Treosulfan, Fludarabine Phosphate, and Total-Body Irradiation in Treating Patients With Hematological Cancer Who Are Undergoing Umbilical Cord Blood Transplant: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Treosulfan, Fludarabine Phosphate, and Total-Body Irradiation in Treating Patients With Hematological Cancer Who Are Undergoing Umbilical Cord Blood Transplant (NCT00796068), a non-randomized phase 2 study. The primary outcome is Number of Participants With Graft Failure/Rejection.

2. Clinical Question

The clinical setting is transplantation using umbilical cord blood from a related or unrelated donor. The record describes conditioning before transplantation as intended to address cancer-cell growth and rejection, and describes post-transplant prophylaxis against graft-versus-host disease. Those descriptions provide context for the regimen; they are not evidence of its effectiveness.

The main statistical question is descriptive: what was the observed frequency of graft failure or rejection under the study regimen, using the registry's definition? A comparative question between the two risk groups is more difficult. Because allocation was non-randomized and the arms were formed according to risk for graft failure, their outcomes should not be interpreted as if participants had been randomly assigned to comparable treatments.

3. Trial Design

This was a phase II, parallel-arm study with non-randomized allocation and no masking reported. The registry lists enrollment of 130 and identifies Fred Hutchinson Cancer Center as the sponsor. The status is completed. The recorded start date is 2009-02-24 and the primary completion date is 2021-12-14.

The two arms were defined by risk for graft failure: Arm I was described as low risk and Arm II as high risk. In the partial Arm I description, participants received fludarabine phosphate and treosulfan as conditioning, followed by total-body irradiation and donor umbilical cord blood transplantation. Arm II is described as receiving conditioning, irradiation, transplantation, and prophylaxis as in Arm I. The registry record identifies cyclosporine and mycophenolate mofetil among the interventions, but the arm descriptions are incomplete, so further regimen details are not reported in the registry record.

Non-randomized allocation matters for interpretation. The risk categories are not interchangeable treatment assignments: participants in the arms may differ in the underlying risk that led to their grouping. Any observed difference could reflect those differences, other participant characteristics, treatment delivery, or chance. The registry record does not report a randomized comparison or a control group suitable for estimating a causal treatment effect.

The study lists 12 outcome measures, including survival, non-relapse mortality, platelet engraftment, graft-versus-host disease, relapse or progression, and graft failure or rejection. Although the registry lists enrollment and a completed status, it does not report participant flow, the number assessed for each outcome, or the primary outcome result. It also does not report a statistical analysis plan or analysis results. These omissions limit what can be concluded from the record beyond its design and stated outcomes.

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: All participants who signed consent were assigned to one of two arms and all completed enrollment.

Overall Study

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 Number of Participants With Graft Failure/Rejection, measured over Up to 100 days.

The primary endpoint is the number of participants with graft failure or rejection, assessed up to 100 days. It is a count outcome: it records participants meeting the endpoint definition rather than measuring the duration or severity of graft failure. The registry record does not report the observed count.

The definition includes several pathways to classify primary graft failure, in the absence of documented disease persistence or recurrence or active bone marrow infection. These include a specified period without neutrophil recovery in combination with host CD3+ peripheral blood chimerism at day 42; lack of neutrophil recovery by day 55; death after day 28 with a very low neutrophil count and no evidence of engraftment; or primary autologous count recovery with low donor CD3+ peripheral blood chimerism and no relapse. The record specifies the relevant thresholds, including neutrophils >500/u1, a host chimerism threshold of 50%, neutrophils <100/u1, and donor CD3+ chimerism <5% for relevant criteria.

As a general statistical point, a defined endpoint makes outcome classification more consistent: readers can understand which clinical events count and over what follow-up period. The endpoint is relevant to transplantation because it captures failure to establish donor-derived blood-cell recovery under the study definition. It is not a complete measure of all transplant outcomes. Survival, relapse, graft-versus-host disease, and other outcomes are listed separately. Without the observed endpoint count and the number of participants evaluated, the frequency and precision of graft failure cannot be assessed from the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary outcome is a binary event at the participant level: each participant either meets the registry's definition of graft failure or rejection within the stated follow-up window, or does not. The registry describes the outcome as a count of participants. To interpret such a count as a frequency, readers also need the number of participants evaluated for that outcome. Neither the primary count nor its evaluable denominator is reported in the registry record, so an event rate cannot be stated.

As a general statistical concept, a confidence interval describes uncertainty around an estimate. For a binary outcome, an interval around an event proportion helps show how much uncertainty remains given the observed events and the number assessed. A narrow interval generally indicates greater precision, while a wide interval indicates less precision. An interval is not reported for the primary outcome in this registry record. No interval should be inferred from the enrollment figure or from safety counts because they refer to different information.

The endpoint definition combines clinical recovery, blood-count, donor-chimerism, and survival criteria. A composite definition can capture more than one pathway to a clinically relevant failure classification. Its interpretation depends on applying the criteria consistently and having the necessary measurements and follow-up. The registry states that disease persistence or recurrence and active bone marrow infection affect whether the listed criteria apply. It does not report how often those exclusions arose, how missing measurements were handled, or how endpoint classification was adjudicated.

