High-Dose Post-Transplant Cyclophosphamide and Bortezomib (CyBor) for the Prevention of Graft-versus-Host Disease Following Allogeneic Hematopoietic Stem Cell Transplantation (HSCT): Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for High-Dose Post-Transplant Cyclophosphamide and Bortezomib (CyBor) for the Prevention of Graft-versus-Host Disease Following Allogeneic Hematopoietic Stem Cell Transplantation (HSCT) (NCT03945591), a na phase 2 study. The primary outcome is Percentage of Participants Who Experience Acute GvHD.

2. Clinical Question

The study asks whether acute graft-versus-host disease (GvHD) occurs among adults with hematological malignancies who undergo allogeneic hematopoietic stem cell transplantation (HSCT) and receive post-transplant cyclophosphamide and bortezomib as prophylaxis. The primary endpoint is the percentage of participants who experience acute GvHD by Day 120 Post-Transplant. Because the study has a single group, it describes outcomes among participants receiving the study regimen; it does not compare that regimen with a concurrent control group.

3. Trial Design

This is a phase II, open-label, single-group study. The registry lists allocation as not applicable and masking as none. The study enrolled 23 participants and is marked completed. Its stated aim is prevention of GvHD following allogeneic HSCT using post-transplant cyclophosphamide and bortezomib, referred to in the brief summary as PTCyBor.

Eligible participants are described as adults with hematological malignancies undergoing transplantation from a matched-related or unrelated donor. The brief summary says patients receive either a reduced-intensity or a myeloablative conditioning regimen consisting of fludarabine, busulfan, and rabbit anti-thymocyte globulin, followed by PTCyBor as GvHD prophylaxis. The record does not describe how the conditioning choice was made or report additional regimen details.

Because there is only one study group, the design can describe outcomes among participants who received the regimen, but it cannot isolate the regimen’s effect by comparing outcomes with a concurrent untreated or alternative-treatment group. Differences from outcomes in other populations or studies would not be a randomized comparison. The registry identifies cyclophosphamide and bortezomib as the interventions.

The recorded study start date is 2019-06-20, and the primary completion date is 2022-12-29. The record’s completion status does not itself establish that every planned endpoint has a posted result. The primary outcome is acute GvHD at Day 120 Post-Transplant; the registry also lists secondary outcomes concerning graft failure and function, treatment-related mortality, relapse, GvHD relapse-free survival, and overall survival. Detailed eligibility criteria, treatment administration schedules, and the rationale for the chosen enrollment target 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: 23 participants were consented. 2 of these participants did not initiate the study.

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 Percentage of Participants Who Experience Acute GvHD, measured over Day 120 Post-Transplant.

The primary endpoint is the percentage of participants who experience acute GvHD by Day 120 Post-Transplant. The registry describes it as the rate of acute GvHD after transplantation and says that the analysis includes participants who received a transplant and any prophylactic treatment. The stated dispersion measure is a 95% confidence interval.

A percentage is a binary-outcome summary: each participant is classified according to whether the event occurred within the specified assessment period, and the summary expresses the proportion with the event. The confidence interval communicates uncertainty around the estimated percentage. In general, a narrower interval indicates greater precision, while a wider interval indicates less precision. The interval does not remove uncertainty or establish that the observed percentage would be the same in another population.

Acute GvHD is relevant to this study because prevention of GvHD is the stated purpose of the prophylaxis regimen. The endpoint places the outcome within a defined period after transplant, making clear which events the primary measure is intended to capture. The registry record does not report the numerical percentage, confidence interval, diagnostic or grading criteria, or procedures for handling participants without endpoint assessment. Those details are needed to fully assess how the endpoint was measured and estimated.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry describes a single-group phase II study and specifies a percentage with a 95% confidence interval for its primary outcome. It does not report a detailed statistical analysis plan or numerical primary outcome result. The concepts below explain how these methods are generally interpreted; they do not establish which additional procedures were used in this study.

What does a percentage measure?

For a binary outcome, each participant is classified as having experienced the event or not having experienced it within the specified assessment period. The percentage is a summary of the event frequency in the analysis population. For this study, the endpoint is acute GvHD by Day 120 Post-Transplant, and the primary outcome description says the analysis includes participants who received a transplant and any prophylactic treatment. The numerical event count, denominator used for the endpoint, and percentage are not reported in the registry record. The 23 participants enrolled should not automatically be treated as the primary analysis denominator, because the outcome description defines a particular analysis population and does not report how many participants met it.

How should a confidence interval be read?

In general, a confidence interval expresses the statistical uncertainty around an estimate. A 95% confidence interval is a method-based range intended to show values compatible with the observed data under the procedure’s assumptions. It is not a guarantee that the true value lies within a particular interval, nor is it a range of individual participant outcomes. Interpretation depends on seeing both the estimate and its interval. Because neither is reported for the primary endpoint, its precision cannot be evaluated. The interval method and any adjustments are also not reported in the registry record.

