
| Age Continuous | years | 30 (20 to 40) |
| Sex: Female, Male: Female | Participants | 10 |
| Sex: Female, Male: Male | Participants | 10 |
| Region of Enrollment: United States | participants | 20 |
6. Primary Endpoint
The registry lists the primary outcome as Composite Success Rate, measured over Baseline to Day 100, assessment at Day 100.
| Element | Registry entry |
|---|---|
| Result type | Number |
| Measure of spread | not applicable |
| Unit | Percentage of participants |
| Endpoint classification | Binary Endpoint |
The primary endpoint is a composite success rate assessed at day 100. A participant counts as a success only if all specified conditions are met: alive at day 100, without Grade 3–4 GVHD, without Grade 4 toxicity unrelated to infection, and engrafted. The record states that toxicity grades follow Common Toxicity Criteria (CTC) Common Terminology Criteria for Adverse Events (CTCAE), version 3.0.
Composite endpoints are used to capture several clinically relevant outcomes in a single measure. In general, they can summarize whether participants meet a broader definition of success, rather than focusing on only one event. Their interpretation depends on the exact components: failure to meet any one condition prevents classification as a composite success, even if the other conditions are met. The endpoint therefore does not reveal, on its own, which component most often determined the result.
The study’s stated objective sets 40% as the level the composite success rate was intended to be assessed against. The registry record does not report the observed percentage or the component-specific outcomes. It is therefore not possible from the posted results to assess whether the endpoint met that objective or to understand the separate contribution of survival, GVHD, toxicity, and engraftment.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record describes a study with a prespecified composite day-100 outcome and an objective framed around a 40% success-rate threshold. However, it does not report the observed composite success rate. Without that result, the central numerical question—whether the rate was likely to be at least 40%—cannot be evaluated from the posted results. The record also does not provide a confidence interval or a statistical test for this endpoint.
The record identifies the primary endpoint as a percentage of participants and says that the analysis was per protocol. It notes that one participant was inevaluable, but does not report the number included in the endpoint analysis or explain the handling of the inevaluable participant. Enrollment is listed as 20; that figure should not be assumed to be the denominator for the endpoint because the record separately describes the per-protocol population and an inevaluable participant.
The study has no randomized comparator. Its primary endpoint, if reported, would describe the composite outcome in the study group; it would not establish how outcomes would have differed under another regimen or under no treatment. The multiple regimen components also mean that an outcome could not be attributed to any single component using this design alone.
The registry lists secondary objectives for chronic GVHD, overall survival, and disease-free survival, but reports no results for them. It also reports no analysis count. As a result, the record does not support interpretation of time-to-event outcomes, follow-up completeness, or the uncertainty around any secondary estimates. The primary endpoint is the only outcome measure identified in the record, yet its numeric result is absent.
The adverse-event information is separate from the primary endpoint. It lists serious and other adverse-event counts for the study group and identifies increased bilrubin among the top serious terms. Those figures do not substitute for the missing composite endpoint result. They also do not describe whether any adverse event overlapped with a primary-endpoint component or how adverse events were adjudicated.
Overall, the registry record supplies the design, endpoint definition, and some safety counts, but not the primary efficacy result or inferential statistics. Any conclusion about the observed rate, its precision, or whether the objective was reached would require information not reported in the registry record.
9. Statistical Methods Explained
What does a confidence interval communicate?
General: A confidence interval expresses the uncertainty around an estimate. For a percentage, it helps distinguish a relatively precise estimate from one compatible with a broad range of possible underlying rates. A point estimate alone cannot show that uncertainty. The registry record does not report a confidence interval for the composite success rate, and it does not report the observed rate needed to interpret one.
The objective refers to whether the rate was likely to be at least 40%. In general, evaluating an estimate against a threshold requires attention to both the estimate and its uncertainty, as well as the statistical method used to make that assessment. The registry record does not report a test, interval, decision rule, or other inferential result for this threshold. The objective statement is not itself evidence that the threshold was reached.
What does a composite endpoint capture?
General: A composite endpoint combines multiple criteria into one outcome. Here, success requires being alive at day 100, avoiding the specified GVHD and toxicity grades, and engrafting. Because every condition must be met, the overall rate summarizes joint success across the criteria. It does not identify which criterion was most influential. Component-specific results would be needed to examine that question, and they are not reported in the registry record.
The composite also uses a defined time point: baseline to day 100, with assessment at day 100. This makes the endpoint a status assessment over that stated period, rather than a report of longer-term survival. The registry record lists chronic GVHD and survival outcomes as secondary objectives, but it does not report their results or specify their analysis details.
How should the study design shape interpretation?
General: A single-group design estimates outcomes for the group receiving the recorded regimen. Without a concurrent comparator, it cannot separate the regimen’s effect from other explanations for observed outcomes, such as participant characteristics or the course of disease. Nonrandomized allocation also means there is no randomized assignment to balance such factors across treatment groups. In this study, there is no separate control arm to support a direct comparative estimate.
The regimen includes radiation, drugs, and a stem cell infusion. Even if an outcome estimate were available, this design would not identify the contribution of each component. The record does not describe an analysis that separates component effects.
