Multivirus-specific T Cells for the Treatment of Virus Infections After Stem Cell Transplant: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Multivirus-specific T Cells for the Treatment of Virus Infections After Stem Cell Transplant (NCT02108522), a na na study. The primary outcome is Number of Patients Where a Suitable VST Line Could be Found.

2. Clinical Question

3. Trial Design

The registry describes a completed, single-group study of multivirus-specific T cells for infections after stem cell transplant. It lists phase as NA, allocation as NA, and masking as none. Enrollment is listed as 82. The study start is recorded as 2014-06, and primary completion as 2018-12. The sponsor is AlloVir.

Participants were to receive banked, partially HLA-matched multivirus-specific T cells by intravenous infusion. The intervention description specifies one infusion of 2 x 10^7 VSTs/m2. It also notes that a lower number of cells could be infused in the rare case that insufficient banked product was available; the remaining explanation of this circumstance is truncated in the registry record. The record describes the cell product as coming from healthy donors and intended to target multiple viruses.

The study rationale addresses the time required to make donor-specific T cells for an individual patient. The brief summary says that this can take 1-2 months and describes the use of banked cells as an alternative for patients who already have an infection. This rationale explains the approach being studied; it does not establish the treatment’s effects.

The brief summary names EBV, CMV, BK virus, JC virus, adenovirus, and HHV6. The official title names EBV, CMV, adenovirus, HHV6, and BK virus. The record lists several secondary outcome topics, including viral response at 42 days, antiviral immune reconstitution, persistence of VSTs, HLA matching and viral outcomes, clinical response at 3 months, non-target viral reactivations within 12 months, and secondary graft failure at 30 days. The registry record does not report numerical results for these outcomes.

Because this was a single-group study, its design does not provide a randomized, concurrent control for separating intervention-associated outcomes from other influences. The registry record does not report further details of the statistical plan, allocation procedures beyond NA, or masking beyond none.

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.

Screening Period

Period 1: Initial Cohort

Period 2: Expansion Cohort

Analysis population for the primary outcome, as defined in the registry: Includes all patients screened for the 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.

Population: Investigational product was administered to 58 unique patients, however one patient was enrolled twice for two separate infections. An additional 24 patients were screened but did not receive investigational product.

6. Primary Endpoint

The registry lists the primary outcome as Number of Patients Where a Suitable VST Line Could be Found, measured over within 24 hours of receiving recipient HLA information.

The primary endpoint is the number of patients for whom a suitable VST line could be found. Its stated timeframe is within 24 hours of receiving recipient HLA information, and the endpoint population includes all patients screened for the study. The registry description characterizes the aim as assessing the feasibility of finding a sufficiently matching VST line.

This endpoint is used to assess a practical step required before treatment: whether an appropriate banked cell line can be identified for a screened patient. It is not itself a measure of viral clearance, immune reconstitution, survival, or clinical response. Those topics appear among the listed secondary outcomes, but their numerical results are not reported in the registry record.

The primary endpoint is a count of participants. To interpret that count fully, readers would need the number screened, the number with a suitable line found, and clear information about how unsuccessful or incomplete screening was handled. The registry record does not report the observed endpoint count or the total screened. Enrollment is listed as 82, but the primary endpoint population is all patients screened; those figures should not be assumed to be identical.

As the primary outcome result is not reported in the registry record, the feasibility question cannot be answered from the posted information. The endpoint definition describes what investigators intended to assess, not the result of that assessment.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The record describes a participant-count endpoint: the number of patients for whom a suitable VST line could be found. In general, a count reports how many individuals meet a defined event condition. For this endpoint, the event condition is finding a sufficiently matching VST line within the stated timeframe after recipient HLA information is received. The definition identifies the intended measure, but without the observed count and screened population it cannot be converted into a proportion or interpreted as an observed feasibility rate. The registry record does not report either of those values.

What a single-group design can show

In general, a single-group study describes outcomes among participants who receive the study intervention, but it lacks a concurrent comparison group that experiences the same study setting without that intervention. A randomized comparison can help distinguish treatment-group differences from differences arising through other factors, because allocation determines group membership. This record lists a single-group model and allocation as NA, so it does not describe such a randomized contrast. Outcomes in this study can be described, but causal attribution requires caution.

Masking is listed as none. In general, masking means keeping participants, clinicians, or outcome assessors unaware of treatment assignment where a comparison is being made. The registry record does not identify masked assessment. It also does not report additional procedures for reducing the influence of knowledge of treatment on outcome assessment.

What a confidence interval would mean

In general, a confidence interval describes the statistical uncertainty around an estimate under a specified analysis. A narrower interval indicates greater precision under that method, while a wider interval indicates more uncertainty. The registry record does not report an estimate or confidence interval for the primary endpoint. It is therefore not possible to describe the precision of the feasibility result from the posted information. No numerical uncertainty measure should be inferred from enrollment alone.

