T-cell Depleted Alternative Donor Transplantation: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for T-cell Depleted Alternative Donor Transplantation (NCT00968864), a na phase 2 study. The primary outcome is Number of Participants With Severe Graft vs. Host Disease (GVHD)..

2. Clinical Question

3. Trial Design

This was a phase II study of T-cell depletion with the CliniMACS® device in alternative-donor stem cell transplant recipients. The registry describes a single-group design, with no masking and allocation listed as not applicable. Enrollment was 53. The study began in 2009-08, primary completion was recorded in 2016-11, and the current status is terminated. The reason for termination is not reported in the registry record; termination alone does not establish why the study ended or whether planned enrollment or follow-up was completed.

Recipients were categorized by donor relationship: mismatched related donors in Cohort A and unrelated donors in Cohort B. Both cohorts received the T-cell-depletion intervention; the registry does not describe either cohort as a control. The treatment process included conditioning therapy, with its regimen based on the disease being treated. The record does not report enough detail to characterize the conditioning regimens across participants or to determine how those regimens varied.

The primary objective concerned severe acute GVHD within 30 days of transplant. Secondary objectives covered engraftment and time to engraftment, post-transplant infections, EBV-related PTLD, leukemia relapse, transplant-related mortality and toxicities, overall survival, and the doses of CD34+ and CD3+ cells given. The registry lists nine secondary outcome measures. Their inclusion identifies outcomes of interest, but does not itself supply their results or the methods used to analyze them.

Because there is no separate comparator group, the design can describe outcomes among recipients treated under the study approach but cannot, by itself, isolate the effect of T-cell depletion from other influences. No randomization, allocation procedure, or masking procedure is described beyond the registry entries of not applicable and none. The registry record does not report a detailed statistical analysis plan, sample-size justification, or reason for termination.

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: Subjects were enrolled to two cohorts based on donor type, Mismatched Related Donor (MMRD) and Matched Unrelated Donor (MUD).

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 Number of Participants With Severe Graft vs. Host Disease (GVHD)., measured over Within 30 days after stem cell transplant.

The primary endpoint counts participants with severe graft-versus-host disease, defined in the registry as grade III/IV GVHD, within 30 days after stem cell transplant. This is a binary participant-level outcome: each recipient either meets the stated endpoint definition during the specified window or does not. The registry expresses the measure as a count of participants, rather than reporting a continuous measure of disease severity.

Such an endpoint is used to assess the occurrence of a serious post-transplant complication over a defined period. A consistent grading threshold makes the outcome more interpretable than an unrestricted label of GVHD, while a stated follow-up window clarifies which events qualify for the primary measure. The 30-day window is the endpoint's stated timeframe; it should not be treated as the duration of follow-up for the secondary outcomes, whose timeframes are not reported in the registry record.

A count needs its corresponding population at risk to be interpreted as a frequency. The registry record does not report the primary count or a corresponding estimate of uncertainty. Therefore, the endpoint definition is available, but the posted record does not show how many participants met it, nor how precisely the event frequency can be estimated. The definition alone is not evidence that the intervention prevented severe GVHD.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

Statistical methods determine how observed outcomes are summarized and how much uncertainty should accompany them. For this study, the registry identifies a participant count as the primary outcome measure, but does not report an analysis method or a result for that endpoint. The concepts below are general statistical explanations; they should not be taken as a description of analyses actually carried out for this study.

What does a participant count represent?

A binary endpoint classifies each participant according to whether a specified event occurred during the stated observation window. The primary endpoint applies this structure to grade III/IV GVHD within 30 days after transplant. A count is not, on its own, an event rate: interpretation also requires a clearly defined denominator, meaning the participants whose outcomes were included in the calculation. An analysis should also make clear how participants without complete outcome information were handled. Those details for the primary endpoint are not reported in the registry record.

Counts are often accompanied by an estimated proportion and an uncertainty interval. A confidence interval describes a range of values compatible with the observed data under the method's assumptions. It conveys precision, not certainty that the true value lies within a particular interval, and it does not resolve limitations in the study design. No interval for the primary outcome is reported in the registry record.

Why does the design matter for inference?

A single-group study can describe outcomes among enrolled recipients, but there is no concurrent control group in the registry design against which to estimate a treatment contrast. For this reason, even a precise estimate of an event frequency would not by itself show what would have happened under another approach. Potential differences in patient characteristics, donor relationship, underlying disease, conditioning, or follow-up could affect observed outcomes. The record does not report analyses that would adjust for such factors.

The donor cohorts distinguish mismatched related donors from unrelated donors. Cohort membership is not the same as random assignment. General statistical interpretation therefore requires caution about treating a difference between cohorts as a causal effect: donor type may coincide with other characteristics, and no adjusted comparison is listed in the registry record. No randomized comparison is reported.

What is over-dispersion, and is it relevant?

