Reduced Intensity Conditioning Using CD3+/CD19+ Depletion for Non Malignant Transplantable Diseases: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Reduced Intensity Conditioning Using CD3+/CD19+ Depletion for Non Malignant Transplantable Diseases (NCT02277639), a non-randomized phase 2 study. The primary outcome is Number of Participants With Engraftment.

2. Clinical Question

In practical terms, the study asks whether the conditioning and graft approach can be followed by donor-cell engraftment that remains durable and stable at the stated one-year timeframe. The registry describes two conditioning regimens depending on diagnosis and age, but the arm descriptions list the same chemotherapy agents and transplant approach. The particular differences between the regimens, including any age-based distinction, are not reported in the registry record.

The study enrolled 2 participants and is marked completed. With no randomized comparator, its primary question is descriptive rather than a controlled estimate of how the approach compares with another treatment. The registry record does not report participant-level outcome data or an estimate of event-free survival. Therefore, it does not allow the primary question to be answered from the posted outcome information.

3. Trial Design

The registry identifies NCT02277639 as a Phase II study sponsored by Children's Hospital of Philadelphia. It is listed as non-randomized, unmasked, and single-group, with enrollment of 2. The study started in 2011-11, had primary completion in 2016-03, and is marked completed. These administrative details describe the record but do not establish how many participants completed follow-up or contributed to the primary outcome.

The trial concerns reduced intensity conditioning followed by transplantation of CD3+/CD19+ depleted peripheral stem cells from mismatched donors. The listed device intervention is the CliniMACs device. The two arm descriptions are organized by diagnosis: Bone Marrow Failure Syndrome and Immunodeficiency / Dysregulation. Each describes chemotherapy followed by stem cell infusion, and each lists Busulfan, Fludarbine, and Cyclophosphamide. The brief summary says that two conditioning regimens depend on diagnosis and age; the specific regimen differences and age criteria are not reported in the registry record.

Because the design is single-group and non-randomized, there is no concurrent randomized control group against which to estimate a treatment contrast. The diagnosis categories should not be interpreted as randomized arms. The registry explicitly cautions that the arms are not a like-for-like control comparison. As a result, the trial design is suited to describing outcomes within the enrolled group, not to isolating a comparative effect from the posted information.

The registry lists one outcome measure, “Number of Participants With Engraftment,” with a timeframe of One Year. It gives the objective as event free survival with durable stable engraftment of donor cells at one year. However, no primary outcome count or analysis is reported in the registry record. The record also does not report a detailed statistical plan, analysis populations, or the rationale for the enrollment target. These omissions limit interpretation of both the design and the outcome evidence.

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

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 Engraftment, measured over One Year.

The primary outcome is titled “Number of Participants With Engraftment” and is measured in participants. Its stated timeframe is One Year. The accompanying description identifies the primary objective as determining event free survival with durable stable engraftment of donor cells at one year. Thus, the endpoint is intended to represent a clinically relevant transplant milestone over a defined follow-up period, rather than an immediate procedural measure.

The registry does not specify the operational criteria for engraftment, what makes it durable or stable, how event-free survival is defined, or which events count against that status. It also does not report the number of participants who met the endpoint. Those details matter because outcome definitions determine how observations are classified and whether different readers would count the same clinical course in the same way.

In general, a participant count can communicate how many people met a binary outcome, while a time-to-event measure can incorporate when events occur and how long participants are observed. The registry uses both event-free survival language and a participant-count title, but does not provide an analysis explaining how these concepts were operationalized together. Without a reported count, denominator for the outcome, or uncertainty estimate, the endpoint's observed frequency and precision cannot be assessed from the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry describes a single-group, non-randomized study and lists one binary outcome measured as a count of participants with an event. It does not report a statistical analysis for that outcome. The explanations below are general statistical context; they do not describe an analysis plan confirmed for this trial.

What a count outcome can show

In general, a binary outcome classifies each participant according to whether a defined event or condition occurred. A count then records how many participants met the definition. To interpret that count as a rate or proportion, the denominator must also be clear: it should be apparent which participants were eligible for the outcome assessment and which were actually assessed. The registry lists enrollment of 2, but does not report the primary outcome count, the number assessed at One Year, or the denominator used for an outcome analysis.

For this study, the outcome title refers to the number with engraftment, while the description refers to event free survival with durable stable engraftment of donor cells at one year. In general, an analysis needs an operational definition for each part of such an endpoint. Definitions can specify the criteria for engraftment, the period over which stability is judged, the events included in event-free survival, and how incomplete follow-up is handled. These definitions are not reported in the registry record.

Precision and confidence intervals

In general, an estimate from a sample has uncertainty because the observed participants are only one possible set of participants from a broader population. A confidence interval expresses that uncertainty under specified statistical assumptions. For a binary outcome, the width of an interval depends on the amount of information in the observations and on the estimation method. Small datasets commonly yield limited precision, and a count alone does not communicate that precision. No confidence interval or other uncertainty measure for engraftment is reported in the registry record.

