Pilot Study PBSCT With TCRab Depletion For Hemoglobinopathies: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Pilot Study PBSCT With TCRab Depletion For Hemoglobinopathies (NCT04523376), a non-randomized na study. The primary outcome is Rate of Graft Failure.

2. Clinical Question

The clinical question concerns the feasibility and observed outcomes of a transplant approach in patients with two hemoglobin disorders. The registry record describes peripheral blood stem cell transplantation from closely matched unrelated donors after conditioning regimens specific to sickle cell disease or beta thalassemia major. The grafts undergo ex vivo depletion of TCRαβ+ T cells and CD19+ B cells using CliniMACS.

The primary outcome is a count of participants with graft failure, with definitions covering failure to achieve neutrophil engraftment and loss of engraftment after it has occurred. The outcome is assessed up to 1 year after transplantation. Secondary outcomes listed in the registry record include treatment-related deaths, event-free survival, overall survival, and viral reactivation or symptomatic viral infection.

This is not a randomized comparison of the transplant strategy against another treatment. The registry record does not report a numerical primary-outcome result, so the central question can be described from the endpoint definition, but its observed answer cannot be stated from this record.

3. Trial Design

This is a completed pilot study listed as phase NA, with non-randomized allocation, no masking, and a parallel model. The brief summary characterizes it as a single-arm study of peripheral stem cell transplantation with ex vivo T-cell receptor alpha beta and CD19+ B-cell depletion of unrelated donor grafts. Enrollment is listed as 8.

The registry record describes separate disease-specific care for sickle cell disease and beta thalassemia major. Participants in each group are described as receiving previously established, disease-specific chemotherapy-based conditioning before transplantation with TCRαβ and B-cell-depleted peripheral blood stem cells from closely matched unrelated donors. The record identifies CliniMACS as the device intervention. It does not describe a randomized allocation process or a concurrent control treatment.

The listed study start date is 2020-05-14, and the primary completion date is 2025-06-23. The status is completed. These administrative details do not establish when every outcome was assessed or how long each participant was followed; follow-up details beyond the endpoint timeframe are not reported in the registry record.

Because the study is single arm and non-randomized, the disease groups should not be read as two arms testing competing interventions. Their treatments share the transplant approach but use conditioning described as specific to each disease. Differences between the groups could reflect patient characteristics, disease, or other factors, rather than an effect of one treatment compared with another. The enrollment is small, and the registry record does not give a rationale for that enrollment target or a sample-size justification.

The registry record lists 8 outcome measures and 0 analyses. It names the primary endpoint and several secondary outcomes, but numerical primary-outcome results and detailed analysis methods are not reported in the registry record. The listed design therefore supports a descriptive account of the study structure, but not a claim about comparative efficacy.

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:

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 Rate of Graft Failure, measured over Up to 1 year post-transplantation.

The primary endpoint is the number of participants with graft failure up to 1 year post-transplantation. It includes primary graft failure, defined in the registry record as no evidence of neutrophil engraftment by day +30 after stem cell infusion. It also includes secondary graft failure: an absolute neutrophil count below 500 for at least 7-10 days after initial engraftment, in the absence of known infection or drug-mediated suppression, with confirmation by hypocellular bone marrow biopsy and/or total donor chimerism from blood or bone marrow below 10 percent.

In general, a count endpoint is useful when the clinical question is how many participants experience a clearly defined event during a specified period. Combining primary and secondary graft failure captures different patterns of unsuccessful or lost engraftment, although interpretation depends on applying the endpoint definitions consistently. The component definitions matter because a count may combine events that occur at different stages after transplantation.

The registry record gives the endpoint definition and timeframe but does not report the observed primary-outcome count. It is therefore not possible to describe the study's primary graft-failure result from this record. The count also should not be confused with the secondary survival outcomes, which describe time-to-event probabilities rather than simply the number meeting this graft-failure definition.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

Statistical methods determine how observations are converted into estimates and how uncertainty is represented. The registry record gives the primary endpoint definition, the study design labels, and several outcome names. It does not report the statistical analysis plan, numerical primary-outcome result, confidence interval, or detailed methods for the secondary outcomes. The following concepts are general explanations, not claims about methods used in this study.