Over-dispersion is a general concern when data show greater variability than a statistical model assumes. It can make standard errors too small if a model treats observations as more independent or more uniform than they are. It is especially relevant to some count or clustered-data models. The primary endpoint is described as a participant count for a binary event, and no modeling approach or over-dispersion assessment is reported. It would therefore be inappropriate to assert that this issue was assessed or that it affected the study's results.

How should planning calculations be read?

General sample-size calculations estimate how many participants might be needed under stated assumptions to detect a chosen effect at a chosen significance level and power. They are planning exercises, not evidence that a study had a particular chance of success after its results were observed. The registry's planning assumptions describe a two-sided significance level of 0.05, equal allocation between two arms, a normal approximation, and effects defined as fractions of the observed effect. The illustrations are not the study's actual single-group design, which has no listed two-arm allocation. They must not be read as observed power or as proof that the study was adequately sized.

A planning calculation depends on the effect used as its target. If that effect is based on the observed primary outcome, readers need the outcome estimate and its definition to judge whether the target is meaningful. The primary observed effect is not reported in the registry record, and the registry does not report a sample-size justification for the trial's own design. Consequently, the planning assumptions do not fill the gap in the primary outcome reporting.

What can p-values and intervals tell readers?

In general, a p-value measures how surprising data at least as extreme as those observed would be under a specified statistical null model. It is not the probability that a treatment works, nor does it quantify the size or clinical importance of an effect. A confidence interval provides an estimate and its precision under a method's assumptions. Both require a defined analysis and observed data. The registry record lists no analyses and no primary endpoint p-value or confidence interval, so neither significance nor precision can be evaluated for the primary question.

More broadly, statistical uncertainty and design limitations answer different questions. A narrow interval can still describe a non-comparative study that cannot establish what a control group might have experienced. Conversely, missing outcome reporting prevents readers from judging the uncertainty even for a descriptive estimate. In this record, the primary outcome result and the detailed statistical analysis plan are not reported.

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("T Cell Depletion Using CliniMACS®")
n      <- c(52)
events <- c(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  T Cell Depletion Using CliniMACS®  52  0  0.0  0.0  6.8  0.0  6.9  0.0  6.7

11. Multiplicity, Missing Data and Analysis Populations

The study lists a primary endpoint and nine secondary outcome measures. When many outcomes are tested, the chance of at least one apparently unusual finding can increase if each is assessed separately without accounting for the number of tests. General approaches include specifying a primary hypothesis in advance, adjusting inference across selected tests, or treating secondary analyses as exploratory. The registry record does not report whether any multiplicity adjustment or hierarchy among outcomes was planned or applied.

The record lists no statistical analyses. It does not report an analysis population for the primary endpoint, the number of participants with evaluable follow-up, or how missing outcome information was handled. Missing data can affect estimates when participants with unknown outcomes differ from those with observed outcomes; the direction and extent of any effect depend on the pattern and reasons for missingness. No imputation method, censoring rule, or sensitivity analysis is reported in the registry record.

Similarly, the record does not report whether analyses followed an intention-to-treat principle, included only recipients who received the intervention, or used another population definition. These choices matter because the analyzed group determines the denominator and the meaning of an estimate. The enrollment figure does not establish how many participants contributed to each outcome analysis.

These omissions limit interpretation of both primary and secondary outcomes. They do not demonstrate that the investigators failed to conduct such analyses; they mean that the registry record does not report them. Without defined analysis populations, missing-data methods, and multiplicity procedures, readers cannot fully assess the robustness or inferential status of reported outcome findings.

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 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: fever (61.5%), hhv-6 reactivation (17.3%), graft vs. host disease (17.3%), thrombotic microangiopathy (11.5%), acute gastroenteritis/ diarrhea (9.6%).

The registry reports 52 participants at risk for serious adverse events, with 45 affected, and 52 at risk for other adverse events, with 33 affected. It also records 15 deaths. These are safety-reporting counts for the T-cell depletion group. The serious-event terms listed most often are fever at 61.5%, HHV-6 reactivation at 17.3%, graft-versus-host disease at 17.3%, thrombotic microangiopathy at 11.5%, acute gastroenteritis/ diarrhea at 9.6%, and CMV reactivation at 7.7%.

The term percentages are reproduced as registry entries; the record does not report a term-specific denominator or observation window in the information summarized. The term list should not be treated as a complete list of adverse events. Participants may have experienced more than one event, but the overlap is not reported. The record also does not establish whether each event was caused by the device, the transplant, conditioning, the underlying disease, or another factor.

Serious-event reporting and the primary GVHD endpoint are distinct presentations. The primary endpoint is specifically grade III/IV GVHD within 30 days, whereas the safety listing names graft-versus-host disease without giving its grade or a matching timeframe. The safety figures therefore cannot substitute for the missing primary result. They describe reported event burden, not a comparison with another treatment or a causal safety effect.

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

The registry record describes a phase II, single-group study of CliniMACS® T-cell depletion among alternative-donor stem cell transplant recipients. It identifies severe acute GVHD within 30 days as the primary outcome and lists several additional outcomes related to engraftment, infection, relapse, mortality, toxicity, survival, and cell dose. It also records adverse-event counts, selected serious-event terms, and deaths.

