Multi-center Study of Myeloablative Allo Stem Cell Transplant for Non-remission AML Using CloBu4 Regimen: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Multi-center Study of Myeloablative Allo Stem Cell Transplant for Non-remission AML Using CloBu4 Regimen (NCT01457885), a na phase 2 study. The primary outcome is Cumulative Incidence of Non Relapse Mortality (NRM).

2. Clinical Question

The investigators also described a broader objective: assessing safety and efficacy, with one-year overall survival named as the measure of efficacy. The registry lists the percentage alive at 1 year and incidence of relapse as secondary outcomes. Those questions are distinct from the primary endpoint, which concerns non-relapse mortality.

The record gives no numerical result for the primary endpoint, overall survival, or relapse. It therefore does not permit a numerical assessment of any of these outcomes. Nor does the single-group design estimate how outcomes would compare with another conditioning regimen or with no transplant. The trial addresses what was observed in the treated study population, while a comparative treatment effect would require a suitable comparison design.

3. Trial Design

This was a multicenter, single-group phase II study of myeloablative allogeneic stem cell transplantation using the CloBu4 conditioning regimen for non-remission AML. The intervention description specifies Clofarabine/Busulfan x 4 followed by peripheral blood stem cell transplantation. Allocation is listed as not applicable, and masking is recorded as none. The registry does not describe a randomized or masked comparison.

The record reports 75 patients enrolled and 74 treated. It states that 3 pediatric patients were excluded from analysis. The analysis population is therefore described by those registry statements, but no further participant-flow detail or analysis denominator is reported for the primary endpoint. The brief summary says the investigators expected enrollment from about fifteen sites; the registry does not establish how many sites ultimately contributed patients.

The study started in 2011-11, had primary completion in 2014-11, and is marked completed. Its stated main objective was to assess safety and efficacy, with one-year overall survival identified as the efficacy measure. The recorded primary outcome, however, is cumulative incidence of non-relapse mortality at 1 year. The registry lists percentage alive at 1 year and incidence of relapse as secondary outcomes.

A single-group phase II study can describe outcomes among people receiving the regimen and can contribute evidence about feasibility and safety. Without a concurrent control group, it cannot isolate the regimen's effect from other influences on outcomes. The registry record does not report a protocol-level statistical plan, sample-size justification, planned interim analyses, or the criteria used to decide whether the study met its objectives.

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

Analysis population for the primary outcome, as defined in the registry: 75 patients were enrolled. Only 74 patients were treated. 3 of the 74 patients were pediatric and were therefore left off of analysis.

5. Baseline Characteristics

The table reproduces the baseline characteristics posted in the registry, which describe the participants analysed at baseline and help show whether the randomized groups were comparable.

Population: 75 patients were enrolled. Only 74 patients were treated. Of the treated patients, 3 were pediatric and were left off of the analysis. 71 adult patients were analyzed.

6. Primary Endpoint

The registry lists the primary outcome as Cumulative Incidence of Non Relapse Mortality (NRM), measured over 1 year.

The primary endpoint is cumulative incidence of non-relapse mortality (NRM), measured at 1 year and expressed as a percentage of patients. The registry describes it as the percentage of patients who “passed without relapse/recurrence” at 1 year. It does not provide a numerical endpoint estimate or confidence interval bounds, although it identifies a 95% confidence interval as the dispersion measure.

In general, NRM concerns mortality that occurs without a preceding relapse. It is relevant after transplantation because death without relapse and relapse are different outcomes, and relapse can affect whether a later death is classified as non-relapse mortality. In general, a cumulative-incidence measure is intended to describe the occurrence of an event over time while accounting for a competing event. The registry does not report the specific computational method or event-classification rules used for this endpoint, so those details cannot be confirmed for this analysis.

NRM complements overall survival rather than replacing it. Overall survival concerns whether a patient is alive at a given time, regardless of cause or relapse status; NRM focuses on mortality without relapse. The registry's secondary outcomes include the percentage alive at 1 year and incidence of relapse, but it does not report their numerical results.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry identifies a binary-percentage outcome type, meaning that the intended result is a percentage of participants with an event. The primary outcome is named as cumulative incidence of non-relapse mortality at 1 year. The record specifies a 95% confidence interval as the dispersion measure, but does not report the point estimate or interval bounds. Thus, readers can identify the intended summary and its uncertainty measure, but cannot assess the actual estimate or its precision.

What does a confidence interval describe?

In general, a confidence interval expresses statistical uncertainty around an estimate under a specified analysis and its assumptions. It is not a guarantee that the true value lies inside the interval, nor is it a measure of the range of individual outcomes. A narrower interval generally indicates greater precision, while a wider interval indicates more uncertainty. Here, the registry does not give the interval limits, so its width and the range of values compatible with the reported analysis cannot be assessed.

What does cumulative incidence mean?

