Consolidation Therapy for Acute Myeloid Leukemia Guided by Leukemia Stem Cell Behavior: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Consolidation Therapy for Acute Myeloid Leukemia Guided by Leukemia Stem Cell Behavior (NCT01588951), a non-randomized phase 2, phase 3 study. The primary outcome is Relapse Free Survival.

2. Clinical Question

3. Trial Design

The registry record describes a parallel study with phase 2 and phase 3 listed. Its enrollment is 10, and its status is terminated. The recorded start is 2013-12 and the primary completion is 2017-04. These entries describe the registry record; the reason for termination is not reported in the registry record.

The study objective was to compare two-year RFS for people with AML in CR1 considered at high risk of relapse because LSCs were present in bone marrow. The stated treatment approaches were standard cytarabine-based chemotherapy and allogeneic SCT. The record lists three arm descriptions: participants without LSCs receiving cytarabine consolidation, participants with LSCs receiving cytarabine consolidation, and participants with LSCs receiving allogeneic transplant.

There is an important inconsistency in the design information. The overall allocation is recorded as non-randomized, while the descriptions of the two LSC-positive arms say participants were randomized between treatments. The registry record does not explain this discrepancy. It also explicitly cautions that this is not a randomized comparison and that the arms are not a like-for-like control comparison. Consequently, any contrast between the treatment groups would need to be interpreted cautiously: differences could reflect who entered each group as well as the treatment received.

Masking is recorded as none. The record does not report procedures for allocation, concealment, or blinding of outcome assessment. It lists one outcome measure and no analyses. More detail on the protocol, analysis populations, follow-up completeness, and conduct of the study is not reported in the registry record. The small enrollment and terminated status provide context for the limited information available, but the registry does not state why enrollment ended or what consequences termination had for planned analyses.

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:

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 Relapse Free Survival, measured over 2 years.

The primary endpoint is relapse-free survival at two years, expressed as the percentage of participants who are alive and without relapsed disease at that time. This definition combines two clinically relevant events: relapse and death. A participant must meet both conditions to count as alive and relapse-free at the specified time.

RFS is commonly used in cancer studies because it captures whether participants remain alive without the disease returning over a defined follow-up period. It is different from an endpoint that counts relapse alone, because death also means a participant is no longer alive and relapse-free. The interpretation depends on the endpoint definition and how the study determines participants’ status and follow-up at the specified time.

In this study, the stated two-year timeframe makes the endpoint a fixed-time measure. For a comparison, the group-specific percentages and their uncertainty would be needed, along with information about how incomplete follow-up and missing status were handled. Those results and methods are not reported in the registry record. The record therefore defines what the endpoint was intended to measure, but does not show the percentage achieved in either treatment group or establish the precision of any comparison.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What the endpoint represents. The registered primary outcome is a percentage at a fixed time: the percentage of participants alive and without relapsed disease at two years. In general, a binary endpoint classifies each participant into one of two outcome states at the specified assessment. A group percentage then describes how often the outcome state occurred among the participants included in that calculation. The registry record identifies the endpoint type and definition, but it does not give the group counts or percentages.

Fixed-time percentages and time-to-event methods. In general, a fixed-time percentage treats outcome status at a particular assessment as the quantity of interest. A time-to-event analysis instead uses the timing of events and can account for participants whose event status is not observed through the full follow-up, subject to the method’s assumptions. The registered measure is described as a percentage at two years. The registry record does not report whether the analysis used a simple fixed-time calculation, a time-to-event estimator, or another approach. It also does not report the event dates, censoring rules, or follow-up distribution. Those details matter because incomplete follow-up can affect which participants contribute information and how uncertainty is estimated.

Uncertainty and confidence intervals. In general, an estimate is more informative when accompanied by a confidence interval. The estimate gives the observed result under the chosen method; the interval conveys statistical uncertainty and the range of values reasonably compatible with the data and assumptions. A confidence interval is not a guarantee that the true value lies within its limits. Its width depends on factors such as the amount of information and the method used. No confidence interval for RFS or for a treatment comparison is reported in the registry record, so the precision of the primary result cannot be evaluated.

Comparing groups. A comparison requires a clearly defined contrast, such as the difference in the endpoint between treatment groups, together with an uncertainty estimate and an analysis method. In general, randomization is intended to make treatment groups comparable at baseline, on average, and supports a causal interpretation when the trial is properly conducted and analyzed. Non-randomized groups may differ for reasons related to treatment selection or prognosis. Here the overall allocation is recorded as non-randomized, and the record warns that the arms are not like-for-like controls. The arm descriptions nevertheless use the term randomized for the LSC-positive groups. The record does not resolve this inconsistency or report an adjusted analysis. No treatment effect estimate is available to interpret.