Counts, event rates, and denominators

Counts are easiest to interpret when the population at risk and the event definition are clear. The primary endpoint is specified for all patients screened, whereas the enrollment figure is 82. The registry record does not state the screened total or whether it matches enrollment. For safety, the record lists 58 participants at risk for serious adverse events and 17 affected, and 58 at risk for other adverse events and 15 affected. Those denominators should be retained when reading the figures. The record also lists 6 deaths, but does not provide a corresponding denominator or further detail in the adverse-event information presented.

In general, event counts and event rates answer related but distinct questions. A count gives the number of people with an event; a rate or proportion relates that count to a defined population or follow-up time. Without the relevant denominator, time at risk, and event definition, a count alone cannot describe the frequency in a way that supports comparison across studies. The record does not give enough detail to construct a comparative safety estimate.

Planning illustrations are not trial results

The stated planning illustration assumptions use a two-sided significance level of 0.05, equal allocation between two arms, a normal approximation, and an effect defined as a fraction of the observed effect. In general, these assumptions describe a hypothetical sample-size calculation under a specified comparison and target effect. The record says that per-arm counts are used except for time-to-event calculations, which use a total event count. These calculations are planning illustrations, not observed power and not the study’s own design justification. The study itself is listed as single group, so hypothetical equal allocation between two arms does not describe its reported design. Numerical planning results are not reported in the registry information available for this analysis.

Outcome families and multiplicity

The registry lists 12 outcome measures and multiple secondary outcome topics. In general, examining many outcomes can increase the chance that at least one appears notable by chance when each is tested separately. Statistical approaches to address this issue can include prespecified hierarchies or adjusted significance thresholds. The registry record does not report whether any multiplicity strategy was planned or used, so none should be assumed. It also lists zero analyses; no analysis results are reported for interpreting the listed outcome topics.

The registry record does not report the statistical analysis plan, the handling of missing observations, or details of analysis populations beyond the primary endpoint’s statement that it includes all patients screened. It does not report an interim analysis plan or a sample-size justification for the trial. Those omissions limit appraisal of how outcomes would have been analyzed and how complete the results are. General statistical principles can clarify what such information would mean, but cannot replace the missing analysis details or outcome results.

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("Multivirus Specific T Cells")
n      <- c(82)
events <- c(80)
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  Multivirus Specific T Cells  82  80  97.6  91.5  99.7  91.5  99.3  91.6  99.2

11. Multiplicity, Missing Data and Analysis Populations

The registry lists 12 outcome measures, including the primary feasibility endpoint and several secondary outcomes. In general, when many outcomes are examined, the chance of at least one apparently unusual result can rise if each is assessed separately. A prespecified hierarchy or another multiplicity approach can help control that issue. Whether investigators planned or used such an approach is not reported in the registry record.

The record lists zero analyses and does not provide numerical results for the primary endpoint or the named secondary outcomes. It therefore does not report which analysis methods were used, whether analyses were adjusted, or how estimates and uncertainty were calculated. The statistical analysis plan is not reported in the registry record. Interim analyses are also not reported in the registry record.

The primary endpoint population is defined as all patients screened. The record does not state how many patients were screened, whether any screening information was missing, or how incomplete screening or unavailable HLA information was handled. It also does not report missing-data methods for the secondary outcomes or explain whether outcome-specific analysis populations differed.

These absences matter because analysis populations and missing-data handling can affect the meaning of reported counts and estimates. They cannot be reconstructed from enrollment alone. The listed enrollment is 82, but it should not be treated as the screened denominator without an explicit statement in the registry record. No sample-size justification for the study is reported. Planning illustrations based on an observed effect do not establish that the trial was designed around those assumptions.

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 2% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: respiratory failure (5.2%), aspartate aminotransferase increased (5.2%), vomiting (5.2%), multi-organ failure (5.2%), hypoxia (3.4%).

The registry lists one intervention group, with 58 participants at risk for serious adverse events and 17 affected. For other adverse events, it lists 58 at risk and 15 affected. The record also lists 6 deaths. These are descriptive figures; they do not, on their own, establish that the intervention caused the events or deaths. The single-group design has no concurrent randomized comparison for estimating how these figures differ from an alternative treatment or background risk.

The serious adverse event terms listed with percentages are Respiratory Failure, Aspartate Aminotransferase Increased, Vomiting, and Multi-organ failure, each at 5.2%, and Hypoxia and Fever, each at 3.4%. These entries describe the posted serious-event terms and percentages. The registry record does not give further event-level details, such as timing, duration, recurrence, or attribution. The percentages should not be treated as proof of causation.

For sound interpretation, distinguish the number of participants affected from the number or type of events, and retain the listed at-risk population. The record reports participants affected, but does not explain all event-level counting details. It also does not provide a comparative safety estimate. The information supports a descriptive reading of reported adverse events, not a conclusion about relative safety.

