Donor Natural Killer Cells and Aldesleukin in Treating Patients w/High Risk AML Undergoing Donor Stem Cell Transplant: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Donor Natural Killer Cells and Aldesleukin in Treating Patients w/High Risk AML Undergoing Donor Stem Cell Transplant (NCT00303667), a non-randomized phase 1, phase 2 study. The primary outcome is Disease-free Survival at 6 Months.

2. Clinical Question

3. Trial Design

This is a phase I/II study listed as completed, with a reported enrollment of 50. The record gives a start date of 2005-01 and a primary completion date of 2011-03. It identifies Masonic Cancer Center, University of Minnesota as the sponsor. The study concerns patients with high-risk myeloid malignancies receiving donor stem cell transplantation; the official title specifies those unsuitable for fully myeloablative transplantation.

The design is non-randomized, has no masking, and is identified as a single-group model. The registry nevertheless describes two treatment schemas: an extended schema and a short schema. The extended-schema description lists fludarabine phosphate at a daily dose of 35mg/m^2 and cyclophosphamide on Days -15 and -16. The short-schema description lists fludarabine phosphate at a daily dose of 40mg/m^2 and cyclophosphamide on Day -15 only. Both descriptions also name cyclosporin A, total body irradiation, natural killer cells, aldesleukin, and Thymoglobulin, although the descriptions are truncated in the registry record.

The intervention list includes allogeneic hematopoietic stem cell transplantation, natural killer cells, aldesleukin, chemotherapy, radiation, and other biological or drug interventions. This combination is important when interpreting outcomes: the registry describes a treatment approach rather than an isolated comparison of natural killer cells against no natural killer cells.

The record lists disease-free survival at Month 6 as the primary outcome and several additional outcomes, including donor natural killer cell expansion, graft failure, graft-versus-host disease, treatment-related mortality, relapse, and post-transplant lymphoproliferative disorder. It does not report a randomized comparison between the schemas. Their outcomes should therefore be read descriptively rather than as evidence from a controlled head-to-head trial.

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: 50 patients were originally enrolled; only 47 patients were treated. 4 patients received a natural killer cell (NK) infusion but did not get a transplant because of an early death.

Overall Study

Reasons for not completing this period:

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 at 6 Months, measured over Month 6.

The primary endpoint is the number of patients alive without evidence of disease at 6 months after transplant. Its timeframe is recorded as Month 6, and its unit is participants. In other words, the registry defines the endpoint as a count at a specified follow-up time, rather than reporting a continuous measurement.

A fixed-time disease-free status can convey whether participants are both alive and without evidence of disease at that assessment. This makes it a clinically interpretable summary that combines survival and disease status. However, the registry record does not specify how disease status was assessed, how deaths or unavailable assessments were handled, or whether a formal time-to-event analysis was performed. Although the outcome title uses the phrase “Disease-free Survival,” the posted description is a number of participants meeting the stated status at Month 6.

The record does not report the number meeting this endpoint, the number assessed at Month 6, or an uncertainty interval. Without those results, the endpoint definition can be described, but its observed frequency and precision cannot be assessed. The distinction between the planned outcome and its reported result matters: listing an endpoint does not establish what the trial observed.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The posted primary outcome is a binary status summarized as a participant count: alive without evidence of disease at Month 6. A count states how many participants met the endpoint, while interpretation of that count ordinarily also depends on the relevant denominator. The registry record does not report the primary endpoint count or its denominator, so a proportion cannot be described. No additional proportion or rate is calculated.

General explanation: For a binary endpoint, an uncertainty interval can communicate how precisely the observed participant frequency is estimated. Wider intervals generally indicate less precision, while narrower intervals generally indicate greater precision. The registry record does not report an interval for the primary endpoint, so its precision cannot be assessed statistically from the posted outcome information.

The outcome’s fixed Month 6 assessment is distinct from a time-to-event analysis. A fixed-time count describes status at that assessment. A time-to-event method instead uses the timing of events and can account for differing follow-up under specified assumptions. The record does not report a time-to-event analysis for the primary outcome, nor does it describe censoring or assessment procedures. It would therefore be inappropriate to treat the endpoint title alone as evidence that such an analysis was conducted.

The trial is described as non-randomized and single-group, with short and extended treatment schemas. Random allocation can, in general, help make groups comparable with respect to both measured and unmeasured characteristics. Without randomization, group differences may be associated with baseline or treatment differences, and a direct causal interpretation is not assured. The registry record specifically notes that the schemas are not a like-for-like control comparison. Their descriptive safety counts should not be read as a randomized treatment contrast.

The registry lists zero analysis records. It does not report an inferential model, an adjustment strategy, or hypothesis tests for the primary outcome. The statistical plan, including any planned handling of covariates or interim analyses, is not reported in the registry record. Consequently, there is no basis in the posted information for describing an adjusted treatment estimate or a prespecified testing sequence.