What does the single-group design allow?

In general, a single-group study can describe outcomes observed among people receiving a regimen. Without a concurrent comparison group, it cannot separate the regimen’s contribution from other influences, such as participant characteristics, transplant procedures, or the course of the underlying illness. This is a design limitation, not a defect that can be resolved by interpreting a percentage more strongly. The registry lists no randomized comparison and no masking.

What does the record say about analysis planning?

The primary endpoint has a stated assessment period and confidence-interval measure, but details such as the statistical model, confidence-interval construction, endpoint definition criteria, and missing-data procedures are not reported in the registry record. A sample-size justification and details of interim analyses are likewise not reported. These omissions mean the analysis choices cannot be checked against a prespecified plan using this record.

How should planning illustrations be distinguished from observed findings?

General sample-size illustrations can estimate the number of participants per arm needed under stated assumptions to detect an effect. The assumptions described for the illustrations associated with this study are a two-sided significance level of 0.05, equal allocation between two arms, a normal approximation, and an effect set as a stated fraction of the observed effect. For time-to-event outcomes, the illustration uses a total event count under the Schoenfeld approach; other outcomes use participants per arm. These are planning illustrations, not the trial’s design justification, and they are not observed power. They do not convert this single-group trial into a two-arm comparison. Numerical illustration results are not reported in the registry record, so no resulting sample-size figure can be interpreted.

Why does event frequency matter for precision?

In general, estimates based on fewer observed events or a smaller analysis population often have greater uncertainty. A confidence interval makes some of that uncertainty visible, but it does not address selection, measurement, or confounding. In a single-group study, even a precise estimate would describe the study group rather than provide a controlled treatment contrast. The absence of a reported endpoint estimate and interval prevents assessment of both the observed rate and its precision.

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("Cyclophosphamide and Bortezomib")
n      <- c(13)
events <- c(5)
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  Cyclophosphamide and Bortezomib  13  5  38.5  13.9  68.4  17.7  64.5  17.7  64.9

11. Multiplicity, Missing Data and Analysis Populations

The registry lists a primary endpoint and several secondary outcomes, including graft failure, poor graft function, treatment-related mortality, relapse, GvHD relapse-free survival, and overall survival. When a study examines multiple outcomes, there can be more than one opportunity to observe an apparently notable result. Statistical methods sometimes address this multiplicity through prespecified prioritization or adjustment. Whether any such approach was planned or used is not reported in the registry record. The listed outcomes alone do not establish that all were tested inferentially or that their results were adjusted.

The record does not report a detailed statistical analysis plan, endpoint-specific analysis populations, or numerical results for the primary or secondary outcomes. It therefore does not show whether analyses followed a prespecified hierarchy or how endpoint estimates were to be interpreted together. No interim-analysis plan is reported.

Missing-data handling is also not reported in the registry record. For the primary endpoint, the description says the analysis includes participants who received a transplant and any prophylactic treatment, but it does not give the number meeting that definition or explain how participants without an assessment by Day 120 were handled. It does not state whether missing outcomes were excluded, imputed, or addressed through another method. These choices can affect the denominator and the interpretation of a percentage, so they matter when assessing the endpoint.

The record does not provide enough detail to determine whether every enrolled participant was included in every outcome analysis, or how follow-up time and incomplete observation were handled for time-to-event outcomes. These are reporting limitations; they do not demonstrate that data were missing or that any particular analysis method was used.

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.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: anemia (25.0%), fever (25.0%), syncope (25.0%), abdominal pain (18.8%), cytomegalovirus infection reactivation (18.8%).

The registry lists a safety group titled Cyclophosphamide and Bortezomib. In that group, 16 participants were at risk for serious adverse events and 7 were affected. For other adverse events, 16 were at risk and 10 were affected. The record also lists 2 deaths. These are separate reported categories; the record does not explain whether participants could appear in more than one category or how events were attributed.

The serious adverse-event terms and percentages listed include Anemia, Fever, and Syncope at 25.0% each; Abdominal Pain, Cytomegalovirus Infection Reactivation, and COVID Infection at 18.8% each. These percentages should be read as registry-reported term-level figures, not as proof of a causal relationship with treatment. The registry record does not report the definitions, attribution rules, event timing, or whether a participant could contribute more than one event term.

The safety counts do not establish that the treatment caused an event or death. The record does not state whether the deaths were treatment-related, nor does it provide enough information to interpret the counts beyond the listed categories and group. The safety information is descriptive and should be kept distinct from the primary acute GvHD endpoint.

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

The record establishes the question and design of a phase II study of post-transplant cyclophosphamide and bortezomib for GvHD prophylaxis after allogeneic HSCT. It specifies acute GvHD by Day 120 Post-Transplant as the primary endpoint and describes which participants are intended to be included in its analysis. It also records safety counts and lists other outcomes of interest.

