In Vivo Treg Expansion and Graft-Versus-Host Disease Prophylaxis: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for In Vivo Treg Expansion and Graft-Versus-Host Disease Prophylaxis (NCT01927120), a na phase 2 study. The primary outcome is Regulatory T Cells (Tregs)/Total CD4+ Cells at Day 30 Post-HCT.

2. Clinical Question

The clinical question links a treatment regimen with an immune-cell measurement and a prophylaxis context. The study description proposes that adding IL-2 to sirolimus and tacrolimus will optimize regulatory T-cell reconstitution and prevent GVHD. Those statements describe the rationale and intention; they are not, by themselves, evidence of an observed change in cell percentages or a reduction in GVHD.

The primary measure is a biomarker: the proportion of blood CD4+ cells identified as regulatory T cells at a specified post-transplant time. The registry also lists clinical outcomes, including survival, relapse, acute and chronic GVHD, non-relapse death, and adverse events. It lists additional immune measurements as well. For those outcomes, the endpoint names and time points are available, but their results are not reported in the registry record.

Because the trial has a single group, it can describe what was observed among participants who received the regimen, if those data are reported. It cannot by itself separate the regimen's effect from other explanations for an observed value. The historical median of 16% supplies context for the endpoint rationale, but differences in participants, care, measurement, or study conduct between trials could also contribute to any cross-trial contrast. The registry does not report a concurrent comparison that would address those issues.

3. Trial Design

This is a completed Phase 2 study with a single-group model. The registry lists enrollment of 20 and names the group GVHD Regimen. Participants received IL-2 with sirolimus and tacrolimus after allogeneic HCT, as described in the intervention and arm information. The study concerns graft-versus-host disease, with prophylaxis as the treatment context.

The record lists allocation as not applicable and masking as none. It is therefore not a randomized, masked comparison. There is no concurrent control group against which to estimate a between-group treatment contrast. The primary endpoint description invokes a previous trial in which the median under sirolimus and tacrolimus alone was 16%; this historical value is not a control arm enrolled alongside the current group.

The study started on 2014-03-25, reached primary completion on 2016-08-25, and has status completed. The primary endpoint is regulatory T cells as a percentage of total CD4+ cells at 30 days post-HCT, summarized by the median and full range. The registry lists 12 outcome measures, including primary and secondary outcomes, while the count of analyses is 0. Outcome names and planned time points do not establish that results were reported.

The secondary outcomes cover overall survival at day +365; cumulative incidence of relapse; cumulative incidence of grade II-IV acute GVHD by day +100; cumulative incidence of chronic GVHD by day +365; non-relapse death; unexpected or serious adverse events; regulatory T cells among blood CD4+ T cells at day +90; and STAT3, STAT5 (Y694), and S6 phosphorylation among regulatory and non-regulatory T cells at day 30. The registry record does not report results for these listed outcomes.

In a single-group design, descriptive summaries can characterize the observed participants, but the design does not create an exchangeable comparison group. Changes over time, background risks, participant selection, transplant-related factors, and other care can all matter when interpreting outcomes. The registry record does not report enough detail to characterize a comparative effect, an adjusted analysis, or the study's sample-size justification. The listed enrollment is a study descriptor, not evidence of a particular level of statistical precision.

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.

6. Primary Endpoint

The registry lists the primary outcome as Regulatory T Cells (Tregs)/Total CD4+ Cells at Day 30 Post-HCT, measured over 30 days post HCT.

The primary endpoint is the percentage of blood CD4+ T cells that are regulatory T cells at day 30 after HCT. It describes the composition of a defined immune-cell population at a specified time following transplantation. The registry specifies that the measure is to be summarized as a median and full range. The observed median and range are not reported in the registry record.

The rationale is to assess regulatory T-cell reconstitution after use of IL-2 with sirolimus and tacrolimus. The endpoint description says the result was intended for comparison with sirolimus and tacrolimus alone data from a previous trial, whose median was 16%. It also describes the study as designed to capture an increase from a median of 16.0% at day +30. These values express the historical reference and design rationale; they are not the current study's observed result.