What can be inferred from a percentage?
General: A percentage is the number meeting an outcome divided by the relevant analysis denominator. Interpretation depends on how the denominator was defined and how missing or unevaluable outcomes were handled. Here, the registry says the primary analysis was per protocol and notes one participant was inevaluable, but it does not report the endpoint denominator or the handling rule. Enrollment is recorded as 20, but the endpoint denominator cannot be inferred from enrollment alone.
For safety, the registry lists 19 participants at risk for serious adverse events and 1 affected, and lists 19 at risk for other adverse events and 19 affected. These are safety figures, not the denominator for the primary composite endpoint. The record also lists increased bilrubin at 5.3% among the top serious terms. Each figure should be read within its own recorded safety category; the record does not explain how the term-level percentage was calculated.
What do the planning assumptions mean?
General: Sample-size calculations are planning tools that estimate how many participants may be needed under specified assumptions. They are not observed outcomes and should not be treated as observed power. The planning assumptions associated with this record describe a two-sided significance level of 0.05, equal allocation between two arms, a normal approximation, and an effect to detect defined as a stated fraction of the observed effect. The assumptions also distinguish calculations for time-to-event outcomes, expressed as total events, from other calculations, expressed as participants per arm.
Those assumptions are described as a planning illustration computed from the observed effect, not as the study’s own design. The record does not report the original sample-size justification or a statistical plan establishing that the study was designed with those assumptions. Nor does it provide the inputs or resulting sample-size values in the registry entries. The illustration therefore cannot be used to reconstruct the trial’s design rationale or infer the precision of its results.
More generally, planning calculations depend on the chosen effect, outcome definition, allocation, significance level, and approximation. A calculation based on a fraction of an observed effect is retrospective planning context, not proof that the study had adequate power or that a finding was present. No such adequacy conclusion can be drawn from the information reported in this registry record.
10. Multiplicity, Missing Data and Analysis Populations
The registry record identifies one primary outcome measure, the composite success rate, and lists secondary objectives for chronic GVHD, overall survival, and disease-free survival. It does not report results for those secondary objectives. The record does not describe a multiplicity adjustment, a hierarchy among outcomes, or a procedure for controlling the chance of false-positive findings when considering multiple outcomes. These details are not reported in the registry record.
The primary endpoint analysis is described as per protocol. The record notes that one participant was inevaluable, but does not explain why the participant was inevaluable, whether the participant was excluded from the endpoint analysis, or how missing component data were handled. The number analyzed for the primary endpoint is not reported in the registry record. Enrollment is listed as 20, but that does not establish the denominator for the per-protocol analysis.
The registry does not describe an intention-to-treat analysis, imputation, sensitivity analysis, or other missing-data method. It also does not explain whether incomplete day-100 assessments could affect classification of the composite outcome. Since success requires all endpoint components, the treatment of an unavailable component could matter to the resulting percentage.
Analysis populations and missing-data rules influence how an estimate should be interpreted and how broadly it may apply. Without those details and without the observed endpoint result, readers cannot assess the sensitivity of the primary finding to exclusions or missing information. A full statistical analysis plan and participant-level accounting are not reported in the registry record.
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 |
|---|---|---|---|
| Radiation + Chemotherapy + BSCT | 1 | 19 | 5.3% |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 5% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Radiation + Chemotherapy + BSCT | 19 of 19 |
Most frequent serious adverse event terms
| Event term | Organ system | Radiation + Chemotherapy + BSCT |
|---|---|---|
| increased bilrubin | Hepatobiliary disorders | 1 of 19 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Radiation + Chemotherapy + BSCT |
|---|---|---|
| Gastrointestinal other | Gastrointestinal disorders | 13 of 19 |
| nausea | Gastrointestinal disorders | 9 of 19 |
| increased ALT | Hepatobiliary disorders | 9 of 19 |
| headache | Nervous system disorders | 9 of 19 |
| hyperglycemia | Metabolism and nutrition disorders | 8 of 19 |
| low blood pressure | Cardiac disorders | 7 of 19 |
| fatigue | General disorders | 7 of 19 |
| other general disorders | General disorders | 7 of 19 |
| fever | General disorders | 7 of 19 |
| increased Alkaline phosphatase | Hepatobiliary disorders | 7 of 19 |
Serious events with the highest arm-level rate: increased bilrubin (5.3%).
The registry lists a serious adverse-event group titled “Radiation + Chemotherapy + BSCT.” For serious adverse events, it records 19 participants at risk and 1 affected. For other adverse events, it records 19 at risk and 19 affected. These are separate safety categories as recorded; they should not be combined or treated as the primary endpoint denominator.
The top serious adverse-event term is listed as “increased bilrubin” at 5.3%. The record does not provide further context for this term-level percentage, such as its calculation details, severity breakdown, timing, or relationship to treatment. It also does not report deaths in the safety listing.
