Total Body Irradiation +/- Total Lymphoid Irradiation & Anti-Thymocyte Globulin in Non-myeloablative Hematopoietic Cell Transplantation: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Total Body Irradiation +/- Total Lymphoid Irradiation & Anti-Thymocyte Globulin in Non-myeloablative Hematopoietic Cell Transplantation (NCT03734601), a na phase 2 study. The primary outcome is Full-dose Donor Chimerism (FDC) at Day 28 Following TLI/ATG/TBI Conditioning..

2. Clinical Question

3. Trial Design

This was a phase 2, single-group study sponsored by Stanford University. The registry lists the study as completed, with a start date of 2018-11-05 and primary completion date of 2019-12-26. Enrollment is listed as 22. The design does not include a randomized comparator: allocation is recorded as not applicable, and masking is recorded as none. Consequently, the study can describe outcomes among those treated with the recorded conditioning regimen, but the design does not support a like-for-like comparison of that regimen with another conditioning strategy.

The regimen of interest combined very low-dose TBI with TLI and ATG before non-myeloablative hematopoietic cell transplantation. TBI was described as a single 80-centigray exposure on Day -1. TLI was 120 centigray per day for 9 days, with weekends excluded, and ATG was 1.5 mg/kg. Tacrolimus and mycophenolate mofetil were also listed as interventions. The registry record identifies the study aim as evaluating whether adding low-dose TBI to TLI and ATG conditioning would augment donor chimerism without reducing tolerability or increasing graft-versus-host disease risk. That stated aim is not itself evidence that any of those outcomes occurred.

The primary outcome was the number of participants achieving full-dose donor chimerism by Day 28. Secondary outcomes listed in the record include disease progression, overall survival, event-free survival at 1 Year, non-relapse mortality, and graft-versus-host disease. The registry record lists 6 outcome measures, but the analysis information does not include outcome estimates for these measures. It also does not report a detailed statistical analysis plan, eligibility criteria, participant flow, or the distribution of participants across the listed conditions. These omissions limit how fully the study conduct and outcome analyses can be reconstructed.

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 Full-dose Donor Chimerism (FDC) at Day 28 Following TLI/ATG/TBI Conditioning., measured over Day 28.

The primary endpoint concerns donor chimerism, meaning the extent to which donor-derived cells are present after transplantation. In this study, full-dose donor chimerism was defined specifically as at least 95% donor type in the CD3+ lineage, assessed by short tandem repeat testing. The endpoint was whether that threshold was reached by Day 28 after donor cell infusion, and the planned measure was a participant count.

This endpoint is relevant to the study's stated purpose because the registry describes the intervention as intended to augment donor chimerism. A fixed threshold and assessment time make the outcome operational: each participant can be classified according to whether the definition was met by the stated time point. That clarity does not, by itself, establish how the endpoint relates to later clinical outcomes, and the registry record does not report such a relationship.

The registry describes the primary measure as a count without dispersion. It does not report the observed count or the number assessed for this endpoint in the results information available for this analysis. Thus, neither the observed proportion meeting the definition nor uncertainty around that proportion can be stated. The endpoint definition and measurement method are reported; the endpoint result is not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

Statistical methods determine how observed outcomes are summarized, how uncertainty is represented, and whether comparisons or adjustments are made. The registry record identifies the primary outcome as a count of participants meeting a binary definition: full-dose donor chimerism by Day 28. It does not report the statistical analysis plan or the observed primary outcome result. That means the endpoint can be explained from its definition, but the analysis actually used to estimate or test it cannot be reconstructed from the record.

What does a binary endpoint convey?

In general, a binary endpoint classifies each participant into one of two categories, such as meeting or not meeting a prespecified definition. A count reports how many participants fall into a category, while a proportion relates that count to the number assessed. For the primary outcome, the classification rule was at least 95% donor type in the CD3+ lineage by Day 28. The record specifies a participant count as the measure but does not report the count or the number assessed. A proportion therefore cannot be stated from the available record, and no new calculation should be inferred.

A confidence interval, in general, expresses the statistical uncertainty around an estimate under a stated method and assumptions. For a binary outcome, an interval around a proportion can help readers understand how much precision the observed data offer. No confidence interval for the primary outcome is reported in the registry record. With no endpoint result or interval, there is no basis to characterize the precision of the estimated frequency of Day 28 full-dose donor chimerism.

What can a single-group design estimate?

A single-group design records outcomes among people receiving the study regimen. It can describe the frequency of an outcome or the occurrence of safety events in that group, if those results are reported. It does not include a concurrent randomized group receiving a different regimen. Therefore, it cannot by itself estimate the contrast between TBI+TLI and TLI/ATG without TBI. Differences between participants, care over time, and other influences are not separated through random assignment in this design. The registry lists allocation as not applicable and the model as single group.

