Reduced Intensity Donor Peripheral Blood Stem Cell Transplant in Treating Patients With De Novo or Secondary Acute Myeloid Leukemia in Remission: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Reduced Intensity Donor Peripheral Blood Stem Cell Transplant in Treating Patients With De Novo or Secondary Acute Myeloid Leukemia in Remission (NCT00045435), a na phase 2 study. The primary outcome is Disease-free Survival-incidence of Survival Without Relapse.

2. Clinical Question

3. Trial Design

This was a phase II, single-group study of nonmyeloablative allogeneic PBSC transplantation for patients with de novo or secondary AML in remission. The official title specifies first complete remission and older patients. The registry record lists enrollment of 17 and identifies Fred Hutchinson Cancer Center as the sponsor. Study start is recorded as 2002-04, primary completion as 2009-01, and status as completed.

All participants were assigned to the treatment strategy; there was no randomized allocation and no control arm. Masking is recorded as none. These design features mean the trial describes outcomes in a treated group, rather than estimating a randomized contrast between transplant and another treatment or no transplant. Any comparison with outcomes from another population would require separate data and assumptions not reported in the registry record.

The treatment description combines reduced-intensity conditioning with donor cell transplantation and post-transplant immunosuppression. Participants received fludarabine phosphate intravenously on days -4 to -2 and total-body irradiation on day 0, with allogeneic PBSC transplant on day 0. The description says cyclosporine was given orally twice daily on days -3 to 56, with taper to day 77. The mycophenolate mofetil schedule is incomplete in the registry record; its full dosing details are not reported in the registry record.

The registry lists overall survival, relapse, rejection, and acute and chronic graft-versus-host disease among secondary outcomes. It identifies six outcome measures and two analyses, but detailed definitions and analysis methods for the secondary outcomes are not reported in the registry record. Enrollment is the only overall participant count reported in the trial information; numbers analyzed for the primary endpoint 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

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 Disease-free Survival-incidence of Survival Without Relapse, measured over By 1 year after transplant.

The primary endpoint is described as disease-free survival, with the title clarifying the concept as survival without relapse. Its timeframe is by one year after transplant, and the unit is percentage of participants. In broad terms, a disease-free survival endpoint combines being alive with remaining free of the specified disease event during the stated follow-up period. This can summarize more than relapse alone, but the precise operational definition, including how deaths and other events were handled, is not reported in the registry record.

As a general statistical concept, a time-specific disease-free survival measure focuses on the proportion of a study population remaining alive and without the defined event by a chosen time. It is useful when both relapse and death are relevant to the clinical course, provided that the event definition and follow-up rules are clear. The registry record’s title and description indicate survival without relapse, but do not give enough detail to establish every component of the endpoint.

The registry states that sufficient evidence would be an observed one-year DFS rate corresponding to a one-sided 95% confidence interval whose upper limit is lower than 35%. This is a stated decision criterion, not a reported result. The observed rate, confidence interval, and endpoint analysis are not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The statistical information available in the registry record is limited. It identifies a percentage-based primary endpoint and a planned decision criterion, but does not report the observed outcome, confidence interval, analysis population, or detailed analysis procedure. The explanations below distinguish the registry’s stated plan from general statistical concepts.

What does a confidence interval describe?

As a general statistical concept, a confidence interval expresses uncertainty around an estimate under a specified statistical method. A narrower interval indicates greater precision under that method; a wider interval indicates more uncertainty. The interval does not guarantee that the true value lies within its particular bounds, and it does not replace the point estimate or the assumptions used in the analysis. In this trial, the registry describes a one-sided 95% confidence interval criterion, but does not provide the interval itself or the method used to calculate it.

A one-sided interval focuses on one direction of uncertainty rather than giving bounds in both directions. The registry states that its criterion uses an upper limit lower than 35% for the one-year DFS rate. That wording is the posted criterion. The record does not explain why this threshold and direction were selected, so no rationale should be inferred. Without an observed rate and its interval, neither the estimate nor whether it met the stated criterion can be assessed.

What does the single-group design allow?

As a general concept, a single-group study can describe outcomes observed among people who received a specified treatment strategy. It does not create a randomized control group, so it cannot provide a randomized estimate of the difference between that strategy and an alternative. In this trial, allocation is recorded as not applicable, masking as none, and the model as single group. The design therefore supports a within-group description, subject to available follow-up and outcome reporting, rather than a direct between-group comparison.

Enrollment of 17 describes the number entered in the trial, not necessarily the number with complete information at the endpoint. In general, endpoint analyses may use fewer participants if follow-up or outcome data are unavailable, but the number analyzed and the handling of missing observations are not reported in the registry record. No inference about completeness can be made from enrollment alone.

Why does the event definition matter?

