Viral Specific T-Lymphocytes to Treat Adenovirus, CMV and EBV: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Viral Specific T-Lymphocytes to Treat Adenovirus, CMV and EBV (NCT04364178), a na phase 1, phase 2 study. The primary outcome is Number of Patients With Grade III-IV Acute Graft Versus Host Disease.

2. Clinical Question

The central clinical question is whether infusion of these cellular products can be evaluated for safety and antiviral activity in this varied population. The registry summary frames the intervention as a way to reconstitute antiviral immunity, while the primary endpoint specifically monitors a serious potential complication attributed to the cells. These are different questions: the primary endpoint is a safety count, whereas response and survival are listed among the secondary outcomes.

The trial enrolled 8 participants, and the record states that 3 of the total enrolled participants did not receive treatment after screening. The enrolled group is therefore not identical to the group that received an infusion. The registry does not report enough outcome detail to determine response rates, survival results, or the primary endpoint count. The design also has no control group, so any observed events or changes could not be compared within this trial against outcomes under a separate treatment strategy.

3. Trial Design

This was a phase I/II, single-group study with no masking and allocation listed as not applicable. The registry lists 8 enrolled participants and a terminated status. The start date is 2020-08-12, and the primary completion date is 2023-02-09. The record identifies Jessie L. Alexander, MD, as sponsor.

The intervention was a category of viral-specific T-lymphocytes, with products directed against adenovirus, cytomegalovirus, or EBV. The study summary describes partially matched cells, with at least 2/6 HLA matching, for people with a transplant history or compromised immunity. It describes collecting donor peripheral blood mononuclear cells, stimulating them with viral-specific antigens, and selecting cells using interferon gamma and cytokine-capture technology. The arm description in the registry record is incomplete, so further manufacturing details are not reported in the registry record.

Because this is a single-group study, it does not include a registered control arm. The three named interventions describe virus-specific products, not randomized treatment arms or a like-for-like comparison. The registry states that 3 participants did not receive treatment after screening; it does not give an explanation for each person’s non-treatment or report the outcomes separately by product.

The primary endpoint covers the period from day 0 through 90 days after the last cellular infusion, with the last infusion occurring up to 38 days post day 0. Other registered outcomes include survival at 6 months and one year, complete viral response, time to complete response, time until antiviral treatment was discontinued, and time to T-cell immune reconstitution. Numerical findings for these outcomes are not reported in the registry record.

The record does not report the protocol’s statistical plan, a sample-size justification, interim analyses, or reasons for termination. The trial status and enrollment describe the record, but do not explain why the study ended or how far its planned work progressed.

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

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: 3 of the total enrolled participants did not receive treatment after screening

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 Number of Patients With Grade III-IV Acute Graft Versus Host Disease, measured over Day 0 through 90 days after last cellular infusion (last infusion occurred up to 38 days post day 0).

The primary endpoint is the cumulative number of participants who develop grade III-IV acute graft-versus-host disease attributed to the viral-specific T-cells. Its registered observation window is day 0 through 90 days after the last cellular infusion; the record notes that the last infusion occurred up to 38 days post day 0. The measure is a participant count, not a rate per unit of follow-up or a time-to-event estimate.

This endpoint is used to monitor a serious safety outcome associated in the registry description with the cellular intervention. In general, a prespecified safety endpoint helps define which event the study is tracking and over what period. A count can communicate how many participants experienced the event, but interpretation also depends on the number and characteristics of participants assessed, the event definition, and the completeness of follow-up.

The registry record does not report the primary endpoint count. It also does not give participant-level follow-up or explain how attribution to the cells was assessed. The posted adverse-event figures are not a substitute for this endpoint: they report a separate grouping of serious and other adverse events, with listed terms, rather than the specified grade III-IV acute GVHD result. The primary endpoint’s result and its precision are therefore not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry describes a single-group study, not a randomized comparison. Allocation is listed as not applicable and masking as none. This design can describe outcomes among participants who received the intervention, but it does not create a concurrent control group. General statistical principle: without a comparison group, differences from an external expectation or from a participant’s earlier condition cannot by themselves isolate the effect of the intervention.

What does a participant count convey?

The primary endpoint is a count of participants who develop grade III-IV acute graft-versus-host disease attributed to the viral-specific T-cells. A count is a direct description of the number meeting the endpoint definition, but it is not, by itself, a measure of how precisely the underlying risk is known. In general, precision depends on the number observed and the amount and completeness of follow-up. The primary endpoint count and an uncertainty interval are not reported in the registry record, so neither can be interpreted numerically.

The timeframe is part of the endpoint definition: day 0 through 90 days after the last cellular infusion, with the final infusion occurring up to 38 days post day 0. That time window matters because an event outside it would not be counted under the stated endpoint period. The record does not report participant-level infusion dates, follow-up duration, or endpoint adjudication details.

How should adverse-event figures be read?

