Busulfan, Melphalan, and Thiotepa Followed By a Donor Stem Cell Transplant in Treating Patients With High-Risk Ewing's Tumors: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Busulfan, Melphalan, and Thiotepa Followed By a Donor Stem Cell Transplant in Treating Patients With High-Risk Ewing's Tumors (NCT00357396), a na phase 2 study. The primary outcome is Overall Objective Response.

2. Clinical Question

Statistically, the question concerns the observed response experience in a treated group, not a randomized estimate of the difference between treatments. Without a concurrent control group, a response count would describe what was recorded among participants receiving the regimen. It would not, by itself, show what would have happened to comparable patients under another treatment or without the regimen.

The brief summary gives the rationale for combining chemotherapy, donor transplantation, and medicines intended to prevent graft-versus-host disease. That background explains the treatment strategy, but it does not supply evidence about the endpoint. The registry record does not report the response results or the criteria used to classify response. Consequently, the primary clinical question is identifiable, while its answer cannot be read from the posted outcome information.

3. Trial Design

This is a phase II, single-group study sponsored by Memorial Sloan Kettering Cancer Center. The registry lists the study as completed, with enrollment of 10. The recorded start is 2005-06 and primary completion is 2009-10. These dates describe the registry record; they do not establish when every participant was enrolled, treated, or assessed.

The treatment strategy combines intravenous busulfan, melphalan, and thiotepa as a myeloablative preparative regimen, followed by an allogeneic hematopoietic stem cell transplant from a donor. The listed interventions also include allogeneic bone marrow transplantation, peripheral blood stem cell transplantation, and graft-versus-host disease prophylaxis or therapy. The registry’s arm description refers to a chemotherapy regimen followed by donor stem cell transplantation. Detailed treatment delivery beyond the available description is not reported in the registry record.

Allocation is listed as not applicable, masking as none, and the model as single-group. This is therefore not a randomized comparison. The related donors recorded in the safety information are not an untreated or alternative-treatment control group. A contrast between patients and donors would not answer whether the regimen changes response among patients with high-risk Ewing’s tumors.

The primary outcome is overall objective response, measured in participants, with a timeframe of 2 years. Although the registry lists one outcome measure, it records no analyses. The statistical analysis plan, including the response criteria, rules for handling assessments outside the timeframe, and approach to incomplete follow-up, is not reported in the registry record. A protocol-specific sample-size justification or interim-analysis plan is also not reported. The design and enrollment describe the study, but do not establish the precision of an outcome estimate that is not posted.

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:

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 Overall Objective Response, measured over 2 years.

The primary endpoint is overall objective response, expressed as a number of participants, with assessment over a timeframe of 2 years. It is a binary outcome at the participant level: a participant is classified as having or not having the defined response. The registry record does not state the response criteria, which tumor assessments were used, or whether response required confirmation. Those details are important because the definition determines which observations count toward the endpoint.

In general, objective response is used to describe whether tumors meet prespecified criteria for response to treatment. A count can communicate how many participants met those criteria in the study group. If the count and analysis population are reported, readers can consider the observed response alongside the number assessed and the uncertainty in the estimate. The endpoint does not, by itself, establish that a treatment caused the response; a comparison design and an appropriate analysis are needed to estimate a treatment contrast.

The registry identifies the endpoint and timeframe but posts no response count or analysis estimate. It therefore does not support a numerical description of the observed response, nor an assessment of how precisely response was estimated. The endpoint definition and population included in its analysis are also not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does a binary endpoint represent?

General statistical explanation: A binary endpoint classifies each participant into a defined outcome category, such as response or no response. The number classified as having an event is a count; it is not automatically a rate. To interpret a count as a proportion, the relevant analysis denominator and the rules for including participants must also be clear. For this study, the registry names overall objective response and describes the unit as participants, but does not post the count, denominator, or response definition.

Outcome definitions matter before calculation. If response criteria, assessment timing, confirmation requirements, or handling of unevaluable assessments are unclear, different analytic choices could produce different summaries. Such choices should follow a prespecified plan. The protocol-specific criteria and rules are not reported in the registry record, so they cannot be reconstructed from the endpoint title alone.

What can a single-group study estimate?

General statistical explanation: A single-group study can describe outcomes observed in the enrolled group, provided the outcome data and analysis population are reported. It does not inherently estimate a treatment contrast, because it has no concurrent group receiving a different strategy. Comparisons with historical experience may be considered in some settings, but they require an explicitly defined external reference and assumptions about comparability. No such comparison is reported in the registry record.

The registry lists the model as single-group and allocation as not applicable. Thus, the study should not be interpreted as randomized evidence comparing treatments. The donor group in the adverse-event record has a different role and does not serve as a response control group for the patients.

How should uncertainty be understood?

