Fludarabine, Cyclophosphamide, and Total-Body Irradiation in Treating Patients Who Are Undergoing a Donor Bone Marrow Transplant for Hematologic Cancer: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Fludarabine, Cyclophosphamide, and Total-Body Irradiation in Treating Patients Who Are Undergoing a Donor Bone Marrow Transplant for Hematologic Cancer (NCT00134004), a na phase 2 study. The primary outcome is Transplant-related Mortality.

2. Clinical Question

The study asks about transplant-related mortality following a non-myeloablative, partially HLA-mismatched donor bone marrow transplant using fludarabine, cyclophosphamide, and total-body irradiation as conditioning. The registered population includes patients with hematologic malignancies and related disorders, including leukemia, lymphoma, multiple myeloma and plasma cell neoplasm, myelodysplastic syndromes, and chronic myeloproliferative disorders. The record describes a transplant regimen intended for patients undergoing donor bone marrow transplantation.

This is a study of outcomes after a specified transplant approach, not a randomized test against another conditioning regimen or transplant strategy. Its primary question concerns a defined mortality endpoint. Although the registry record also lists graft failure and hematologic and non-hematologic toxicities among secondary outcomes, the primary outcome result is not reported in the registry record.

3. Trial Design

This is a phase II, single-group trial registered as NCT00134004. Its official title describes non-myeloablative conditioning and transplantation of partially HLA-mismatched bone marrow for patients with hematologic malignancies. The registry lists the allocation as NA, masking as none, and the model as single group. Those design features mean that the record does not describe random assignment to competing treatment arms or a masked comparison.

The listed intervention combines drug treatment, radiation therapy, and an allogeneic bone marrow transplant. The arm description identifies a non-myeloablative haploidentical transplant with fludarabine, cyclophosphamide, and total-body irradiation as the preparative regimen. It also identifies post-transplant cyclophosphamide, mycophenolate mofetil, and tacrolimus for GVHD prophylaxis. These details describe the treatment strategy registered for the study; they do not by themselves establish the treatment’s effects.

The registry reports enrollment of 210. The study status is completed, with a start date of 2004-10 and a primary completion date of 2015-01. These dates and the enrollment figure describe the registered study, not the number of participants with complete follow-up or an analyzed population. Those analysis-population details are not reported in the registry record.

The primary outcome is transplant-related mortality, defined in the record as the percentage of participants who die for any reason other than recurrence of disease. Its timeframe is cumulative incidence for the entire study, up to 11 years. The listed secondary outcomes include graft failure rate and hematologic and non-hematologic toxicities measured using NCI Common Toxicity Criteria for Adverse Events, v 3.0, with weekly assessment until 1 year after transplantation.

A single-group design can describe outcomes among participants treated under the registered strategy, but it cannot by itself isolate the strategy’s effect relative to another approach. The registry record does not report a statistical analysis plan, details of eligibility criteria, or a rationale for the enrollment target.

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

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 Transplant-related Mortality, measured over Cumulative incidence for the entire study, up to 11 years.

The primary endpoint is transplant-related mortality, expressed as a percentage of participants. The registry defines it as death for any reason other than recurrence of disease and describes the measure as cumulative incidence over the entire study, up to 11 years. This definition is important: it identifies which deaths count toward the endpoint and distinguishes them from deaths following disease recurrence.

In general, mortality endpoints are used to describe a consequential outcome after treatment. A cumulative-incidence measure describes the occurrence of a particular event over time while accounting for the fact that another event can prevent that event from being observed. In this study’s definition, recurrence matters because a death after recurrence is excluded from the transplant-related mortality endpoint. The specific estimator and handling of recurrence in the analysis are not reported in the registry record.

The registry record does not report the primary endpoint’s numerical result, an uncertainty interval, or an analysis population for that result. Therefore, the endpoint definition and follow-up timeframe can be described, but the observed cumulative incidence and its precision cannot be assessed from the reported information. The endpoint label should not be read as proof that a death was caused by the transplant; the registered operational definition includes any death other than recurrence.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry identifies a single-group study and a cumulative-incidence primary endpoint, but it does not report the detailed statistical methods used to estimate or compare outcomes. The explanations below are general statistical context, not a claim about analyses conducted in this study. The registry record does not report a statistical analysis plan, an estimator, confidence intervals, hypothesis tests, or adjusted analyses.

What does a single-group design tell us?

In general, a single-group study describes outcomes among participants receiving a specified intervention. It can characterize what happened in the enrolled group, provided the outcome and analysis are reported clearly. Without a concurrent comparison group, it cannot distinguish the effect of the intervention from other influences on outcomes. For example, participant characteristics, changes in supportive care, and differences in follow-up could contribute to observed outcomes. This is why a single-group result should not be interpreted as a randomized treatment contrast.

In this record, the intervention is a transplant strategy involving non-myeloablative conditioning, a partially HLA-mismatched donor bone marrow transplant, and post-transplant medications. The registry identifies the design as single group and allocation as NA. It therefore does not define a treatment contrast for which a between-group effect estimate could be reported. No causal comparison against another regimen is available from the registered design information.

