Autologous CMV-Specific Cytotoxic T Cells and Temozolomide in Treating Patients With Glioblastoma: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Autologous CMV-Specific Cytotoxic T Cells and Temozolomide in Treating Patients With Glioblastoma (NCT02661282), a na phase 1, phase 2 study. The primary outcome is Maximum Tolerated Dose (MTD) (Recurrent Glioblastoma Participant Cohort)- Phase I.

2. Clinical Question

The trial asked whether autologous cytomegalovirus-specific cytotoxic T cells could be given with temozolomide to people with glioblastoma, and, in its phase I recurrent-glioblastoma cohort, what dose level could be administered without dose-limiting toxicity (DLT) during the stated assessment period. The study also included phase II cohorts and listed outcomes involving progression, response, and response duration.

The study’s stated purpose includes examining side effects and identifying a best dose, as well as assessing how the treatment approach performs in the listed cohorts. These are distinct questions: dose tolerability concerns observed toxicity at dose levels, while progression and response outcomes describe disease status over time or response categories. The record lists secondary phase II outcomes, but does not report their numerical results in the information available for this analysis.

3. Trial Design

This was a phase I/II, parallel-design clinical trial sponsored by M.D. Anderson Cancer Center. The registry lists enrollment of 65 and a completed status. It records no masking and lists allocation as NA. Thus, the design information does not establish randomized assignment or a blinded comparison. The registry record explicitly identifies the arms as not a like-for-like control comparison.

The phase I primary outcome concerns participants with recurrent glioblastoma and maximum tolerated dose. It is defined as the number treated at the respective dose level without DLT during a timeframe of up to 42 days. The dose-level groups named in the adverse-event record include 5 x 10^6, 1 x 10^7, 5 x 10^7, and 1 x 10^8. The record does not give a dose-escalation algorithm or explain how dose levels were selected.

The two arm descriptions both include temozolomide and CMV-specific T-cell transfer. Arm I is titled as including surgery, and its description says surgery occurs on day 30 of cycle 1. Arm II is titled without surgery. The descriptions specify temozolomide on days 1-21 and cell transfer on day 22, with treatment repeating every 42 days for up to 4 cycles in the absence of progression or unacceptable toxicity. The descriptions then continue with additional temozolomide details but are truncated in the registry record, so the full subsequent schedules are not reported there.

The listed phase II outcomes include time to progression in the recurrent glioblastoma cohort, and overall objective response rate, median duration of response, and progression-free survival in the newly diagnosed glioblastoma cohort. These outcomes address different aspects of disease course and response. The registry record lists 8 outcome measures overall, but does not report their numerical results in the information available for this analysis. Dates for trial start and primary completion are recorded, but the record’s completion status alone does not establish that every planned analysis was performed or reported.

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: 65 participants were consented, 40 participants were inevaluable

Overall Study

5. Baseline Characteristics

The table reproduces the baseline characteristics posted in the registry, which describe the participants analysed at baseline and help show whether the randomized groups were comparable.

Only the first 6 of 7 groups are shown.

6. Primary Endpoint

The registry lists the primary outcome as Maximum Tolerated Dose (MTD) (Recurrent Glioblastoma Participant Cohort)- Phase I, measured over Up to 42 days.

The primary outcome is the number of participants in the recurrent-glioblastoma phase I cohort who were treated at a respective dose level without DLT. Its stated assessment timeframe is up to 42 days. This is a count endpoint: it describes how many participants met the stated tolerability condition at each dose level, rather than measuring tumor response or time until progression.

Maximum tolerated dose is used in early-phase research to inform dose selection for further study. In general, dose-finding considers whether treatment-related toxicities occur at particular dose levels over a defined observation period. The endpoint is therefore relevant to tolerability and dose selection, but it does not by itself establish efficacy, comparative benefit, or longer-term safety.

The registry record does not provide the number of participants without DLT at any dose level, a selected maximum tolerated dose, or the criteria used to define DLT. It also does not report the dose-finding procedure or how incomplete observation was handled. Those omissions limit interpretation: the endpoint’s definition identifies the intended count, but the posted record does not provide the result needed to assess it. The other listed outcomes, including progression and response measures, are separate from the primary dose-tolerability outcome and should not be treated as substitutes for it.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry describes a parallel phase I/II study, but reports no analyses. The following concepts explain how the listed outcomes are generally interpreted; they do not assert that any particular method was used in this trial. The statistical plan, including any specified models, hypothesis tests, and missing-data procedures, is not reported in the registry record.

What does a count endpoint convey?

The primary outcome is a count of participants treated at a dose level without DLT. Counts describe how many people met a defined condition. To interpret a count fully, readers ordinarily need the denominator at that dose level, a clear definition of the event condition, and information about participants whose assessment period was incomplete. The registry gives the endpoint’s wording and timeframe but does not report its result, DLT definition, or missing-observation handling. The count therefore cannot be converted into an interpretable dose-level rate from the registered primary outcome information.

