Donor Lymphocyte Infusion (DLI) of T-cells Genetically Modified With iCasp9 Suicide Gene: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Donor Lymphocyte Infusion (DLI) of T-cells Genetically Modified With iCasp9 Suicide Gene (NCT01875237), a na phase 1, phase 2 study. The primary outcome is To Evaluate the Safety of Donor Lymphocyte Infusion Followed by Dimerizer Drug, AP1903 by Number of Participants With Adverse Events..

2. Clinical Question

The clinical context is a sequence of transplant, planned donor lymphocyte infusion, and possible AP1903 use. In general, a safety endpoint based on participant counts can indicate how many people had at least one event within the defined assessment, but it does not by itself describe event severity, timing, duration, or causal attribution. Those details require their own definitions and results.

The registry record gives enrollment as 3 and status as terminated. Enrollment alone does not establish how many participants received each component or contributed to the primary endpoint. The record does not report the number who received both donor lymphocyte infusion and AP1903, nor does it report a primary endpoint estimate with uncertainty. The intended clinical question can therefore be described, but the posted information does not support a comparative conclusion about clinical benefit or a precise estimate of risk.

3. Trial Design

The registry describes a Phase 1/2 trial with a single-group model, no masking, and allocation recorded as NA. It lists an enrollment of 3, a start date of 2013-12-27, a primary completion date of 2017-03-07, and a terminated status. These record details describe the trial's design and administrative history; they do not establish the number of participants who completed treatment or endpoint follow-up.

The intervention concept combines allogeneic stem cell transplantation with planned donor lymphocyte infusion of T-cells genetically modified with the iCasp9 suicide gene. AP1903 is identified as the dimerizer drug used after the infusion in the study's GvHD treatment rationale. The brief summary also lists fludarabine, melphalan, and alemtuzumab as chemotherapy, while the interventions list includes transplant, immune suppression, G-CSF, and DLI components. The complete treatment schedule and the actual treatment received by each participant are not reported in the registry record.

A single-group design can describe outcomes among participants receiving the study regimen, but it does not create a concurrent randomized control group. The record identifies a transplant-only group and a transplant-plus-DLI group in its adverse-event information. That listing does not change the stated single-group design, and it does not support treating the groups as equivalent randomized arms. The record itself cautions that this is not a randomized comparison and that the arms are not a like-for-like control comparison.

The primary endpoint is the number of participants with adverse events among participants who received DLI and AP1903, assessed up to 3.5 years. Secondary outcomes refer to disease-free survival, non-relapse mortality, chimerism, GvHD, Epstein-Barr virus reactivation or PTLD requiring therapy, GvHD response, treatment failure, and GvHD flare. The registry lists 10 outcome measures, but zero analyses. Outcome names describe planned assessments; they do not constitute reported results.

The record does not report a sample-size justification, an interim-analysis plan, or a complete statistical analysis plan. It also does not report how termination affected recruitment, treatment delivery, or follow-up. These omissions limit interpretation of the trial's operating plan and of the completeness of the observations.

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: patients who do not have GVHD on day 42 receive genetically modified donor lymphocytes with suicide gene to be activated by drug AP1903 if GVHD occurs.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Participant who received Donor Lymphocyte infusion and AP 1903

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 To Evaluate the Safety of Donor Lymphocyte Infusion Followed by Dimerizer Drug, AP1903 by Number of Participants With Adverse Events., measured over up to 3.5 years.

The primary endpoint counts participants with adverse events after donor lymphocyte infusion of iCasp9-modified T-cells followed by AP1903. Its stated population is participants who received both donor lymphocyte infusion and AP1903, and its timeframe is up to 3.5 years. This makes the endpoint a participant-level safety measure: the count concerns people experiencing an event, rather than the total number of events across all participants.

Safety endpoints are used in early-phase research to characterize harms observed during treatment and follow-up. In general, recording whether a participant had an event provides a direct summary of the proportion or count affected when the relevant denominator is known. A participant may have multiple events, so a count of participants should not be interpreted as a count of all event episodes. The registry record does not report a detailed event definition, severity grading approach for the primary endpoint, attribution rules, or an endpoint estimate for the stated population.

The endpoint's broad label also matters. “Adverse events” can include events with different severity and clinical relevance. Serious adverse events are reported separately in the registry information, but that does not mean the primary endpoint is restricted to serious events. The record does not specify whether the primary endpoint counts all adverse events, events meeting a particular threshold, or events considered related to treatment.