General statistical explanation: An estimate is subject to sampling variability: another group of eligible participants could have a different observed result, even if recruited and assessed under similar procedures. A confidence interval expresses uncertainty around an estimate under a specified statistical model. It does not account automatically for bias from missing outcomes, a poorly defined endpoint, or differences between the study participants and a target population.

No primary response estimate or interval is posted. The uncertainty around response therefore cannot be evaluated quantitatively from the registry record. A confidence interval cannot substitute for knowing the endpoint definition, analysis denominator, or missing-data approach; all contribute to understanding what the estimate represents.

What do the planning assumptions mean?

General statistical explanation: Sample-size planning asks how much information a future study might need to detect a specified effect under stated assumptions. It is not a measurement of what the completed study achieved. The planning assumptions associated with the record specify a two-sided significance level of 0.05, equal allocation between two hypothetical arms, and a normal approximation. They also describe effects as fractions of the observed effect. For time-to-event outcomes, the stated approach uses a total number of events; for other outcomes, it gives participants per arm.

Those are planning illustrations, not the study’s reported design rationale and not observed power. The completed study is listed as single-group, whereas the planning assumptions describe equal allocation between two arms. These assumptions therefore should not be mistaken for the trial’s actual allocation or evidence that it tested a two-arm contrast. A protocol-specific sample-size justification is not reported in the registry record.

When a planning illustration is based on an observed effect, its output depends on that effect estimate and the assumptions used. It does not show the probability that the completed study’s conclusion is correct, and it cannot repair the absence of a reported primary result. Because the registry record does not post a primary response estimate, the stated assumptions alone do not make the response effect or its uncertainty interpretable.

Why does over-dispersion matter in general?

General statistical explanation: Over-dispersion means that observed variability is greater than a model expects. If a model assumes less variability than the data contain, standard errors can be too small and confidence intervals too narrow. Methods that allow for extra variability may be needed when the outcome structure supports them. The registry record does not report an over-dispersion assessment or a statistical model for the primary endpoint. Since the endpoint is listed as a participant count and no analysis is posted, there is no basis for describing a trial-specific over-dispersion adjustment.

Overall, the statistical methods relevant to interpreting response are only partly specified. The registry states the design and primary endpoint, but not the response definition, analysis population, estimator, interval method, or missing-data rules. General statistical principles can explain why those elements matter; they cannot supply the unreported analysis choices or outcome values.

10. Multiplicity, Missing Data and Analysis Populations

The registry record does not report a statistical analysis plan addressing multiplicity, missing data, or analysis populations. It lists overall objective response as the primary outcome, but does not describe whether additional endpoints or repeated analyses were planned, how outcomes were prioritized, or whether adjustments for multiple testing were intended. Without that information, the approach to controlling the chance of false-positive findings across analyses cannot be assessed.

General statistical explanation: Multiplicity arises when several hypotheses, endpoints, timepoints, or subgroup comparisons are examined. Considering many results can increase the chance that at least one appears notable by chance. Prespecified primary outcomes and analysis strategies help readers distinguish confirmatory questions from exploratory ones. The registry’s identification of a primary outcome clarifies its stated priority, but does not reveal the full analysis plan.

The record also does not state how incomplete response assessments, withdrawals, or participants without evaluable follow-up were handled. In general, missing outcomes can affect interpretation if the likelihood of missingness is related to prognosis or response. Analyses may use different assumptions about missing observations, and those assumptions can change the meaning of the result. No specific imputation, exclusion, or sensitivity-analysis method is reported.

The analysis population is not described. Enrollment of 10 does not establish how many participants were included in the primary endpoint analysis, and it should not be used as a denominator for an unreported response result. These omissions limit reproducibility and make it difficult to assess potential bias or compare the result with other studies.

11. 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: hypoxia (50.0%), renal failure (33.3%), constitutional symptoms, other (16.7%), death not assoc w ctcae term-disease prog nos (16.7%), infection w/ gr 3/4 neut, abdomen nos (16.7%).

The safety record separates patients with high-risk Ewing’s sarcoma family tumors from related donors. In the patient group, the registry lists 6 at risk for serious adverse events and 4 affected; it also lists 6 at risk for other adverse events and 6 affected. For related donors, it lists 4 at risk and 0 affected for serious adverse events, and 4 at risk and 0 affected for other adverse events. These are the record’s event-category counts, not findings about the primary response endpoint.

The listed serious adverse-event terms include hypoxia at 50.0%, renal failure at 33.3%, constitutional symptoms, other at 16.7%, death not associated with a CTCAE term—disease progression, NOS at 16.7%, infection with grade 3/4 neutropenia, abdomen, NOS at 16.7%, and infection with grade 3/4 neutropenia, blood at 16.7%. The registry does not give enough detail in this record to interpret these percentages as risks for a broader population or to determine their exact relationship to treatment exposure.