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

The registry record establishes that a completed, single-group study was conducted to evaluate banked multivirus-specific T cells in the setting of viral infections after stem cell transplant. Its primary endpoint focuses on whether a sufficiently matching cell line could be found for screened patients within 24 hours of receiving recipient HLA information. This is a feasibility question about identifying a cell product for a patient.

The record does not report the primary endpoint count or the number of patients screened. It therefore does not show how often a suitable line was found. It also does not report numerical results for the secondary outcomes listed, including viral response, immune reconstitution, VST persistence, clinical response, non-target viral reactivations, or secondary graft failure. The intended questions are clear, but their outcome results cannot be assessed from the registry record.

The safety information gives descriptive counts and selected serious adverse event terms. It does not provide a concurrent control group, establish causation, or quantify comparative risk. The listed deaths likewise do not establish their relationship to the intervention.

More generally, results observed in a single group cannot by themselves show what would have happened to comparable patients under another approach. The absence of reported outcome estimates, uncertainty measures, and analysis details further limits interpretation. The registry record does not report a sample-size justification or the statistical analysis plan, so the adequacy of planned precision and the handling of analysis choices cannot be evaluated from the posted information.

Accordingly, the registry record describes the study’s rationale, intervention, design, and planned outcomes, but does not report enough outcome data to conclude whether the primary feasibility objective was met or to characterize viral and clinical outcomes. That absence should not be mistaken for a finding of benefit, no benefit, or harm.

14. Why This Trial Matters Statistically

This trial is statistically notable for separating an operational feasibility question from clinical outcome questions. Finding a sufficiently matching VST line within the stated timeframe is a prerequisite measure about the availability of a cell product for screened patients. It is not equivalent to measuring viral response, immune recovery, or clinical response. Treating those distinct outcomes as interchangeable would obscure what the primary endpoint actually asks.

The single-group design is also central to interpretation. It allows outcomes among participants receiving the intervention to be described, but offers no randomized concurrent group for estimating a comparative treatment effect. The registry record lists a range of secondary outcomes that could describe viral, immune, and clinical events, yet their numerical results are not reported. Without results and a comparator, neither the magnitude nor the precision of a treatment contrast can be assessed.

The gap between enrollment and the primary endpoint denominator is important as well. Enrollment is listed as 82, while the primary outcome population includes all patients screened. The screened total and the number with a suitable line found are not reported. This means the key feasibility quantity cannot be interpreted from the enrollment figure alone.

Finally, the record illustrates why a list of planned outcomes and adverse-event counts is not a substitute for a full statistical report. Analysis methods, missing-data handling, multiplicity strategy, and the sample-size justification are not reported. Those details shape how estimates should be read, particularly when several outcomes are considered. The available information can define the study question and some design features, but it does not establish an outcome effect or its statistical precision.

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 largest limitation for interpretation is that the registry record does not report the primary endpoint result. It defines the outcome as the number of patients with a suitable VST line among all screened patients, but gives neither the number screened nor the number with a suitable line found. Enrollment of 82 cannot be substituted for the screened denominator based on the information in the record.

The design is single group, with allocation listed as NA and masking listed as none. There is no concurrent randomized control group to support a direct comparative estimate. The record does not report numerical results for the listed secondary outcomes, including viral response, immune reconstitution, persistence, clinical response, non-target viral reactivations, or secondary graft failure.

Important analysis details are also not reported in the registry record. These include the statistical analysis plan, methods for handling missing data, analysis populations beyond the stated primary endpoint population, interim analysis details, and the study’s sample-size justification. The total listed number of outcome measures is 12, but a multiplicity strategy is not reported.

The safety information is descriptive and lacks a concurrent comparator. It lists 58 participants at risk and 17 affected for serious adverse events, 58 at risk and 15 affected for other adverse events, and 6 deaths. The record does not provide additional event-level information needed to assess timing or attribution. The intervention description notes that a lower cell number could be infused when product was insufficient, but the explanation of this exception is incomplete in the registry record.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Multivirus-specific T Cells for the Treatment of Virus Infections After Stem Cell Transplant — NCT02108522.
• Registry record last updated 2021-07-20; status last verified 2021-07.
• Results first posted 2021-07-19.
• 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, single-group study sponsored by AlloVir, with enrollment listed as 82. The study start is recorded as 2014-06 and primary completion as 2018-12. Phase and allocation are listed as NA; masking is listed as none.

The intervention was banked, partially HLA-matched multivirus-specific T cells, described as a single intravenous infusion. The primary endpoint was the number of patients for whom a suitable VST line could be found within 24 hours of receiving recipient HLA information, among all patients screened.

The record lists 12 outcome measures and describes secondary viral, immune, clinical, and safety outcomes. It reports safety counts and selected serious adverse event terms, but does not report the primary endpoint result or numerical results for the listed secondary outcomes. The statistical analysis plan, missing-data methods, and sample-size justification are not reported in the registry record.