What does a count endpoint express?

In general, a count endpoint reports how many participants meet an event definition during a stated follow-up period. Here, the primary endpoint is defined as the number of participants with primary or secondary graft failure up to 1 year post-transplantation. A count is straightforward to interpret as an observed total, but it does not by itself show the uncertainty around the experience in a wider population. A count also depends on who was included, how long they were observed, and whether the event criteria were applied consistently.

For a binary outcome, each participant is classified according to whether the specified event occurred within the relevant period. The registry record identifies the primary outcome in terms of participants and gives definitions for both primary and secondary graft failure. These definitions include timing and clinical criteria. In general, a clear definition helps avoid ambiguity about what qualifies as an event, while combining distinct forms of failure means that component-level results can be important for interpretation. Component results are not reported in the registry record.

What does a confidence interval add?

In general, a confidence interval expresses the statistical uncertainty around an estimate under the assumptions of the analysis. It is not a guarantee that the true value lies inside the interval, nor does it describe every source of uncertainty, such as differences in patients or limitations in event ascertainment. For a small study, estimates may be imprecise even when the observed count is known. No confidence interval for the primary endpoint is reported in the registry record, so precision cannot be quantified from the posted primary-outcome information.

Why does the design matter?

The study is listed as non-randomized, unmasked, and parallel, while the brief summary calls it single arm. In general, randomization helps balance measured and unmeasured characteristics between treatment groups, though it does not remove all uncertainty. Without a randomized control group, observed outcomes cannot isolate the effect of the intervention from the natural course of disease, patient selection, concurrent care, or other influences. The two disease groups described in the record are not a like-for-like comparison because their underlying conditions and disease-specific conditioning differ.

Masking concerns whether participants or study personnel are kept unaware of assigned treatment. The record lists no masking. In general, lack of masking can affect subjective assessments or decisions about outcome classification, although the registry record does not report whether such effects occurred in this study. The primary endpoint includes defined clinical criteria, but the process for judging or confirming events is not further described.

What are planning sample sizes?

In general, a sample-size calculation is a planning exercise based on an assumed event effect, significance level, allocation, and statistical method. The registry record describes a planning illustration based on the observed effect, with two-sided significance level 0.05, equal allocation between two arms, and a normal approximation. It states that the effect to detect is a specified fraction of the observed effect. Time-to-event calculations are described as total event counts using the Schoenfeld method; other calculations are described as participants per arm.

These are planning assumptions, not observed results or observed power. A planned sample size does not show what the study found, and a calculation based on an observed effect is not evidence that the effect is reliable. The registry record does not report numerical sample-size outputs or a trial-specific sample-size justification. The two-arm assumptions also should not be mistaken for the actual single-arm design described in the brief summary.

How should event and survival outcomes differ?

In general, an event count records the number of participants with an event, while a time-to-event analysis incorporates when events occur and may account for participants whose event status is not observed over the full period. Survival probability estimates describe the probability of remaining alive or event-free over time, under the analysis definition. The registry lists event-free survival and overall survival as secondary outcomes, but the analysis methods, time points, censoring approach, and numerical results are not reported in the registry record. Those details are needed to interpret survival estimates and their uncertainty.

Over-dispersion is a general issue for count data when observed variability exceeds what a chosen model expects. It matters because a model that understates variability can produce confidence intervals that are too narrow. The primary endpoint is described as a count of participants with an event, not as a repeated-event rate, and the registry record does not report a count model or dispersion estimate. It would therefore be inappropriate to assert that over-dispersion was assessed or that it affected the results.

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("Sickle Cell Disease", "Beta Thalassemias Major")
n      <- c(7, 1)
events <- c(2, 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  Sickle Cell Disease  7  2  28.6  3.7  71.0  8.2  64.1  8.5  65.1
ARM  Beta Thalassemias Major  1  0  0.0  0.0  97.5  0.0  79.3  1.3  84.2

11. Multiplicity, Missing Data and Analysis Populations

The registry record lists a primary outcome and several secondary outcomes: treatment-related deaths, event-free survival, overall survival, and viral reactivation or symptomatic viral infection. It also reports 8 outcome measures and 0 analyses. The record does not describe a multiplicity adjustment, a hierarchy for testing outcomes, or which outcomes were intended to support formal statistical claims. These details are not reported in the registry record.