Planning assumptions are not trial findings. The registry’s sample-size assumptions describe a planning illustration based on an observed effect, with a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. These assumptions are not a report of the trial’s own design justification or analysis. The numerical planning outputs and the effect values on which the illustration relies are not reported in the registry record. Such sample-size calculations are planning illustrations, not observed power and not evidence that an effect was present. The record does not report a sample-size justification for the actual trial.

Over-dispersion and binary outcomes. In general, a simple model for binary outcomes may assume that participants contribute independent outcomes and that the model adequately represents their variability. Over-dispersion means the observed variation is greater than the model expects. If present and not addressed, standard errors may be too small and confidence intervals may be too narrow. Whether over-dispersion is relevant depends on the data structure and model. The registry record does not report a model, a dispersion assessment, or enough data to evaluate this issue for the RFS endpoint.

Analysis populations and missing follow-up. In general, an analysis population defines which participants are included in an estimate and can affect how a result is interpreted. For example, a protocol may specify analyses based on assigned treatment, treatment received, or another population. Handling missing status also matters: excluding participants with unknown outcomes, imputing outcomes, or using a time-to-event method can lead to different assumptions. The analysis population, missing-data rules, and completeness of follow-up are not reported in the registry record. They should not be inferred from the enrollment total or arm labels.

Multiplicity and prespecification. In general, testing many outcomes, groups, or time points can increase the chance of a false-positive finding if the analysis does not account for those multiple opportunities. A prespecified primary endpoint helps focus interpretation, but does not by itself describe how other analyses were handled. The record lists one outcome measure and no analyses; it does not report a multiplicity strategy, a full statistical analysis plan, or whether additional comparisons were planned. Thus, neither the presence nor the absence of multiplicity adjustments can be established 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("No Leukemia Stem Cells - Consolidation", "Leukemia Stem Cells - Consolidation", "Leukemia Stem Cells - Transplant")
n      <- c(2, 2, 5)
events <- c(0, 0, 0)
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  No Leukemia Stem Cells - Consolidation  2  0  0.0  0.0  84.2  0.0  65.8  0.8  70.8
ARM  Leukemia Stem Cells - Consolidation  2  0  0.0  0.0  84.2  0.0  65.8  0.8  70.8
ARM  Leukemia Stem Cells - Transplant  5  0  0.0  0.0  52.2  0.0  43.4  0.4  45.9

11. Multiplicity, Missing Data and Analysis Populations

The registry record lists one outcome measure, two-year RFS, and no analyses. It does not report a multiplicity strategy, a statistical analysis plan, or whether additional outcomes, subgroup analyses, or time points were considered. In general, multiplicity matters when several statistical comparisons are made, because the chance of a false-positive result can increase across a set of tests. With no reported analyses, it is not possible to determine how this issue was addressed.

Missing-data methods are also not reported in the registry record. The record does not state how participants with unknown RFS status, incomplete follow-up, or other missing information were handled. For a fixed-time endpoint, missing status can affect the denominator and the estimated percentage. In general, different approaches to missing data rely on different assumptions, so a clear description is needed to judge their implications.

The analysis populations are not reported in the registry record. It is therefore unclear which participants would have been included in the primary analysis and how the group assignments were handled for analysis. The record also does not describe adherence, crossover, or exclusions after enrollment. These omissions are important when reading a trial with non-randomized allocation and an unresolved discrepancy in the arm descriptions. No specific population or missing-data approach should be presumed.

12. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Deaths

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 0% reporting threshold.

The registry lists serious-event and other-event figures for each arm, along with the number at risk and deaths. For the No Leukemia Stem Cells - Consolidation group, 2 were at risk for serious events and 0 were affected; 2 were at risk for other events and 0 were affected, with 0 deaths. For the Leukemia Stem Cells - Consolidation group, the corresponding figures are 2 at risk and 0 affected for serious events, 2 at risk and 0 affected for other events, and 0 deaths. For the Leukemia Stem Cells - Transplant group, 6 were at risk and 0 were affected for serious events, 6 were at risk and 0 were affected for other events, and 1 death is listed.

These entries describe what the registry record lists; they do not establish the cause of the death or whether it was related to treatment. The record does not provide event terms among the top serious-event terms, nor does it report additional detail on timing, duration, severity grading, or attribution. A zero in an affected count means no affected participants are listed for that category in the record; it should not be treated as proof that no safety events occurred outside the reported categories or reporting period. The small group sizes and the limited safety detail constrain interpretation. The safety entries are not a substitute for the missing primary RFS results.

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

The study addresses a focused clinical research question: whether two-year RFS differed between cytarabine-based consolidation and allogeneic SCT among people with AML in CR1 and LSCs present in bone marrow. It also includes an arm of participants without LSCs who received cytarabine consolidation. The registry record describes the question and treatment groups, but does not report the primary outcome values or any analyses. Therefore, it does not establish the direction, size, or precision of a treatment-group difference.

