Safety Study of Bone Marrow Transplant Using Mismatched Tissue Followed by Chemotherapy: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Safety Study of Bone Marrow Transplant Using Mismatched Tissue Followed by Chemotherapy (NCT00796562), a na phase 2 study. The primary outcome is Engraftment as Measured by Donor Chimerism.

2. Clinical Question

3. Trial Design

This was a Phase II, single-group study of myeloablative conditioning and partially HLA-mismatched bone marrow transplantation for patients with hematologic malignancies. The registry lists enrollment of 107 participants and a completed status. The recorded study dates are 2008-12 for start and 2014-06 for primary completion.

The study is not described as randomized: allocation is listed as NA, and the design model is single group. Masking is listed as none. These features mean that the registry record does not describe a concurrently assigned control group against which the transplant approach could be compared. Outcomes observed in this group therefore cannot, by themselves, separate treatment effects from differences in patient characteristics, clinical care or other influences.

The listed interventions are busulfan, cyclophosphamide and total body irradiation. The arm description names a myeloablative haploidentical bone marrow transplant. It gives a regimen for participants other than those with acute lymphoblastic leukemia and lymphoblastic lymphoma, then begins a separate description for participants with acute lymphocytic leukemia without completing the details. The complete treatment schedule and subgroup-specific regimens are not reported in the registry record.

The primary outcome is donor chimerism at Day 60. Secondary outcomes listed are non-relapse mortality, acute and chronic graft-versus-host disease, survival and relapse. Six outcome measures are recorded, but the registry record does not provide the results for those additional outcomes in the information available for interpretation. Detailed eligibility criteria, the full protocol, and the planned statistical analysis are not reported in the registry record.

4. Participant Flow and Accounting

The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.

Before assignment: 11 participants were screen failures.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: 8 participants were not evaluable for this outcome because they died prior to Day 60.

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: The entire set of participants was analyzed as one group, and the analysis was planned this way from the beginning of the study.

6. Primary Endpoint

The registry lists the primary outcome as Engraftment as Measured by Donor Chimerism, measured over Day 60.

The primary endpoint is the percentage of participants who achieved donor chimerism of at least 95% at Day 60. Donor chimerism describes the extent to which blood-forming cells after transplantation are from the donor. The endpoint uses a threshold, so participants are classified according to whether their measured donor chimerism reached that threshold at the specified assessment time.

This kind of measure is used to describe early donor-cell establishment after transplantation. It is a biological outcome at a defined follow-up point, not a direct measure of survival, relapse or long-term disease control. Those outcomes are listed separately as secondary outcomes in the registry record.

The registry specifies a 95% confidence interval for the endpoint, but the observed percentage and interval are not reported in the registry record. Eight participants were not evaluable for this outcome because they died before Day 60. The record does not give the endpoint result among evaluable participants, explain how deaths were handled in any analysis, or describe whether additional participants lacked a measurement for another reason. As a result, the endpoint's observed frequency and precision cannot be assessed from the recorded information.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

Design and comparison. The registry classifies this as a single-group study, with allocation listed as NA and masking listed as none. In general, a single-group design describes outcomes among participants receiving the study approach without a concurrent control arm. That can be useful for characterizing observed outcomes, but it does not provide a randomized estimate of the difference between treatment strategies. Other explanations for an observed outcome cannot be ruled out through a within-trial comparison when no comparator group is present.

Binary endpoint. The primary endpoint is expressed as a percentage of participants who reached the specified donor-chimerism threshold by Day 60. This is a binary outcome for each participant: the threshold was either reached at the assessment or it was not. The group-level percentage summarizes the frequency of participants meeting the definition. It does not describe the distribution of chimerism values among participants or show how far measurements were from the threshold.

Confidence intervals. The registry lists a 95% confidence interval as the endpoint's dispersion measure, but does not report the interval or the percentage estimate. In general, a confidence interval conveys the statistical uncertainty around an estimate under the assumptions of the analysis. A narrower interval indicates greater precision than a wider interval, while neither interval width nor the point estimate alone resolves limitations from study design, outcome measurement or missing observations. The confidence level does not mean that an individual participant's result has a 95% probability of lying within the interval.

Assessment time and non-evaluability. The outcome is specified at Day 60. The registry states that eight participants were not evaluable because they died before that assessment. In general, a fixed-time outcome depends on who can be assessed at that time and on how outcomes that preclude assessment are treated. Death before assessment is not interchangeable with an unrecorded measurement: it is a clinical event that can affect interpretation of the endpoint. The registry record does not report the analysis population, denominator, or method used to address these deaths. It also does not state whether there were other unavailable measurements.

Analysis plan and multiplicity. The record lists six outcome measures, including the primary endpoint and secondary outcomes. It does not report a detailed statistical analysis plan, hypothesis-testing procedures, or any adjustment for evaluating multiple outcomes. In general, when several outcomes or hypotheses are examined, the chance of at least one apparently unusual result can increase if each is assessed separately. Methods that address multiplicity may be prespecified, but whether they were planned or used is not reported in the registry record. The record lists zero analysis entries, so inferential results such as test statistics and p-values are not available in the recorded information.

