Early Administration of ATG Followed by Cyclophosphamide, Busulfan and Fludarabine Before a Donor Stem Cell Transplant in Patients With Hematological Cancer: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Early Administration of ATG Followed by Cyclophosphamide, Busulfan and Fludarabine Before a Donor Stem Cell Transplant in Patients With Hematological Cancer (NCT00787761), a non-randomized phase 2 study. The primary outcome is Achievement of > 90% (Full) Donor Chimerism in the T-cell Lineage as Measured by PCR at Day 30 Post-transplantation.

2. Clinical Question

3. Trial Design

This was a phase II, completed, non-randomized, single-group study with no masking. The registry reports enrollment of 24. All participants were assigned to an ATG, cyclophosphamide, busulfan, and fludarabine-based allogeneic transplant regimen. The study title and official title describe early ATG before donor stem cell transplantation, and the official title specifies reduced-intensity allogeneic peripheral blood progenitor cell transplantation from matched-related donors.

The registry lists tacrolimus and methotrexate among the interventions and describes them in the rationale as medicines given after transplantation. The listed procedure is nonmyeloablative allogeneic HSCT. Doses, detailed schedules, treatment adherence, and any deviations from the intended regimen are not reported in the registry record.

The study began in 2007-04, had primary completion in 2010-07, and is marked completed. Northside Hospital, Inc. is listed as sponsor. The registered conditions span hematological cancers and kidney cancer. The record does not give a detailed eligibility description, baseline characteristics, or outcome-specific participant flow beyond noting that only 15 patients treated on study had Day 30 chimerism results.

Because this was a single-group study, its design can describe outcomes among treated participants but does not provide a randomized comparison with another regimen. The registry record does not report a comparator group, a random allocation procedure, or masking. A sample-size planning illustration is described as based on the observed effect, with two-sided significance level 0.05, equal allocation between two arms, and a normal approximation. Those illustration assumptions are not evidence of the trial’s original design rationale; that rationale is 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: 29 patients signed consent for this study. 2 patients were initially screen failures but eventually were determined eligible \& were treated on study. 1 patient was considered a screen failure due to having an ineligible donor. One patient had progressive disease and one patient had compliance-related issues prohibiting them from particiapting.

Overall Study

Analysis population for the primary outcome, as defined in the registry: only 15 of the patients treated on study had Day 30 chimerism results.

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 Achievement of > 90% (Full) Donor Chimerism in the T-cell Lineage as Measured by PCR at Day 30 Post-transplantation, measured over Day 30.

The primary endpoint is achievement of greater than 90% donor chimerism in the T-cell lineage at Day 30 after transplantation, assessed by PCR. Chimerism is a measure of the donor-derived contribution to a participant’s blood-cell population. The endpoint defines a threshold outcome: each assessed participant either meets the stated greater-than-90% threshold or does not. The registry describes separating peripheral blood mononuclear cells into T-cell and myeloid components before assessment, with PCR for STR/VNTR used for chimerism analysis.

As a general statistical concept, a threshold endpoint converts a continuous or graded biological measurement into a binary outcome. This can make a clinical question easier to state and summarize, but it also means that values on either side of the threshold are treated as different categories even if they are close together. The endpoint therefore answers whether the specified threshold was reached, not how far above or below it a measurement fell.

The registry notes that only 15 of the patients treated on study had Day 30 chimerism results. It does not report the number achieving the endpoint, the underlying measurements, or a confidence interval. Thus, the endpoint is defined, but its observed result and precision are not reported in the registry record. The rationale for choosing this threshold is not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The design determines what statistical conclusions the data can support. This study is registered as a single-group, non-randomized phase II trial with no masking. In general, a single-group study can describe outcomes observed among participants who received the intervention. It cannot make the same direct treatment comparison as a randomized controlled trial, because it does not assign participants to concurrent intervention and control groups. Differences between treated participants and an external population, if considered, could reflect characteristics or care beyond the intervention itself.