A confidence interval is not a guarantee that the true value lies within its endpoints, nor does it resolve limitations in study design or outcome measurement. It describes uncertainty under the model and data used. In general, intervals from a single-group study concern the outcome in that group; they do not create a valid treatment comparison where no control group exists.

Why the design matters

In general, random allocation helps make treatment groups comparable, on average, with respect to both measured and unmeasured factors. This study is explicitly non-randomized and single-group, so there is no randomized control group. Outcomes may be described for participants enrolled, but a contrast with an unobserved alternative outcome cannot be identified from this design alone. The registry also states that the diagnosis-based groups are not a like-for-like control comparison. Differences between those groups, if any, could reflect participant or disease characteristics, regimen choices, or other factors rather than a treatment effect.

The brief summary says that two conditioning regimens depend on diagnosis and age. The registry's arm descriptions name the same drugs and transplant approach for the two diagnosis categories, without specifying the distinctions. In general, comparing groups that receive different regimens requires clear descriptions of who received each regimen, how assignment occurred, and what outcome each group experienced. Those details and a comparative analysis are not reported in the registry record.

Over-dispersion and model choice

In general, over-dispersion describes greater variability in observed data than a statistical model expects. It is often considered for count outcomes when counts vary more than a simple model allows; ignoring it can make uncertainty appear too small. For a binary participant-level endpoint, the analysis should use a method appropriate to the outcome definition and study design rather than assume a count model without justification. The registry does not report a model, dispersion assessment, or any inferential analysis, so it is not possible to assess whether over-dispersion was relevant or how uncertainty was handled.

Planning illustrations are not observed evidence

In general, sample-size planning asks how many observations would be needed under assumptions about an effect, variability, significance level, allocation, and analysis method. The registry record does not report the trial's own sample-size justification. The associated planning illustration is described as computed from an observed effect, with a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation; the effect to detect is a stated fraction of the observed effect. Those are assumptions for an illustration, not evidence that the trial was designed that way, and the illustration is not observed power.

The trial itself is listed as single-group and non-randomized, while the illustration's assumptions refer to equal allocation between two arms. That distinction matters: planning assumptions should not be mistaken for the actual trial design. The record does not provide a reported primary outcome effect from which to evaluate the precision of the trial's observed result. It also does not report a recalculated analysis of that outcome. Without an outcome estimate and its uncertainty, a planning illustration cannot substitute for the missing clinical result.

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("Immunodeficiency / Dysregulation")
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  Immunodeficiency / Dysregulation  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 lists one outcome measure and zero analyses. It does not report a statistical analysis plan, a hierarchy of outcomes, or whether any additional analyses were planned or conducted. The primary objective is described as event free survival with durable stable engraftment at one year, while the outcome title is a count of participants with engraftment. The record does not explain whether these are components of one prespecified endpoint or how they were combined for analysis.

In general, multiplicity arises when multiple hypotheses or outcomes are examined. Repeated testing can increase the chance of finding an apparently notable result by chance, so an analysis plan may specify which outcomes are primary and how testing is handled. The registry does not report multiplicity procedures or enough analysis detail to determine whether they were needed. The absence of listed analyses should not be interpreted as evidence that a particular procedure was or was not used.

The record does not report missing-data methods, handling of loss to follow-up, or the number of participants with an evaluable one-year outcome. In general, missingness can affect a count outcome if the participants without assessments differ in outcome from those assessed. Appropriate interpretation depends on knowing who was included, how missing observations were treated, and whether sensitivity analyses were used. None of these details is reported in the registry record.

Analysis populations are also not described. In general, a report should clarify which enrolled participants contributed to each analysis and whether the analysis follows an intention-to-treat, per-protocol, or other definition. The registry's enrollment count alone does not establish the number analyzed for engraftment or safety. The record does not report a sample-size justification or a full statistical plan, so neither should be inferred from the planning illustration.

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.

The registry reports serious and other adverse-event counts by diagnosis group. In Bone Marrow Failure Syndrome, 0 participants are listed at risk for serious adverse events and 0 at risk for other adverse events; 0 are listed as affected in each category, and deaths are 0. In Immunodeficiency / Dysregulation, 2 participants are listed at risk for serious adverse events and 2 for other adverse events; 0 are listed as affected in either category, and deaths are 0. No serious adverse event terms are listed.

These figures describe the registry's recorded risk sets and counts. The Bone Marrow Failure Syndrome group has no participants listed at risk, so its zero affected count should not be interpreted as an observed absence of events among assessed participants. The other group has a small recorded risk set. In general, when few participants are observed, zero recorded events cannot rule out events that could occur in a larger population or under longer observation.

The registry record does not report event definitions, detailed observation time, or whether all participants completed safety follow-up. The counts therefore do not support a precise estimate of adverse-event frequency or a comparison between groups. They should be read as the safety figures recorded, not as proof of safety or as a basis for treatment advice.