Sample-size planning. The study's sample-size justification is not reported in the registry record. A separate planning illustration is described as based on an observed effect, two-sided significance level 0.05, equal allocation between two arms and a normal approximation. It is explicitly a planning illustration, not the trial's own design rationale. Because this study is single group, a hypothetical equal-allocation comparison does not describe its actual design. Any illustrated sample size is a planning quantity, not observed power and not evidence that an effect was detected. No planning counts are reported in the registry information.

Safety counts. The record reports counts of participants at risk and affected for serious and other adverse events. These are descriptive counts. Without a comparator, they do not estimate excess risk attributable to the intervention. General interpretation of adverse-event summaries also depends on definitions, observation periods, event collection and whether a participant can contribute to more than one event category. Those details are not reported in the registry record. Listed serious-event terms have percentages, but the record does not specify in the information available whether those percentages refer to participants, events or another denominator.

What statistical methods can establish. Statistical summaries can quantify observed frequencies and their uncertainty when the outcome data and analysis details are reported. They cannot repair the lack of a control group or establish causation from an uncontrolled set of observations. Here, the primary estimate, confidence limits, and detailed analysis choices are not reported in the registry record, so the endpoint's magnitude and precision cannot be evaluated.

10. Exact Estimates for Each Arm

No two-arm comparison is shown for this trial, but each arm's result can still be summarized with exact interval estimates computed from the posted counts. The Clopper-Pearson interval is exact and conservative; the Wilson interval is a common closer-to-nominal alternative; the Bayesian credible interval uses a uniform Beta(1, 1) prior. For small groups the three can differ noticeably.

R code and output

arm    <- c("Myeloablative Haploidentical BMT")
n      <- c(88)
events <- c(80)
for (i in seq_along(n)) {
  ci <- binom.test(events[i], n[i])$conf.int          # Clopper-Pearson exact interval
  cr <- qbeta(c(0.025, 0.975), 1 + events[i], 1 + n[i] - events[i])   # Bayesian, uniform Beta(1,1) prior
  wi <- (function(x, n) { p <- x / n; z <- qnorm(0.975); d <- 1 + z^2 / n
    c((p + z^2 / (2 * n) - z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d, (p + z^2 / (2 * n) + z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d) })(events[i], n[i])
  cat(sprintf("ARM|%s|%d|%d|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f\n", arm[i], n[i], events[i], 100 * events[i] / n[i],
              100 * ci[1], 100 * ci[2], 100 * wi[1], 100 * wi[2], 100 * cr[1], 100 * cr[2]))
}

ARM  Myeloablative Haploidentical BMT  88  80  90.9  82.9  96.0  83.1  95.3  83.1  95.3

11. Multiplicity, Missing Data and Analysis Populations

The registry lists a primary endpoint and secondary outcomes covering non-relapse mortality, acute and chronic graft-versus-host disease, survival and relapse. Six outcome measures are recorded. The detailed statistical plan, any hierarchy among secondary outcomes, and any procedure for accounting for multiple analyses are not reported in the registry record. In general, multiplicity matters because examining several outcomes can increase the chance of finding an apparently notable result by chance when each is interpreted independently. The record does not establish whether this issue was addressed in the study analysis.

Eight participants were not evaluable for the primary outcome because they died before Day 60. The registry record does not report the denominator used for the endpoint, how those deaths were handled analytically, or whether all other enrolled participants had an outcome assessment. It also does not report an analysis population definition, such as whether the primary analysis included all enrolled participants or only those evaluable at the scheduled time. These choices matter because the resulting percentage can describe different groups depending on the denominator and handling of outcomes that cannot be measured.

The primary endpoint's result and confidence interval are not reported in the registry record. Results for the listed secondary outcomes are also not reported in the information available for interpretation. The registry record does not report interim analyses, missing-data procedures, or sensitivity analyses. Their presence or absence in the study's actual conduct cannot be inferred from the information recorded.

12. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Deaths

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: renal failure (9.4%), respiratory failure (6.2%), fungal pneumonia (3.1%), multisystem organ dysfunction syndrome (3.1%), sepsis (3.1%).

For the myeloablative haploidentical bone marrow transplant group, the registry records 22 participants affected by serious adverse events among 96 at risk and 37 affected by other adverse events among 96 at risk. It also records 49 deaths. These are descriptive counts in a single study group, not a comparison of event frequencies between treatment strategies.

The listed serious-event terms include renal failure at 9.4%, respiratory failure at 6.2%, and fungal pneumonia, multisystem organ dysfunction syndrome, sepsis and veno-occlusive disease at 3.1% each. The registry record does not clarify the denominator or whether the percentages count affected participants or events. It also does not report event timing, severity details beyond the serious-event listing, or attribution to the intervention in the information.

Adverse-event categories can overlap: a participant may experience more than one event, and the record does not state whether the serious and other categories are mutually exclusive. The 49 deaths should not be assumed to be caused by the intervention or to correspond to the listed serious events. The registry information does not specify how deaths relate to those event counts.