As a general matter, disease-free survival depends on which events count as failures, when follow-up begins, and how participants without a recorded event are handled. A time-to-event analysis can account for different follow-up durations, while a percentage at a fixed time can summarize status at that time; the choice and implementation affect interpretation. The registry describes the endpoint as survival without relapse by one year after transplant, but the detailed operational definition and statistical method are not reported in the registry record. In particular, it is not stated how deaths, withdrawals, or incomplete follow-up contribute to the endpoint.

General statistical methods for time-to-event outcomes may also need to address competing events. For example, an event that prevents a later relapse from being observed can affect how relapse is estimated. This is a general methodological issue, not evidence that a particular approach was used in this study. The registry record does not report whether competing-risk methods were used for relapse or other secondary outcomes.

What can the serious-event percentages establish?

As a general concept, an adverse-event percentage describes the frequency recorded within a defined group and observation period. Interpretation depends on how the event was defined, how long participants were followed, whether each participant can contribute more than one event, and whether events may overlap. For the serious events listed in this record, the treatment group has 17 participants at risk and 5 affected. The record does not report the observation window, event-level counts, or participant-level overlap for the listed terms. The percentages attached to individual terms should therefore be read as registry-reported figures, not as a complete account of safety or proof that treatment caused an event.

The record names six outcome measures and two analyses, but does not give a full statistical analysis plan. It does not report the estimator, model, treatment of missing data, or any adjustment strategy for multiple outcomes. As a result, methodological details beyond the stated endpoint and interval criterion cannot be reconstructed 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("Treatment (Nonmyeloablative Donor PBSC Transplant)")
n      <- c(17)
events <- c(8)
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 (Nonmyeloablative Donor PBSC Transplant)  17  8  47.1  23.0  72.2  26.2  69.0  26.0  69.2

11. Multiplicity, Missing Data and Analysis Populations

Multiplicity arises when several outcomes or statistical tests are examined: the chance of at least one apparently notable result can increase unless the analysis plan accounts for the number and relationship of the tests. This is a general statistical issue. The registry record lists six outcome measures and two analyses, including the primary endpoint and secondary outcomes such as overall survival, relapse, rejection, and acute and chronic graft-versus-host disease. It does not report whether these outcomes were tested inferentially, which analyses were confirmatory, or whether any multiplicity adjustment or testing hierarchy was used. No adjustment should be assumed.

The registry describes the primary endpoint’s one-sided confidence-interval criterion, but a complete analysis plan is not reported in the registry record. The record does not state whether there were interim analyses, how the sample size was justified, or how departures from the planned analysis would be handled. These details are not reported in the registry record and cannot be inferred from the phase II designation or enrollment.

Missing data are another important consideration. The total enrollment was 17, but the number with evaluable one-year endpoint information is not reported in the registry record. The record also does not explain how loss to follow-up, withdrawal, or other unavailable outcome information was handled. Without these details, it is not possible to assess whether the reported endpoint population, if any, would match all enrolled participants or how missing observations could affect the estimate.

The analysis populations are not described in sufficient detail. The record does not state whether the primary analysis included all enrolled participants, only those who received transplant, or another defined group. It also does not provide participant flow or exclusions from analyses. These omissions limit assessment of the endpoint’s denominator and the potential impact of missing or excluded participants.

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 (11.8%), flank pain (5.9%), gvhd (5.9%), secondary malignancy (5.9%), ventricular arrhythmia (5.9%).

The serious adverse event listing identifies the treatment group, with 17 participants at risk and 5 affected by serious adverse events. It also reports 4 affected by other adverse events. These are separate registry counts; they should not be added together or treated as mutually exclusive categories without further information. The record does not explain whether any participant contributed to both categories.

The registry lists sepsis at 11.8%, and flank pain, GVHD, secondary malignancy, and ventricular arrhythmia at 5.9% each among the top serious-event terms. These are reported percentages for the terms as recorded. The registry information does not specify the number of episodes per term, the timing or duration of events, whether a participant had multiple listed events, or the period during which events were collected.

As a general interpretation point, a serious adverse event listing does not by itself establish that the treatment caused an event. It also does not provide a complete comparison of safety between treatment options, because this was a single-group study without a concurrent control arm. The registry record does not report a complete event narrative, causal assessment, or follow-up period for the serious-event figures. They should therefore be read as reported safety counts and terms, not as a comparative risk estimate.

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

The record describes a completed phase II study of nonmyeloablative allogeneic PBSC transplantation in patients with de novo or secondary AML in remission. It records enrollment of 17, a single treatment group, and a primary endpoint of disease-free survival by one year after transplant. The treatment description includes fludarabine phosphate, total-body irradiation, donor PBSC transplantation, cyclosporine, and mycophenolate mofetil.