General statistical explanation: a median represents the middle of an ordered set of observations and is less influenced by extreme values than the arithmetic mean. A full range communicates the lowest and highest observed values, but does not show how values are distributed between those endpoints. The median and range can help describe a small study's data without assuming a symmetric distribution. They do not, by themselves, quantify uncertainty around the median or establish a treatment effect.

As a biomarker endpoint, the measure is distinct from clinical outcomes such as GVHD, relapse, survival, or adverse events. A biomarker can address whether a biological measurement was observed, but its value alone does not establish whether a clinical outcome changed. The registry lists clinical outcomes separately; their results are not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does a median and full range describe?

General statistical explanation: the median is the center of an ordered set of observations. It is a location summary that can be useful when data are skewed or include extreme values. The full range reports the smallest and largest observations, conveying the span of the data while omitting the pattern of values between the endpoints. A median and range are descriptive summaries. Neither is a test of a hypothesis nor a confidence interval, and neither alone gives a direct measure of sampling uncertainty.

For this trial, the endpoint is the percentage of blood CD4+ T cells that are regulatory T cells at day 30 after HCT. The registry specifies the median and full range as the summary approach, but does not report the observed values. No further distributional description or confidence interval for this endpoint is reported in the registry record. The stated previous-trial median of 16% supplies context, but does not fill in the current study's missing result.

What can a single-group study estimate?

General statistical explanation: a single-group study can summarize outcomes among participants receiving the study regimen. Without a concurrent comparison group, it cannot directly estimate how those outcomes would differ under another regimen. A before-and-after or historical contrast may be informative in some settings, but interpretation depends on whether the measurements and populations are sufficiently comparable and on whether other changes could explain the contrast.

This study is recorded as single group, with allocation not applicable and no masking. Its primary endpoint description refers to data from a previous trial of sirolimus and tacrolimus alone. That historical median is not a randomized control. The registry record does not report a comparative analysis or enough information to assess comparability with the previous trial. It therefore does not support attributing a difference from the historical value to IL-2.

Why does the choice of summary matter?

General statistical explanation: a summary should reflect the kind of data and the question being asked. The median emphasizes a typical rank position rather than a mean level. A range shows extremes, which can be useful for understanding spread but can be strongly influenced by unusually low or high observations. When sample sizes are limited, individual observations may substantially affect these summaries. Reporting the underlying data, or additional measures of spread and uncertainty, can help readers understand how stable a summary may be.

The registry labels the endpoint's dispersion as full range but does not report the actual range or individual observations. No standard error, confidence interval, or formal comparison for the primary endpoint is reported in the registry record. A confidence interval, in general, is a range of values generated by a statistical procedure to express uncertainty about an estimate; it does not guarantee that the true value lies in that interval, and its interpretation depends on the method and assumptions. There is no endpoint interval to interpret in the posted record.

What do the event summaries mean?

General statistical explanation: safety reporting may distinguish participants with events from event terms or event episodes. Those are not interchangeable quantities. A participant can have more than one event, and an event-term percentage does not automatically identify the number of participants affected unless the reporting definition makes that clear. The registry's safety information gives at-risk counts and affected counts for serious and other events, as well as percentages for selected serious-event terms. Readers should interpret each value according to the category in which it is reported rather than treating the terms as mutually exclusive categories or adding them together.

The registry does not provide detailed definitions, event-level data, follow-up time by participant, or a comparative safety analysis in the material recorded. The serious-event summary reports 11 affected among 20 at risk, and the other-event summary reports 4 affected among 20 at risk. Selected serious-event terms include fever at 15.0%, nausea at 10.0%, vomiting at 10.0%, hepatobiliary disorders - Other, VOD at 10.0%, acute kidney injury at 10.0%, and anemia at 5.0%. These are descriptive registry entries, not comparative estimates.

How should planning calculations be understood?

General statistical explanation: sample-size planning asks how many participants a future study might need under a specified effect size, allocation, significance level, and statistical model. Such calculations depend on assumptions; changing the target effect or model can change the planning result. A planning calculation is not a measurement of the study's observed power and does not show that the study did or did not detect an effect.