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

The study addresses whether a myeloablative conditioning and partially HLA-mismatched bone marrow transplant approach is associated with donor chimerism at a defined early follow-up point. Its primary endpoint is clearly framed as the percentage achieving at least 95% donor chimerism by Day 60. The record also identifies a group of participants who could not be evaluated at that time because they died before Day 60.

The registry record does not report the primary endpoint percentage or its 95% confidence interval. It therefore does not support a numerical statement about the frequency of reaching the threshold, nor a judgment about the precision of that frequency. The listed secondary outcomes likewise do not have results reported in the information available for interpretation.

The design is single group, with no comparator arm described. Even if group outcomes are reported, a single-group result cannot show what would have happened to comparable participants receiving another approach. It cannot isolate the contribution of conditioning, transplant, post-transplant chemotherapy, supportive care or other factors. The design does not establish a causal treatment effect.

The safety figures document recorded adverse events and deaths in the study group. They do not establish that the study intervention caused those events, and the registry information does not clarify overlap, timing or event attribution. Nor do the counts alone establish how the group's safety experience compares with another treatment strategy.

Thus, the registry record identifies the question and some descriptive safety information, but leaves the main efficacy estimate and important analysis details unreported. The absence of those results in the registry record should not be read as a finding of no effect, just as the existence of a study and its recorded outcomes should not be read as proof of benefit. Interpretation requires the reported endpoint estimates, their uncertainty, the analysis population and fuller outcome information.

14. Why This Trial Matters Statistically

This trial is statistically notable for pairing a specific early transplant endpoint with a single-group Phase II design. Donor chimerism at Day 60 provides a defined threshold-based outcome, while the single-group structure means that any reported frequency would characterize the enrolled participants rather than quantify a randomized contrast. Keeping that distinction clear is central to interpreting uncontrolled clinical studies.

The record also makes the role of outcome availability visible: eight participants were not evaluable for the primary outcome because they died before Day 60. In general, an outcome that cannot be measured after an intervening clinical event raises questions about the target population and analysis denominator. Reporting how such cases are handled is necessary to understand what a percentage represents.

Safety summaries pose a related interpretive challenge. Counts of participants with serious or other adverse events can describe the observed experience, but a comparator is needed to make a direct relative assessment. Clear definitions, time windows, denominators and attribution information also matter when readers assess adverse-event summaries.

Finally, the record illustrates the difference between naming an endpoint and reporting its evidence. It specifies the endpoint and a confidence-interval measure, yet the estimate and interval are not reported in the registry information available for interpretation. Without those values, neither the magnitude nor precision of the primary result can be assessed. The lesson is methodological rather than a conclusion about the treatment: design, missing outcomes, analysis details and complete result reporting shape what a trial can support.

15. Limitations

• The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
• Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.

The most consequential limitation for interpreting the primary outcome is that its observed percentage and confidence interval are not reported in the registry record. The outcome is defined at Day 60, and eight participants were not evaluable because they died before that time, but the analysis denominator and handling of those deaths are not described. Without those details, the endpoint cannot be reconstructed or its precision evaluated.

The single-group design provides no concurrent control. Consequently, the study cannot estimate a randomized difference between the transplant approach and another strategy. Masking is listed as none, and the record does not describe measures to reduce assessment or reporting bias. The extent to which these features affected outcome assessment cannot be determined from the registry information.

The arm description is incomplete for acute lymphocytic leukemia: it starts a separate regimen description but does not give the full details. The complete treatment schedule for all subgroups is therefore not available in the registry record. Detailed eligibility criteria and the full statistical plan are also not reported. The record does not state the endpoint analysis population, missing-data methods, multiplicity procedures, interim analyses or sensitivity analyses.

Results for the secondary outcomes are not reported in the information available for interpretation. The safety record gives adverse-event counts and selected term percentages, but the denominator for the term percentages, event timing, overlap, attribution and relationship between events and deaths are not specified. These limitations restrict what can be concluded from the descriptive safety information and the trial record as a whole.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Safety Study of Bone Marrow Transplant Using Mismatched Tissue Followed by Chemotherapy — NCT00796562.
• Registry record last updated 2019-03-14; status last verified 2019-03.
• Results first posted 2019-03-14.
• Data retrieved from ClinicalTrials.gov on 2026-11-09.
• Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.

19. Record Summary

This completed Phase II study enrolled 107 participants with hematologic malignancies and used a single-group, unmasked design. It evaluated a myeloablative haploidentical bone marrow transplant approach, with busulfan, cyclophosphamide and total body irradiation listed as interventions.

The primary endpoint was the percentage achieving donor chimerism of at least 95% at Day 60. Eight participants were not evaluable because they died before Day 60. The primary percentage and confidence interval are not reported in the registry record. Secondary outcomes included non-relapse mortality, graft-versus-host disease, survival and relapse, but their results are not reported in the information available for interpretation.

The record reports serious and other adverse-event counts and 49 deaths in the study group. Because there was no comparator, these data are descriptive and do not establish comparative effects or causation.