Clofarabine Pre-conditioning Followed by Stem Cell Transplant for Non-remission AML: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Clofarabine Pre-conditioning Followed by Stem Cell Transplant for Non-remission AML (NCT04002115), a na phase 2 study. The primary outcome is Complete Remission (CR) Rate at Day 30 Post HSCT.

2. Clinical Question

The clinical question concerns an early post-transplant outcome in patients with acute myeloid leukemia who were not in remission before transplant consideration. Complete remission at day 30 is the stated primary outcome. It is a measure of disease status at a specified point after transplant, rather than a measure of long-term disease control, survival, or quality of life.

The study record describes a treatment sequence, not a comparison with an untreated group or another regimen. As a result, the reported remission observation describes the enrolled participants in this study; it does not by itself estimate how the outcome would differ under another treatment. The registry also lists secondary outcomes concerning mortality, engraftment, and acute and chronic graft-versus-host disease. Their numerical results are not reported in the registry record.

The question is therefore narrow: what was recorded for complete remission at the stated follow-up point among participants in this regimen? The record reports 2/2 at day 30. The small enrollment and absence of a concurrent comparator limit how broadly that observation can be interpreted. Details about eligibility criteria beyond the population description, and about how remission was assessed, are not reported in the registry record.

3. Trial Design

This is a phase 2 study with a sequential design. The registry lists allocation as NA and masking as none. Enrollment was 2. The record gives a start date of 2020-06-03, a primary completion date of 2022-08-30, and a status of terminated. The reason for termination is not reported in the registry record.

The planned treatment sequence is clofarabine pre-conditioning followed by hematopoietic stem cell transplant, with post-transplant cyclophosphamide named in the official title. The population is described as patients with acute myeloid leukemia who were not in remission before considering allogeneic transplant with haploidentical donors. The arm description begins with clofarabine 30 mg/m^2 from day -14 through day -10 and lists subsequent conditioning agents and procedures. The available registry description is truncated during the later regimen details, so the complete sequence and any distinctions between regimen variants are not fully reported in the registry record.

There is no randomized allocation or like-for-like control arm described. The study therefore provides an observed outcome in the treated participants, rather than a randomized estimate of a treatment contrast. The sequential designation describes the design category in the registry; further operational details of the sequence are not reported in the registry record.

The primary outcome is complete remission at day 30 after stem cell transplant infusion. The registry reports the result as 2/2. Secondary outcomes are listed for non-relapse related mortality, neutrophil engraftment, acute graft-versus-host disease rate and severity, and chronic graft-versus-host disease rate and severity. Numerical findings for these outcomes are not reported in the registry record. A detailed statistical analysis plan, including any planned comparisons or analytic methods, is also 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.

Before assignment: Both subjects were between age 56 and 75 years old, therefore they were assigned treatment of Regimen B.

Overall Study

Analysis population for the primary outcome, as defined in the registry: The CR rate at 30 days (Day +30) post stem cell transplant infusion was 2/2.

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 Complete Remission (CR) Rate at Day 30 Post HSCT, measured over 30 days.

The primary endpoint is the complete remission rate at day 30 after stem cell transplant infusion. The registry describes it as a percentage of participants and identifies the measure as a number. The outcome is intended to capture whether participants had reached complete remission at a prespecified early post-transplant assessment point. The result is recorded as 2/2.

A remission endpoint is clinically interpretable as a disease-status outcome at the time of assessment. Specifying day 30 gives the observation a defined time context: it is not a report of remission at an unspecified follow-up or of how long remission lasted. It also does not, by itself, describe survival, relapse after that assessment, or later complications. Those are different outcomes and require their own follow-up and reporting.

For a binary outcome such as remission status, the observed result is naturally expressed as the number with the event relative to the number assessed. A percentage can make the result easier to compare across studies, but the underlying count and denominator matter, especially when enrollment is small. The registry reports 2/2; it does not report a confidence interval, a more detailed definition of complete remission, the assessment procedures, or how missing outcome data would be handled. These details would help readers assess the precision and reproducibility of the endpoint.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry describes a phase 2 study with a sequential design, allocation recorded as NA, and no masking. These features matter when deciding what kind of inference the results can support. A randomized comparison assigns participants to groups using a random process and can support a direct comparison under appropriate assumptions. No such comparison is described. The posted remission finding is therefore an observation in the study group, not an estimate of a difference between treatments.

What does a binary endpoint record?

Complete remission at day 30 is a binary endpoint: a participant either meets the outcome definition at that assessment or does not. For this kind of outcome, the registry reports the number of participants with the event and the number represented in the result. The primary finding is 2/2. This count-based presentation is useful because it preserves the denominator, which is particularly important when enrollment is small. A percentage alone can conceal how much information supports the estimate.

A binary outcome can be summarized as a proportion, but a proportion from a small group is inherently uncertain as an estimate of outcomes in a broader population. A confidence interval is a statistical range that communicates uncertainty around an estimate under a specified method and assumptions. It does not give a guarantee that the true value lies within the range. No confidence interval for the primary result is reported in the registry record, so readers cannot use one to gauge the uncertainty in the reported remission rate.