What does the primary endpoint count?

The primary outcome is a binary threshold measure: achievement of greater than 90% donor chimerism in the T-cell lineage by Day 30, assessed by PCR. For a binary endpoint, the basic descriptive result is the number meeting the definition and the number assessed. A proportion can then describe the frequency among those assessed, and a confidence interval can communicate uncertainty around that estimate. In general, a confidence interval represents a range of values compatible with the observed data under the method’s assumptions; it is not a guarantee that the true value lies within that range. The registry does not report the endpoint count, an estimated proportion, or a confidence interval.

The record says that only 15 of the patients treated on study had Day 30 chimerism results. This is the stated available population for that endpoint, not a basis for assuming what happened to other participants. The registry does not specify why the measurements were unavailable, whether the endpoint was assessed for all participants as planned, or whether any statistical method was used to address missing outcomes. As a general principle, a result based only on participants with observed measurements can be affected if availability of those measurements is related to the outcome.

What can a single-group design estimate?

In general, a single-group study can estimate the frequency of a defined event within the observed group, provided the outcome data and analysis are reported. It does not directly estimate the difference between treatment groups because no separate comparator is registered. Descriptive outcome estimates may still be useful for characterizing a study group, but they do not isolate the effect of treatment from other possible explanations. Here, even a descriptive primary endpoint estimate cannot be reviewed because the registry record does not report the number meeting the chimerism threshold.

The registry lists 8 outcome measures and reports 0 analyses. The registered outcomes include the Day 30 primary endpoint and secondary measures of chimerism, graft-versus-host disease, non-relapse mortality, disease-free survival, and overall survival. Listing an outcome does not show that an analysis was completed. The record does not give effect estimates, test statistics, p-values, confidence intervals, or analysis populations for the registered outcomes.

Why do confidence intervals and sample size matter?

As a general statistical concept, the precision of an estimate depends partly on the amount and quality of outcome information available. A confidence interval is one way to show that precision. A narrower interval indicates greater precision under its assumptions, while a wider interval indicates more uncertainty. Since neither the primary endpoint estimate nor its interval is reported, the statistical precision of the Day 30 result cannot be evaluated.

The registry describes a planning illustration based on an observed effect, with a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. For time-to-event outcomes, the illustration is described as using a total number of events; for other outcomes, it is described in participants per arm. These are planning assumptions, not evidence of the original study’s sample-size justification. A sample-size illustration is not an observed trial result and is not observed power. The registry record does not report the trial’s own sample-size rationale or a statistical analysis plan.

Why does over-dispersion matter?

For a binary count, statistical models often assume a particular relationship between the expected event frequency and the variability of observed counts. In general, over-dispersion means that the observed variability is greater than the model assumes. If it is ignored, uncertainty estimates can be too small, making results appear more precise than warranted. This is a general consideration, not a reported feature of this study. The registry record does not identify a model, report a dispersion assessment, or provide enough outcome data to assess over-dispersion.

Time-to-event outcomes such as disease-free survival and overall survival have a different structure from a simple event count: they concern the timing of an event and may include participants whose event status is not known by the end of follow-up. In general, time-to-event analyses need details about follow-up, censoring, and the analysis method. The registry lists these outcomes at 24 months but does not report the corresponding results, follow-up distributions, or analysis methods. Consequently, their statistical interpretation is not available from the registry record.

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("Transplant Recipients")
n      <- c(15)
events <- c(12)
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  Transplant Recipients  15  12  80.0  51.9  95.7  54.8  93.0  54.4  92.7

11. Multiplicity, Missing Data and Analysis Populations

The registry lists 8 outcome measures: a primary Day 30 T-cell chimerism endpoint and secondary measures covering later chimerism, graft-versus-host disease, non-relapse mortality, disease-free survival, and overall survival. When a study evaluates multiple outcomes, there can be more than one opportunity to identify an apparently noteworthy result. As a general statistical concept, multiplicity procedures can address this issue by controlling the interpretation of a collection of statistical tests. The registry record does not report whether any multiplicity adjustment was planned or performed, or how the outcomes were prioritized beyond identifying the primary endpoint.