The study is non-randomized, and the arms represent different levels of graft-failure risk. In general, random allocation helps balance measured and unmeasured characteristics between treatment groups, on average. Without randomization, baseline risk and other group differences can complicate comparisons. Adjustment can sometimes address measured differences, but it cannot guarantee removal of unmeasured confounding. The registry record does not report an adjusted analysis, covariates, or a method for comparing the arms. As a result, arm-specific outcomes, if considered, should be interpreted descriptively rather than as estimates of a causal treatment contrast.

The record lists 12 outcome measures and 0 analyses. That registry entry does not establish whether analyses were conducted outside the record; it means that analysis results are not reported there. The record does not identify a model for the primary endpoint, a method for handling repeated or competing events, or an approach to uncertainty estimation. Those methods are not reported in the registry record.

Multiplicity refers, in general, to the increased chance of false-positive findings when many hypotheses are tested. A study with multiple outcomes may use a hierarchy, adjustment, or another prespecified strategy to guide interpretation. The registry lists multiple primary and secondary outcome measures but does not report how multiplicity was handled. It would therefore be inappropriate to assume that any particular adjustment or outcome hierarchy was used.

The record's planning assumptions describe an illustration based on an observed effect, with a two-sided significance level of 0.05, equal allocation between arms, and a normal approximation. For time-to-event planning, it identifies the Schoenfeld method and describes the target in terms of total events; other planning quantities are described as participants per arm. The illustration is explicitly not the trial's own design justification. It is a planning exercise, not observed power, and it does not fill in the missing primary result. The record does not report the trial's sample-size justification or a prespecified effect used to design the study.

As a general point, power is a property of a planned design under specified assumptions; it does not measure the probability that a result is true after data have been observed. A planning illustration based on an observed effect is especially dependent on that effect estimate and its uncertainty. The registry record does not provide the numerical planning outputs, so no sample-size requirement can be stated from it. Any such illustration should be read as hypothetical planning information rather than evidence about the study's findings.

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("Arm I (Low Risk for Graft Failure)", "Arm II (High Risk for Graft Failure)")
n      <- c(66, 64)
events <- c(2, 5)
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  Arm I (Low Risk for Graft Failure)  66  2  3.0  0.4  10.5  0.8  10.4  0.9  10.4
ARM  Arm II (High Risk for Graft Failure)  64  5  7.8  2.6  17.3  3.4  17.0  3.5  17.0

11. Multiplicity, Missing Data and Analysis Populations

The registry lists 12 outcome measures, including the primary graft-failure outcome and secondary measures related to survival, non-relapse mortality, engraftment, graft-versus-host disease, relapse, and progression. It reports 0 analyses. This indicates that analysis results are not reported in the registry record; it does not establish whether analyses were conducted or reported elsewhere. The record does not describe a prespecified hierarchy among outcomes, a multiplicity adjustment, or another strategy for interpreting multiple tests. Those details are not reported in the registry record.

Missing-data handling is also not described. The record does not state how participants with incomplete follow-up, unavailable blood-count or chimerism measurements, or other missing endpoint information were treated. It does not provide the number assessed for the primary outcome or explain whether the outcome was analyzed in an intention-to-treat, evaluable-participant, or other analysis population. These methods and population definitions are not reported in the registry record.

This matters because a participant count without a clear denominator does not determine an event frequency, and missing outcome information can affect interpretation. In general, excluding participants with missing data may change the makeup of the analyzed group, while different assumptions about missing outcomes can lead to different estimates. These are general considerations, not claims about what occurred in this study.

Although the registry records enrollment of 130 and a completed status, those details do not establish the number included in each outcome analysis or the extent of follow-up. Without participant flow, analysis populations, and missing-data methods, the scope and completeness of the posted outcome evidence cannot be assessed.

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 0% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: sepsis (4.7%), left ventricular systolic dysfunction (4.5%), respiratory failure (4.5%), hypoxia (4.5%), hypotension (3.1%).

The safety figures are organized by the two registry arms, which are labeled low risk and high risk for graft failure. For Arm I, the record lists 66 at risk for serious adverse events and 27 affected; it lists 66 at risk for other adverse events and 63 affected, with 16 deaths. For Arm II, it lists 64 at risk for serious adverse events and 23 affected; it lists 64 at risk for other adverse events and 59 affected, with 20 deaths. These are registry safety figures, not the primary graft-failure results.

The record also lists serious adverse-event terms with percentages: sepsis, 4.7%; left ventricular systolic dysfunction, 4.5%; respiratory failure, 4.5%; hypoxia, 4.5%; hypotension, 3.1%; and sinusoidal obstruction syndrome, 3.1%. The registry excerpt does not state the denominator or event-attribution details for these percentages, so they should be read as reported rather than used to calculate comparisons.

In general, an adverse event occurring during a study is not automatically caused by the study treatment. The registry figures do not establish causality, and the non-randomized arms are not comparable control groups. The listed death counts do not, on their own, establish treatment-related deaths or explain the circumstances of death.