Why does study design affect interpretation?

The sequential design and the absence of a listed comparator mean that the record does not offer a direct treatment contrast. Even if an outcome is observed after treatment, a single-group observation cannot separate the contribution of the individual regimen components from other influences. The regimen includes clofarabine pre-conditioning, transplant, and other listed treatments. Without a suitable comparison group and a prespecified analysis, the observed outcome cannot be attributed to one component or interpreted as a causal treatment effect.

Masking is recorded as none. Masking can reduce the possibility that knowledge of treatment assignment influences outcome assessment or related decisions. Whether this could affect the endpoint depends on how the endpoint is defined and assessed; the assessment procedures are not reported in the registry record. The record also does not describe whether remission was assessed by a blinded reviewer.

What can the sample-size illustration tell readers?

The planning illustration is described as based on the observed effect, with a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. It considers an effect to detect stated as a fraction of the observed effect. These are assumptions for a planning exercise, not evidence about the study’s own planned enrollment or design. The registry does not report a sample-size justification for this trial. Any sample-size illustration should be understood as planning information, not as observed power and not as a retrospective test of whether the study succeeded.

In general, a sample-size calculation asks how much information might be needed to detect a specified effect under chosen assumptions. Its answer depends on those assumptions, the outcome type, and the analysis method. Planning for a smaller effect than the observed effect generally requires more information, but the registry’s illustration is not a substitute for a trial-specific design rationale. No calculated sample-size values or effect fractions are reported in the registry record.

How should uncertainty and repeated outcomes be considered?

The registry lists a primary endpoint and several secondary outcomes, but the number and nature of analyses actually conducted are not described. When investigators examine multiple outcomes or multiple comparisons, the chance of at least one apparently notable result can increase. Statistical methods can address this issue through prespecified testing strategies or adjustments, but the multiplicity approach is not reported in the registry record. No p-value or inferential analysis for the primary outcome is reported.

General statistical interpretation also depends on the analysis population and the handling of missing observations. An analysis of all participants as assigned, an analysis restricted to those who received treatment, and an analysis limited to participants with complete outcome data can answer different questions. The registry does not report an analysis population or a missing-data method for the primary endpoint. The reported 2/2 should therefore be read as the recorded outcome, without assuming additional details about exclusions, assessment completion, or analytic handling.

The main statistical message is that the posted count is descriptive and carries limited information about outcomes beyond the study participants. The design, small enrollment, lack of a comparator, and absence of reported uncertainty estimates all constrain inference. These limitations do not change the recorded result; they define what can responsibly be concluded from it.

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("Clofarabine 30 mg/m^2")
n      <- c(2)
events <- c(2)
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  Clofarabine 30 mg/m^2  2  2  100.0  15.8  100.0  34.2  100.0  29.2  99.2

11. Multiplicity, Missing Data and Analysis Populations

The registry identifies complete remission at day 30 after transplant as the primary outcome and lists secondary outcomes concerning non-relapse related mortality, neutrophil engraftment, acute graft-versus-host disease, and chronic graft-versus-host disease. It records 7 outcome measures. Numerical results for the secondary outcomes are not reported in the registry record. The record does not state how many analyses were conducted; it lists 0 analyses.

Multiplicity arises when statistical testing covers several outcomes, comparisons, or time points. If many tests are considered, the chance of a nominally notable finding occurring by chance can increase. A study may address this by identifying a primary outcome in advance, using a testing hierarchy, or applying a statistical adjustment. The registry identifies a primary outcome, but it does not report an adjustment method, a testing hierarchy, or a plan for interpreting multiple outcomes. The approach to multiplicity is therefore not reported in the registry record.

Missing-data methods and analysis populations are also not reported in the registry record. The record does not say whether the primary result includes all enrolled participants, only those who received the transplant, or only those with an evaluable day-30 assessment. It does not describe how unavailable or indeterminate remission assessments were handled. Although the primary result is stated as 2/2, no further information is reported about assessment completion or exclusions.

These omissions matter because analysis choices can affect which participants contribute to an estimate and how uncertainty is interpreted. They do not justify assuming that data were missing or that any particular analysis was performed. The registry record simply does not provide the details needed to evaluate those questions.

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: pulmonary edema (50.0%), multiorgan failure (50.0%), acute kidney injury (50.0%).

The adverse-event record lists one study group, Clofarabine 30 mg/m^2. For serious adverse events, 2 participants were at risk and 1 was affected. For other adverse events, 2 were at risk and 2 were affected. The record also lists 2 deaths. These entries describe recorded counts in this study; they do not by themselves establish the timing, cause, or relationship of an event to treatment.

The listed serious-event terms include pulmonary edema, Multiorgan failure, and Acute kidney injury, each reported as 50.0%. Those percentages should be read as registry entries for the listed terms, not as a basis for inferring whether events occurred in the same participant or whether each event was treatment-related. The record does not provide the detailed event narratives, onset dates, duration, outcome, or causal assessments needed to make those judgments.

Counts of participants affected and counts of event terms are not interchangeable: a participant may have more than one event, and the registry entry does not explain the overlap among listed terms. The serious and other adverse-event summaries also describe different categories. Without fuller event-level reporting, the safest interpretation is limited to the recorded affected counts and listed terms. A causal relationship between treatment and any reported event is not reported in the registry record.

