T2007-002 Clofarabine, Etoposide, Cyclophosphamide in Relapsed Acute Myelogenous Leukemia (AML): Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for T2007-002 Clofarabine, Etoposide, Cyclophosphamide in Relapsed Acute Myelogenous Leukemia (AML) (NCT00939653), a na phase 2 study. The primary outcome is Achievement of Complete Remission (CR) at Reinduction.

2. Clinical Question

The clinical question is therefore descriptive: what remission outcome and safety experience were recorded among participants receiving the regimen? The study enrolled 6 patients and is marked terminated. The record does not state why the study stopped, whether enrollment reached its intended target, or what enrollment target was intended. Without a comparator, any outcome observed in this group would describe this cohort; it would not, by itself, estimate how outcomes differ from another treatment. The endpoint population is also narrower than enrollment because its description requires completion of at least 1 course. The number meeting that condition is not reported in the registry record.

3. Trial Design

This was a Phase II, single-group study with no masking, recorded under NCT00939653. The registry lists the Therapeutic Advances in Childhood Leukemia Consortium as the sponsor and describes the study as involving clofarabine with etoposide and cyclophosphamide in relapsed or refractory acute myelogenous leukemia. The treatment arm description additionally includes cytarabine and filgrastim, with up to 4 courses of therapy allowed.

The registry records enrollment of 6, a start date of 2009-07-10, primary completion on 2011-07-15, and a status of terminated. The reason for termination, the intended enrollment, and the statistical justification for the study size are not reported in the registry record. These details should not be inferred from the status or the number enrolled.

Allocation is recorded as not applicable, consistent with a single-group design. There is no randomized comparison and no separate control arm. The absence of masking means the record does not describe blinded assessment. It does not, however, establish what safeguards or review procedures may have been used beyond the information recorded.

The stated primary outcome is achievement of complete remission at reinduction. Its assessment window is between Days 22-36 or on Day 43 and weekly thereafter if peripheral counts have not recovered. The outcome description says disease response was assessed after chemotherapy from bone marrow aspirates or biopsies and complete blood count. The primary endpoint population is patients who completed at least 1 treatment course. The registry lists 2 outcome measures, but does not provide their numerical results or analysis results. Details of the statistical plan, including any planned interim analyses, 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.

Treatment Course 1

Treatment Course 2

Treatment Course 3

Treatment Course 4

Analysis population for the primary outcome, as defined in the registry: Patients that completed at least 1 treatment course of study drug.

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 Achievement of Complete Remission (CR) at Reinduction, measured over Between Days 22-36 or on Day 43 and weekly thereafter if peripheral counts haven't recovered.

The primary endpoint is titled “Achievement of Complete Remission (CR) at Reinduction” and is measured as a count of participants. It is a binary outcome at the participant level: each participant either meets the recorded remission definition or does not. The registry description says response was assessed after chemotherapy using bone marrow aspirates or biopsies and a complete blood count. The stated assessment window is between Days 22-36 or on Day 43 and weekly thereafter if peripheral counts have not recovered.

Complete remission is used as a disease-response endpoint because it captures a defined response status at a specified stage of treatment. In a single-group study, the observed count could describe how many participants in the eligible endpoint population achieved that status. It cannot, without a comparator, establish how the result differs from an alternative treatment or from what would have happened without this regimen.

The endpoint population is described as patients who completed at least 1 treatment course of study drug. That qualification matters: the enrolled group and the group eligible for the primary endpoint need not be identical. The number who completed a course, the remission count, and the denominator used for the endpoint are not reported in the registry record. Accordingly, the remission proportion and its statistical precision cannot be interpreted from the posted results.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The methods information recorded for this trial is sparse. The study is identified as Phase II, single-group, unmasked, and without randomized allocation. The primary outcome is a participant count for achievement of complete remission at reinduction. The registry does not report a statistical analysis plan or any analysis results. The explanations below distinguish general statistical principles from what can be established about this particular record.

What does a participant count convey?

A count states how many people meet an outcome definition, but it is not interpretable in isolation. To assess the frequency of an outcome, the count must be read with its denominator: the number of participants eligible for or assessed on that outcome. Here, the endpoint population is described as patients completing at least 1 treatment course, but neither the number who completed a course nor the number achieving complete remission is reported in the registry record. A remission rate or confidence interval therefore cannot be recovered from the posted information.

In general, a confidence interval expresses the uncertainty around an estimate under a stated statistical model. It is not a guarantee that the true value lies within the interval, and its width depends on the amount and pattern of information available. No confidence interval for the primary endpoint is reported in the registry record, so there is no endpoint precision estimate to interpret.

What does the single-group design permit?

In general, a single-group study can describe outcomes among people receiving the study regimen. It cannot provide the direct randomized comparison that helps distinguish treatment-related differences from differences due to patient characteristics, disease course, supportive care, or other factors. This trial has no separate comparator arm, and allocation is recorded as not applicable. The posted results therefore cannot establish a comparative treatment effect.