What the record does not establish is the observed primary endpoint rate. No percentage or confidence interval for acute GvHD is reported in the registry record. Without that estimate, it is not possible to describe the observed frequency or how precisely it was estimated. The record also does not provide numerical results for the listed secondary outcomes. The completed status alone cannot fill those gaps.

Even if outcome estimates were available, a single-group study would describe the experience of its participants rather than directly estimate a contrast against a concurrent control group. It would not, by design alone, distinguish an effect of the prophylaxis from other factors associated with transplantation and participant characteristics. The study’s open-label status and the unreported details of outcome assessment are also relevant when considering how results might be interpreted.

The safety figures indicate reported event counts and term percentages in the listed treatment group, but they do not establish causation. The relationship of the deaths to treatment is not reported in the registry record. The figures should therefore be read as descriptive safety information rather than as proof for or against a treatment effect.

Overall, the registry record supports a careful account of the study structure and planned clinical question. It does not support a conclusion about the size, precision, or comparative meaning of the primary outcome. Those judgments require endpoint results, analysis details, and, for comparative claims, an appropriate comparison design.

14. Why This Trial Matters Statistically

This study raises several statistical issues that are important when interpreting transplant research. First, the primary endpoint is a participant-level event summarized as a percentage within a defined post-transplant period. Such a summary is understandable, but its interpretation depends on the analysis population, outcome definition, and completeness of follow-up. The registry specifies some of this context, while important operational details are not reported.

Second, the single-group design determines what can be learned. It can describe outcomes among participants who received the prophylaxis regimen, but it cannot supply a concurrent estimate of what would have happened under another strategy. A measured rate, if reported, would not by itself be a treatment-effect contrast. This distinction is central to separating descriptive evidence from comparative evidence.

Third, precision matters alongside the event estimate. The primary outcome’s specified 95% confidence interval would communicate uncertainty around its percentage, but neither the percentage nor the interval is reported in the registry record. The enrollment of 23 participants makes transparent reporting of the analysis denominator and uncertainty especially important; the actual precision cannot be judged without the results.

Finally, this record illustrates why planned outcomes, safety counts, and statistical conclusions must be kept distinct. Listing secondary outcomes does not show that every one was analyzed or how multiplicity was handled. Safety term frequencies do not demonstrate causation. Sample-size planning illustrations based on hypothetical two-arm assumptions are not evidence from a randomized comparison and are not observed power. Clear reporting of estimates, intervals, analysis populations, missing-data handling, and prespecified methods would be needed to evaluate the strength and limits of the findings.

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.

The principal limitation for statistical interpretation is that the registry record does not report the numerical result or confidence interval for the primary acute GvHD endpoint. Although the study is marked completed, the completion status does not provide the missing endpoint estimate. Numerical results for the listed secondary outcomes are also not reported in the record.

The study’s single-group design means that outcomes cannot be compared with a concurrent control group. It therefore cannot provide a randomized estimate of the difference between the prophylaxis regimen and another approach. The design is also open-label, and the record does not describe blinded outcome assessment. The influence of these features on outcome measurement cannot be determined from the available details.

The registry states that the primary analysis includes participants who received a transplant and any prophylactic treatment, but does not report the size of that analysis population or explain how incomplete outcome assessments were handled. Diagnostic and grading criteria for acute GvHD, the confidence-interval method, and a full statistical analysis plan are not reported in the registry record. The rationale for the enrollment target and details of interim analyses are also not reported.

The safety information gives counts and term percentages but does not report event attribution, timing, or the relationship of the deaths to treatment. The record also does not clarify overlap among event categories. These limitations restrict interpretation of both efficacy-related and safety-related findings; they do not show that an unreported method or event did or did not occur.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: High-Dose Post-Transplant Cyclophosphamide and Bortezomib (CyBor) for the Prevention of Graft-versus-Host Disease Following Allogeneic Hematopoietic Stem Cell Transplantation (HSCT) — NCT03945591.
• Registry record last updated 2026-04-23; status last verified 2026-04.
• Results first posted 2023-12-06.
• 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

NCT03945591 is a completed, open-label, single-group phase II study sponsored by NYU Langone Health. It enrolled 23 participants and evaluated post-transplant cyclophosphamide and bortezomib as GvHD prophylaxis following allogeneic HSCT. The brief summary describes adults with hematological malignancies receiving transplants from matched-related or unrelated donors, with reduced-intensity or myeloablative fludarabine, busulfan, and rabbit anti-thymocyte globulin conditioning.

The primary outcome is the percentage of participants experiencing acute GvHD by Day 120 Post-Transplant, with a stated 95% confidence interval. The numerical primary result and interval are not reported in the registry record. Safety information lists 16 participants at risk and 7 affected for serious adverse events, 16 at risk and 10 affected for other adverse events, and 2 deaths. The record does not report whether the deaths were treatment-related. Its single-group design does not provide a concurrent treatment comparison.