The chosen measure is appropriate to a safety question in the sense that it focuses on affected participants, but its interpretation depends on follow-up completeness, event definitions, and the denominator actually assessed. Those details, along with a numerical primary endpoint result, are not reported in the registry record. Accordingly, the stated endpoint identifies what the study set out to assess, but the posted information does not quantify that outcome for the stated endpoint population.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The outcome type recorded for this analysis is binary, with the meaning given as participants with an event. A binary outcome classifies each participant into one of two states for a specified assessment, such as whether an event was recorded or not. For a participant-count endpoint, the numerator is the number meeting the event definition and the denominator is the number assessed in the relevant population. Both are needed to interpret an event frequency. The record does not report a numerical primary endpoint numerator or its denominator.

What does a participant count capture?

A count of participants with an event is different from a count of event episodes. If one participant experiences several events, that person may still contribute only once to a participant-level count, depending on the endpoint definition. In contrast, an event-level summary may count each episode separately. The registry's primary endpoint is worded as the number of participants with adverse events. The detailed rules for collapsing repeated events, selecting the observation window for each participant, and defining an event are not reported in the registry record.

Counts are straightforward to describe, but their precision depends on the amount of information available. In general, an estimate from a small number of participants is especially sensitive to each participant's outcome. A confidence interval expresses uncertainty around an estimate under specified assumptions. It is not a guarantee that the true value lies within the interval, and its interpretation depends on the method used. No confidence interval or interval method for the primary endpoint is reported in the registry record.

Why does the design affect interpretation?

A single-group design estimates outcomes among participants receiving the study regimen. Without a randomized comparison group, it does not isolate the regimen's effect from other influences, such as the transplant course, underlying disease, participant characteristics, or other treatment components. A before-and-after pattern, if one were reported, would also not automatically establish causation. In this trial, the registry describes a single-group model, allocation NA, and no masking. It explicitly cautions that the listed groups are not a like-for-like control comparison.

Randomization is a general method for balancing prognostic factors across groups in expectation. It supports a causal comparison when paired with appropriate allocation, follow-up, and analysis. It is not described for this trial. Masking is also recorded as none. In general, lack of masking may affect outcome reporting or assessment, particularly when outcomes require judgment; the registry does not describe whether the primary safety endpoint used blinded assessment or standardized event adjudication.

What does over-dispersion mean for counts?

General statistical explanation: count data are sometimes modeled with a Poisson distribution, which assumes that the mean and variance are equal. Over-dispersion means the observed variability is greater than that assumption allows. If over-dispersion is present and ignored, standard errors can be too small and confidence intervals too narrow. This issue usually concerns counts of events, such as repeated episodes, rather than a simple yes-or-no participant outcome. The primary endpoint is specified as a count of participants with adverse events, and the registry does not report a model for repeated event counts or any assessment of over-dispersion.

For a binary participant outcome, analysts may report the number affected and the number assessed, a proportion, and an uncertainty interval. A model may be useful for adjusted comparisons in a larger study, but a model cannot create information absent from a very small dataset. The registry record does not report a model, adjusted estimate, or inferential analysis for the primary endpoint. The posted group counts remain descriptive.

How should the planning illustration be understood?

The registry's planning assumptions describe an illustration based on an observed effect, a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. General explanation: a sample-size calculation asks how much information might be needed to detect an effect under chosen assumptions. Its output depends on the effect size, variability, statistical test, allocation, and chosen operating characteristics. If the assumptions do not match the design or the eventual analysis, the illustration may not represent a realistic design requirement.

The stated equal-allocation assumption is not the trial's recorded single-group design. The trial is not a randomized comparison, so a two-arm planning illustration should not be interpreted as a direct description of how participants were assigned or treated. The registry record does not report the numerical observed effect or numerical planning estimates in the information used for this analysis. Any planning figures are not observed power. Observed power is not a substitute for reporting an effect estimate and its uncertainty; the actual sample size and observed outcomes should be described directly.

For time-to-event outcomes, a general method such as the Schoenfeld approach relates event information to the precision of a comparative estimate under its assumptions. The registry's planning note distinguishes total events for time-to-event illustrations from participants per arm for other outcomes. This trial's listed secondary outcomes include disease-free survival and non-relapse mortality, but the registry record reports zero analyses. It does not report a time-to-event estimate, event count for those outcomes, or an analysis method. No result for those endpoints should be inferred from their presence in the outcome list.

Interpretation also depends on follow-up. A participant who has not had an event by the end of observed follow-up is not necessarily known to remain event-free throughout the stated timeframe. In general, time-to-event analysis accounts for differing follow-up and censoring; a simple participant count may not. The registry does not report individual follow-up duration, censoring, or completeness of assessment for the primary safety endpoint. The stated timeframe of up to 3.5 years should therefore not be taken to mean that every participant was observed for the same duration.