Adverse-event counts describe events captured under the registry’s safety reporting categories. They are not, by themselves, evidence that an event was caused by the regimen. The registry record does not report attribution details, the event collection period, or a comparison group. The safety figures therefore describe what is recorded for this group but do not support a comparative safety assessment. They also do not establish how any adverse event affected classification on the composite endpoint.
12. What the Result Does, and Does Not, Mean
The registry record defines a clinically broad day-100 composite and states that the study aimed to determine whether its success rate was likely to be at least 40%. However, the numeric result for that endpoint is not reported in the registry record. The central question cannot therefore be answered from the posted results, and the precision of any estimate cannot be assessed.
The design is a nonrandomized, single-group study. In general, a result from such a design describes outcomes among participants in that group; it does not provide a randomized comparison with another treatment or establish what would have happened under a different approach. Because the regimen combines several interventions, the design also cannot identify the separate effect of each component.
The composite definition requires participants to meet all of its conditions. A composite rate, if reported, would not show which condition most often prevented success. Component-specific outcomes would be needed to understand the contributions of survival, GVHD, toxicity, and engraftment. Those component results are not reported in the registry record.
The registry lists secondary objectives and safety figures, but does not report results for chronic GVHD, overall survival, or disease-free survival. Safety counts are not substitutes for the missing primary endpoint estimate. The record also does not provide the endpoint denominator, a confidence interval, a p-value, or the handling rules for the inevaluable participant.
Accordingly, the record supports a description of the study design, planned outcome definition, and listed safety counts. It does not support a conclusion that the 40% objective was or was not achieved, a claim about the comparative effect of the regimen, or an assessment of the statistical precision of the primary endpoint.
13. Why This Trial Matters Statistically
This study illustrates an important distinction between a clearly defined endpoint and a reported endpoint result. The registry specifies a composite success definition and a threshold of 40%, so the intended primary question is understandable. Yet the observed composite rate and its uncertainty are not reported. Without those results, the objective cannot be evaluated statistically from the registry record.
It also highlights how design determines the scope of inference. A nonrandomized, single-group study can describe outcomes within its group, but it does not furnish a concurrent comparison for judging how outcomes differ under another regimen. The combined intervention further limits conclusions about which component might be associated with an outcome. These are design constraints, not defects that can be remedied by interpreting a percentage differently.
The composite endpoint is another useful statistical example. Combining survival, GVHD, toxicity, and engraftment creates a joint measure, but the overall rate can conceal variation across its components. Component-specific reporting and transparent handling of unevaluable outcomes are important for understanding what the composite represents. Here, one participant is noted as inevaluable, while the endpoint denominator and missing-data approach are not reported.
Finally, the record distinguishes trial objectives from the analysis details needed to assess them. It lists secondary aims and safety observations, but does not report the inferential procedures or outcome results needed to quantify uncertainty. The study therefore demonstrates why readers need the observed estimate, its denominator, and its precision—not only the endpoint definition—to judge what the data establish.
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 primary limitation for interpretation is that the registry record does not report the observed composite success rate. It also does not report a confidence interval, test result, or endpoint denominator. Consequently, the main objective cannot be evaluated from the posted results.
The study is nonrandomized and single-group, with no separate comparator. Outcomes within the group cannot establish a treatment contrast, and the design cannot determine the contribution of individual regimen components. The record does not describe participant characteristics beyond the conditions of lymphoma and leukemia, limiting assessment of which patients the findings might represent.
The primary analysis is described as per protocol, and one participant is identified as inevaluable. The record does not explain the reason for inevaluability, the analysis-population rules, or how missing endpoint information was handled. It does not report a statistical analysis plan or a sample-size justification. The planning assumptions associated with a retrospective illustration are not a substitute for those trial-specific details.
The registry lists secondary objectives but does not report their results. It also does not provide outcome-specific follow-up details, multiplicity procedures, or component-level results for the composite. Safety entries include counts and a listed serious term, but further details on attribution, timing, and event definitions are not reported in the registry record. These omissions restrict interpretation of efficacy, precision, missing data, and safety beyond the figures explicitly listed.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Thymoglobulin and Total Lymphoid Irradiation for Hematologic Malignancies — NCT00476229.
- Registry record last updated 2012-08-07; status last verified 2012-08.
- Results first posted 2011-08-09.
- 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
NCT00476229 is a completed, nonrandomized, unmasked, single-group study sponsored by M.D. Anderson Cancer Center. The registry lists the phase as NA, enrollment as 20, a start date of 2006-06, and primary completion in 2009-05. The study concerns lymphoma and leukemia and describes a regimen of total lymphoid irradiation, Thymoglobulin, Rituximab, and blood stem cell transplant.
The primary outcome is a composite success rate assessed at day 100, with success requiring survival, no specified severe GVHD or toxicity, and engraftment. The objective was to determine whether the rate was likely to be at least 40%. The primary analysis is described as per protocol, with one participant noted as inevaluable.
The registry record does not report the primary endpoint result, its denominator, or an uncertainty estimate. Secondary objectives are listed without results. Safety listings record 1 affected among 19 at risk for serious adverse events and 19 affected among 19 at risk for other adverse events; increased bilrubin is listed at 5.3% among top serious terms.