The adverse-event entry distinguishes serious events, other events, and deaths. It lists 1 of 5 at risk with serious events and 5 of 5 at risk with other events, alongside 1 death. The record lists respiratory distress and disseminated CMV as serious terms, each with 20.0%. These categories should be read as the registry’s reported group figures, not as a causal comparison. The record does not explain overlap among categories or provide enough detail to link the death to a specific event or to the intervention.

General statistical principle: a percentage is more informative when its denominator, event definition, observation period, and population are clear. A small denominator can make a percentage change substantially when the event count changes. Even when a percentage is reported, a reader should avoid treating it as a stable estimate of risk without considering uncertainty and the way participants were observed. No confidence intervals for the adverse-event figures are reported in the registry record.

What can a confidence interval add?

General explanation: a confidence interval expresses the uncertainty around an estimated quantity under a specified statistical method. It is not a guarantee that the true value lies within the interval, and it does not resolve design limitations such as the absence of a control group or incomplete outcome reporting. The registry record does not report confidence intervals for the primary endpoint or the posted adverse-event figures.

The registry lists 8 enrolled participants and states that 3 did not receive treatment after screening. The population enrolled is therefore distinct from the population treated, but the record does not give full outcome denominators for the primary endpoint or explain the analysis population. For that reason, a denominator should not be inferred for unreported endpoint results from enrollment alone.

What do the planning assumptions describe?

The sample-size assumptions describe planning illustrations based on an observed effect, with a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. They specify that the effect to detect is a stated fraction of the observed effect. For time-to-event illustrations, the stated quantity is the total number of events; other illustrations use participants per arm. These are planning conventions, not a description of the registered trial, whose model is single-group. The numerical planning results are not reported in the registry record. Such illustrations are not observed power and should not be read as evidence that the study had a particular probability of detecting an effect.

There are no registered analysis rows. The registry record does not report the statistical methods used for the primary endpoint, how missing observations were handled, whether any interim analyses were conducted, or a sample-size justification. General statistical concepts can clarify what those methods would ordinarily address, but cannot fill in details absent from the record.

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("Viral Specific T-Lymphocytes")
n      <- c(5)
events <- c(0)
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  Viral Specific T-Lymphocytes  5  0  0.0  0.0  52.2  0.0  43.4  0.4  45.9

11. Multiplicity, Missing Data and Analysis Populations

The registry lists several secondary outcomes in addition to the primary safety endpoint: survival at 6 months, survival at one year, complete viral response, time to complete response, time until antiviral treatment was discontinued, and time to T-cell immune reconstitution. These outcomes address different aspects of follow-up, but their numerical results are not reported in the registry record.

When a study evaluates multiple outcomes, the chance of at least one apparently unusual result can increase if each is tested separately without an adjustment or a prespecified hierarchy. General statistical principle: multiplicity methods can control or describe this issue, but the appropriate approach depends on the questions and analysis plan. A multiplicity strategy is not reported in the registry record. No statistical analysis rows are listed, and the record does not report which outcomes, if any, were formally tested.

Missing-data handling is also not reported in the registry record. The record states that 3 enrolled participants did not receive treatment after screening, but does not describe reasons, outcome availability, or how such participants were treated in analyses. That statement alone does not establish whether data were missing for treated participants or whether outcomes were complete for those assessed.

The analysis populations are not reported in the registry record. In general, an analysis should make clear whether it includes everyone enrolled, only those who received treatment, or another defined group. These populations answer different questions. The posted record does not specify which population underlies the adverse-event figures or whether the primary endpoint was analyzed in an explicitly defined population.

Because these details are unavailable, readers cannot assess the effect of missing observations, the handling of non-treatment after screening, or the extent to which outcome selection and testing were prespecified. No assumptions about the protocol or analysis procedures can be drawn from the outcome list alone.

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: respiratory distress (20.0%), disseminated cmv (20.0%).

The registry’s adverse-event group is titled Viral Specific T-Lymphocytes. It lists 5 at risk for serious events, with 1 affected; 5 at risk for other events, with 5 affected; and 1 death. The listed serious terms are respiratory distress and disseminated CMV, each reported as 20.0%.

These figures describe what the registry record lists; they do not establish that the intervention caused an event. The record does not give event-level timing, severity detail beyond the serious-event listing, duration, relationship assessment, or information about whether one participant could contribute to more than one event term. The listed death is not attributed to a cause in the record. The serious-event figures are also not the same as the primary endpoint, which specifically counts grade III-IV acute graft-versus-host disease attributed to the cells and has no numerical result reported.

General statistical principle: adverse-event counts are best interpreted with clear denominators, event definitions, observation windows, and information about treatment exposure. The registry gives at-risk counts for the adverse-event group, but does not provide all these details for each event. Because the study has no control group, these figures cannot estimate how event experience would differ under another treatment strategy.

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

The registry record establishes that this was a phase I/II, single-group study of viral-specific T-lymphocytes, with 8 participants enrolled and a terminated status. It identifies grade III-IV acute graft-versus-host disease attributed to the cells as the primary endpoint and gives its observation window. It also lists adverse-event counts and two serious-event terms, each reported as 20.0%.

