Pilot of Abatacept-based Immunosuppression for Prevention of Acute GvHD During Unrelated Donor HCT: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Pilot of Abatacept-based Immunosuppression for Prevention of Acute GvHD During Unrelated Donor HCT (NCT01012492), a na phase 2 study. The primary outcome is Percentage of Participants With Grade III-IV Acute GVHD by Day 100..

2. Clinical Question

3. Trial Design

This completed study is registered as a phase 2, single-group trial of abatacept-based immunosuppression in unrelated-donor hematopoietic cell transplantation. The registry gives enrollment as 11 and identifies Boston Children's Hospital as the sponsor. The recorded study start is 2009-11, and primary completion is recorded as 2012-11.

The intervention arm description includes abatacept, cyclosporine, and methotrexate for acute GVHD prophylaxis. Participants were to receive one of two standard myeloablative conditioning regimens. The description does not give the regimens' names or report how participants were assigned between them. Allocation is recorded as NA, and masking is recorded as none.

The stated primary objective is to determine the safety and tolerability of adding abatacept to acute GVHD prophylaxis in transplants for malignant diseases using unrelated-donor bone marrow or peripheral blood stem cell grafts. The primary outcome is the percentage with grade III-IV acute GVHD by Day 100 post-transplant. Other listed outcomes concern grade III-IV acute GVHD at 2 years, hematologic and immunologic reconstitution, and protective immunity.

A single-group design can describe outcomes observed among people treated under the study regimen. Without a concurrent comparator, it cannot by itself isolate the effect of abatacept from the effects of transplant care, participant characteristics, or other factors. The registry does not report a randomized allocation process, a masking procedure, or a separate control arm. Details of eligibility criteria, treatment assignment between conditioning regimens, and the statistical plan are not reported in the registry record.

4. Participant Flow and Accounting

The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.

Before assignment: One patient signed consent but was determined to be an assignment failure prior to starting study activities.

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 Percentage of Participants With Grade III-IV Acute GVHD by Day 100., measured over Day 100 post-transplant.

The primary endpoint is the percentage of participants with grade III-IV acute graft-versus-host disease by Day 100 post-transplant. The registry says the incidence was measured using the modified Glucksberg scale. The endpoint is binary at the participant level: a participant either meets the stated grade III-IV endpoint within the specified period or does not. Expressing the outcome as a percentage describes the proportion of the study group meeting that definition.

In general, a defined early post-transplant endpoint can summarize the occurrence of clinically important acute GVHD within a common observation window. The grade threshold makes clear which severity range counts toward the endpoint, while the time point limits the period being assessed. Such a summary depends on consistent outcome assessment and on a clear account of which participants were evaluated and how incomplete follow-up was handled.

The registry record does not report the numerical percentage, the count of participants meeting the endpoint, or an uncertainty interval. It also does not give details of endpoint adjudication, censoring, or the analysis population. Consequently, the endpoint definition is available, but the trial's observed primary outcome and its precision cannot be assessed from the posted results.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry identifies a binary percentage endpoint: participants with grade III-IV acute GVHD by Day 100 post-transplant. It also records zero analyses and does not give a statistical analysis plan or a numerical result for the primary endpoint. The methods below explain how this type of endpoint is generally interpreted; they are not a description of unreported procedures used in this trial.

What does a percentage represent?

In general, a participant-level percentage is a proportion: the number of participants meeting the endpoint divided by the number of participants included in the endpoint analysis, expressed as a percentage. Interpreting it requires knowing both the number meeting the definition and the analysis denominator. The enrollment recorded for a study is not necessarily the same as the denominator for a particular outcome. Reasons can include eligibility for that outcome, follow-up status, or a prespecified analysis population, but the registry record does not explain the denominator used for this endpoint.

The registry gives the endpoint timeframe as Day 100 post-transplant and describes assessment using the modified Glucksberg scale. In general, a time-specific endpoint requires clarity about whether participants were followed through the specified time, how deaths or other competing events were treated, and how incomplete observations were handled. Those details can affect the meaning of a reported proportion. They are not reported in the registry record for this outcome.

How should uncertainty be considered?

In general, an estimate of a proportion is subject to sampling uncertainty: another study of a similar population could produce a different observed proportion. A confidence interval communicates the range of values reasonably compatible with the data under the method used. Its width depends on the amount of information and the observed event pattern, as well as the interval method. The registry record does not report an endpoint estimate or confidence interval, so no trial-specific precision statement can be made.

A confidence interval is not a guarantee that the underlying value lies in the interval, nor does an interval alone establish that two treatments differ. In a single-group study, an interval around the observed proportion would describe uncertainty about that group's outcome under the chosen model. It would not supply the missing counterfactual outcome for a control group or establish a causal treatment effect.

What does the design permit?