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

The record describes a phase II study of a treosulfan-based preparative regimen followed by umbilical cord blood transplantation in patients with hematological cancers. It defines graft failure or rejection as the primary outcome, with assessment up to 100 days, and lists other outcomes covering survival, engraftment, graft-versus-host disease, relapse, and progression. These details establish what the study set out to examine.

The record does not report the primary outcome count, its denominator, an effect estimate, or an uncertainty interval. It therefore does not establish the observed frequency of graft failure or rejection. Nor does the completed status establish a particular result. Missing results are not evidence that the event did not occur or that the regimen had a particular effect.

The two arms were assigned by graft-failure risk rather than randomized. They cannot be treated as a like-for-like comparison. Any difference between them could reflect risk-group characteristics as well as other factors, and the record does not report an analysis that would support a causal interpretation. A comparison between these arms should therefore not be framed as a test of whether one treatment is superior.

The safety figures describe adverse-event reporting and deaths in the two arms. They do not show that the regimen caused the listed events or deaths. The registry does not supply the context needed to attribute individual events or to make a causal safety comparison.

In general, a study's design and outcome definitions answer different questions from its results. Design information indicates how the study was organized; endpoint results indicate what was observed; statistical uncertainty indicates how precisely those results were estimated. The registry provides design and outcome-definition information, but the principal result and its precision are not reported in the registry record. Conclusions about efficacy, comparative benefit, or causal safety cannot be drawn from the information recorded.

14. Why This Trial Matters Statistically

This study raises a statistically important question in a complex transplantation setting: how often does graft failure or rejection occur under a specified preparative regimen and endpoint definition? The endpoint combines clinical recovery and donor-chimerism criteria, making clear definitions especially important for consistent classification. Its stated follow-up window also makes the timing of assessment part of the outcome's meaning.

The non-randomized structure is equally important. The arms were separated by risk for graft failure, so their outcomes are not a direct treatment comparison. Recognizing that distinction prevents descriptive arm results from being mistaken for a causal effect. In clinical research, the design determines which comparisons are credible, not just which comparisons can be calculated.

The record also illustrates why an outcome count must be interpreted alongside its denominator and uncertainty. A count alone cannot tell readers how common an event was among those assessed, and an estimate without an interval gives limited information about precision. Here, the primary count, denominator, and uncertainty are not reported in the registry record. That absence limits the statistical conclusions even though the endpoint and study design are described.

Finally, a broad set of outcomes creates questions about analysis populations, missing follow-up, and multiplicity. These are not technical details that can be safely inferred from a list of outcomes. Their absence from the record leaves uncertainty about how the posted outcomes would be interpreted together. The study is therefore useful as an example of why registry design information and outcome definitions must be distinguished from the numerical evidence needed to evaluate findings.

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 primary limitation for interpreting this study record is that the primary outcome result is not reported. The registry identifies graft failure or rejection as the primary outcome and gives its definition and follow-up window, but does not give the number meeting the criteria, the number assessed, or an uncertainty estimate. The frequency and precision of the primary outcome therefore cannot be evaluated from the registry record.

The study is non-randomized, and the arms are defined by low versus high risk for graft failure. This limits direct comparisons between arms because risk classification itself may be associated with outcomes. No adjustment strategy or comparative analysis is reported. Any arm-level difference should not be interpreted as a causal effect.

Descriptions of the treatment arms are incomplete in the registry record. The Arm I description is truncated, and the Arm II description refers back to Arm I rather than giving the full regimen details. The record lists relevant drugs, irradiation, transplantation, and prophylaxis, but the exact regimen cannot be fully reconstructed from the available description.

The record does not report participant flow, the analysis population for each outcome, missing-data methods, endpoint adjudication, or statistical models. It also does not report how multiple outcomes were handled. These omissions prevent assessment of how complete the outcome data were and how results were selected or interpreted.

Safety reporting is limited by the lack of context for the listed event percentages and by the non-randomized group structure. The listed events and deaths should not be attributed to the regimen without supporting information. The registry's completed status and enrollment figure do not resolve these limitations or substitute for outcome results.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Treosulfan, Fludarabine Phosphate, and Total-Body Irradiation in Treating Patients With Hematological Cancer Who Are Undergoing Umbilical Cord Blood Transplant — NCT00796068.
• Registry record last updated 2023-02-17; status last verified 2023-01.
• Results first posted 2023-02-17.
• 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

The record describes a completed phase II, parallel-arm, non-randomized study sponsored by Fred Hutchinson Cancer Center, with enrollment of 130. It evaluates a treosulfan- and fludarabine-based preparative regimen with total-body irradiation before umbilical cord blood transplantation for hematological cancers. The two arms are designated low and high risk for graft failure.

The primary outcome is the number of participants with graft failure or rejection up to 100 days, defined using blood-count, donor-chimerism, and clinical criteria. The registry lists 12 outcome measures and 0 analyses. It does not report the primary outcome result, its denominator, or an uncertainty estimate. Safety counts and selected serious adverse-event terms are listed, but they do not establish causality or support a randomized comparison between arms.