The record does not report the primary endpoint count, numerical viral-response findings, or the listed survival and immune-reconstitution outcomes. This means those results cannot be interpreted quantitatively from the registry record. A missing numerical result is not a zero and does not show that an outcome did or did not occur. The adverse-event entry cannot fill that gap because it does not report the primary endpoint result.

The single-group design also limits conclusions about comparative effects. In general, observing outcomes among treated participants is not equivalent to comparing their outcomes with an appropriate control group. Without a registered comparator, the trial record cannot show whether event frequency or viral response differs from what would have occurred under another strategy. The registry does not report enough information to account for differences in infection, transplant history, immune status, treatment exposure, or follow-up across participants.

The record states that 3 enrolled participants did not receive treatment after screening. This is important context for distinguishing enrollment from treatment exposure, but the reasons and outcome availability for those participants are not reported. The record does not provide analysis populations or missing-data methods to explain how this difference was handled.

Accordingly, the posted information supports a description of the study design and the listed adverse-event figures, not a conclusion about treatment efficacy or comparative safety. It also does not support a conclusion that the intervention did or did not produce a particular outcome. The reason for termination, statistical plan, and numerical results for the primary and secondary endpoints are not reported in the registry record.

14. Why This Trial Matters Statistically

This trial raises a statistical question common to early-stage studies of complex interventions: how to describe safety and potential antiviral activity when the study is small and has no control group. The registry frames the intervention as virus-specific cellular therapy for people with infection after transplantation or with compromised immunity, while the primary endpoint monitors a serious potential safety outcome. Separating that safety question from the secondary response questions is essential to reading the study accurately.

The record also illustrates why enrollment, treatment exposure, and analysis population should not be treated as interchangeable. It reports 8 enrolled participants and notes that 3 did not receive treatment after screening. The registry does not give the analysis population or explain how non-treatment was handled. For any outcome, the denominator and participant set are part of the meaning of the estimate, not merely technical details.

Single-group studies can provide descriptive information, but they cannot provide a like-for-like internal control comparison. That is particularly important when outcomes may depend on participants’ underlying conditions and prior care. A careful statistical reading therefore distinguishes observed counts from causal claims and distinguishes a listed outcome from a reported result.

Finally, this record makes the limits of registry-based interpretation visible. It lists endpoints and adverse-event figures, but not the primary endpoint result, secondary outcome values, statistical analysis plan, or reason for termination. Those omissions constrain what can be learned from the posted material. In general, transparent reporting of outcome counts, denominators, uncertainty, analysis populations, and missing-data handling makes it easier to assess both the strength and limits of evidence.

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 registry record provides limited outcome detail. It identifies the primary endpoint and its timeframe but does not report the endpoint count, a confidence interval, or an inferential analysis. Although secondary outcomes are listed, their numerical results are not reported in the registry record. The available figures therefore do not permit a complete assessment of the planned safety and response questions.

The design is single-group, with allocation listed as not applicable and no masking. There is no registered control group for estimating comparative outcomes. The design can describe observed events, but cannot separate intervention effects from other influences on those events. The registry’s terminated status does not explain why the study ended or how termination affected outcome collection.

The record states that 3 of the 8 enrolled participants did not receive treatment after screening, but does not report reasons or the analysis population. It does not explain the denominator for the primary endpoint, how follow-up was handled, or whether data were missing. The adverse-event entry includes at-risk counts and event counts, but does not clarify overlap among event terms, event timing, attribution, or the cause of the listed death.

Some intervention details are incomplete in the registry record, including the end of the arm description. The record does not report the statistical plan, sample-size justification, multiplicity handling, interim analyses, or missing-data methods. The sample-size assumptions describe planning illustrations using two-arm allocation, whereas the registered design is single-group; the numerical illustrations are not reported in the registry record. These limitations prevent a detailed evaluation of the statistical rationale and analysis choices.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Viral Specific T-Lymphocytes to Treat Adenovirus, CMV and EBV — NCT04364178.
• Registry record last updated 2026-05-27; status last verified 2026-05.
• Results first posted 2026-05-27.
• 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

This terminated phase I/II study evaluated viral-specific T-lymphocytes in a single-group design, with no masking and allocation listed as not applicable. The registry lists 8 participants enrolled and states that 3 did not receive treatment after screening. The primary endpoint was the count of participants with grade III-IV acute graft-versus-host disease attributed to the cells, from day 0 through 90 days after the last infusion.

The adverse-event entry lists serious events in 1 of 5 at risk, other events in 5 of 5 at risk, and 1 death. Respiratory distress and disseminated CMV are each listed as serious terms at 20.0%. Numerical results for the primary endpoint and the listed secondary outcomes are not reported in the registry record. The record also does not report the reason for termination, statistical analysis plan, analysis populations, or missing-data methods. Without a comparator and fuller outcome reporting, the posted information supports a limited description rather than a comparative assessment.