In general, random allocation can help balance measured and unmeasured prognostic factors between treatment groups, while masking can reduce certain sources of assessment or conduct bias. This trial is recorded as single group, allocation NA, and masking none. There is no registry-described randomized comparison. As a result, even if a primary endpoint estimate were available, it would describe the treated group rather than a contrast between treatment strategies.

The listed regimen includes abatacept, cyclosporine, and methotrexate, and the arm description includes one of two standard myeloablative conditioning regimens. Because these treatments and transplant procedures occur together, a single-group outcome cannot separate the contribution of any one component. The record does not state how the conditioning regimens were selected or whether their use was analyzed as a factor.

What is not available about the analysis?

The registry record does not report a statistical analysis plan, an analysis population definition, a missing-data method, an endpoint adjudication process, or adjustment for other factors. It does not report an interim analysis or a multiplicity strategy. These omissions mean that readers cannot determine whether the planned analysis differed from a simple proportion, how incomplete follow-up was addressed, or whether any inferential testing was intended. No unreported method should be presumed.

The record lists one primary endpoint and three secondary outcome areas: grade III-IV acute GVHD at 2 years, hematologic and immunologic reconstitution, and protective immunity. It records four outcome measures in total, but the available entry does not provide results for those outcomes. Multiple outcomes can create interpretive concerns when many estimates or tests are examined. In general, multiplicity procedures can control the chance of misleading findings across a family of tests, but the appropriate approach depends on the analysis plan and scientific aims. No such strategy is reported.

Sample-size planning is also distinct from analysis of observed results. A planned sample size reflects assumptions made before or during study design; it is not an observed treatment effect and does not guarantee a precise result. The record does not report a trial-specific sample-size justification. Any planning illustration elsewhere should be understood as a hypothetical calculation under its stated assumptions, not as observed power or evidence about the trial outcome.

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("Abatacept")
n      <- c(10)
events <- c(1)
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  Abatacept  10  1  10.0  0.3  44.5  1.8  40.4  2.3  41.3

11. Multiplicity, Missing Data and Analysis Populations

The registry lists a primary endpoint of grade III-IV acute GVHD by Day 100 and three secondary outcome areas: grade III-IV acute GVHD at 2 years, hematologic and immunologic reconstitution, and protective immunity. It records four outcome measures in total, but no analysis results. A multiplicity plan describing whether and how conclusions across outcomes were coordinated is not reported in the registry record.

In general, examining several outcomes or statistical tests can increase the chance that at least one result appears notable by chance. A prespecified hierarchy, adjustment procedure, or clear distinction between primary and exploratory analyses can help readers understand how to interpret multiple results. The registry identifies the primary endpoint but does not report a statistical plan, testing hierarchy, or multiplicity adjustment. No particular approach can be attributed to the investigators from this record.

The analysis populations are not defined in the registry entry. Although enrollment is recorded as 11, the record does not state which participants were included in the primary outcome analysis or how exclusions, withdrawals, or incomplete follow-up were handled. A missing-data method is also not reported. These details matter because the denominator and treatment of unavailable outcomes can change the interpretation of a percentage.

The safety entry uses 10 participants at risk for both serious and other adverse events, while overall enrollment is recorded as 11. The reason for this difference is not reported in the registry record. It should not be assumed that the same denominator applied to the primary endpoint, or that a particular participant was excluded for a particular reason.

12. 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: febrile neutropenia (40.0%), bacteremia with coagulase negative staphylococcus (10.0%), upper respiratory infection - parainfluenza (10.0%), bacteremia with e. coli (10.0%), upper respiratory infection - rhinovirus (10.0%).

The registry's Abatacept safety group records 10 participants at risk for serious adverse events and 7 affected. For other adverse events, it records 10 at risk and 8 affected. These are the posted group-level figures. The record does not report deaths in this entry.

The serious adverse event terms listed include febrile neutropenia at 40.0%, bacteremia with coagulase negative staphylococcus at 10.0%, upper respiratory infection - parainfluenza at 10.0%, bacteremia with E. coli at 10.0%, upper respiratory infection - rhinovirus at 10.0%, and perianal cellulitis at 10.0%. The entries identify reported terms and percentages; they do not establish whether a participant could have experienced more than one term, and the registry does not explain the counting rules in this record.

In general, adverse event counts in a single treated group describe what was recorded during the study, not the amount caused by a treatment. Without a comparison group and fuller context about observation time, event definitions, and attribution, these figures cannot isolate the contribution of abatacept from the transplant and accompanying prophylaxis. The registry does not explain why the safety group denominator is 10 when enrollment is 11.

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

The registry record establishes the question the investigators set out to address: safety and tolerability of adding abatacept to acute GVHD prophylaxis in unrelated-donor transplantation for malignant diseases. It describes a phase 2, completed, single-group study and specifies a primary endpoint of grade III-IV acute GVHD by Day 100 post-transplant, measured using the modified Glucksberg scale. It also provides limited group-level safety entries.