General causal interpretation requires a comparison that can help distinguish what happened under one treatment strategy from what might have happened under another. Randomization is one way to support that comparison. This study's listed design does not offer such an internal comparison. The study purpose refers to adding TBI to a standard preparation, but the record does not list a control arm that omits TBI. Consequently, an observed result, even if reported, would describe outcomes under the combined regimen rather than isolate the contribution of TBI.

What do the safety counts represent?

The registry lists 2 participants with serious adverse events and 0 with other adverse events in the TBI+TLI group, with 22 at risk in each category. It separately lists 6 deaths. These are counts, not adjusted comparative estimates. In general, a count does not convey the timing, duration, severity distribution, or causal attribution of events unless those details are reported. The record does not report the safety observation period or those further details. The three serious-event terms each listed at 4.5% are febrile neutropenia, chronic graft versus host disease, and sepsis. The record does not clarify whether individual participants experienced more than one listed term.

What are planning illustrations?

In general, a sample-size calculation estimates how many participants or events might be needed for a future study under specified assumptions. It is a planning tool, not a summary of the current study's evidential strength. The registry's stated assumptions describe illustrations based on the observed effect, a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation; the effect to detect is specified as a fraction of the observed effect. The record also distinguishes illustrations expressed as participants per arm from those expressed as total events for time-to-event outcomes. These assumptions do not describe the design of the recorded single-group study and do not amount to observed power. No numerical planning outputs are reported in the information available for this analysis.

Statistical methods also depend on the analysis population, handling of missing measurements, endpoint timing, and choice of model. These details are not reported in the registry record. Without them, readers cannot determine whether the primary outcome was analyzed in all enrolled participants, only those with an assessment, or another defined group, nor can they assess how missing endpoint data may have affected a result. The registry record lists 0 analyses in the information, so no inferential method or model can be attributed to the study from these details.

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("TBI+TLI")
n      <- c(22)
events <- c(13)
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  TBI+TLI  22  13  59.1  36.4  79.3  38.7  76.7  38.5  76.8

11. Multiplicity, Missing Data and Analysis Populations

The registry lists a primary outcome of full-dose donor chimerism by Day 28 and secondary outcomes of disease progression, overall survival, event-free survival at 1 Year, non-relapse mortality, and graft-versus-host disease. It also lists 6 outcome measures. When a study evaluates multiple outcomes, the chance of at least one apparently notable result can depend on how many tests are conducted and how they are interpreted. In general, a prespecified multiplicity strategy may address that issue, for example by defining which outcomes are primary or by adjusting inference across selected tests. The registry record does not report a multiplicity strategy, hierarchy among secondary outcomes, or details of planned hypothesis testing.

The analysis information lists 0 analyses. No p-values, confidence intervals, or outcome estimates are reported for the primary or secondary outcomes in the information available for this analysis. It is therefore not possible to determine whether any statistical tests were performed, which tests were used, or whether any multiplicity adjustment was applied. Naming an outcome in the registry does not establish that it was analyzed or that its result was reported.

Missing-data handling and analysis populations are also not reported in the registry record. For the Day 28 endpoint, the record gives the definition and says the outcome would be expressed as a participant count, but does not report the number assessed or how participants without an assessment were treated. It does not report an imputation method, a missingness assumption, or whether analysis was based on all enrolled participants. These omissions matter because the denominator and handling of unobserved outcomes can affect the interpretation of a binary endpoint. The information available supports describing these limitations, not assuming a particular approach.

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

Serious events with the highest arm-level rate: febrile neutropenia (4.5%), chronic graft vs host disease (4.5%), sepsis (4.5%).

The registry lists a TBI+TLI group with 22 participants at risk for serious adverse events and 2 affected. It lists 22 at risk for other adverse events and 0 affected. The record also reports 6 deaths. These figures should be read as separate registry counts: they do not specify when events occurred, how long participants were followed for safety, or whether an event was considered related to the regimen. The death count is not accompanied by a stated cause or time frame.

The most frequent serious-event terms are febrile neutropenia, chronic graft versus host disease, and sepsis, each listed at 4.5%. These percentages describe the registry's term listings; the record does not provide further detail about event timing, severity, recurrence, or overlap among terms. Nor does it provide a comparison group. The figures therefore describe what is recorded for this group and do not establish a comparative safety difference or a causal relationship between the regimen and any event.

In general, adverse-event counts depend on definitions, observation periods, and reporting procedures. Because those details are not reported in the registry record, the counts should not be interpreted as a complete account of risk over a specified period. They are also distinct from the primary donor-chimerism endpoint and cannot substitute for its unreported result.

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

The registry record describes a completed phase 2, single-group study of a conditioning regimen that combined TBI with TLI and ATG before non-myeloablative hematopoietic cell transplantation. It defines a primary endpoint—full-dose donor chimerism by Day 28—and reports selected safety counts. This information establishes what the study set out to measure and identifies some recorded safety data. It does not report the observed primary endpoint count, so the central outcome cannot be quantified from the record information available for this analysis.