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("Transplat Plus DLI")
n      <- c(1)
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  Transplat Plus DLI  1  1  100.0  2.5  100.0  20.7  100.0  15.8  98.7

11. Multiplicity, Missing Data and Analysis Populations

The registry lists 10 outcome measures and zero analyses. Multiple outcomes raise a general multiplicity issue: when many outcomes or comparisons are tested, the chance of at least one apparently unusual result can increase if each is assessed without adjustment. Whether adjustment is needed depends on the prespecified goals, hierarchy of endpoints, and intended interpretation. The registry record does not report a multiplicity strategy, a hierarchy among the secondary outcomes, or the statistical plan used to address multiple testing. With no reported analyses, there are no posted p-values or adjusted comparisons to interpret.

Missing data are also consequential for a participant-count safety outcome. An unobserved participant cannot simply be assumed to have had no adverse event. In general, analysts should report the number assessed, the amount and reasons for missingness, and the approach used to handle missing outcomes. For a safety endpoint with follow-up up to 3.5 years, the timing and completeness of observation matter because participants may have different time under observation. The registry record does not report missing outcome counts, reasons for missingness, follow-up completeness, or an imputation approach.

The analysis population is described for the primary endpoint as participants who received DLI and AP1903. The number meeting that description is not reported in the registry record. The record does not describe an intention-to-treat population, a treated population definition beyond that endpoint wording, exclusions from analysis, or participant disposition by treatment component. Enrollment of 3 should not be substituted for the endpoint denominator without evidence that all enrolled participants received the specified treatments and were assessed.

The record does not report an interim-analysis plan, stopping boundaries, or whether any interim safety review occurred. The terminated status alone does not explain why the study stopped or how termination affected analysis. These omissions mean that the number of potential analyses, treatment of incomplete observations, and relationship between planned and analyzed populations cannot be evaluated from the registry information.

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: infection (100.0%).

The adverse-event summary reports zero at risk and zero affected for serious and other adverse events in the “Transplant Only” group, with zero deaths. For the transplant-plus-DLI group, it reports one participant at risk and one affected for serious adverse events, one at risk and one affected for other adverse events, and one death. The group title appears in the registry as “Transplat Plus DLI”; the description above identifies it by its DLI label.

These entries are counts, not a comparative effect estimate. The zero-at-risk group does not provide a denominator from which to estimate an event frequency. The registry record cautions that the groups are not a like-for-like control comparison, and the single-group design does not support a randomized safety contrast. The primary endpoint population is participants who received DLI and AP1903, while the adverse-event grouping does not establish that its denominator is identical to that endpoint population.

Infection is listed at 100.0% among the top serious-event terms. The record does not report the denominator or counting rules for this term summary, so it should not be converted into a population-level risk estimate. Serious and other adverse-event counts may describe overlapping participants or event categories; they should not be added together to produce a total number of affected people.

The one death is a reported count, but its cause and relationship to treatment are not reported in the registry record. It should not be described as treatment-caused. With such limited counts, each observation has substantial influence, and the summary cannot establish the frequency of harms in a broader group.

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

The record documents a trial intended to assess the safety of donor lymphocyte infusion with genetically modified T-cells followed by AP1903. It also describes a broader rationale involving post-transplant response and the management of GvHD. The primary endpoint is a participant count for adverse events, with assessment up to 3.5 years. These details establish the clinical question and the type of outcome the trial was designed to examine.

The posted information does not provide a numerical result for that primary endpoint, a confidence interval, or an inferential analysis. It reports enrollment of 3, a terminated status, and zero analyses. It also includes limited adverse-event counts, including one affected participant in the DLI group for serious events and one death. Those counts are descriptive and do not establish whether an event was caused by treatment. Nor do they provide a reliable estimate of how often adverse events would occur in a larger population.

The study's single-group model and lack of randomization also limit causal interpretation. The record's transplant-only and transplant-plus-DLI labels do not create a valid control comparison, and the record explicitly warns against treating them as like-for-like groups. The posted information cannot separate effects of the modified T-cells or AP1903 from effects of transplantation, chemotherapy, other listed treatments, or the underlying clinical circumstances.

In general, a result can be statistically uncertain even when a point estimate is available; precision is best conveyed with an appropriate uncertainty interval and a clearly defined denominator. Neither is reported for the primary endpoint. The sample-size planning illustration described in the record is not a measure of what the trial observed and is not observed power.