In general, early-phase dose-finding uses observed toxicities to guide which dose levels merit further evaluation. The design may specify rules about how toxicity findings affect subsequent dosing, but no such rules are reported in the registry record. It would be inappropriate to infer a particular escalation method or to assume a maximum tolerated dose from the names of the dose groups. A dose-level label alone does not say how many participants received that dose for the primary endpoint or how many experienced a DLT.

How do response and time-to-event outcomes differ?

Overall objective response rate is generally a proportion of participants meeting specified response criteria. Interpreting it requires the response definition, the assessment schedule, the population analyzed, and the number evaluable. The registry lists this outcome for the newly diagnosed cohort but does not report its result or details of the assessment criteria.

Time to progression and progression-free survival are time-to-event outcomes. In general, these outcomes describe time until a defined event, with censoring used when a participant has not had the event by the end of observation or is no longer followed. A median time is an estimate of the point by which half the modeled population has experienced the event, under the analysis definition. Reading these outcomes requires event definitions, follow-up information, censoring rules, and uncertainty estimates. The registry lists time to progression for recurrent glioblastoma and progression-free survival for newly diagnosed glioblastoma, but does not report results or those analytic details.

Median duration of response concerns the time a response is maintained among participants who respond, under a specified definition. Because it is conditional on response, it does not describe all participants in the study. The registry lists this outcome for the newly diagnosed cohort, but the result and details of the responder population are not reported in the registry record.

What is statistical uncertainty?

In general, an estimate is subject to sampling variability: another study of similar participants might produce a different estimate. A confidence interval gives a range of values compatible with the observed data under a statistical model and its assumptions. A wider interval generally indicates less precision than a narrower interval. Confidence intervals are not reported for the outcomes in the registry information available for this analysis, so their precision cannot be evaluated.

For binary counts, statistical methods can estimate uncertainty around an event proportion when both the count and denominator are available. For time-to-event outcomes, methods can account for different follow-up times and censoring. These methods answer different questions and are not interchangeable. The registry’s outcome titles alone do not identify which estimators, models, or variance calculations were used. No p-values or analysis results are reported in the registry record.

Why does the design matter?

A randomized comparison can, under appropriate implementation and analysis, reduce systematic differences between treatment groups. This trial is not described as randomized, and its allocation is recorded as NA. The registry cautions that the arms are not a like-for-like control comparison. Accordingly, even if arm-specific outcome estimates were available, observed differences would not automatically identify a causal treatment effect. The record does not report adjustment methods that might address measured differences, and adjustment cannot necessarily remove unmeasured confounding.

Multiplicity is a general concern when several outcomes, cohorts, or comparisons are examined: the chance of at least one apparently notable result can increase unless the analysis plan accounts for the number and role of tests. The registry lists multiple secondary outcomes and 8 outcome measures overall, but does not report a multiplicity strategy. This does not prove that no strategy existed; it means the strategy is not reported in the registry record.

Similarly, sample-size planning and statistical power depend on assumptions about the target effect, outcome variability or event rate, allocation, and analysis method. The registry record does not report the trial’s sample-size justification or power calculation. No planning illustration can be interpreted as the study’s original design rationale, and no sample-size calculation is an observed result. The registry record reports enrollment of 65, but enrollment alone does not establish adequate precision for any particular outcome.

10. Exact Estimates for Each Arm

No two-arm comparison is shown for this trial, but each arm's result can still be summarized with exact interval estimates computed from the posted counts. The Clopper-Pearson interval is exact and conservative; the Wilson interval is a common closer-to-nominal alternative; the Bayesian credible interval uses a uniform Beta(1, 1) prior. For small groups the three can differ noticeably.

R code and output

arm    <- c("Phase I: Recurrent Glioblastoma Dose Level 5 x 10^", "Phase I: Recurrent Glioblastoma Dose Level 1 x 10^", "Phase I: Recurrent Glioblastoma Dose Level 5 x 10^", "Phase I: Recurrent Glioblastoma (MTD) Dose Level 1")
n      <- c(3, 3, 3, 7)
events <- c(3, 3, 3, 7)
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  Phase I: Recurrent Glioblastoma Dose Level 5 x 10^  3  3  100.0  29.2  100.0  43.9  100.0  39.8  99.4
ARM  Phase I: Recurrent Glioblastoma Dose Level 1 x 10^  3  3  100.0  29.2  100.0  43.9  100.0  39.8  99.4
ARM  Phase I: Recurrent Glioblastoma Dose Level 5 x 10^  3  3  100.0  29.2  100.0  43.9  100.0  39.8  99.4
ARM  Phase I: Recurrent Glioblastoma (MTD) Dose Level 1  7  7  100.0  59.0  100.0  64.6  100.0  63.1  99.7

11. Multiplicity, Missing Data and Analysis Populations

The registry lists 8 outcome measures, including a phase I dose-tolerability outcome and phase II measures of progression and response in different cohorts. It does not report an analysis plan describing which outcomes were primary or secondary for statistical testing beyond the outcome labels, nor whether any adjustment for multiple comparisons was planned or performed. When several outcomes or subgroups are examined, multiplicity can make chance findings more likely; in general, a prespecified testing strategy helps clarify how results should be interpreted. The record does not report such a strategy, so the implications of multiple testing cannot be assessed.