What is cumulative incidence?

In general, cumulative incidence estimates the probability of experiencing a specified event over time while recognizing that a competing event can occur first and alter whether the event of interest can subsequently be observed. This differs from methods that treat every event other than the event of interest as if it were ordinary loss to follow-up. Which approach is appropriate depends on the question and the event structure.

The registered endpoint counts death for any reason other than recurrence of disease. Recurrence is therefore relevant to how the endpoint is defined. The record calls the measure cumulative incidence and gives the timeframe as the entire study, up to 11 years, but the exact estimator, event coding, and handling of recurrence are not reported in the registry record. The endpoint label alone does not reveal those technical choices.

Why does uncertainty matter?

In general, an estimate from a study is subject to sampling variability. A confidence interval conveys a range of values compatible with the data under the method’s assumptions. A narrow interval indicates greater precision than a wide interval, though precision does not remove possible bias or limitations in design. A point estimate without an uncertainty measure gives an incomplete picture of how precisely an outcome has been estimated.

No primary outcome estimate or confidence interval is reported in the registry record. Therefore, neither the magnitude nor precision of the primary endpoint can be evaluated from the reported information. A p-value is also not reported, and the single-group design does not specify a comparator against which a treatment effect would be tested.

How should event counts and percentages be read?

In general, an event count records the number of observed events or affected participants according to a defined reporting convention, while a percentage expresses a numerator relative to a denominator. Interpretation depends on whether the numerator counts people, events, or event episodes, and on the denominator and observation period. Participants may experience more than one event, so categories are not necessarily mutually exclusive.

The registry reports serious adverse-event and other adverse-event counts for the Mini-haplo BMT group, along with percentages for selected serious-event terms. It does not report the denominator basis for those term percentages or clarify whether each term counts participants or events. The counts and listed percentages should therefore be read as registry-reported safety entries, not as a complete incidence analysis with a specified time-at-risk method.

What do planning calculations mean?

In general, sample-size calculations are planning illustrations based on assumptions about the outcome, effect to detect, allocation, significance level, and statistical method. They are not observed clinical outcomes. A calculation that uses an effect estimated from study data is especially dependent on that estimate and should not be mistaken for an independent confirmation of the effect. Sample sizes are planning illustrations, never observed power.

The registry record does not report the study’s own sample-size justification or a statistical plan. Any planning figures should therefore not be treated as evidence about the observed endpoint, and they cannot replace a reported estimate with uncertainty. The record’s enrollment figure is 210, but enrollment alone does not establish the number analyzed or whether the study met a prespecified precision or power target.

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("Mini-haplo BMT")
n      <- c(210)
events <- c(38)
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  Mini-haplo BMT  210  38  18.1  13.1  24.0  13.5  23.9  13.5  23.9

11. Multiplicity, Missing Data and Analysis Populations

The registry lists a primary outcome and secondary outcomes that include graft failure rate and hematologic and non-hematologic toxicities. It also reports five outcome measures, but the registry record does not describe a multiplicity strategy or state whether the outcomes were organized into a formal hierarchy. When a study evaluates multiple outcomes, the chance of at least one apparently notable result can increase if each is assessed independently. General approaches to multiplicity include prioritizing a primary endpoint or adjusting inferential thresholds, but whether either approach was used in this study is not reported in the registry record.

The registry reports zero analyses. It does not provide outcome estimates, confidence intervals, p-values, or a detailed analysis plan. It also does not report how missing observations or incomplete follow-up were handled, whether participants were analyzed according to a defined analysis population, or how participants who experienced recurrence were included in the mortality analysis. These omissions limit assessment of the results and of the methods used to address incomplete data.

In general, missing-data methods can affect an estimate when the likelihood of missingness is related to a participant’s outcome or characteristics. Reporting the amount and pattern of missing data, as well as the analysis population and assumptions, helps readers evaluate that risk. None of those details is reported for the primary endpoint in the registry record. Enrollment of 210 should not be interpreted as evidence that all enrolled participants contributed complete endpoint data.

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: respiratory failure (3.8%), sepsis (2.9%), pneumonia (2.4%), renal failure (1.9%), fungemia (1.4%).

The registry reports safety figures for the Mini-haplo BMT group. It lists 210 at risk for serious adverse events, with 20 affected, and 210 at risk for other adverse events, with 11 affected. These are separate registry entries; they should not be added together or assumed to represent mutually exclusive participants. The record does not report whether the affected counts refer to individuals or event episodes in a way that resolves possible overlap.

For serious events, the listed terms and percentages are respiratory failure at 3.8%, sepsis at 2.9%, pneumonia at 2.4%, renal failure at 1.9%, fungemia at 1.4%, and subdural hematoma at 1.4%. The denominator and method used to calculate these term percentages are not reported in the registry record. The listed terms are not a complete account of all possible adverse events, and the figures do not establish a comparison with another regimen.

The death count in the adverse-event entry is not reported in the registry record. These safety entries also do not supply the missing numerical result for the primary transplant-related mortality endpoint. They describe reported adverse-event categories and should be interpreted separately from that endpoint.