The allocation information also matters. The overall design is recorded as non-randomized, and the registry cautions that the arms are not like-for-like control groups. The arm descriptions say participants with LSCs were randomized between treatments, but the discrepancy is not explained. Without clarification, the apparent comparison cannot be interpreted as a clearly documented randomized contrast. In general, differences between non-randomized groups may reflect baseline differences as well as treatment, but the record does not identify whether such differences occurred.

The outcome definition is specific: participants must be alive and without relapsed disease at two years to meet the RFS endpoint. That definition does not provide the observed outcome by itself. Nor does the listed enrollment of 10 supply information about how many participants completed follow-up, how many had relapsed disease, or how many were included in an analysis. Those details are not reported in the registry record.

The appropriate conclusion is limited to what is documented: the registry records the objective, endpoints, arms, enrollment, and terminated status, but does not report the primary results, uncertainty estimates, or analysis methods needed to assess the comparison. It is not possible to conclude from these entries that either treatment approach had higher or lower RFS, or to attribute the listed death to a particular cause.

14. Why This Trial Matters Statistically

This trial is statistically notable because its question depends on both treatment and a biological grouping: the presence or absence of LSCs in bone marrow at CR1. Such a structure makes it especially important to distinguish the intended treatment comparison from differences between groups defined by participant characteristics. The registry describes a comparison of cytarabine-based chemotherapy and allogeneic SCT in the LSC-positive population, while also listing an LSC-negative consolidation group.

The record’s allocation inconsistency illustrates why design labels need to be read together with arm descriptions. Overall allocation is recorded as non-randomized, yet the LSC-positive arm descriptions say randomized. The registry itself cautions that the arms are not like-for-like controls. Clarifying allocation would be important for understanding what kind of comparison was actually conducted and how strongly it could support causal interpretation.

The missing outcome results are equally important. A defined endpoint and a stated objective do not establish a finding. Without group-specific RFS estimates, a treatment contrast, and uncertainty measures, readers cannot judge either the direction or precision of the primary comparison. The absence of a reported analysis plan also leaves important questions about follow-up, analysis populations, and missing data unanswered.

More broadly, the record illustrates that statistical interpretation depends on transparent reporting of design, outcomes, and analysis—not only on the clinical question. Its limited reported information makes it possible to describe the intended study, but not to assess the primary comparison. That distinction is central when reading any registry record with incomplete results.

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 registry record reports enrollment of 10 and a terminated status, but does not explain why the study was terminated, whether follow-up was completed, or whether the planned primary analysis was conducted. These gaps make it difficult to understand how much of the intended study was completed. The record lists a primary completion date, but does not provide the endpoint results associated with that date.

The allocation description is internally inconsistent: the overall allocation is non-randomized, while the LSC-positive arm descriptions use the term randomized. The record does not clarify which description reflects the actual assignment process. It also warns that the arms are not a like-for-like control comparison. This limits interpretation of any hypothetical difference between groups, even if outcome values were available.

Participant characteristics, eligibility details, group-specific follow-up, and the number analyzed for the primary endpoint are not reported in the registry record. The record also does not describe treatment adherence, loss to follow-up, missing-data handling, or analysis populations. These omissions prevent assessment of comparability, outcome completeness, and the assumptions underlying any estimate.

No primary RFS percentages, group contrast, confidence interval, p-value, or analysis method is reported. The registry does not state the reason for termination or provide a sample-size justification for the actual study. Safety reporting is limited to the listed counts and a death; details such as event terms and attribution are not reported in the registry record. These limitations concern the available record and should not be taken as proof that the study did not collect additional information.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Consolidation Therapy for Acute Myeloid Leukemia Guided by Leukemia Stem Cell Behavior — NCT01588951.
• Registry record last updated 2018-08-14; status last verified 2018-07.
• Results first posted 2017-06-05.
• 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

The registry record describes a parallel study of consolidation therapy for AML guided by LSC behavior. It lists phase 2 and phase 3, non-randomized allocation, no masking, enrollment of 10, and terminated status. The primary objective was to compare two-year RFS for participants with AML in CR1 and LSCs in bone marrow, using cytarabine-based chemotherapy or allogeneic SCT. A separate arm describes cytarabine consolidation for participants without LSCs.

The primary endpoint is the percentage of participants alive and without relapsed disease at two years. The record lists one outcome measure and no analyses, and does not report RFS results, uncertainty estimates, or analysis methods. The overall non-randomized allocation conflicts with arm descriptions that say the LSC-positive participants were randomized; the discrepancy is not explained. The record cautions that the arms are not like-for-like controls. It does not report the reason for termination, missing-data methods, or analysis populations.