The registry reports 0 analyses. It therefore does not provide outcome estimates, confidence intervals, p-values, or testing details for the listed measures. Without reported analyses, it is not possible to determine whether the outcomes were analyzed, whether any particular analysis was prespecified, or whether statistical conclusions were adjusted for multiple outcomes. The statistical analysis plan is not reported in the registry record.

For the primary endpoint, the record states that only 15 of the patients treated on study had Day 30 chimerism results. The reasons for unavailable measurements and the approach to missing data are not reported in the registry record. No imputation procedure, sensitivity analysis, or assumption about missing outcomes is described. As a general principle, missing outcome data can affect both the estimate and its interpretation, particularly if availability is associated with participants’ outcomes.

The registry does not specify an analysis population for the primary or secondary outcomes, such as whether analyses were to include all enrolled participants or only those with a particular set of observed data. It also does not give participant flow for the outcome measures beyond the Day 30 chimerism note. Accordingly, the available record does not permit assessment of how missing data, outcome multiplicity, or analysis-population choices were handled.

12. 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: death (16.7%), fever (12.5%), abdominal abcess (4.2%), cardiac tamponade (4.2%), hyperglycemia (4.2%).

The registry reports a safety group titled “RIC Transplant Using ATG, Busulfan, Fludarabine and Cytoxan.” It lists 13 participants affected by serious adverse events and 24 affected by other adverse events. These are separate registry summaries; they should not be added together or treated as mutually exclusive categories. The record does not specify the event-level counting rules or provide a breakdown of repeated events within participants.

The most frequently listed serious adverse event terms are Death at 16.7%, Fever at 12.5%, and Abdominal Abcess, Cardiac Tamponade, Hyperglycemia, and Chemotherapy reaction at 4.2% each. These percentages are reported as adverse-event terms. They should not be interpreted as a complete account of all clinical outcomes or as evidence about the cause of an event. Death appears as a serious adverse event term, but a separate death count is not reported in the registry record.

In general, adverse-event summaries describe events recorded under a study’s reporting definitions; they do not establish how frequently the same events would occur under another treatment. This study has no randomized comparator group. The registry record does not report a comparative safety analysis or further detail about event timing, severity beyond the serious-event classification, or attribution.

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

The trial record contributes a defined question and a description of the treatment regimen studied. It identifies early ATG with cyclophosphamide, busulfan, and fludarabine before allogeneic donor transplantation, and sets a primary endpoint of greater than 90% donor chimerism in the T-cell lineage at Day 30. It also registers longer-term chimerism, graft-versus-host disease, non-relapse mortality, disease-free survival, and overall survival outcomes.

What the record does not provide is the observed primary endpoint result. Although Day 30 chimerism results were available for only 15 of the patients treated on study, the number meeting the threshold is not reported. There is also no reported estimate of uncertainty, such as a confidence interval, and no registry analysis result for the primary or secondary outcomes. The outcome definitions therefore cannot be treated as evidence that the outcomes occurred at any particular frequency.

The design also limits interpretation. This was a non-randomized, single-group study without masking or a comparator arm. In general, outcomes observed in a single treated group cannot establish what would have happened to the same participants under another regimen. A comparison with an external expectation would require additional information and assumptions that are not reported in the registry record.

The adverse-event summaries provide information about events recorded in the study group, including the listed serious adverse-event terms. They do not demonstrate that the regimen caused each event, and they do not quantify comparative risk. The record gives no separate death count in the adverse-event summary.

Accordingly, this registry record documents the study’s design, outcome definitions, incomplete availability noted for the primary endpoint, and adverse-event summaries. It does not provide enough outcome analysis to estimate the primary result or its precision, establish a treatment effect, or compare safety and efficacy with another approach. No conclusion that the treatment works or does not work follows from the posted data.

