Phase II Trial of Pentostatin and Targeted Busulfan: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Phase II Trial of Pentostatin and Targeted Busulfan (NCT00496340), a na phase 2 study. The primary outcome is Incidence of Greater Than or Equal to 50% Donor Chimerism.

2. Clinical Question

The trial asks whether a reduced-intensity conditioning regimen involving pentostatin and busulfan can facilitate donor-cell engraftment after allogeneic hematopoietic cell transplantation, with immunosuppression guided by CD4+ laboratory measurements. Its primary question focuses on whether participants achieve at least 50% donor chimerism in CD3+ peripheral blood lymphocytes by day +28 after transplant.

3. Trial Design

The registry identifies this as a Phase II, single-group trial, with enrollment of 42 and completed status. Allocation is listed as NA and masking as none. These features describe a study in which participants received the study regimen without a randomized comparison group or masking. The registry record does not report a control group, a randomization procedure, or a blinding procedure.

The treatment approach combines pentostatin and busulfan with allogeneic hematopoietic cell transplantation; rituximab is also listed among the interventions. The brief summary frames the objective as facilitating engraftment of partially compatible sibling and unrelated donor transplants through CD4+-guided immunosuppression. The primary endpoint population is listed as all participants. The brief summary refers to 41 transplant patients meeting inclusion criteria, while the enrollment figure is 42; the record does not explain the difference between these counts.

The arm description names a single group, “Conditioning Followed by HCT.” It states that participants receive pentostatin 4 mg/m^2 on day -28 before conditioning and may receive additional doses on days -21 and -14 depending on cell counts. The description of the conditioning regimen is incomplete in the registry record, so its full schedule cannot be characterized from this information.

The registry lists a primary outcome and secondary outcomes concerning engraftment, T-cell and myeloid chimerism, non-relapse mortality, infections, graft-versus-host disease, and progression-free survival. It lists 10 outcome measures overall. No analysis results are reported, and the registry record does not describe the statistical plan, sample-size justification, interim analyses, or follow-up completeness.

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

Analysis population for the primary outcome, as defined in the registry: All participants

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.

Population: All participants. Bone marrow chimerism data were available for only 38 patients at day +28 and for only 36 patients at day +100.

6. Primary Endpoint

The registry lists the primary outcome as Incidence of Greater Than or Equal to 50% Donor Chimerism, measured over 28 days post-transplant.

The primary endpoint is the incidence of achievement of at least 50% donor chimerism in CD3+ peripheral blood lymphocytes by day +28 (± 7) after allogeneic hematopoietic cell transplantation. Chimerism describes the proportion of measured blood cells attributed to the donor. The endpoint applies a threshold to a specific cell lineage and a specified post-transplant assessment period.

A threshold endpoint turns a measured biological quantity into a yes-or-no outcome for each participant: the threshold is either achieved within the stated assessment window or it is not. The group-level incidence would describe how many participants met that definition, relative to the analysis population. The registry record lists the primary population as all participants, but does not report the observed number, percentage, or uncertainty interval for the endpoint.

In general, a defined early post-transplant endpoint can provide a consistent way to describe engraftment-related status across participants. It is important to interpret the result according to its exact definition: the cell type is CD3+ peripheral blood lymphocytes, the threshold is at least 50% donor chimerism, and the assessment is by day +28 (± 7). This endpoint alone does not describe every aspect of transplant recovery or establish how outcomes compare with another regimen. The registry record does not report how missing or unevaluable endpoint measurements were handled.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry identifies the study as a single-group Phase II trial. This design provides a description of outcomes among participants receiving the regimen, but it does not create a randomized treatment contrast. Allocation is listed as NA and masking as none. No comparator group is listed. Consequently, any outcome rate would be a within-group description rather than an estimate of the difference between the regimen and a control treatment.

What does a binary endpoint represent?

The primary outcome is expressed as the incidence of reaching a specified chimerism threshold. For each participant, the outcome is classified according to whether at least 50% donor chimerism in CD3+ peripheral blood lymphocytes was reached by day +28 (± 7). A group incidence summarizes the number meeting that definition relative to the relevant population. It is distinct from the underlying continuous measurement of donor chimerism: a threshold classification does not show how far a participant’s measurement was above or below the cutoff.

The registry record does not report the primary endpoint count or percentage, or an interval estimate. A confidence interval, in general, expresses the statistical uncertainty around an estimate using a range of values compatible with the data and the method used. Its width is informative about precision; a single percentage without an interval would not communicate the same uncertainty. No confidence interval is reported for this endpoint.

How should the study design affect interpretation?

In a randomized comparative trial, random assignment can support estimation of a treatment contrast between groups, subject to the design and analysis. This registry record lists one group, so it does not support a randomized comparison. A result from the group could be described as an observed outcome under the study conditions, but it cannot by itself show what would have happened to comparable participants under another regimen. Other factors that affect transplant outcomes may also contribute to the observed group outcome.

