Haploidentical Hematopoietic Cell Transplantation Using TCR Alpha/Beta and CD19 Depletion: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Haploidentical Hematopoietic Cell Transplantation Using TCR Alpha/Beta and CD19 Depletion (NCT05236764), a na na study. The primary outcome is Cumulative Incidence of Neutrophil Engraftment and Platelet Engraftment.

2. Clinical Question

3. Trial Design

The registry record describes a single-group study of haploidentical allogeneic hematopoietic cell transplantation using donor cells depleted of T-cell receptor alpha/beta-positive cells and CD19-positive cells. The listed intervention is the CliniMACS device. The arm description states that recipients receive donor stem cells after a conditioning regimen consisting of chemotherapy, with or without radiation, and that investigators specially treat the donor blood cells used for transplantation.

The record lists enrollment as 3. It identifies the population broadly as adult and pediatric patients with hematological malignancies and non-malignant disorders, and lists several specific conditions, including leukemias in remission, myelodysplastic syndromes, immune disorders, hemoglobinopathies, and bone marrow failure conditions. The primary analysis population is described as all patients who received transplant.

The study has no listed comparator: allocation is NA, masking is none, and the model is single group. There is consequently no randomized treatment contrast described in the record. The brief summary calls the study phase I/II, while the structured phase field is NA; the registry record does not explain this difference.

Baylor College of Medicine is listed as the sponsor. The recorded start date is 2023-12-06, the primary completion date is 2024-08-29, and the status is active, not recruiting. These design and status details describe the registry entry; they do not establish that a particular analysis has been completed. Numerical primary endpoint results and analysis details 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.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: All patients who received transplant were included in analysis.

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 Cumulative Incidence of Neutrophil Engraftment and Platelet Engraftment, measured over 42 days post-HCT.

The primary endpoint is titled cumulative incidence of neutrophil engraftment and platelet engraftment. It is described as a composite measure reported as a rate with an associated 95% confidence interval, with the timeframe set at 42 days post-HCT. The endpoint asks whether the specified engraftment events occur within that period after transplantation.

The registry defines neutrophil engraftment as the first of 3 consecutive days with a peripheral blood absolute neutrophil count of ≥ 0.5x10^9/L. Platelet engraftment is defined as the first day with a platelet count of ≥ 20 x10^9/L without transfusion support for 7 consecutive days. The record does not provide the observed rate or confidence interval.

In general, engraftment is a measurable post-transplant milestone. A time-bounded endpoint gives a consistent period in which to assess that milestone, while the composite wording records the endpoint as a combined measure. The registry specifies that graft failure and death are competing risks. In general, a competing event can prevent the outcome of interest from occurring in the way it would otherwise be counted; accounting for such events is therefore relevant when estimating cumulative incidence. The registry record does not further explain the composite's operational analysis or report its numerical result.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does cumulative incidence mean?

The registry specifies cumulative incidence for the primary engraftment endpoint and identifies graft failure and death as competing risks. In general, cumulative incidence estimates the probability of an event occurring by a specified time while accounting for competing events. A competing event is an event that changes whether, or how, the outcome of interest can subsequently be observed. Treating such events appropriately is important because simply censoring them as if they were unrelated losses to follow-up can answer a different question.

The stated timeframe is 42 days post-HCT. The endpoint is a composite measure of neutrophil and platelet engraftment, with separate operational definitions for each component. The registry record does not provide further details on how the components are combined for the analysis, such as whether both must occur for the composite to count. That detail is not reported in the registry record and should not be inferred from the title alone.

What does a confidence interval communicate?

The endpoint is to be reported with a 95% confidence interval. In general, a confidence interval conveys the precision of an estimate under the statistical method used. It reflects sampling uncertainty, not every possible source of uncertainty, such as differences between study populations or limitations in outcome ascertainment. A confidence interval does not guarantee that the true value lies within its bounds, and it does not replace consideration of the study design.

No primary estimate or interval is reported in the registry record. It is therefore not possible to judge the observed rate, the interval's width, or the degree of precision. The registry describes the intended measure and method, rather than presenting enough outcome information to evaluate them.

Why account for competing risks?