Those design and treatment details do not establish what one-year disease-free survival was. The observed endpoint rate and confidence interval are not reported in the registry record. The stated one-sided 95% confidence-interval criterion is a planned standard for interpreting the endpoint, not a result. It cannot be determined from the available record whether the observed data met that criterion.

The single-group design also does not show how outcomes compare with another treatment strategy. A descriptive result, if reported, would apply to the participants and follow-up represented in that analysis. It would not, by itself, isolate the effect of transplantation from other influences. This does not mean the treatment had no effect; rather, a randomized comparison is not part of this trial’s design.

The serious adverse event listing offers selected counts and terms, including reported percentages for several events. It does not establish causality, provide a full account of event timing or overlap, or permit comparison with an untreated or alternatively treated group. Likewise, the listed secondary outcomes cannot be interpreted numerically because their results are not reported in the registry record.

In short, the registry supports an account of the study question, structure, participant count, intervention, and certain safety entries. It does not provide the central numerical efficacy result, its precision, or sufficient details to evaluate missing outcome information and the analysis population. The appropriate conclusion is limited to what the record documents, without inferring a favorable or unfavorable treatment effect.

14. Why This Trial Matters Statistically

This trial is statistically instructive because its primary question is expressed through a one-year disease-free survival endpoint and a confidence-interval criterion, while the posted record does not report the endpoint estimate or interval. That contrast illustrates why a planned threshold and an observed result must be kept distinct. A decision rule describes how evidence is intended to be assessed; it cannot substitute for the result needed to assess it.

The single-group structure is also important. It can frame a description of outcomes among participants receiving the transplant strategy, but it does not supply a randomized contrast. Readers must distinguish a within-group outcome from an estimate of how outcomes differ under an alternative. This distinction is fundamental when interpreting clinical studies that do not include a control group.

The enrollment of 17 makes transparent reporting of participant flow and endpoint completeness especially relevant. The registry record does not state how many participants contributed to the primary analysis or how missing data were handled. Without those details, even a reported percentage would need its denominator and follow-up context to be understood. This is a general principle of interpreting clinical endpoints, not a claim about unreported trial outcomes.

Finally, the record lists several secondary outcomes and serious adverse event terms, but does not provide the complete analysis plan or detailed outcome results. These gaps demonstrate why statistical interpretation depends not only on an endpoint label, but also on outcome definitions, analysis methods, follow-up, multiplicity decisions, and transparent reporting. The record is useful for identifying the design and intended question, while its limits prevent a numerical conclusion about the primary outcome.

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 limitation for interpretation is that the registry record does not report the observed primary endpoint rate or its confidence interval. As a result, the stated one-year DFS criterion cannot be evaluated from the record. The detailed definition of disease-free survival, including the handling of death and other events, is also not reported in the registry record.

The trial enrolled 17 participants and had no concurrent comparison group. Its design therefore cannot provide a randomized estimate of the difference between this transplant strategy and an alternative. The registry record does not report participant flow, the number analyzed for the primary endpoint, or endpoint follow-up completeness. The analysis population and handling of missing data are not reported in the registry record.

Intervention details are incomplete in the arm description: the mycophenolate mofetil schedule is truncated, and the full regimen details are not reported in the registry record. Although secondary outcomes are listed, their definitions, results, follow-up periods, and analysis methods are not described in the information available. The registry also does not report a full statistical analysis plan, including whether multiplicity was addressed or whether interim analyses occurred.

Safety interpretation is limited by the lack of information about event timing, duration, overlap, and the observation period. The listed serious adverse event counts and percentages do not establish causality or permit a comparative safety assessment. These limitations concern what the registry record documents; they should not be taken as evidence that unreported analyses or information did not exist elsewhere.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Reduced Intensity Donor Peripheral Blood Stem Cell Transplant in Treating Patients With De Novo or Secondary Acute Myeloid Leukemia in Remission — NCT00045435.
• Registry record last updated 2020-01-29; status last verified 2020-01.
• Results first posted 2017-03-16.
• 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 evaluated nonmyeloablative allogeneic donor PBSC transplantation in a single group of patients with de novo or secondary AML in remission. The official title specifies older patients in first complete remission. Enrollment was 17; allocation is recorded as not applicable, and masking as none. The sponsor is Fred Hutchinson Cancer Center.

The intervention description includes fludarabine phosphate, total-body irradiation, donor PBSC transplantation, cyclosporine, and mycophenolate mofetil. The primary endpoint was disease-free survival by one year after transplant, described as survival without relapse, with a stated one-sided confidence-interval criterion. The observed primary result and its confidence interval are not reported in the registry record.

Secondary outcomes include overall survival, relapse, rejection, and acute and chronic GVHD. Serious adverse event counts and selected terms are listed, but the record does not provide enough detail for causal or comparative interpretation. The single-group design does not provide a randomized treatment comparison.