Masking is listed as none. In general, masking can reduce the influence of knowledge about treatment assignment on some aspects of care, assessment, or reporting, depending on the trial. The record does not describe additional procedures for outcome assessment or explain how decisions about chimerism measurements were made.

What information is missing for statistical interpretation?

The registry record lists 10 outcome measures and 0 analyses. It does not report an estimate, uncertainty interval, or hypothesis test for the primary outcome. It also does not describe the statistical plan, a multiplicity procedure, missing-data handling, interim analyses, or a sample-size justification. Without these details and the outcome results, it is not possible to assess the planned inferential approach or determine how observed data contributed to any analysis.

The primary population is specified as all participants, while the brief summary refers to 41 transplant patients meeting the inclusion criteria and the enrollment figure is 42. The record does not explain whether these are different populations, whether any participants were excluded from the primary analysis, or whether endpoint measurements were unavailable. The stated analysis population should therefore not be taken as evidence that complete endpoint data were available for every enrolled participant.

What do the planning assumptions mean?

The registry’s sample-size assumptions describe planning illustrations based on an observed effect, not the original trial’s design justification. They specify a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation, with the target effect expressed as a fraction of the observed effect. Those assumptions are not a description of this single-group trial’s allocation. The record does not report the observed effect or specific planning counts in the information available for interpretation, so no participant requirement can be quoted. Planning illustrations are not observed power and cannot replace reporting the trial’s actual endpoint estimate and its precision.

In general, a significance level is a threshold used in a specified testing procedure; it is not the probability that a particular finding is true. A normal approximation uses a mathematical distribution to approximate the sampling behavior of an estimate under stated assumptions. Whether such an approximation is suitable depends on the analysis and data. Since the registry record does not report the primary analysis or its result, these concepts explain the stated illustration assumptions but do not establish which methods were used to analyze the trial.

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("Conditioning Followed by HCT")
n      <- c(42)
events <- c(42)
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  Conditioning Followed by HCT  42  42  100.0  91.6  100.0  91.6  100.0  91.8  99.9

11. Multiplicity, Missing Data and Analysis Populations

The registry lists 10 outcome measures, with the primary endpoint focused on CD3+ donor chimerism by day +28 (± 7). Secondary outcomes span engraftment, chimerism at additional time points, non-relapse mortality, infections, graft-versus-host disease, and progression-free survival. Considering multiple outcomes can raise multiplicity concerns: when many statistical tests are conducted, the chance of at least one apparently notable result can increase. In general, a prespecified testing strategy or adjustment can address that concern, but the statistical plan and any multiplicity approach are not reported in the registry record.

The record lists 0 analyses and does not provide numerical results for the primary or secondary outcomes. It therefore does not support a review of test statistics, confidence intervals, adjusted or unadjusted findings, or the order in which outcomes were analyzed. The lack of a reported result should not be interpreted as a null result.

The primary endpoint population is listed as all participants. Enrollment is 42, while the brief summary refers to 41 transplant patients meeting inclusion criteria. The record does not explain how those groups relate, how many participants had endpoint measurements, or whether any measurements were missing or unevaluable. It does not report an imputation method, a complete-case approach, or sensitivity analyses. In general, missing outcome data can affect both the denominator and the interpretation of an estimated incidence; the direction and extent of any effect depend on why data are missing and how the analysis handles them.

Thus, the registry record identifies an intended population and a set of outcomes, but not enough information to assess multiplicity or missing-data handling. Those omissions limit appraisal of the statistical analysis and of the reliability of any unreported endpoint estimate.

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

Serious events with the highest arm-level rate: death not associated with ctcae term - death nos (11.9%), diarrhea (7.1%), renal failure (7.1%), coagulation - other, right jugular vein occlusion (4.8%), thrombotic microangiopathy (4.8%).

The registry lists 42 participants at risk for serious adverse events and 25 affected participants in the group. It lists 42 at risk for other adverse events and 0 affected. These are registry counts for the group; they should be read as safety reporting, not as a comparison of treatment risks against another group.

The most frequently listed serious event term is “Death not associated with CTCAE term - Death NOS” at 11.9%. Other listed serious terms are diarrhea and renal failure, each at 7.1%; right jugular vein occlusion, thrombotic microangiopathy, and infection with grade 3 or 4 neutrophils - blood, each at 4.8%. The term for death is explicitly described as not associated with a CTCAE term. The separate aggregate deaths value is not reported in the registry record, so the listed term should not be treated as a complete death count.

In general, serious adverse event categories describe events meeting seriousness criteria, while event terms identify reported types. A listed event does not by itself establish that the study regimen caused it. The registry record does not provide a comparison group or a causal attribution analysis. These figures also do not describe event timing, duration, recurrence, or individual participants’ full clinical courses. The serious event counts and term percentages should therefore be interpreted as descriptive registry reports, not as proof of a treatment effect or as a complete account of safety.