In general, competing-risks analysis is used when an event other than the event of interest can alter the chance of observing that event. Here the record explicitly names graft failure and death as competing risks for the engraftment endpoint. A competing-risks approach targets cumulative incidence in the presence of these events, rather than treating all non-engraftment observations as equivalent. The specific estimator, implementation details, and handling of follow-up are not reported in the registry record.

What can be concluded from the analysis population?

The primary analysis population is described as all patients who received transplant. This defines the intended population for the endpoint more narrowly than all patients who might have been considered for the study: the record does not say that people who did not receive a transplant are included in the primary analysis. The registry record does not report participant flow, reasons for any exclusions, endpoint-specific denominators, or whether any outcome data were unavailable.

In general, a clearly defined analysis population helps readers understand which participants contribute to an estimate. It does not, on its own, explain how missing observations or incomplete follow-up are handled. Those details are not reported in the registry record.

How should the planning illustrations be understood?

The record describes planning illustrations based on an observed effect, with a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. It says the effect to detect is a stated fraction of the observed effect. For time-to-event illustrations, the reported quantity is the total number of events; for other illustrations, it is participants per arm.

These assumptions describe planning calculations, not trial observations or evidence that the study had a particular probability of detecting an effect. The illustrations are not observed power. The registry record does not report the numerical observed effect or the particular fraction used, so no planning value can be interpreted from these details alone. The registry record also does not report that these assumptions were the study's own design or statistical plan.

In general, planning calculations depend on the effect size and assumptions about the analysis. A planning target is not a finding about the participants who enrolled, and it cannot substitute for an observed treatment comparison. This distinction is especially important for a single-group design, which does not provide a randomized two-arm comparison.

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("Alpha Beta+ T Cell Depleted CD34+ Stem Cells")
n      <- c(3)
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  Alpha Beta+ T Cell Depleted CD34+ Stem Cells  3  2  66.7  9.4  99.2  20.8  93.9  19.4  93.2

11. Multiplicity, Missing Data and Analysis Populations

The registry record lists 5 outcome measures and names three secondary outcomes: transplant-related mortality, overall survival, and chronic graft versus host disease. The primary outcome is the composite cumulative incidence of neutrophil and platelet engraftment. The record lists zero analyses and does not report numerical outcome results.

Multiplicity arises in general when several outcomes, time points, or statistical comparisons are examined. Considering many analyses can increase the chance of a seemingly notable result arising by chance. A prespecified testing hierarchy or adjustment can address particular multiplicity concerns, but the registry record does not report a multiplicity strategy, an outcome hierarchy, or a statistical analysis plan. It is not possible to determine whether any adjustment was used.

Missing-data handling is also not reported in the registry record. The primary analysis population is described as all patients who received transplant, but that does not specify how unavailable endpoint measurements, loss to follow-up, or incomplete observation are treated. The record does not report endpoint-specific denominators or reasons for missing observations.

These omissions limit assessment of how the analyses were conducted and how complete the outcome information was. They do not establish that data were missing or that multiplicity adjustments were absent in the study conduct; they mean that those methods are not documented 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 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 (33.3%), encephalitis infection (33.3%), viremia (33.3%), confusion (33.3%).

The adverse-event entry lists one study group, titled Alpha Beta+ T Cell Depleted CD34+ Stem Cells. It records 3 participants at risk for serious adverse events and 1 affected by a serious adverse event. For other adverse events, it records 3 at risk and 3 affected. The record lists 1 death. These are registry counts and should be read as reported, not as evidence about cause or attribution.

The serious-event terms listed are fever, encephalitis infection, viremia, and confusion, each with a reported percentage of 33.3%. These are event-term percentages in the registry entry; the record does not explain whether terms can overlap within a participant, or provide further event-level details such as timing, duration, or attribution. The percentages should not be added together or interpreted as a combined rate.

In general, adverse-event counts describe what was recorded among the participants at risk, while interpretation also depends on definitions, follow-up, severity, and assessment procedures. The registry record does not report those details for these entries. With the listed enrollment and event counts, the safety observations are limited in scope. They do not support a comparative safety assessment because the design has no control group, and the record does not establish that the listed events were caused by the intervention.

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

The registry entry describes a study intended to assess outcomes after haploidentical transplantation using donor cells depleted of T-cell receptor alpha/beta-positive cells and CD19-positive cells. Its primary endpoint is the cumulative incidence of a combined neutrophil and platelet engraftment measure by 42 days post-HCT, with graft failure and death treated as competing risks. These definitions identify what the study is set up to measure.