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

The record establishes that a phase II, single-group study evaluated a non-myeloablative, partially HLA-mismatched donor bone marrow transplant strategy for hematologic malignancies and related disorders. It identifies the preparative regimen, post-transplant GVHD prophylaxis, primary endpoint definition, and study timeframe. It also records enrollment of 210 and selected adverse-event information.

What the record does not establish is the numerical result for transplant-related mortality. Although the endpoint is defined as cumulative incidence of death for any reason other than recurrence of disease, its observed value and uncertainty are not reported in the registry record. Without those results, the primary outcome cannot be quantified from the registry information. The listed adverse-event counts and percentages do not fill that gap.

The design also limits what could be concluded even if an outcome estimate were available. A single-group study can describe outcomes in its enrolled population, but it does not provide a randomized, concurrent contrast against another treatment strategy. It cannot by itself show that the regimen caused an outcome or establish how outcomes would differ under an alternative approach.

These limitations do not make the registry information meaningless. The record identifies the clinical question and documents the treatment approach and outcome categories that were registered. It can support a careful account of the study’s design and reporting. It cannot support a claim that the treatment works or does not work, a comparison with another regimen, or a conclusion about the primary endpoint’s frequency or precision. Those conclusions require results and methods that are not reported in the registry record.

14. Why This Trial Matters Statistically

This study is statistically informative as an example of why design and outcome reporting must be read together. The registry defines a clinically consequential primary endpoint and gives a cumulative-incidence timeframe of up to 11 years. It also identifies the endpoint’s operational boundary: deaths after recurrence are not counted as transplant-related mortality. That definition matters because the way competing events are handled affects what a cumulative-incidence estimate represents.

The single-group design is equally important. It frames the study as an evaluation of outcomes following a treatment strategy, not a randomized comparison. Even a fully reported event rate would describe outcomes in the treated group rather than isolate the effect of the regimen relative to an alternative. Statistical interpretation must match the design rather than treating a study’s treatment description as evidence of comparative benefit.

The record also illustrates the distinction between enrollment and analysis. Enrollment is reported as 210, but the registry does not report the primary outcome estimate, analysis population, or missing-data handling. Readers need those details to assess how much information contributed to an estimate and how precisely it was measured. In their absence, the primary outcome cannot be quantitatively interpreted.

Finally, the safety entries show why denominators and reporting definitions matter. Counts and event-term percentages are not self-interpreting when the record does not specify their denominator basis or whether entries can overlap. The useful statistical lesson is to separate what the registry establishes—the design, endpoint definition, and reported safety entries—from what remains unreported, including the primary endpoint result and its uncertainty.

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 this study from the registry record is that the primary transplant-related mortality result is not reported. No estimate or uncertainty measure is available, so the primary outcome’s observed frequency and precision cannot be assessed. The record also reports zero analyses and does not provide a detailed statistical analysis plan.

The single-group design offers no concurrent control group. As a result, the registry information cannot support a treatment-effect comparison with another transplant approach, and outcomes cannot be attributed to the regimen alone. Allocation is listed as NA and masking as none. These features should be considered alongside the absence of comparative results.

The registry reports enrollment of 210 but does not report the primary endpoint analysis population, completeness of follow-up, or handling of missing observations. It also does not specify the estimator used for cumulative incidence or the exact analytical handling of recurrence. Those details matter for assessing the endpoint and its precision.

Safety reporting is also incomplete for interpretation: the record does not report the denominator basis for the selected serious-event percentages or clarify whether event entries count people or episodes. The death count in the adverse-event entry is not reported in the registry record. The sample-size justification, interim analyses, eligibility details, and outcome multiplicity approach are also not reported in the registry record. These limitations concern what can be concluded from the registered information; they do not establish that unreported methods or results were absent from the conduct of the study.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Fludarabine, Cyclophosphamide, and Total-Body Irradiation in Treating Patients Who Are Undergoing a Donor Bone Marrow Transplant for Hematologic Cancer — NCT00134004.
• Registry record last updated 2015-10-06; status last verified 2015-09.
• Results first posted 2015-08-24.
• 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

NCT00134004 is a completed phase II, single-group study of non-myeloablative conditioning and partially HLA-mismatched donor bone marrow transplantation for hematologic malignancies. The registered strategy includes fludarabine, cyclophosphamide, and total-body irradiation, with post-transplant cyclophosphamide, mycophenolate mofetil, and tacrolimus described for GVHD prophylaxis. Enrollment is 210. The study start date is 2004-10 and the primary completion date is 2015-01.

The primary endpoint is cumulative incidence of death for any reason other than recurrence of disease, over the entire study timeframe of up to 11 years. The primary outcome estimate and its uncertainty are not reported in the registry record. The registry also lists graft failure and hematologic and non-hematologic toxicities as secondary outcomes, and reports selected adverse-event counts and serious-event terms. With no comparator group and no reported primary endpoint result, the record supports description of the study design and registered question, but not a quantitative conclusion about the primary outcome or a comparative treatment effect.