The registry's planning illustration is described as a recalculation from an observed effect, with a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. It describes the target effect as a stated fraction of the observed effect. Time-to-event illustrations are specified as total events using the Schoenfeld method; other illustrations are specified as participants per arm. These are planning assumptions, not the trial's own design justification. The registry does not report a sample-size justification for the single-group study, and the observed effect needed to interpret such a recalculation is not reported in the registry record. No planning result should be treated as observed power.

The record lists 0 analyses. It does not report a statistical analysis plan, inferential methods for the primary endpoint, an adjustment strategy, or an interim analysis. Those details are not reported in the registry record, so they cannot be inferred from the named endpoint or the planned summaries.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists 12 outcome measures, including the day-30 regulatory T-cell endpoint and secondary outcomes spanning survival, relapse, GVHD, non-relapse death, adverse events, and immune measures. When a study assesses multiple outcomes, there can be multiple opportunities to observe a notable result by chance. General statistical explanation: a multiplicity strategy may define a primary outcome, order outcomes hierarchically, adjust significance thresholds, or otherwise control the interpretation of multiple tests. The registry record does not report such a strategy.

The record lists 0 analyses. It does not report inferential tests, p-values, confidence intervals, or an analysis plan for the listed outcomes. The presence of outcome names and time points does not establish that analyses were performed or that results were available. Any multiplicity adjustment, if planned or used, is not reported in the registry record.

Missing-data methods and analysis populations are also not reported in the registry record. The primary endpoint population is described as all participants, but the record does not say how many had a day-30 measurement, how missing measurements were handled, whether any observations were excluded, or which participants contributed to each secondary outcome. It does not report imputation, censoring rules, or sensitivity analyses for missing values.

These omissions matter because the amount and pattern of missing information can affect both the representativeness of a summary and its uncertainty. General statistical explanation: missingness can be related to participant characteristics, clinical course, or measurement circumstances, so a complete-case summary may not always describe the originally enrolled group. Without reporting the analysis population and missing-data approach, readers cannot assess whether the primary endpoint summary—if available elsewhere—would represent all enrolled participants or only those with observed data.

11. 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 0% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: fever (15.0%), nausea (10.0%), vomiting (10.0%), hepatobiliary disorders - other, vod (10.0%), acute kidney injury (10.0%).

The registry records safety information for the GVHD Regimen group. Its serious-event summary lists 20 at risk and 11 affected; its other-event summary lists 20 at risk and 4 affected. The deaths field is null, so deaths are not reported in the registry record. These categories should be read as separate registry summaries, not added together or interpreted as a comparison between treatment groups.

The selected serious adverse-event terms are fever at 15.0%, nausea at 10.0%, vomiting at 10.0%, hepatobiliary disorders - Other, VOD at 10.0%, acute kidney injury at 10.0%, and anemia at 5.0%. These percentages are reported as terms in the registry. The record does not provide enough detail to determine whether the terms represent unique participants, event episodes, or overlapping categories; they should not be summed.

General statistical explanation: safety counts are descriptive unless accompanied by a defined comparative analysis. In a single-group study, counts do not estimate how event risks differ from another regimen or from no exposure. Interpretation also depends on the event definitions, observation period, completeness of reporting, and whether events were judged related to treatment. Those details are not reported in the registry record. The listed values therefore describe the registry's recorded events, not comparative safety or causation.

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

The primary scientific question concerns regulatory T-cell representation among blood CD4+ cells at day 30 after HCT. The record gives the endpoint definition and says it was summarized by a median and full range, but does not report the observed median or range. The primary result therefore cannot be described in magnitude or precision from the registry record.

The historical reference is a median of 16% for sirolimus and tacrolimus alone in a previous trial. The study description says it was designed to capture an increase from 16.0% at day +30. These are historical and design-context statements, not the current study's result. They do not establish that the current group had a higher value, and they do not provide a controlled treatment contrast.

The trial is single group, with allocation not applicable and masking none. It can potentially describe outcomes observed among participants receiving the regimen, but the record does not report the primary outcome values or most listed clinical outcomes. A single-group observation also cannot isolate a causal effect from participant characteristics, transplant-related factors, background care, or measurement differences. The rationale that the regimen may support regulatory T-cell reconstitution and prevent GVHD is not a conclusion about what the trial demonstrated.