In general, cumulative incidence describes the probability of an event occurring by a specified time when another event can prevent or alter its occurrence. For NRM, relapse is an important competing event: after relapse, a later death may not meet the definition of death without prior relapse. A cumulative-incidence approach is commonly used to distinguish such event types rather than treating every death as NRM. However, the registry does not describe the estimator, competing-event coding, censoring rules, or handling of follow-up. It is therefore not possible to verify which specific implementation was used.

What does the single-group design allow?

The study is recorded as phase II, single-group, with allocation not applicable and masking none. In general, a single-group design can report outcomes observed after participants receive the regimen, but it does not directly estimate a contrast against another regimen. The observed outcome can reflect treatment as well as patient characteristics, disease status, transplant procedures, and other aspects of care. Without a concurrent control group or a reported adjustment strategy, the registry cannot establish which factors account for an observed outcome.

The enrollment description states that 75 patients were enrolled, 74 were treated, and 3 pediatric patients were excluded from analysis. These are the only population-flow details reported for the primary endpoint. The record does not specify the denominator used for each outcome, how missing outcome data were handled, or whether all treated participants had the same follow-up opportunity. It also does not report a separate intention-to-treat analysis or a per-protocol analysis.

How should planning calculations be read?

Any sample-size calculations associated with the posted results are planning illustrations based on an observed effect, not observed power and not the trial's original design justification. The stated illustration assumptions are a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation, with the effect set to a stated fraction of the observed effect. Those assumptions describe a hypothetical two-arm planning framework, whereas this trial is recorded as single-group. The registry does not report the trial's own sample-size justification, and the planning assumptions should not be mistaken for the protocol's analysis plan. No calculated sample-size values are stated in this record, so none can be interpreted numerically.

In general, sample-size planning asks how many participants would be needed to detect a chosen effect under specified assumptions. It depends on the outcome, target effect, variability or event frequency, significance level, power target, allocation, and analysis method. A planning illustration changes when its assumed effect changes. It does not show that a completed study had a particular probability of finding a result, and it cannot substitute for an estimate with an uncertainty interval.

What statistical details are missing?

The registry record does not report the statistical test or estimator for the primary endpoint, adjustment variables, censoring approach, missing-data method, multiplicity strategy, or interim-analysis plan. It does not provide an analysis-population definition beyond the statement that pediatric patients were excluded. These omissions matter because methods determine how outcomes are classified and summarized. Without them, a reader can explain the endpoint's general statistical meaning but cannot reconstruct or independently assess the trial's analysis.

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("CloBu4 Regimen")
n      <- c(71)
events <- c(15)
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  CloBu4 Regimen  71  15  21.1  12.3  32.4  13.2  32.0  13.3  32.0

11. Multiplicity, Missing Data and Analysis Populations

The registry lists one primary outcome and two secondary outcomes: the percentage of patients alive at 1 year and incidence of relapse. It reports zero analyses, and the record contains no numerical result for any of these outcomes. It does not report whether investigators adjusted for testing multiple outcomes, prespecified a testing hierarchy, or treated secondary analyses as descriptive. The approach to multiplicity is therefore not reported in the registry record.

In general, when several outcomes or statistical comparisons are examined, the chance of at least one apparently notable result can increase. A prespecified multiplicity strategy can control or otherwise describe that issue. The absence of a reported strategy does not show that no strategy existed; it means the registry record does not establish what was planned or used. No inference about statistical significance can be made from the outcome list alone.

Missing-data handling is also not reported. The record does not state how participants without a recorded one-year outcome, incomplete follow-up, or other unavailable measurements were treated. It gives enrollment, treatment, and pediatric-exclusion information, but does not give a complete participant flow or outcome-specific denominators. The stated exclusion of 3 pediatric patients identifies one population decision; it does not explain all analysis-population rules.

The record says that 75 patients were enrolled and 74 were treated. It does not state whether the primary endpoint analysis included every treated participant after the pediatric exclusion, nor does it describe any alternative analysis populations. A complete interpretation would require outcome denominators, missingness details, and the analysis methods. Those details are not reported in the registry record.

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

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: sepsis (9.5%), diarrhea (6.8%), fatigue (5.4%), respiratory failure (5.4%), infections and infestations - other (4.1%).

The adverse-event summary lists one CloBu4 group with 74 participants at risk for serious adverse events and 38 affected. It separately reports 74 at risk and 17 affected for other adverse events. These are registry counts, not a measure of comparative risk: the study has no control group. The record does not explain whether an affected participant could contribute to multiple event terms or how events were attributed to treatment.

The serious adverse-event terms with listed percentages are Sepsis, 9.5%; Diarrhea, 6.8%; Fatigue, 5.4%; Respiratory failure, 5.4%; Infections and infestations - Other, 4.1%; and Lung infection, 4.1%. These percentages are presented as term-level summaries. The registry does not state the event-timing window, duration, severity grading details, or whether the percentages are based on participants or event episodes, so those features should not be assumed.

The deaths entry is not reported. The listed terms do not constitute a complete safety profile, and they do not by themselves establish causality or comparative safety. They should be read as descriptive registry entries from the study group.

