Fludarabine Phosphate, Melphalan, Total-Body Irradiation, Donor Stem Cell Transplant in Treating Patients With Hematologic Cancer or Bone Marrow Failure Disorders: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Fludarabine Phosphate, Melphalan, Total-Body Irradiation, Donor Stem Cell Transplant in Treating Patients With Hematologic Cancer or Bone Marrow Failure Disorders (NCT00856388), a na na study. The primary outcome is Day 100 TRM.

2. Clinical Question

The trial asks whether a reduced-intensity preparative regimen followed by donor stem cell transplantation can be used in patients with hematologic cancer or bone marrow failure disorders, and what treatment-related mortality is observed during the first 100 days. The registry identifies Day 100 TRM as the primary endpoint, measured as a percentage of participants.

This is a descriptive question about outcomes after the transplant strategy, not a randomized estimate of how the strategy compares with another approach. The record also lists secondary outcomes concerning engraftment, donor chimerism, graft-versus-host disease, and overall survival. Numerical results for those outcomes are not reported in the registry record.

3. Trial Design

The official title describes a pilot trial of reduced-intensity allogeneic stem cell transplantation with fludarabine, melphalan, and low-dose total-body irradiation. The registry classifies the study as single-group, with allocation and phase recorded as NA and masking recorded as none. It is marked completed. The sponsor is Roswell Park Cancer Institute.

The intervention description gives a sequence of preparative treatment followed by transplantation: fludarabine phosphate is administered intravenously over 30 minutes on days -5 to -2, melphalan intravenously over 30 minutes on day -2, total-body irradiation on day -1, and allogeneic stem cell transplantation on day 0. The arm description contains an incomplete note concerning melphalan and chromosomal breakage syndromes. Although anti-thymocyte globulin is listed as an intervention, the arm description does not state how or whether it was administered.

The registry enrollment is 62, and the single treatment group’s serious-adverse-event record lists 62 participants at risk. These figures describe enrollment and the safety record; they do not establish that every enrolled participant was included in the primary endpoint analysis. The endpoint population is specifically described as all treated and eligible patients, but the number in that population is not reported in the registry record.

With no control arm and no randomization, outcomes can be described for the treated group, but the design does not support a randomized comparison against another regimen. The registry record does not report a detailed protocol, eligibility criteria, recruitment process, or rationale for the enrollment target. The trial’s pilot designation comes from its title; further details about the pilot objectives 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.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: All treated and eligible patients

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 Day 100 TRM, measured over First 100 days.

Day 100 treatment-related mortality (TRM) is the primary endpoint. It is defined in the registry as a percentage of participants, with a timeframe covering the first 100 days and an analysis population of all treated and eligible patients. The endpoint is intended to summarize deaths attributed to treatment during that specified period, rather than all deaths over any duration.

As a general statistical concept, a time-limited mortality endpoint focuses attention on events occurring within a defined follow-up window. Reporting it as a percentage makes the result interpretable as the proportion of the eligible analysis population with the event, provided the event count and denominator are available. A confidence interval conveys uncertainty around that estimated proportion; a wider interval generally indicates less precision, while a narrower interval indicates greater precision.

The registry description states that an exact 95% confidence interval will be provided. However, the observed number of TRM events, the percentage estimate, and the interval are not reported in the registry record. Consequently, the endpoint’s observed frequency and precision cannot be assessed from this record. The endpoint definition also does not provide operational details about how treatment-relatedness was adjudicated or how deaths with uncertain attribution were handled; those details are not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry identifies a single-group study and names Day 100 TRM as a percentage endpoint with an exact 95% confidence interval. It does not report the observed primary endpoint data, the method used to determine treatment-relatedness, or a statistical analysis plan. The distinctions below explain the general statistical ideas relevant to the design and the endpoint, without implying that unreported analyses were performed.

What does a percentage endpoint represent?

For a binary outcome, each participant is classified according to whether the event occurred within the specified definition and timeframe. The event count is interpreted relative to the eligible analysis population to obtain a proportion, which may be expressed as a percentage. In this trial, the intended population is all treated and eligible patients, and the defined window is the first 100 days. The registry record does not give the event count or the size of this endpoint population, so the percentage cannot be reconstructed from the record.

Using the stated analysis population matters because enrollment and analysis denominators need not be identical. Participants may be excluded from an analysis for reasons defined by a protocol, or endpoint status may be unavailable. Whether any such exclusions or unavailable outcomes occurred, and how they were handled, is not reported in the registry record. The enrollment figure alone should not be treated as proof of the primary endpoint denominator.

What does a confidence interval add?

As a general concept, a confidence interval expresses the statistical uncertainty associated with an estimate. A 95% confidence interval is generated by a procedure designed, over repeated applications under its assumptions, to cover the underlying parameter at the stated rate. It is not a statement that the true value has a 95% probability of lying inside one particular calculated interval.

The registry says that an exact 95% confidence interval will be provided for the primary endpoint. An exact interval for a proportion is generally based on the discrete event-count structure rather than relying on a large-sample normal approximation. Such intervals can be especially relevant when event counts are small. The record does not include the interval or state further implementation details, so its width, bounds, and relation to the observed estimate cannot be evaluated.