In general, testing multiple outcomes can increase the chance that at least one result appears noteworthy by chance. A prespecified hierarchy or adjustment can help control that issue, but the appropriate approach depends on the study aims and analysis plan. The presence of multiple registered outcomes alone does not establish that formal hypothesis testing was conducted. With 0 analyses listed, no specific multiplicity method can be inferred.

Missing-data handling and analysis populations are not reported in the registry record. In general, missing outcome information can affect estimates if participants differ in whether their outcomes are observed, and the method used to handle such information can influence interpretation. An analysis population specifies which participants are included in a given analysis, for example according to enrollment or treatment received. The registry record does not say whether all enrolled participants were included in each outcome summary or how incomplete follow-up was treated.

The primary endpoint has a defined timeframe of up to 1 year post-transplantation, but the registry record does not give participant-level follow-up or explain how outcome status was established for every participant. The completion status does not, by itself, document completeness of endpoint data. Without the analysis population, missing-data approach, and outcome-specific denominators for the primary endpoint, the degree to which the posted counts represent all enrolled participants cannot be evaluated.

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: secondary graft failure (28.6%).

The registry record lists serious and other adverse-event counts separately for the two disease groups. In the sickle cell disease group, 2 of 7 participants are listed as affected by serious adverse events and 7 of 7 by other adverse events. In the beta thalassemia major group, 0 of 1 is listed as affected by serious adverse events and 1 of 1 by other adverse events. The record lists 1 death in the sickle cell disease group and 0 in the beta thalassemia major group.

The most common serious adverse-event term listed is secondary graft failure, at 28.6%. The registry record does not provide further detail about the number of occurrences, timing, severity, or relationship to treatment for that term. A term-level percentage and the group-level number of participants affected are different summaries and should not be treated as interchangeable.

These counts are descriptive and come from small groups. In general, a serious adverse event is a safety classification, not by itself proof that an intervention caused the event. The registry record does not state the attribution for each listed event or give a detailed adverse-event observation period. The death counts should likewise be read as reported counts, not as evidence of causation. Small denominators make each participant's experience influential, so the summaries should not be interpreted as precise estimates of risk in a broader population.

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

The record establishes that a completed pilot study evaluated a single-arm transplant approach using TCRαβ+ T-cell and B-cell-depleted peripheral blood stem cell grafts from closely matched unrelated donors in patients with sickle cell disease or beta thalassemia major. It defines graft failure as the primary outcome, with assessment up to 1 year post-transplantation, and lists several secondary clinical and safety outcomes.

The posted information does not report the numerical primary graft-failure result, a confidence interval, or detailed analyses of the secondary outcomes. Therefore, it does not support a quantified conclusion about the primary endpoint or the precision of any treatment effect. The adverse-event and death counts offer descriptive safety information, but the small group sizes and lack of a control group limit what can be inferred from them.

In general, a single-arm pilot study can describe what happened among its participants and can inform later research questions. It cannot, on its own, establish how outcomes would have differed under another treatment or no treatment. Differences between the sickle cell disease and beta thalassemia major groups cannot serve as a treatment comparison because the groups have different conditions and disease-specific conditioning regimens.

The record does not report a trial-specific sample-size justification, missing-data approach, analysis populations, or statistical plan. Its planning assumptions should not be confused with observed evidence or treated as observed power. The completed status indicates the study is listed as completed, but does not fill in missing outcome estimates or explain the completeness of follow-up.

Accordingly, the registry record supports a careful description of the design, endpoint definitions, and selected event counts. It does not establish that the transplant approach is more or less effective than another strategy, and it does not provide enough primary-outcome detail to assess the observed graft-failure experience quantitatively.