Accordingly, the record supports a description of the intended safety assessment, trial design, enrollment, status, and a small set of adverse-event counts. It does not support a conclusion about comparative safety, treatment efficacy, the cause of the reported death, or the likely frequency of events among other patients. The absence of a reported analysis is not evidence that an outcome did or did not occur.

14. Why This Trial Matters Statistically

This trial raises several statistical issues that are especially important in early clinical research. Its single-group design makes descriptive safety reporting central: who received the intervention, who was observed, what counted as an event, and how long each person was followed. The primary endpoint is clearly framed as a participant count, but its assessed denominator and numerical result are not reported in the registry record.

The small enrollment makes the interpretation of counts particularly sensitive to individual observations. In general, one participant's outcome can materially change a summary when only a few people are enrolled. This does not make descriptive reporting unhelpful; it makes complete reporting of denominators, event definitions, follow-up, and uncertainty especially important. The adverse-event entries should be read as a limited record of observed counts, not as precise population estimates.

The registry also demonstrates why group labels do not automatically establish a comparison. A transplant-only group and a transplant-plus-DLI group may appear to invite a contrast, but allocation is NA, the stated model is single group, and the record says the groups are not a like-for-like control comparison. Without a valid comparative design and analysis, numerical differences between group summaries would not establish a causal treatment effect.

There is an additional distinction between a planning calculation and an analysis of trial results. The record describes a planning illustration with two-arm and equal-allocation assumptions, even though the stated design is single group. Such an illustration can only be understood through its assumptions, and cannot be treated as evidence of observed power or as a result from this trial.

Finally, a study's outcome list is not the same as a set of analyzed findings. The record lists multiple safety, GvHD, disease, and chimerism outcomes, but reports zero analyses. Without estimates, uncertainty measures, or detail on missing data and analysis populations, readers cannot assess the precision or completeness of those outcomes. Statistical transparency is therefore essential to distinguish study aims from 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.

Several trial-specific limitations affect interpretation. Enrollment is recorded as 3 and the study status is terminated, but the record does not state why the trial was terminated, how many participants completed treatment, or whether termination changed the planned assessments. The number of participants who received both DLI and AP1903 is not reported, although that is the stated primary endpoint population.

The study is recorded as single group, with allocation NA and masking none. The adverse-event information includes transplant-only and transplant-plus-DLI labels, but the record cautions that they are not like-for-like control groups. No randomized comparison or adjusted analysis is reported. As a result, those group counts cannot be interpreted as a comparative estimate of treatment-related risk.

The primary endpoint lacks a posted numerical result and denominator. The record also does not report detailed adverse-event definitions, severity criteria for the primary endpoint, attribution methods, event timing, follow-up completeness, or missing-data handling. The one reported death has no stated cause or attribution. Infection is listed at 100.0% among serious-event terms, but the denominator and term-counting rules are not reported.

The registry lists multiple outcomes, including disease-free survival, non-relapse mortality, chimerism, and several GvHD assessments, but reports zero analyses. No statistical analysis plan, multiplicity approach, sample-size justification, or interim-analysis plan is reported in the registry record. Consequently, the intended analyses and the relationship between planned outcomes and observed data cannot be assessed.

The enrollment and limited event counts are insufficient to support precise generalization. Even a complete report from a small sample would require caution about uncertainty; the missing endpoint results and follow-up details further restrict interpretation. These limitations do not establish that an outcome was absent. They define what cannot be concluded from the posted registry information.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Donor Lymphocyte Infusion (DLI) of T-cells Genetically Modified With iCasp9 Suicide Gene — NCT01875237.
• Registry record last updated 2019-07-16; status last verified 2019-06.
• Results first posted 2019-07-16.
• 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

NCT01875237 is a Phase 1/2, single-group, unmasked trial sponsored by M.D. Anderson Cancer Center. It evaluated planned donor lymphocyte infusion of T-cells genetically modified with the iCasp9 suicide gene, followed by AP1903, in a transplant setting. The registry lists enrollment of 3, a start date of 2013-12-27, a primary completion date of 2017-03-07, and terminated status.

The primary endpoint is the number of participants with adverse events among participants who received DLI and AP1903, assessed up to 3.5 years. Secondary outcomes include measures related to disease outcomes, chimerism, Epstein-Barr virus, and GvHD. The registry lists 10 outcome measures and zero analyses.

Adverse-event information reports one participant at risk and affected for serious events in the transplant-plus-DLI group, one at risk and affected for other events, and one death. The transplant-only group has zero at risk and zero affected in the listed categories. Infection is listed at 100.0% among serious-event terms. The record cautions that the groups are not a like-for-like control comparison. A numerical primary endpoint analysis and details needed to determine event attribution, denominator, and follow-up completeness are not reported in the registry record.