What can a single-group design estimate?

A single-group study can describe the event frequency observed among participants who received the study regimen. A randomized controlled comparison has a different purpose: it estimates a contrast between treatment groups under the allocation process. This registry record reports no control group and no random allocation. Thus, even if an outcome estimate were posted, it would describe the study group and would not by itself estimate a treatment effect relative to another regimen.

As a general principle, causal comparisons require attention to how groups were formed and whether differences between them could explain outcome differences. Because this study has no concurrent comparator, there is no within-trial control for those differences. Historical comparisons, if any, and methods for making them are not reported in the registry record.

How should the safety counts be understood?

The serious-adverse-event record gives a number at risk and a number affected for the study group. Those figures describe participants classified in that registry safety record. A person can experience more than one event term, so event-term percentages should not be added to estimate a count of people. The registry does not report the event-level records or explain how recurrent events were summarized.

The reported percentages for serious-event terms are descriptive entries. They do not, on their own, establish event severity beyond the registry’s serious-event classification, treatment causality, timing, or the number of unique participants represented by multiple terms. The record also gives 0 affected for other events, but it does not explain the scope or coding rules behind that field. These safety summaries should not be substituted for the primary TRM endpoint, which has its own timeframe, attribution definition, and analysis population.

What do planning assumptions mean?

General sample-size planning uses assumptions about a target effect, error rates, allocation, and an analysis method to illustrate how much information a future study might require. Such planning values are not observed outcomes and are not evidence that a study had a particular probability of detecting an effect after it was completed. The stated planning assumptions describe a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation, with the effect to detect expressed as a fraction of an observed effect. They are planning assumptions, not a description of this single-group trial’s allocation.

The registry record does not report the resulting planning counts, an observed effect used for those illustrations, or the study’s own sample-size justification. It also does not report whether interim analyses were conducted, what inferential tests were planned, or what adjustments were intended for secondary analyses. Those methods cannot be inferred from the endpoint list or from the fact that the trial is marked completed.

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("Treatment (Reduced Intensity Allogeneic Stem Cell ")
n      <- c(61)
events <- c(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  Treatment (Reduced Intensity Allogeneic Stem Cell   61  5  8.2  2.7  18.1  3.6  17.8  3.6  17.8

11. Multiplicity, Missing Data and Analysis Populations

The record lists a primary endpoint and several secondary outcomes, but does not report a plan for controlling multiplicity across outcomes or analyses. Multiplicity is a general statistical concern: when many hypotheses are tested, the chance of at least one apparently notable finding can increase unless the analysis plan accounts for the number and structure of tests. The registry record does not state whether any outcomes were designated for formal hypothesis testing, whether secondary analyses were exploratory, or whether adjustments were planned.

Missing-data methods are not reported in the registry record. The record does not explain how incomplete follow-up, unavailable endpoint status, withdrawal, or death with uncertain treatment attribution would be handled for the primary endpoint or secondary outcomes. It also does not state whether any imputation, censoring rules, sensitivity analyses, or complete-case approach was planned. Therefore, the potential effect of missing outcome information on estimates cannot be assessed.

The primary endpoint population is described as all treated and eligible patients, but the number in that analysis population and its relationship to enrollment are not reported in the registry record. The record does not provide a participant flow description or clarify whether eligibility was assessed before or after treatment. The serious-adverse-event figures have their own at-risk entries and should not be assumed to use an identical population definition without further information.

These gaps do not establish that the trial lacked prespecified methods; they mean that those methods are not reported in the registry record. The interpretation should remain confined to the explicitly stated endpoint and the descriptive safety entries, without assuming an adjustment strategy or a particular handling of missing observations.

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 0% reporting threshold.

Most frequent serious adverse event terms

Serious events with the highest arm-level rate: hospitalisation (19.4%), graft versus host disease (12.9%), death (8.1%), pyrexia (8.1%), cardiac disorder (3.2%).

The serious-adverse-event record lists 34 participants affected among 62 at risk for serious events in the treatment group. For other events, it lists 0 affected among 62 at risk. The serious-event terms reported with percentages are Hospitalisation at 19.4%, Graft versus host disease at 12.9%, Death at 8.1%, Pyrexia at 8.1%, Cardiac disorder at 3.2%, and Bacteraemia at 3.2%.

These figures are descriptive safety entries. The event-term percentages should be read individually, not added together: one participant may be associated with more than one event term, and the record does not provide detail that would identify overlap. The percentages do not establish treatment causality. Nor does the term Death at 8.1% mean that all such deaths met the primary endpoint definition of treatment-related mortality during the first 100 days. That endpoint’s result is not reported in the registry record.

The serious-event entry also reports deaths as null, which does not supply a numerical death count. The record does not describe event timing, attribution procedures, or the coding rules used for the listed terms. The at-risk figures are specific to the safety record and should not automatically be substituted for the primary endpoint analysis population.