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

The record establishes that a phase II, single-group study of CloBu4 conditioning and peripheral blood stem cell transplantation was completed and that it enrolled 75 patients. It also records 74 treated patients and states that 3 pediatric patients were excluded from analysis. Its primary outcome is cumulative incidence of non-relapse mortality at 1 year, while overall survival and relapse are listed among secondary outcomes.

What the registry record does not establish is the observed numerical value of the primary outcome, its confidence interval, or the numerical secondary-outcome results. Without those estimates, there is no basis in this record for describing the observed rate, its precision, or whether it met a target. The study's completion status is not itself evidence of a favorable or unfavorable outcome.

The single-group design also does not show how outcomes compare with another conditioning regimen. Even if outcome estimates were available, a descriptive result in one treated group would not alone identify a causal effect of CloBu4. A comparison would need an appropriate control and an analysis that addresses differences between groups.

The safety entries provide counts and selected serious adverse-event terms, but not full detail on timing, attribution, recurrence, or comparative risk. They can describe reported events in the study group, not prove that the regimen caused them or establish how the event frequency differs from another treatment.

In general, a registry record is most informative when endpoint definitions, analysis populations, methods, estimates, and uncertainty measures are all reported together. Here, the study question and some design and safety details are available, but key outcome and analysis information is not reported in the registry record. Interpretation should remain limited to those documented details.

14. Why This Trial Matters Statistically

This trial is statistically relevant because it focuses on a population the investigators describe as having poor transplant results: non-remission AML. Its stated rationale is that earlier work suggested replacing Fludarabine in a standard FluBu4 regimen with Clofarabine might increase anti-leukemia activity without adding significant toxicity. That is the investigators' rationale, not a result established by this registry record.

The primary outcome also illustrates why outcome definitions matter. Overall survival and non-relapse mortality answer different questions. Overall survival records whether a person is alive at a specified time, whereas NRM focuses on mortality without relapse. Relapse is relevant to how NRM is classified, so the choice of endpoint and its competing-event method can affect interpretation. The registry names the endpoint and time point but does not report the analytical details or estimate.

The design is statistically important as well. A single-group phase II study can describe outcomes after a regimen in a selected population, but cannot provide a randomized comparison. This limits causal conclusions, especially when outcomes may reflect disease status, transplant practice, or other features in addition to conditioning. The absence of a numerical endpoint result further means that even the descriptive outcome cannot be evaluated from this record.

Finally, the different population counts and the exclusion of pediatric patients underline the importance of a clear analysis population and outcome-specific denominators. The record gives some enrollment and treatment information, but not enough detail to reconstruct every analysis set. For clinical researchers, the case demonstrates the value of complete reporting: an endpoint estimate, uncertainty interval, analysis methods, missing-data handling, and population flow are all needed to interpret a trial result responsibly.

15. Limitations

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

The most consequential limitation of the registry record is that it does not report numerical estimates for the primary NRM endpoint or the secondary outcomes of one-year survival and relapse. Although the primary endpoint description names a 95% confidence interval, its bounds and point estimate are absent. The record therefore does not support an assessment of outcome magnitude or precision.

The single-group design limits interpretation even apart from missing results. There is no concurrent comparator, and the record does not report a randomized allocation or an adjusted comparative analysis. Outcomes cannot be used to estimate a treatment contrast against another regimen from these registry entries alone.

Important analysis details are also absent. The registry does not describe the endpoint estimator, competing-event implementation, censoring rules, outcome-specific denominators, missing-data handling, multiplicity approach, or interim analyses. It does not give a full participant-flow account. The reported enrollment and treatment counts and pediatric exclusion are informative, but do not resolve these issues.

Safety reporting is limited to group counts and selected serious adverse-event terms. The record does not provide the deaths entry, event timing, attribution, duration, recurrent-event information, or a comparator. The summary therefore cannot establish causality or provide a complete account of safety.

The registry describes an expected enrollment from about fifteen sites, but does not report how many sites ultimately enrolled participants. It also does not report the study's sample-size justification or detailed statistical plan. These gaps limit assessment of both generalizability and the design's intended operating characteristics.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Multi-center Study of Myeloablative Allo Stem Cell Transplant for Non-remission AML Using CloBu4 Regimen — NCT01457885.
• Registry record last updated 2017-06-02; status last verified 2017-05.
• Results first posted 2016-07-25.
• 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

NCT01457885 is a completed, multicenter, single-group phase II study of CloBu4 conditioning followed by peripheral blood stem cell transplantation for non-remission AML. The registry reports enrollment of 75 patients and treatment of 74; it says 3 pediatric patients were excluded from analysis. The study started in 2011-11 and reached primary completion in 2014-11.

The primary endpoint is cumulative incidence of non-relapse mortality at 1 year, with a 95% confidence interval specified as the dispersion measure. The record does not report the endpoint estimate or interval bounds. Percentage alive at 1 year and incidence of relapse are listed as secondary outcomes, but their numerical results are also not reported. Selected serious adverse-event counts and term-level percentages are available. The single-group design does not provide a direct comparison with another regimen.