14. Why This Trial Matters Statistically

This study illustrates why a registry’s outcome definition and its outcome result are different kinds of information. The primary endpoint is specific: greater than 90% donor chimerism in the T-cell lineage, measured by PCR at Day 30. Yet the registry record does not report how many participants met that definition or an estimate of uncertainty. Without those results, readers cannot judge the observed frequency or its precision.

The note that only 15 of the patients treated on study had Day 30 chimerism results also highlights the importance of reporting analysis populations and missing outcomes. A clear account of who was assessed, why other measurements were unavailable, and how missing data were handled can affect the interpretation of a result. Those details are not reported in the registry record.

Design is equally important. This phase II study is non-randomized and single-group, so it can describe the treated participants but has no concurrent control group for a direct treatment comparison. The design does not remove alternative explanations for an observed outcome. This is a statistical limitation of the comparison that can be made, regardless of the biological motivation for measuring donor chimerism.

The registry also lists 8 outcomes but reports 0 analyses. This makes the difference between outcome registration and statistical reporting particularly clear. In general, multiple outcomes require transparent reporting of which analyses were performed and how their results should be interpreted. The registry does not report a multiplicity strategy or statistical analysis plan.

Finally, the adverse-event summaries are useful descriptive information but are not a comparative safety analysis. Taken together, the record is informative about the question the study set out to examine, while leaving its primary estimate, statistical precision, and comparative interpretation unreported.

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 main limitation for interpreting the primary question is that the registry record defines the Day 30 chimerism endpoint but does not report its result. It notes that only 15 of the patients treated on study had Day 30 chimerism results, without explaining why results were unavailable for others or how missing data were handled. The endpoint count, estimate, and uncertainty are not reported in the registry record.

The study is non-randomized and single-group, with no separate comparator. Consequently, the registered design does not allow a direct randomized treatment contrast. The record does not report an adjusted comparative analysis, and no causal interpretation can be made from the design description alone.

The registry lists secondary outcomes, including chimerism at later time points, graft-versus-host disease, non-relapse mortality, disease-free survival, and overall survival. It reports 0 analyses, so results for these outcomes cannot be reviewed. Follow-up details, analysis populations, and methods for time-to-event outcomes are not reported in the registry record.

Further details relevant to interpretation are also absent: participant characteristics, detailed eligibility criteria, treatment doses and schedules, adherence, outcome-specific participant flow, the statistical analysis plan, the trial’s sample-size rationale, and any multiplicity or missing-data procedures. The record’s planning illustration assumptions do not replace a report of the original design rationale or the trial’s analysis methods.

Safety information is limited to group-level counts and listed adverse-event terms. A separate death count is not reported in the registry record, and there is no comparative safety analysis. These limitations mean that the registry supports description of the registered study and posted summaries, but not a precise efficacy estimate or a comparison of outcomes against another treatment.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Early Administration of ATG Followed by Cyclophosphamide, Busulfan and Fludarabine Before a Donor Stem Cell Transplant in Patients With Hematological Cancer — NCT00787761.
• Registry record last updated 2012-10-01; status last verified 2012-08.
• Results first posted 2012-10-01.
• 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 was non-randomized, single-group, and unmasked, with enrollment of 24. It examined an ATG, cyclophosphamide, busulfan, and fludarabine-based allogeneic transplant regimen. The primary endpoint was achievement of greater than 90% donor chimerism in the T-cell lineage at Day 30, measured by PCR.

The registry notes that only 15 of the patients treated on study had Day 30 chimerism results, but does not report the number meeting the endpoint or any analysis results. It lists 8 outcome measures and reports 0 analyses. Safety summaries list 13 participants affected by serious adverse events and 24 affected by other adverse events. The record does not provide a comparator, statistical analysis plan, or comparative treatment-effect estimate.