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

The registry records complete remission at day 30 after stem cell transplant infusion as 2/2. This means the posted primary outcome is an observed finding in the study participants at the stated assessment point. It is not, by itself, a comparative estimate of benefit, a measure of long-term disease control, or evidence about what would have happened under another regimen.

The study has no concurrent comparator described and is not a randomized comparison. The result cannot separate the effects of clofarabine from those of transplant, the other conditioning components, or post-transplant treatments. It also cannot establish that the same outcome would occur in a broader population. Enrollment was 2, and no confidence interval or other quantified uncertainty measure is reported for the primary result.

The timing matters. Day 30 is an early post-transplant assessment. The posted remission result does not report whether remission persisted, whether later relapse occurred, or how survival and other outcomes developed over time. The secondary outcomes are listed, but their numerical results are not reported in the registry record. A complete picture of outcomes is therefore unavailable from the registry entry.

The record also lists adverse events and deaths. Those counts provide safety information about what was recorded, but they do not establish causality. The registry does not report detailed event timing, attribution, or narratives. Similarly, the study’s terminated status is recorded, but the reason for termination is not reported.

The appropriate reading is narrow and descriptive: the registry documents a day-30 complete remission result of 2/2 in a small sequential study. It does not answer whether the regimen is superior to another treatment, establish a causal effect, or resolve uncertainty about later outcomes. Those questions require comparative evidence, fuller outcome reporting, and analysis details that are not reported in the registry record.

14. Why This Trial Matters Statistically

This study is statistically notable because its primary outcome is clear and clinically interpretable, while its enrollment is very limited. The registry reports complete remission at day 30 after transplant as 2/2. Retaining the count alongside the endpoint is important: the denominator shows the scale of the evidence underlying the observed result, and prevents readers from treating a percentage as if it came from a large study.

The design also illustrates the difference between describing an outcome and estimating a treatment effect. A sequential study without a concurrent comparator can report what happened among its participants, but it cannot establish how those outcomes differ from a counterfactual treatment strategy. The lack of random allocation means that a between-treatment causal contrast is not available in the record.

The study also highlights why time-specific endpoints should be interpreted at their stated horizon. A day-30 remission result answers a question about disease status at that early assessment, not about persistence of remission or later survival. The listed secondary outcomes could add context, but their numerical results are not reported in the registry record.

Finally, the record demonstrates the value of reporting analysis details alongside outcome counts. Confidence intervals, analysis populations, missing-data methods, and multiplicity plans help readers judge uncertainty and understand how results were produced. Those details are not reported in the registry record. The result remains a useful description of the recorded observation, but its statistical meaning is constrained by the small enrollment, non-comparative design, and limited inferential reporting.

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 main trial-specific limitation is enrollment of 2. A result reported as 2/2 is based on very limited participant information and cannot precisely characterize outcomes in a broader population. The registry does not report a confidence interval for the primary endpoint or another measure of its uncertainty.

The record describes a sequential study with allocation recorded as NA and no masking. It does not describe a concurrent control group, so there is no like-for-like comparison from which to estimate a treatment contrast. The treatment sequence includes clofarabine, transplant, and other listed drugs and procedures; the contribution of any individual component cannot be isolated from this single-group result.

The primary outcome is assessed at day 30. Later remission status, relapse, survival, and longer-term follow-up findings are not reported in the registry record. Although secondary outcomes are listed, their numerical results are not reported. The record also does not give a detailed remission definition, assessment procedure, or assessor information.

The regimen description is truncated, leaving the complete treatment sequence and any distinctions between regimen variants unclear. The record does not report a trial-specific sample-size justification, detailed statistical analysis plan, analysis population, missing-data method, or multiplicity approach. It lists the study as terminated, but the reason for termination is not reported in the registry record. These gaps limit assessment of the planned design, completeness of follow-up, and interpretation of the posted result.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Clofarabine Pre-conditioning Followed by Stem Cell Transplant for Non-remission AML — NCT04002115.
• Registry record last updated 2023-09-14; status last verified 2023-09.
• Results first posted 2023-09-14.
• 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 phase 2 sequential study of clofarabine pre-conditioning followed by hematopoietic stem cell transplant with post-transplant cyclophosphamide for acute myeloid leukemia not in remission. Allocation is recorded as NA and masking as none. Enrollment was 2. The study started on 2020-06-03, had a primary completion date of 2022-08-30, and is listed as terminated.

The primary endpoint is complete remission at day 30 after transplant infusion. Its recorded result is 2/2. Secondary outcomes include mortality, engraftment, and acute and chronic graft-versus-host disease, but numerical findings for those outcomes are not reported in the registry record. The adverse-event entry records serious events, other events, deaths, and selected serious-event terms.

The study has no concurrent comparator described. The registry does not report a confidence interval for the primary result, a detailed analysis plan, missing-data handling, analysis populations, or the reason for termination. The primary finding is therefore a descriptive observation in the enrolled participants, with limited ability to support broader or comparative conclusions.