14. Why This Trial Matters Statistically

This study matters statistically because it illustrates the gap between a clearly specified clinical endpoint and a reported numerical result. The registry record defines primary and secondary graft failure in detail and sets a primary outcome timeframe of up to 1 year post-transplantation. Yet the numerical result for that primary endpoint is not reported in the registry record. Without the observed result and a measure of uncertainty, readers cannot quantify the primary outcome's magnitude or precision.

The pilot design also makes the distinction between description and comparison especially important. The study is listed as non-randomized, and its brief summary calls it single arm. The two disease groups receive disease-specific conditioning and are not comparable control arms. Statistical interpretation therefore has to focus on what was observed in the enrolled participants rather than attributing outcomes to the intervention through a between-group contrast.

The registry record lists enrollment of 8 and provides safety counts for the disease groups. Such small groups can describe individual experiences, but they are not a basis for precise estimates across a broader population. In general, small samples often leave substantial uncertainty around event rates, and the registry record does not provide primary-outcome uncertainty measures.

The record also names outcomes that address survival, treatment-related death, and viral events. Reporting outcome definitions and numerical results together is important because a list of intended measures does not show what happened. The record lists 0 analyses, and detailed analysis methods, missing-data handling, and analysis populations are not reported. Those omissions constrain reproducibility and prevent evaluation of how estimates were obtained.

These statistical limitations do not negate the descriptive role of a pilot study. They define the boundary of what the registry record can support: design and endpoint descriptions, along with selected safety counts, rather than a precise or comparative estimate of 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.

Several limitations specific to this trial shape interpretation. The registry record describes the study as single arm and lists non-randomized allocation. There is no concurrent control treatment described, so outcomes cannot be contrasted with an alternative strategy under randomized conditions. The two disease groups are not interchangeable comparators: they involve different conditions and disease-specific conditioning regimens.

Enrollment is listed as 8, with 7 participants in the sickle cell disease safety group and 1 in the beta thalassemia major safety group. Such small group counts limit the stability and precision of descriptive safety summaries. A count in the smaller group is particularly difficult to generalize beyond the participants represented, and the record does not provide uncertainty intervals for these safety summaries.

The primary endpoint is defined in detail, but its observed numerical result is not reported in the registry record. The record also does not provide numerical results or detailed analyses for the listed secondary outcomes. This prevents assessment of the primary endpoint's observed magnitude and leaves survival and viral-outcome interpretation unresolved.

The statistical analysis plan, sample-size justification, missing-data methods, and analysis populations are not reported in the registry record. Nor does the record give details about endpoint adjudication, participant-level follow-up, or adverse-event attribution. The listed planning illustration uses assumptions for two-arm calculations, while the study itself is described as single arm; the record does not provide numerical planning outputs or a trial-specific justification to clarify that relationship.

Finally, the completed status and listed completion date do not establish that every outcome was observed for every participant or that all analyses were posted. These limitations concern the information available in the registry record and should not be mistaken for findings about what did or did not happen clinically.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Pilot Study PBSCT With TCRab Depletion For Hemoglobinopathies — NCT04523376.
• Registry record last updated 2026-04-28; status last verified 2026-03.
• Results first posted 2026-04-28.
• 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

NCT04523376 is a completed pilot study of peripheral blood stem cell transplantation with TCRαβ+ T-cell and CD19+ B-cell depletion for patients with sickle cell disease or beta thalassemia major. It is listed as non-randomized, unmasked, and parallel; the brief summary describes a single-arm study. Enrollment is 8, and CliniMACS is the listed device intervention.

The primary endpoint is the number of participants with primary or secondary graft failure up to 1 year post-transplantation. Secondary outcomes include treatment-related deaths, event-free survival, overall survival, and viral reactivation or symptomatic viral infection. The record lists 8 outcome measures and 0 analyses.

Safety summaries include serious and other adverse-event counts by disease group, along with death counts. The numerical primary-outcome result, detailed secondary analyses, statistical analysis plan, missing-data approach, and analysis populations are not reported in the registry record. The record therefore describes the study design and endpoints but does not provide a quantified primary graft-failure result.