The registry record does not report a numerical primary endpoint result or confidence interval. It therefore does not show the observed engraftment rate or its precision. The listed secondary outcomes and adverse-event entries likewise do not provide a comparative estimate of benefit or harm. The brief summary's statements about expected reductions in graft versus host disease and possible elimination of post-transplant immunosuppressive therapy are rationale, not evidence that those expectations were achieved.

The single-group design has no randomized comparator. In general, outcome frequencies from such a design can describe what occurred in the study group, but cannot by themselves separate an intervention effect from patient characteristics, conditioning, other transplant procedures, or care. The registry record does not report an adjusted comparison that would address these issues.

The listed enrollment is 3, so any conclusions based on this record would also be constrained by the limited amount of information available. No conclusion about the treatment's efficacy or safety should be drawn from the endpoint definitions or planning assumptions alone. The record is most informative about the intended population, intervention, primary outcome, competing risks, and the absence of a comparator; outcome interpretation remains limited because numerical results and fuller analysis details are not reported.

14. Why This Trial Matters Statistically

This study raises a statistical question that is central to transplant outcome assessment: how to describe the occurrence of engraftment when graft failure and death can intervene. The registry explicitly identifies those events as competing risks and specifies cumulative incidence for the primary endpoint. That choice makes the estimand more informative than a simple count that ignores how competing outcomes affect observation of engraftment.

The composite endpoint also makes the definition of success important. Neutrophil and platelet engraftment have separate thresholds and timing rules in the registry record. Readers need those definitions to understand what the endpoint represents and to compare it appropriately with other studies. The registry calls the endpoint composite but does not describe the rule for combining its components, so that interpretive detail remains unresolved.

The design is also statistically important. Because this is a single-group study, it can describe outcomes in the treated study group but does not provide a randomized comparison. This limits what can be learned about comparative effects, regardless of the endpoint's measurement precision. The listed enrollment of 3 further constrains the amount of information available for estimating outcome rates and safety events.

Finally, the record distinguishes an intended endpoint and analysis approach from actual results. It identifies the outcome timeframe and confidence interval, but does not report the numerical estimate, interval, or analyses. Recognizing that distinction prevents design language and study rationale from being mistaken for evidence of observed outcome performance.

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 lists enrollment as 3, and the study has a single group with no comparator. This limits both the amount of outcome information and the ability to make comparative claims. No numerical primary endpoint estimate or confidence interval is reported, so neither the observed rate nor its precision can be assessed from the record.

The primary endpoint is described as a composite of neutrophil and platelet engraftment, but the registry does not explain the operational rule for combining the components. It names graft failure and death as competing risks without reporting the number of such events, the estimator used, or other implementation details. Those omissions limit independent assessment of the endpoint analysis.

The analysis population is described as all patients who received transplant. The registry record does not report participant flow, endpoint-specific denominators, missing-data procedures, follow-up completeness, or reasons for unavailable outcome information. It also does not report a multiplicity plan or detailed statistical analysis plan.

The adverse-event entry gives counts and listed terms but does not provide further details on event timing, duration, attribution, or overlap among terms. The single-group design does not permit a like-for-like safety comparison. The status is active, not recruiting, but the registry does not clarify whether all results have been entered. These limitations concern what is documented in the registry record and do not establish how the study was conducted beyond those details.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Haploidentical Hematopoietic Cell Transplantation Using TCR Alpha/Beta and CD19 Depletion — NCT05236764.
• Registry record last updated 2026-10-08; status last verified 2026-09.
• Results first posted 2025-10-30.
• 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

NCT05236764 is a single-group registry study of haploidentical allogeneic hematopoietic cell transplantation using T-cell receptor alpha/beta and CD19 depletion. Baylor College of Medicine is the listed sponsor, and CliniMACS is the named device. The record lists enrollment as 3 and identifies adult and pediatric patients with hematological malignancies and non-malignant disorders.

The primary endpoint is cumulative incidence of neutrophil and platelet engraftment, assessed by 42 days post-HCT, with graft failure and death treated as competing risks. Secondary outcomes include transplant-related mortality, overall survival, and chronic graft versus host disease. The status is active, not recruiting. Numerical primary endpoint results, confidence intervals, and analysis details are not reported in the registry record.