The registry does provide selected adverse-event summaries. They are descriptive, have no concurrent control comparison, and lack detail about attribution and follow-up in the record. The null deaths field means deaths are not reported in the registry record; it should not be interpreted as a count of zero.

Accordingly, the record supports statements about the study's design, intended endpoint, historical rationale, and selected recorded safety entries. It does not support a conclusion about the observed primary biomarker result, the regimen's effect on GVHD or other clinical outcomes, or comparative safety. An unreported result is not evidence that an outcome did not occur, that there was no effect, or that an analysis was statistically inconclusive. Those conclusions require results and methods that are not reported in the registry record.

13. Why This Trial Matters Statistically

This trial is statistically notable because it connects a biological endpoint with clinical outcomes in a transplant prophylaxis setting, while using a single-group design. The primary endpoint asks about the percentage of regulatory T cells among blood CD4+ T cells at day 30. The registry's use of the median and full range indicates a descriptive focus for that measure, but the actual summaries are not reported in the registry record.

The record also makes clear why historical benchmarks and concurrent controls should not be treated as equivalent. A previous-trial median of 16% provides context for the study rationale, but it cannot control for differences between trials. Without a concurrent comparator, any observed value would remain a description of this group rather than a clean estimate of what adding IL-2 changed.

The broader outcome list spans biological measures, adverse events, and clinical events such as relapse, survival, and GVHD. That breadth can be valuable in characterizing a study, but it also makes clear why readers need an analysis plan, defined populations, missing-data handling, and an approach to multiple outcomes. Those details are not reported in the registry record. The listed count of 12 outcome measures and 0 analyses does not provide the missing inferential information.

Finally, this record illustrates an important distinction between a completed study and a reported result. Completion status, enrollment, endpoint definitions, and adverse-event entries do not substitute for the primary endpoint estimate or outcome analyses. Precise interpretation depends on the actual observed values and how they were analyzed; for the primary endpoint, those results are not reported in the registry record.

14. 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.

A central limitation is that the registry record does not report the observed primary endpoint median or full range. Without those values, the day-30 regulatory T-cell result cannot be described or compared with the historical median of 16%. The record also does not report an interval estimate or formal statistical test for the endpoint, so its precision and inferential status cannot be assessed.

The design is single group, with allocation listed as not applicable and no masking. There is no concurrent control group, and the historical reference comes from a previous trial. The record does not report enough information to determine how comparable the populations, transplant settings, measurement procedures, or follow-up were across the studies. Any cross-trial contrast would therefore have substantial interpretive limitations.

The registry lists 12 outcomes but 0 analyses. Results are not reported for the listed secondary clinical and immune outcomes. The analysis plan, missing-data methods, outcome-specific analysis populations, multiplicity strategy, and sample-size justification are not reported in the registry record. It is also unclear from the record how the listed safety percentages were defined or how overlapping event terms were handled. The null deaths entry does not provide a reported death count.

Enrollment of 20 describes the study size but does not, on its own, establish adequate precision for any outcome. The record does not provide enough information to assess statistical power, outcome-specific completeness, or the reliability of estimates. These limitations constrain interpretation of the registry information; they do not show that an unreported result was unfavorable, favorable, or absent.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: In Vivo Treg Expansion and Graft-Versus-Host Disease Prophylaxis — NCT01927120.
• Registry record last updated 2017-07-02; status last verified 2017-03.
• Results first posted 2017-07-02.
• 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.

18. Record Summary

The registry record describes NCT01927120, a completed Phase 2, single-group study of IL-2 with sirolimus and tacrolimus after allogeneic HCT. Enrollment was 20. The study began on 2014-03-25, reached primary completion on 2016-08-25, and is listed as completed.

The primary endpoint is the percentage of blood CD4+ T cells that are regulatory T cells at day 30 post-HCT, summarized by median and full range. The registry cites a previous-trial median of 16% as context, but the current study's endpoint values are not reported in the registry record. The listed secondary outcomes include survival, relapse, GVHD, non-relapse death, adverse events, and immune measurements. The record lists 12 outcome measures and 0 analyses.

Selected adverse-event summaries are recorded for the GVHD Regimen group. The study has no concurrent control arm, and the registry record does not report comparative outcome results, a statistical analysis plan, or missing-data methods.