What the posted information does not show is the primary endpoint count or an estimate of the frequency of severe GVHD. It also does not report an uncertainty interval or a statistical test for that endpoint. Consequently, the central study question cannot be answered from the primary outcome information in the registry record. The design has no separate control group, so an outcome among treated recipients would not by itself establish what the outcome would have been under another transplant strategy.

The adverse-event entries are useful as a description of reported safety events in the registry, but they do not establish causation. The record does not provide enough information to link particular events or deaths to the device or to separate effects of the intervention from conditioning, transplantation, underlying disease, or other factors. The listed safety information also does not define the grade or timing of the GVHD terms in a way that makes them equivalent to the primary endpoint.

Study status is recorded as terminated, with primary completion in 2016-11. The reason for termination and the degree to which planned follow-up was completed are not reported in the registry record. Termination should not be interpreted as evidence of benefit, harm, or a specific operational problem. Overall, the record supports a description of the study question, design, and selected safety entries, but does not provide the primary result needed to judge the study's stated objective.

14. Why This Trial Matters Statistically

This study illustrates why a clear endpoint definition is not enough to support a statistical conclusion. The primary endpoint specifies a clinically important event, a severity threshold, and an observation window: grade III/IV GVHD within 30 days after transplant. Yet the registry record does not report the endpoint count or its uncertainty. Readers can identify what the study intended to measure, but cannot estimate the reported occurrence of that outcome from the posted primary result.

The design is also important. A single-group study can provide descriptive information in a defined transplant setting, but it does not provide a contemporaneous comparison for estimating a treatment contrast. Separating recipients by donor relationship does not create a randomized control group. This distinction helps prevent descriptive outcomes from being mistaken for evidence that an intervention caused an outcome or prevented it.

The record also shows the importance of reporting analysis details alongside outcome definitions. The number of participants included in each analysis, the handling of missing outcomes, and the statistical methods all affect interpretation. Those details are not reported in the registry record, and no analyses are listed. The absence of those details limits assessment of precision, robustness, and potential bias.

Finally, safety counts and primary efficacy outcomes answer different questions. The safety entries document reported events, while the primary endpoint concerns a specific grade of GVHD during a defined period. Keeping those measures distinct is necessary when interpreting transplant studies, where events may have multiple possible explanations and may overlap. The statistical value of this record is therefore in clarifying the intended question and the limits of the posted results, rather than establishing a comparative treatment effect.

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 limitation for interpreting the stated primary objective is that its result is not reported in the registry record. Without the primary event count, a denominator for the endpoint, or an estimate of uncertainty, readers cannot assess the observed frequency of severe GVHD or its precision. The registry identifies the definition and timeframe but not the outcome value.

The single-group design has no listed control arm. As a result, it cannot directly estimate how outcomes would differ under another approach. The two donor cohorts are defined by donor relationship, not by randomized assignment, and should not be treated as equivalent treatment and control groups. The record does not report adjusted analyses that might address differences among recipients or clinical settings.

Enrollment was 53, but the number contributing to each endpoint analysis is not reported. The record does not state how missing observations, incomplete follow-up, or participants who did not receive the planned intervention were handled. It also does not report a detailed analysis plan, methods for handling multiple outcomes, or the study's own sample-size justification. These omissions make it difficult to evaluate the planned inferential framework or assess whether results might be sensitive to analytic choices.

The status is terminated, but the reason for termination is not reported in the registry record. The record also does not explain whether the specified follow-up was completed for all participants. Safety entries include participant counts, deaths, and selected serious-event terms, but do not provide the event-level timing, detailed attribution, or overlap needed for a complete causal assessment. In particular, the serious-event GVHD listing does not give the grade and timeframe required to identify it with the primary endpoint. These limitations restrict both efficacy interpretation and detailed safety attribution.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: T-cell Depleted Alternative Donor Transplantation — NCT00968864.
• Registry record last updated 2022-04-22; status last verified 2017-10.
• Results first posted 2017-11-08.
• 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

NCT00968864 is a phase II, single-group study sponsored by Wake Forest University Health Sciences. It enrolled 53 participants with malignant or non-malignant diseases who received alternative-donor stem cell transplants using the CliniMACS® T-cell-depletion approach after conditioning therapy. The registry identifies mismatched related and unrelated donor cohorts, but no separate control group or masking.

The primary endpoint was the number of participants with grade III/IV GVHD within 30 days after transplant. The registry record does not report that endpoint's result or list statistical analyses. Secondary outcomes included engraftment, infections, EBV-related PTLD, leukemia relapse, transplant-related mortality and toxicities, overall survival, and cell doses. Safety reporting records 45 of 52 participants affected by serious adverse events, 33 of 52 affected by other adverse events, and 15 deaths.

The study began in 2009-08, reached primary completion in 2016-11, and is recorded as terminated. The reason for termination is not reported in the registry record.