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

The registry record establishes that a completed single-group pilot evaluated a reduced-intensity allogeneic transplant regimen and designated treatment-related mortality during the first 100 days as its primary endpoint. It also gives descriptive serious-adverse-event figures for the treatment group and lists secondary outcomes relating to engraftment, donor chimerism, graft-versus-host disease, and survival.

What the posted record does not establish is the observed Day 100 TRM percentage, its event count, or its confidence interval. It does not provide numerical results for the listed secondary outcomes. Without those primary and secondary outcome estimates, their precision and pattern cannot be assessed. The safety entries do not fill that gap because they are not reported as the primary endpoint analysis and do not supply the same event definition and timeframe.

Even if outcome estimates were available, a single-group design would describe what happened among participants receiving the regimen, not demonstrate how outcomes compare with an alternative treatment. Without random allocation or a control group, other characteristics and circumstances could contribute to the observed outcomes. No comparative treatment effect can be derived from the record.

General statistical interpretation also separates absence of a reported result from evidence that an event did or did not occur. The registry’s missing primary endpoint result should not be interpreted as zero mortality, and the absence of secondary outcome estimates should not be interpreted as absence of those events. The reported safety entries are the available descriptive figures, with the limitations of their definitions and timing noted above.

The record therefore supports a description of the trial design, intended endpoint, treatment sequence, and reported safety terms. It does not support a conclusion about the magnitude or precision of Day 100 TRM, a comparative benefit or harm, or an overall assessment of the regimen’s effects.

14. Why This Trial Matters Statistically

This trial is statistically instructive because its primary question is framed as a proportion within a defined population and follow-up window, while the registry record does not report the estimate or its uncertainty. The contrast between a clearly named endpoint and unavailable numerical results illustrates why an endpoint definition alone cannot answer how often an outcome occurred or how precisely it was estimated.

The single-group design also makes the distinction between description and comparison important. A descriptive estimate can characterize outcomes in the treated group, but it does not supply a randomized counterfactual. Readers should distinguish a reported event frequency from a treatment effect, especially when the registry does not provide a comparator or an inferential analysis.

The safety record demonstrates another useful distinction: participant-level summaries and event-term percentages are not interchangeable. Multiple terms may relate to the same participant, and a safety listing does not necessarily match the attribution and timeframe of a separate primary endpoint. The record’s serious-event counts, term percentages, and Day 100 TRM definition therefore answer different questions.

Finally, the broad range of conditions listed makes the endpoint population definition and analysis details consequential. The registry names all treated and eligible patients as the primary population, but does not report the number analyzed, missing-data methods, or subgroup results. These features limit assessment of precision and of how outcomes may vary across the listed conditions. The statistical lesson is not a judgment about the regimen, but the need to keep design, endpoint, denominator, uncertainty, and comparison aligned when interpreting a clinical study.

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 immediate trial-specific limitation is that the registry record does not report the primary endpoint result. The observed Day 100 TRM estimate, event count, and exact 95% confidence interval are unavailable. Numerical results for the secondary outcomes are also not reported in the registry record, limiting assessment of the outcomes named in the study.

The study is single-group, with no random allocation or control arm recorded. It can therefore provide no randomized within-trial comparison with another treatment strategy. The registry’s broad condition list covers multiple types of hematologic cancer and bone marrow failure disorder, but it does not report subgroup outcome estimates or explain how the varied diagnoses were represented in analyses.

Several details needed to interpret the endpoint are not reported in the registry record: the number included in the primary analysis, the operational criteria for treatment-related mortality, the treatment of uncertain attribution, and the handling of incomplete follow-up. The primary population is described as all treated and eligible patients, but the record does not provide participant flow or explain how eligibility and treatment status determined inclusion.

The safety record provides serious-event figures and selected term percentages, but not event timing, causality assessments, overlap among terms, or the underlying event-level data. The arm description also ends with an incomplete note about melphalan, and the role of anti-thymocyte globulin is not specified in that description. Finally, the registry does not report the detailed statistical plan, sample-size justification, interim analyses, or multiplicity and missing-data procedures. These omissions constrain interpretation; they do not establish that such procedures were absent from the conduct of the study.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Fludarabine Phosphate, Melphalan, Total-Body Irradiation, Donor Stem Cell Transplant in Treating Patients With Hematologic Cancer or Bone Marrow Failure Disorders — NCT00856388.
• Registry record last updated 2019-11-13; status last verified 2019-10.
• Results first posted 2016-06-13.
• 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

NCT00856388 is a completed, single-group pilot trial sponsored by Roswell Park Cancer Institute. It evaluates reduced-intensity allogeneic stem cell transplantation following fludarabine phosphate, melphalan, and low-dose total-body irradiation in patients with hematologic cancer or bone marrow failure disorders. The registry lists enrollment of 62 and identifies Day 100 treatment-related mortality as the primary endpoint for all treated and eligible patients.

The registry describes an exact 95% confidence interval as planned for the primary endpoint, but the endpoint estimate and interval are not reported in the registry record. The serious-adverse-event record lists 34 affected among 62 at risk, while other events list 0 affected among 62 at risk. Numerical results for the listed secondary outcomes are not reported in the registry record. With no comparator or random allocation, the record supports descriptive interpretation only.