Adverse events occurring during a study do not, by themselves, establish causation. The registry does not report death counts in the adverse-event group summaries. Safety counts should therefore be read as descriptive registry entries, with their group labels and denominators kept in view.

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

The record shows that a phase II, single-group study evaluated a chemotherapy-based regimen followed by donor stem cell transplantation in patients with high-risk Ewing’s tumors. It identifies overall objective response by 2 years as the primary outcome and records enrollment of 10. It also contains safety information for patients and related donors. These registry entries describe the study’s intent and some reported events.

The record does not show whether participants had an objective response. No response count, response estimate, confidence interval, or primary analysis is posted. It is therefore not possible to describe the observed response frequency, its precision, or how the results compare with a benchmark from the registry record alone. The endpoint criteria, analysis population, and handling of missing assessments are also not reported.

Even a complete response summary from a single group would not, by itself, show that the treatment caused the outcome. A comparison with another treatment would require a suitable comparator and a design and analysis that support that contrast. This registry record lists no concurrent patient control group, and the related donors are not a treatment comparator.

Safety counts can describe events recorded in the registry, but they do not establish that the treatment caused those events. Nor do the safety entries answer the primary response question. Conclusions should remain limited to the information actually reported: the study design, treatment strategy, endpoint and timeframe, enrollment, and the listed safety counts and terms. Claims about response or comparative benefit are not supported by the posted results in this record.

13. Why This Trial Matters Statistically

Statistically, the record illustrates the difference between a clearly named research question and a reportable result. The primary endpoint is identifiable: overall objective response in participants at 2 years. Yet the registry does not post the endpoint analysis. Without an outcome count and an analysis denominator, readers cannot estimate response or assess its uncertainty, regardless of how clearly the treatment strategy is described.

The single-group design also defines the scope of any possible inference. It can support a descriptive account of outcomes in the treated group if those outcomes are reported. It does not provide a randomized comparison with another treatment. Keeping that distinction clear prevents a within-group result from being mistaken for an estimate of comparative effectiveness.

The record also highlights why endpoint definitions and analysis populations are essential. A count is interpretable only when readers know what qualified as response, which participants were assessed, and how incomplete data were handled. Those details are not reported. Without them, even a posted count could be difficult to reproduce or compare across studies.

Finally, sample-size planning assumptions are not evidence of observed power, and planning scenarios should not be confused with a completed trial’s outcome. The assumptions associated with the record describe a hypothetical two-arm allocation, while the study itself is listed as single-group. A careful statistical reading therefore separates the stated design, any planning illustration, the safety record, and the unreported primary result.

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.

Several limitations specific to this record restrict interpretation. The primary endpoint is named, but its response criteria and analysis result are absent. The registry lists enrollment of 10, but does not state how many participants contributed to the endpoint analysis or had an evaluable assessment. The observed response and its precision therefore cannot be determined.

The study is listed as single-group, with no concurrent patient comparator. Any reported outcomes from that design would be descriptive of the treated group and could not alone establish a comparative treatment effect. The related donors listed in the safety record do not resolve this design limitation.

Details needed to judge outcome validity are not reported in the registry record, including the analysis population, rules for incomplete assessments, and the statistical method used for the primary endpoint. The record also does not report a protocol-specific sample-size justification, interim-analysis plan, or full statistical plan. These gaps limit assessment of prespecification and reproducibility.

The safety summaries are descriptive and do not establish treatment causation. Death counts are not reported in the adverse-event group summaries. The record’s planning assumptions describe a two-arm illustration even though the trial model is single-group; those assumptions should not be interpreted as the completed study’s design or as observed power. Together, these limitations mean the registry record supports a description of the study’s stated design and some safety entries, but not a conclusion about the primary response outcome.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Busulfan, Melphalan, and Thiotepa Followed By a Donor Stem Cell Transplant in Treating Patients With High-Risk Ewing's Tumors — NCT00357396.
• Registry record last updated 2015-11-25; status last verified 2015-10.
• Results first posted 2015-11-25.
• 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.

18. Record Summary

The registry describes a completed phase II, single-group study sponsored by Memorial Sloan Kettering Cancer Center. It records enrollment of 10, a start of 2005-06, and primary completion in 2009-10. The intervention combines busulfan, melphalan, and thiotepa with an allogeneic donor stem cell transplant. The primary outcome is overall objective response among participants, with a 2-year timeframe.

No primary outcome analysis is reported. The record therefore does not provide a response count, estimate, or measure of precision. It lists safety counts for patients and related donors and percentages for serious adverse-event terms. The single-group design offers no concurrent patient comparator, and the record does not report key endpoint and analysis details such as response criteria, analysis population, or missing-data handling. The posted information establishes the study’s stated question and design, but does not answer the primary response question.