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

The registry record establishes the trial’s design and intended primary outcome: a single-group Phase II study, with a primary endpoint of at least 50% donor chimerism in CD3+ peripheral blood lymphocytes by day +28 (± 7). It also records enrollment of 42 and describes a regimen involving pentostatin, busulfan, rituximab, and allogeneic hematopoietic cell transplantation. These details explain what was studied, but they do not establish the trial’s primary result.

The numerical primary endpoint result is not reported in the registry record. No estimate of the proportion achieving the threshold, confidence interval, or statistical test is available. Therefore, the posted registry information cannot show how often the endpoint occurred or how precisely it was estimated. The absence of a reported result is not evidence that the endpoint was or was not achieved.

The single-group design also limits what any group result could establish. Without a control group, an observed outcome would not directly quantify a difference versus another treatment or distinguish the regimen’s contribution from other influences on outcomes. The registry lists several secondary outcomes, but it does not report their results or analyses either.

The adverse event information documents serious and other event counts and several serious event terms with percentages. These are descriptive reports. They do not establish causation, and the record does not provide a concurrent comparison for assessing relative safety. The aggregate deaths value is not reported in the registry record.

In short, the registry describes the research question, the main endpoint definition, and selected safety information, but it does not provide the outcome analysis needed to judge the primary endpoint. Any interpretation of efficacy, statistical significance, or precision would go beyond the reported results.

14. Why This Trial Matters Statistically

This trial is statistically informative as an example of the distinction between a defined endpoint and a reported result. The primary outcome has a clear threshold, cell population, and assessment window: at least 50% donor chimerism in CD3+ peripheral blood lymphocytes by day +28 (± 7). That definition helps clarify what an analysis would count. Yet a well-defined outcome does not tell readers how many participants met it, or how uncertain an estimated incidence might be; those results are not reported in the registry record.

The design also matters. The study is listed as a single-group Phase II trial, with no randomized comparison. This means the intended evidence is descriptive for the group receiving the regimen, rather than a randomized estimate of a difference between treatment strategies. Recognizing that distinction prevents an outcome rate, if reported, from being interpreted as a comparative treatment effect.

The record lists 10 outcome measures, ranging from engraftment and chimerism to mortality, infection, graft-versus-host disease, and progression-free survival. This breadth illustrates why a statistical plan matters: multiple outcomes may require clear prioritization and interpretation. The registry record does not describe its analysis plan or multiplicity approach, and it lists no analyses.

Finally, the record separates safety reporting from the missing primary endpoint result. Serious adverse event counts and listed terms are available, but they cannot substitute for the endpoint estimate or establish causation. Taken together, these features show why sound statistical interpretation depends on both a precise outcome definition and transparent reporting of analysis, uncertainty, and study design.

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 direct limitation for interpreting the primary endpoint is that its numerical result is not reported in the registry record. The record gives the endpoint definition and analysis population, but no count, percentage, confidence interval, or test result. This prevents assessment of the observed incidence and its precision.

The single-group design has no listed randomized or concurrent comparator. Any reported group outcome would therefore lack a direct trial-based contrast with another regimen. The registry also lists no masking. These design features constrain causal and comparative interpretation.

There is an unresolved difference between the enrollment figure of 42 and the brief summary’s reference to 41 transplant patients meeting inclusion criteria. The record does not explain how these counts relate or whether the primary endpoint was available for all participants. Missing-data methods and sensitivity analyses are not reported. The full conditioning schedule is also not available in the arm description, which ends before its details are complete.

The record lists 10 outcomes but does not report analyses, statistical methods, a multiplicity strategy, interim analyses, or sample-size justification. Its planning assumptions describe an illustration rather than the original trial design, and the observed effect and specific planning counts are not reported in the information available for interpretation.

Safety reporting is limited to aggregate counts and selected serious event terms. The registry does not provide a comparison group, causal attribution analysis, or the aggregate deaths value. These limitations mean the recorded adverse events should be read descriptively, not as a complete estimate of comparative risk.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Phase II Trial of Pentostatin and Targeted Busulfan — NCT00496340.
• Registry record last updated 2014-06-05; status last verified 2014-03.
• Results first posted 2014-06-05.
• 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 NCT00496340, a completed Phase II, single-group trial of pentostatin and targeted busulfan with allogeneic hematopoietic cell transplantation for hematologic malignancies. Enrollment is 42; allocation is listed as NA and masking as none. The primary outcome is achievement of at least 50% donor chimerism in CD3+ peripheral blood lymphocytes by day +28 (± 7), with all participants listed as the primary population.

The record lists 10 outcome measures and safety counts for serious and other adverse events. It does not report a numerical primary outcome result or statistical analyses. It also does not report the analysis plan, missing-data methods, or sample-size justification. The registry status is completed, but completion status alone does not supply the missing outcome estimates needed for statistical interpretation.