Unmasked assessment can also matter in general when an outcome involves judgment. The registry describes response assessment using bone marrow aspirates or biopsies and a complete blood count, but does not report whether response assessors were independent or whether any additional procedures were used to reduce assessment bias. No further assumptions about these procedures are warranted.

What can the enrollment tell us about precision?

The record reports enrollment of 6. A small cohort generally yields limited information about the range of outcomes that might be seen in a broader population, and an estimate based on few observations would usually be imprecise. That general principle does not supply an estimate for this study: the primary endpoint count and denominator are missing. Enrollment alone cannot substitute for those outcome data or establish the precision of an endpoint estimate.

Planning sample sizes are different from observed results. Any planning illustrations based on a stated fraction of an observed effect and assumptions about significance level, allocation, and approximation are hypothetical design calculations. They are not observed power, and they do not indicate what this study was designed to recruit. The record does not report the trial's own sample-size justification. The assumptions underlying planning illustrations should not be mistaken for the study's protocol or its analysis plan.

How should adverse-event summaries be read?

The registry lists aggregate numbers at risk and affected for serious and other adverse events, along with selected serious-event terms and percentages. Such summaries describe recorded event experience within the enrolled group. In general, they do not by themselves show that a study drug caused an event. Causal interpretation would require context about timing, clinical attribution, exposure, and other factors; those details are not reported in the registry record. Aggregate summaries also do not show which events occurred in the same participant or the duration of observation.

What is missing from the statistical record?

The registry lists 2 outcome measures and 0 analyses. It does not report the numeric primary endpoint result, an analysis population size, missing-outcome handling, a model, a confidence interval, or a hypothesis test. It also does not report an interim analysis plan, multiplicity adjustment, or a prespecified approach to missing data. Without those details, statistical significance, robustness, and sensitivity to analytic choices cannot be evaluated. General statistical concepts can explain what such procedures are for, but they cannot fill gaps in the 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("Enrolled Patients")
n      <- c(6)
events <- c(1)
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  Enrolled Patients  6  1  16.7  0.4  64.1  3.0  56.4  3.7  57.9

11. Multiplicity, Missing Data and Analysis Populations

The registry identifies complete remission at reinduction as the primary endpoint and lists 2 outcome measures overall. It does not report the numerical results for either outcome or describe an analysis plan. The record therefore does not establish whether the outcomes were tested, whether one was designated as secondary, or whether a hierarchy or multiplicity adjustment was planned. Any approach to controlling the chance of false-positive findings across multiple tests is not reported in the registry record.

Missing-data handling is also not described. For the primary endpoint, the analysis population is characterized as patients who completed at least 1 treatment course, but the number meeting that criterion is unknown. The record does not say how participants who did not complete a course, lacked an assessment, or had unevaluable response data were handled. It also does not report whether any imputation or sensitivity analysis was used. Those omissions make it impossible to assess whether the endpoint population differed from the full enrolled group in ways relevant to the outcome.

The registry records 6 enrolled patients, but it does not give a participant flow or endpoint denominator. This prevents a reader from distinguishing non-completion from missing assessment or from other reasons an enrolled participant might not contribute to the primary endpoint. No analysis results are listed, so there is no reported estimate to evaluate for sensitivity to these issues.

In general, multiplicity procedures address the interpretation of multiple statistical tests, while missing-data methods address outcomes that are unavailable or not observed. Neither should be inferred from the number of outcomes alone. The protocol's rules, analysis populations, and handling of incomplete observations are not reported in the registry record.

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.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: febrile neutropenia (50.0%), renal failure nos (33.3%), hypoxia (33.3%), grade 3 infection (blood) (33.3%), grade 4 infection (33.3%).

The serious adverse-event summary is for enrolled patients. It lists 6 patients at risk and 6 affected. The separate summary for other adverse events also lists 6 at risk and 6 affected. Four deaths are recorded. The registry does not report their causes, timing, relationship to treatment, or whether they occurred during or after a particular course.

The listed serious-event terms are Febrile Neutropenia (50.0%), Renal failure NOS (33.3%), Hypoxia (33.3%), Grade 3 Infection (blood) (33.3%), Grade 4 Infection (33.3%), and Grade 4 ANC (33.3%). These are registry-listed percentages; they should be read as descriptions of the reported safety data, not as evidence that the regimen caused each event. The registry record does not provide event-level detail, exposure time, or information about overlap among terms. A participant may contribute to more than one event category, so the listed percentages should not be added together.

Because the study has no comparator and enrolled 6 patients, these summaries do not support a comparative safety estimate. They also do not establish the reason for any death. Interpretation is limited to the aggregate counts and terms recorded.

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

The registry record documents a Phase II, single-group study of a regimen containing clofarabine, etoposide, cyclophosphamide, cytarabine, and filgrastim in relapsed or refractory acute myelogenous leukemia. It records enrollment of 6, a terminated status, the intended primary endpoint, its assessment window, and aggregate adverse-event information. These details describe the study and its reported safety experience, but they are not a substitute for the missing remission result.