It does not report the numerical result for the primary endpoint. The record therefore cannot establish the observed percentage of participants who met that endpoint or how precise an estimate would be. The absence of a result in the registry should not be interpreted as a zero event rate, a favorable result, or an unfavorable result.

The design also does not support a direct treatment comparison. There is no separate control arm recorded, and allocation is marked NA. Outcomes in this single group cannot determine what would have happened to similar participants under a different prophylaxis regimen. The combined regimen includes abatacept, cyclosporine, and methotrexate, alongside transplant conditioning; any observed outcome would not, by itself, identify the independent contribution of abatacept.

The serious and other adverse event counts provide a description of entries in the safety record, not a causal estimate of risk. The listed serious terms and percentages should be read in the context of a small recorded group and the lack of a comparator. The registry does not provide enough information to resolve the difference between the safety denominator and overall enrollment, or to describe event attribution and follow-up in detail.

Overall, this record is informative about the study's objective, regimen, design, and endpoint definitions. It is not sufficient to draw a quantitative conclusion about the primary outcome, to compare treatment strategies, or to determine whether abatacept changes GVHD or adverse event risk.

14. Why This Trial Matters Statistically

This trial illustrates why a registry's design information and outcome results need to be read separately. The record gives a clear clinical objective and identifies grade III-IV acute GVHD by Day 100 as the primary endpoint. Yet it does not provide the numerical endpoint result or any analysis results. Knowing what was measured is not the same as knowing what the study observed.

It also highlights the inferential limits of a single-group design. A treated-group outcome can describe what happened among participants receiving a regimen, but it cannot show what would have happened under a different regimen in comparable participants. That distinction remains important even when the outcome is clinically relevant and the study is completed. Without a comparator, the role of abatacept cannot be separated from other prophylaxis components and transplant care.

The record also demonstrates the importance of denominators and analysis populations. Enrollment is recorded as 11, while the safety group lists 10 at risk. The reason for that difference is not reported, and a reader should not assume the endpoint denominator or the treatment of incomplete observations from the enrollment figure alone. Clear reporting of outcome counts, denominators, uncertainty, and missing-data handling is essential for interpreting a proportion.

Finally, registry entries can offer partial safety information without establishing treatment-related risk. The listed adverse event figures describe recorded events in the study group. They do not substitute for a controlled comparison or a complete account of event definitions and attribution. Taken together, these features make the trial a useful example of how design, outcome reporting, and statistical precision jointly determine what can be concluded.

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 follow directly from the registry record. The study is listed as single group, allocation is NA, and masking is none. No separate control group is recorded, so the design cannot provide a like-for-like comparison of prophylaxis strategies or isolate the effect of abatacept from the other regimen components.

The primary endpoint result is not reported, and the record lists zero analyses. Consequently, the observed percentage, event count, denominator, and statistical precision for grade III-IV acute GVHD by Day 100 cannot be assessed. Results for the listed secondary outcomes are also not reported in the entry.

The study's enrollment is recorded as 11, whereas the safety group lists 10 participants at risk for both serious and other adverse events. The reason for this difference is not reported in the registry record. The record also does not provide a detailed analysis population, missing-data approach, follow-up accounting, event attribution rules, or endpoint adjudication details.

The registry describes two possible standard myeloablative conditioning regimens but does not specify their names or explain how participants received them. It does not report whether outcomes were examined by conditioning regimen. Since the intervention is part of a broader transplant and prophylaxis regimen, a single-group outcome would not separate the effects of its components even if the primary estimate were available.

Finally, details of eligibility criteria, the statistical analysis plan, sample-size justification, interim analyses, and multiplicity handling are not reported in the registry record. Their absence limits assessment of how the study was planned and how its outcomes were intended to be interpreted.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Pilot of Abatacept-based Immunosuppression for Prevention of Acute GvHD During Unrelated Donor HCT — NCT01012492.
• Registry record last updated 2019-11-21; status last verified 2019-10.
• Results first posted 2017-09-15.
• 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

NCT01012492 is a completed phase 2, single-group trial sponsored by Boston Children's Hospital. The registry records enrollment of 11, a start date of 2009-11, and primary completion in 2012-11. It records no masking and allocation as NA.

The study evaluates abatacept as part of acute GVHD prophylaxis with cyclosporine and methotrexate in unrelated-donor hematopoietic cell transplantation for malignant diseases. Participants were to receive one of two standard myeloablative conditioning regimens. The primary endpoint is grade III-IV acute GVHD by Day 100 post-transplant, assessed using the modified Glucksberg scale.

The numerical primary endpoint result and analysis results are not reported in the registry record. Safety entries list 7 of 10 participants affected by serious adverse events and 8 of 10 affected by other adverse events; the reason for the difference between the safety denominator and enrollment is not reported.