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

The registry record establishes that a completed Phase II study was conducted with enrollment of 2 under a single-group, non-randomized design. It identifies reduced intensity conditioning and CD3+/CD19+ depleted peripheral stem cell grafts as the study approach, and states that the primary objective concerns event free survival with durable stable engraftment at one year. It also records adverse-event counts by diagnosis group.

Those details do not answer whether the primary endpoint was achieved. The number of participants with engraftment, an event-free survival estimate, and any measure of uncertainty are not reported in the registry record. A reader cannot determine the observed outcome frequency or its precision from the endpoint description alone. Completion status does not fill that gap.

Even with a reported outcome count, the design would support description of the enrolled participants rather than a randomized treatment comparison. The registry identifies no separate comparator, and it cautions that the diagnosis groups are not like-for-like controls. Thus, the record does not establish a causal advantage or disadvantage relative to another regimen or care approach.

The safety figures are similarly limited. They record no affected participants among the stated risk sets, but the enrollment is small and one diagnosis group has zero participants at risk in the record. Zero recorded events in these circumstances should not be taken as proof that events cannot occur. The record also does not provide detailed follow-up or event definitions.

In general, clinical interpretation depends on both the observed results and the design, measurement, and analysis that produced them. Here, the outcome result, analysis methods, and several details needed to judge completeness are not reported in the registry record. The most defensible interpretation is therefore narrow: the registry documents the study design and limited safety counts, but it does not report enough primary outcome evidence to assess the engraftment objective.

14. Why This Trial Matters Statistically

This study is statistically notable because its clinical question centers on a binary, participant-level outcome in a very small enrolled group. The registry lists enrollment of 2, yet does not report the primary engraftment count or an uncertainty estimate. This makes the distinction between an endpoint definition and an endpoint result especially important: specifying what a study intends to measure is not the same as reporting what was observed.

The non-randomized, single-group design also illustrates why outcome description and causal comparison are different tasks. A single-group result, if reported, could characterize participants in the study. It would not by itself show how those outcomes compare with an alternative regimen. The diagnosis-specific descriptions cannot serve as randomized controls, and the registry expressly cautions against treating them as like-for-like comparisons.

The record also highlights how much interpretation depends on transparent reporting. The endpoint refers to event-free survival with durable stable engraftment, while its title expresses a participant count. The record does not specify operational criteria, analysis populations, missing-data handling, or the statistical analysis. Those omissions make it difficult to judge what the intended result represents, how complete follow-up was, and how precisely the outcome was estimated.

Finally, planning illustrations and observed evidence answer different questions. A planning exercise uses assumptions to explore sample-size needs; it is not a substitute for a reported outcome and is not observed power. Keeping these distinctions clear helps prevent a design description, a safety count, or a planning calculation from being read as proof of a clinical 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 record constrain interpretation. First, the registry lists enrollment of 2, while the primary outcome count and any estimate of event-free survival are not reported. No confidence interval or other measure of precision is reported for the primary endpoint. This leaves the central study objective without a posted result that can be evaluated statistically.

Second, the study is single-group and non-randomized. There is no randomized comparator for estimating a treatment contrast. The two diagnosis-based descriptions are not like-for-like controls, and the registry does not report the details needed to compare outcomes across them. The brief summary mentions regimen variation by diagnosis and age, but the specific differences and assignment details are not reported.

Third, the endpoint's operational definition is incomplete in the registry record. Although the objective refers to durable stable donor-cell engraftment and event-free survival at one year, the record does not define the criteria for engraftment, stability, or events. It also does not state how incomplete one-year assessments were handled or how many participants were evaluated.

Fourth, the record does not report the statistical analysis plan, analysis populations, missing-data procedures, or sample-size justification. It lists zero analyses. The safety figures include a group with zero participants at risk and another with 2 at risk; these counts provide limited information about event frequency and cannot characterize uncommon harms. The record is marked completed, but that status does not resolve these reporting gaps.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Reduced Intensity Conditioning Using CD3+/CD19+ Depletion for Non Malignant Transplantable Diseases — NCT02277639.
• Registry record last updated 2018-04-11; status last verified 2018-03.
• Results first posted 2018-04-11.
• 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

NCT02277639 is a completed Phase II, non-randomized, single-group study sponsored by Children's Hospital of Philadelphia. It enrolled 2 participants, started in 2011-11, and reached primary completion in 2016-03. The study concerns reduced intensity conditioning and transplantation of CD3+/CD19+ depleted peripheral stem cells for non-malignant diseases.

The primary outcome is the number of participants with engraftment at One Year; the stated objective concerns event free survival with durable stable donor-cell engraftment. The primary outcome result and statistical analysis are not reported in the registry record. Safety counts list 0 affected participants in the reported categories, with 0 participants at risk in the Bone Marrow Failure Syndrome group and 2 at risk in the Immunodeficiency / Dysregulation group. No serious adverse event terms are listed.

The single-group design does not provide a randomized comparison, and the registry cautions that the diagnosis-based groups are not like-for-like controls. Important details about endpoint definitions, analysis populations, missing data, and statistical methods are not reported.