The record includes a sample-size planning illustration based on an observed effect. It describes a two-sided significance level of 0.05, equal allocation between two arms, a normal approximation, and an effect defined as a stated fraction of the observed effect. These are features of the illustration, not a reported design justification for this trial. The registry record does not report the trial’s own sample-size justification or calculated planning results. Any sample-size values associated with that illustration are planning quantities, not observed power and not evidence that the trial had a particular probability of detecting an effect.

General explanation: Over-dispersion matters when data vary more than a model’s assumptions allow; a model that ignores that extra variation may express more precision than is warranted. That concept is especially relevant to count outcomes modeled statistically, but the primary endpoint is described as a participant count, and the registry record does not report a count model or a dispersion parameter. There is no basis for attributing an over-dispersion adjustment to this study.

The adverse-event reporting gives numbers of participants at risk and affected for serious and other adverse events in each schema. These are descriptive safety summaries. Affected counts do not, by themselves, show event timing, severity distribution, recurrence, or a causal relationship to a particular component of the treatment approach. The registry’s serious-event terms include percentages, but the record does not state the denominator or detailed calculation method for those term percentages. They should be quoted as reported rather than reinterpreted as incidence estimates with an unstated denominator.

For a full statistical assessment, the registry would need to report the endpoint counts and denominators, missing-assessment handling, analysis population, and any inferential estimates with their uncertainty. Those details are not reported in the registry record. General statistical concepts can clarify what such information would mean, but they cannot replace absent trial results.

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("SCT w/Donor Natural Killer Cells - Short Schema", "SCT w/Donor Natural Killer Cells - Extended Schema")
n      <- c(8, 39)
events <- c(0, 4)
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  SCT w/Donor Natural Killer Cells - Short Schema  8  0  0.0  0.0  36.9  0.0  32.4  0.3  33.6
ARM  SCT w/Donor Natural Killer Cells - Extended Schema  39  4  10.3  2.9  24.2  4.1  23.6  4.2  23.7

11. Multiplicity, Missing Data and Analysis Populations

The registry lists a primary outcome and additional outcomes concerning donor natural killer cell expansion, graft failure, acute and chronic graft-versus-host disease, treatment-related mortality, disease relapse, and post-transplant lymphoproliferative disorder. It reports nine outcome measures in total, but no analysis records. The registry record does not describe how multiple outcomes were prioritized for statistical testing, whether any multiplicity adjustment was planned, or how secondary outcomes were intended to support interpretation.

Multiplicity is a general statistical concern when several outcomes or comparisons are tested: the more opportunities there are to identify a result by chance, the more important it can be to interpret the testing plan. No testing hierarchy, family-wise error strategy, or other multiplicity approach is reported in the registry record. There is therefore no basis for saying that any particular adjustment was or was not applied in an analysis.

Missing data are also important for a fixed-time endpoint. A participant without a recorded Month 6 assessment cannot automatically be classified as alive and disease-free or as having an event without an explicit rule. The registry does not report the number of participants assessed at Month 6, the number with missing status, or any imputation or sensitivity analysis. The primary endpoint analysis population and the handling of withdrawals or incomplete follow-up are not reported in the registry record.

The enrollment of 50 does not establish the denominator for every outcome. Outcome-specific populations, exclusions, and follow-up denominators are not reported. The safety groups have their own at-risk counts, which should not be treated as the primary endpoint population absent an explicit statement linking them. These omissions limit assessment of both missingness and the comparability of outcome summaries.

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: infection with unknown anc (100.0%), dyspnea (15.4%), infection with normal anc (15.4%), cns hemorrhage (15.4%), infection with grade 3 or 4 anc (12.8%).

The adverse-event record lists an extended-schema group with 39 participants at risk for serious adverse events and 38 affected. For other adverse events, it lists 39 at risk and 39 affected. The short-schema group has 8 participants at risk and 8 affected for serious adverse events, and 8 at risk and 8 affected for other adverse events. These are the counts as reported; they do not establish that the schemas can be compared causally.

The listed serious-event terms include infection with unknown ANC at 100.0%, dyspnea at 15.4%, infection with normal ANC at 15.4%, CNS hemorrhage at 15.4%, infection with Grade 3 or 4 ANC at 12.8%, and veno-occlusive disease at 12.5%. The registry record does not specify the denominator or calculation details for these term percentages. They should therefore be read as reported registry figures, not converted into counts or compared across schemas without further information.

The death count is not reported in the registry record. The record also does not give enough detail to determine event timing, recurrence, attribution, or the number of distinct participants represented by each term. These safety summaries are descriptive and do not establish whether an event was caused by a particular treatment component.