The primary endpoint is achievement of complete remission at reinduction among patients who completed at least 1 treatment course. The registry does not report the remission count or the endpoint denominator. It is therefore not possible to determine the observed remission frequency or how precisely it was estimated. No p-value, confidence interval, or other analysis result is listed.

The design also sets limits on what any cohort outcome could establish. With one treatment group and no randomized comparator, outcomes cannot be interpreted as a direct estimate of difference from another treatment. The absence of masking is recorded, but further details about endpoint review are not. The record does not report a rationale for termination, an intended enrollment target, or a sample-size justification, so none should be inferred from the enrollment count.

The safety summaries report serious and other adverse-event counts, selected serious-event terms and percentages, and 4 deaths. They do not identify causes or establish attribution. In general, an event recorded during a trial is not by itself proof that treatment caused it; interpreting safety requires context that is not available in the registry record.

Accordingly, the study record can inform readers that this small cohort was enrolled and that aggregate safety events were recorded, while leaving the central remission outcome unreported. It cannot establish comparative efficacy, determine the cause of deaths, or resolve how missing endpoint information was handled. Those limits are central to interpreting the available information.

14. Why This Trial Matters Statistically

This study matters statistically because it illustrates the difference between a named endpoint and an interpretable endpoint result. The registry specifies complete remission at reinduction as the primary outcome and describes how and when response was assessed. Yet the numerical remission result and its denominator are not reported. Without both, readers cannot estimate the outcome frequency or its uncertainty.

The single-group design is another important feature. It can document what was recorded among participants receiving the regimen, but it does not offer a randomized comparison. This distinction is essential when interpreting clinical trial results: an observed outcome in one group does not, on its own, identify the effect of treatment relative to an alternative. The unmasked design and limited record of assessment procedures add further uncertainty about how response was evaluated.

The small enrollment and terminated status make transparency about participant flow especially important. The record states enrollment of 6 and defines the primary endpoint population by completion of at least 1 treatment course, but does not give the number who completed treatment or contributed endpoint data. That gap prevents a clear account of how the enrolled population relates to the endpoint population.

Finally, aggregate safety reporting is informative but limited. It identifies serious-event terms and reports deaths, while omitting the timing, attribution, and participant-level overlap needed for fuller interpretation. The statistical lesson is not to stretch these summaries beyond their scope: descriptive counts, inferential comparisons, and causal conclusions answer different questions. The registry record supports the first only in part and does not provide the primary remission result needed for an efficacy interpretation.

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.

Several limitations are specific to the available record. First, the primary outcome is named, but its numerical result is not reported in the registry record. The endpoint denominator is also absent, despite the description limiting the population to patients who completed at least 1 treatment course. This means the central response outcome cannot be interpreted quantitatively.

Second, the study enrolled 6 patients and is marked terminated. The reason for termination, intended enrollment, and sample-size justification are not reported in the registry record. The enrollment count alone does not explain whether the study stopped early, reached its goal, or followed another course.

Third, the single-group, unmasked design has no randomized comparator. It cannot directly estimate a treatment difference, and the record does not describe additional protections for response assessment. The combination regimen also includes multiple drugs, so the posted information does not isolate the contribution of any one component.

Fourth, the registry lists aggregate adverse-event counts and percentages but does not report timing, attribution, participant-level overlap, or causes of death. Four deaths are recorded, but their circumstances are not available. Safety summaries therefore cannot establish causation or permit a comparison with another group.

Finally, the record lists 2 outcome measures and 0 analyses but does not provide statistical methods, analysis populations, missing-data procedures, multiplicity handling, or inferential estimates. These omissions limit assessment of the robustness and precision of any outcome. They should be treated as missing registry information, not filled in by assumptions about typical trial practice.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: T2007-002 Clofarabine, Etoposide, Cyclophosphamide in Relapsed Acute Myelogenous Leukemia (AML) — NCT00939653.
• Registry record last updated 2020-02-19; status last verified 2020-02.
• Results first posted 2020-02-19.
• 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

NCT00939653 is a Phase II, single-group, unmasked study of clofarabine with etoposide, cyclophosphamide, cytarabine, and filgrastim for relapsed or refractory acute myelogenous leukemia. The registry records enrollment of 6, a start date of 2009-07-10, primary completion on 2011-07-15, and terminated status.

The primary endpoint is achievement of complete remission at reinduction among patients who completed at least 1 treatment course. The registry describes the assessment window and response methods but does not report the remission result or its denominator. It lists 2 outcome measures and 0 analyses.

Safety summaries list 6 patients at risk and 6 affected for both serious and other adverse events, and record 4 deaths. Serious-event terms and percentages are listed, but causes, timing, and attribution are not reported in the registry record. The reason for termination, statistical plan, and sample-size justification are also not reported.