The record's purpose states that the study would evaluate whether adding low-dose TBI could augment donor chimerism without reducing tolerability or increasing graft-versus-host disease risk. That wording describes the research question, not a conclusion. Since the primary outcome result and secondary outcome estimates are not reported, the record does not establish whether donor chimerism was augmented, whether tolerability was maintained, or whether graft-versus-host disease risk changed.

The safety counts—2 participants with serious adverse events, 0 with other adverse events, and 6 deaths—must also be interpreted within the available design and reporting detail. There is no randomized comparison group, and the registry information does not specify the safety observation period or event attribution. These figures do not provide a comparative effect estimate and should not be used to claim that the regimen caused or prevented an event.

In general, results from a single group are descriptive of participants treated under that regimen. A comparison with another strategy would be needed to estimate a treatment contrast, and methods for such a comparison would need to address uncertainty and the study design. No such contrast is listed. The registry record also does not report analysis methods, missing-data handling, or confidence intervals. Accordingly, interpretation should remain limited to the design, endpoint definition, and recorded counts, without inferring unreported results or comparative conclusions.

14. Why This Trial Matters Statistically

This study is statistically notable for the gap between a clearly defined primary endpoint and the absence of its observed result in the registry information available for this analysis. The endpoint specifies a threshold—at least 95% donor type in the CD3+ lineage—and a time point, Day 28. Such detail makes the intended classification understandable. Yet without the count meeting the definition, the number assessed, and an uncertainty estimate, readers cannot judge the observed frequency or its precision.

The single-group design is also central to interpretation. The registry's stated question concerns the addition of TBI to TLI and ATG, but the study is listed as a single group with allocation not applicable. This can describe outcomes among participants receiving the combination. It cannot supply an internal randomized comparison that isolates the effect of adding TBI. The distinction between a study aim and an estimable treatment contrast is important when translating the research question into statistical conclusions.

Safety interpretation has similar constraints. The record gives counts for serious and other adverse events and lists selected serious-event terms, but it does not report the safety time frame or the analysis details needed to interpret those counts fully. A count is useful descriptive information, but it is not a comparative risk estimate, particularly when no separate control group is listed.

More broadly, this record illustrates why trial registration details, outcome definitions, analysis methods, and results all matter. A well-defined outcome alone does not tell readers what was observed; a result alone may not show how precise it is; and neither supplies a causal comparison absent an appropriate design. The available information supports a careful account of what was planned and what safety counts were recorded, while leaving the principal efficacy result and several analysis details unresolved.

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 study constrain interpretation of the information available. First, the registry record does not report the primary endpoint result: the number of participants who achieved full-dose donor chimerism by Day 28. It also does not report the number assessed for that endpoint, so the result cannot be expressed or evaluated as a proportion from the available record.

Second, the study is listed as single-group, with allocation not applicable and no masking. There is no like-for-like control group in the recorded design. This limits comparative interpretation of the regimen and prevents an internal randomized estimate of the contribution of TBI. The stated goal of evaluating the addition of TBI should not be taken as evidence of an observed added effect.

Third, statistical analysis details are not reported in the registry information. The record lists 0 analyses and does not give inferential estimates, confidence intervals, p-values, a multiplicity approach, missing-data methods, or analysis populations. These omissions limit assessment of the precision and robustness of any outcome findings.

Fourth, the safety information is limited to recorded counts and selected event terms. The observation period, timing, attribution, and additional event-level details are not reported in the registry record. The record lists 6 deaths but does not provide a cause or time frame. Finally, although several conditions are listed, the record information does not describe the condition-specific composition or baseline characteristics of the enrolled group. These gaps limit assessment of how outcomes might vary across the listed conditions or participants.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Total Body Irradiation +/- Total Lymphoid Irradiation & Anti-Thymocyte Globulin in Non-myeloablative Hematopoietic Cell Transplantation — NCT03734601.
• Registry record last updated 2023-12-12; status last verified 2021-05.
• Results first posted 2021-06-11.
• 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

The registry record describes a completed phase 2, single-group study sponsored by Stanford University, with enrollment listed as 22. The study began on 2018-11-05 and had a primary completion date of 2019-12-26. Its regimen combined TBI with TLI and ATG before non-myeloablative hematopoietic cell transplantation. The primary endpoint was full-dose donor chimerism by Day 28, defined as at least 95% donor type in the CD3+ lineage.

The primary endpoint result is not reported in the registry record. Safety listings include 2 participants with serious adverse events, 0 with other adverse events, and 6 deaths; selected serious-event terms are each listed at 4.5%. No randomized comparator is listed. Analysis methods, missing-data handling, and outcome estimates for the secondary outcomes are not reported in the information available for this analysis.