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

The record documents a clinical study of donor natural killer cell infusions and aldesleukin in the setting of allogeneic stem cell transplantation for high-risk myeloid malignancies. It defines disease-free survival at Month 6 as the primary outcome, and it lists two treatment schemas and several additional outcomes. This information describes what the study was designed to examine, but it does not report the primary endpoint result.

Because the Month 6 count and denominator are not reported, the registry does not establish how many participants met the endpoint or how precise an estimate would be. No treatment effect estimate or inferential analysis is posted. The record therefore cannot support a conclusion about the size, direction, or statistical certainty of an outcome difference.

The non-randomized design also matters. The short and extended schemas are not a randomized control comparison, so descriptive differences between them would not isolate the effect of natural killer cells, aldesleukin, or any other individual treatment component. The treatment descriptions include transplantation, chemotherapy, radiation, and additional agents; the record does not separate their contributions.

The safety information provides counts of participants affected and selected serious-event term percentages. Those figures describe registry reporting, but their denominators and detailed event definitions are not fully given. They cannot establish comparative safety or causation. The record’s completed status indicates the study is recorded as completed; it does not fill in unreported efficacy or safety results.

In short, the registry record supports statements about the study’s design, interventions, outcome definitions, and posted safety summaries. It does not establish whether the approach changed disease-free survival, nor does it provide the information needed to quantify that effect. Such conclusions require outcome results and analysis details that are not reported in the registry record.

14. Why This Trial Matters Statistically

This trial raises several statistical issues that are central to interpreting early-phase clinical research. It combines a complex transplant approach with donor natural killer cell infusion and aldesleukin, while listing additional chemotherapy, radiation, and immunosuppressive or biological treatments. Because multiple components are used together, a single-group design cannot separate the contribution of each component.

The presence of short and extended schemas may invite a direct comparison, but the registry identifies the study as non-randomized and explicitly cautions that the arms are not a like-for-like control comparison. This distinction is important: a difference in descriptive outcome counts would not alone show that the schedule caused the difference. Design labels and allocation procedures shape which conclusions can be supported, regardless of how clinically relevant an endpoint may be.

The primary endpoint is a clinically interpretable fixed-time status, yet the registry record does not report its observed count or denominator. This illustrates a basic reporting principle: a well-defined endpoint is not a substitute for its result, and a result without an uncertainty estimate may not convey precision. Here, neither the primary count nor its inferential analysis is reported.

The record also lists multiple outcomes and descriptive adverse-event summaries without analysis records or a reported multiplicity approach. These omissions make it difficult to distinguish planned confirmatory testing from exploratory description. The record can still inform readers about the study question and treatment structure, but it leaves the statistical evidence about outcomes unavailable.

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 central limitation of the registry record is that it does not report the primary endpoint result. The number of participants alive without evidence of disease at Month 6, its denominator, and an uncertainty estimate are not reported in the registry record. No inferential analysis is listed, so statistical significance and precision cannot be evaluated.

The design is non-randomized and identified as a single-group model, with short and extended schemas that the record says are not a like-for-like control comparison. This limits causal interpretation and any direct comparison between schema groups. The registry does not report methods for adjusting for differences between participants or groups.

The detailed eligibility criteria, baseline participant characteristics, analysis populations, and outcome-specific denominators are not reported in the registry record. The treatment descriptions are truncated, and the record does not fully explain assessment procedures, follow-up completeness, or how missing Month 6 status was handled. The statistical plan and sample-size justification are also not reported.

Safety reporting has further limitations. The record gives at-risk and affected counts and selected serious-event percentages, but does not report the calculation denominator for the term percentages, event attribution, or a death count. The posted safety summaries therefore do not support a complete assessment of comparative risks or causal relationships.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Donor Natural Killer Cells and Aldesleukin in Treating Patients w/High Risk AML Undergoing Donor Stem Cell Transplant — NCT00303667.
• Registry record last updated 2017-12-28; status last verified 2017-12.
• Results first posted 2015-07-03.
• 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

NCT00303667 is a completed phase I/II, non-randomized, unmasked, single-group study sponsored by Masonic Cancer Center, University of Minnesota. It reports enrollment of 50, a start date of 2005-01, and primary completion in 2011-03. The study concerns donor natural killer cell infusions and aldesleukin in the setting of allogeneic hematopoietic stem cell transplantation for high-risk myeloid malignancies.

The primary outcome is the number of participants alive without evidence of disease at Month 6 after transplant. The record describes short and extended treatment schemas and lists additional clinical and safety outcomes. It does not report the primary endpoint count, an inferential analysis, or the statistical analysis plan. Adverse-event summaries are posted, but the term-percentage denominators and death count are not reported in the registry record.