The information available for this analysis reports no analyses. It therefore does not give analysis populations, participant flow, exclusions, or denominators for the primary outcome. Handling of missing outcomes, incomplete follow-up, withdrawal, or protocol deviations is not reported in the registry record. For time-to-event measures, censoring rules and the amount of follow-up are also not reported. These details matter because exclusions, missing assessments, and differing follow-up can influence estimates and their precision.

The registry record does not report a statistical analysis plan, sample-size justification, interim analyses, or a prespecified approach to subgroup analysis. Their absence from the record should not be taken as proof that none existed; their status is not reported in the registry record. The record’s enrollment of 65 is not, by itself, evidence of adequate power or precision. No observed treatment-effect estimates, confidence intervals, or p-values are available to evaluate. The analysis population and any relationship between the enrollment count and the participants contributing to each outcome therefore remain unclear.

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 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: headache (33.3%), surgical and medical procedures, other-removal of facial cyst (33.3%), somnolence (33.3%), confusion (14.3%), muscle weakness (14.3%).

The registry lists serious adverse events and other adverse events for six named cohort and dose-level groups, along with deaths. For example, the phase I recurrent-glioblastoma group at 5 x 10^6 has 2 participants with serious adverse events among 3 at risk, 3 with other adverse events among 3 at risk, and 1 death. The phase I recurrent-glioblastoma group at 1 x 10^8 lists 3 with serious adverse events among 7 at risk, 5 with other adverse events among 7 at risk, and 7 deaths. These are registry counts for their respective groups, not comparative estimates.

The record also lists serious-event terms and percentages: Headache, 33.3%; Surgical and medical procedures, other-removal of facial cyst, 33.3%; Somnolence, 33.3%; Confusion, 14.3%; Muscle Weakness, 14.3%; and Cognitive Disturbance, 14.3%. The registry information does not clarify the denominator or attribution for each listed term, so the percentages should be read as recorded rather than as treatment-caused risks.

Counts across groups should not be treated as directly comparable: the group sizes differ, and the arms are not a randomized, like-for-like comparison. The registry record does not state whether deaths or adverse events were judged related to treatment. These figures are descriptive safety information, not proof of causation.

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

The registry record establishes that the study was conducted as a phase I/II trial of autologous CMV-specific cytotoxic T cells given with temozolomide, with two described arms and a planned phase I dose-tolerability outcome. It also records enrollment of 65 and completed status. These registry entries describe the trial’s scope and status; they do not establish that the primary question was answered in the posted results.

The primary outcome is the number of recurrent-glioblastoma participants treated at a respective dose level without DLT during up to 42 days. Because the registry does not report those counts or a selected dose, it does not show which dose level was tolerated according to the trial’s intended measure. The DLT definition and dose-selection rule are also not reported. Thus, the outcome’s presence in the record cannot be mistaken for a reported result.

Likewise, the listed phase II outcomes identify planned or registered questions about progression and response, but numerical findings are not reported in the registry information available for this analysis. No effect estimate or confidence interval is available to describe magnitude or precision. The record therefore does not provide statistical evidence from which to assess comparative efficacy.

The adverse-event entries give counts by group and a list of serious-event terms. They can be described as posted safety data, but they do not establish that the treatment caused an event. The record does not report attribution, and groups differ in size and are not a randomized, like-for-like comparison. The death counts also cannot be interpreted as treatment-related deaths based on the available registry information.

In general, a completed trial can still have incomplete public results. Completion status does not mean that every outcome has a posted estimate, that all participants contributed to each analysis, or that the results are precise. Nor does a count of enrolled participants establish power for a particular outcome. The appropriate statistical conclusion is limited: the registry documents the design and selected adverse-event counts, while the primary and secondary outcome analyses, their uncertainty, and key analysis details are not reported in the registry record.

14. Why This Trial Matters Statistically

This trial raises a set of distinct statistical questions within one clinical program. Its phase I component focuses on dose tolerability in recurrent glioblastoma, while its phase II outcomes concern progression and response in recurrent and newly diagnosed cohorts. Distinguishing these questions matters: a dose-tolerability count is not an efficacy estimate, and a response or progression outcome does not, by itself, establish an acceptable dose.

The registry’s two arm descriptions also make design interpretation important. Both include temozolomide and CMV-specific T-cell transfer, while one arm title includes surgery. Allocation is recorded as NA, and the record cautions that the arms are not a like-for-like control comparison. In this setting, a simple difference between arms would not necessarily isolate the effect of surgery or any other treatment component. The study’s structure must be considered before attributing outcome differences to a specific intervention.

For researchers, the record illustrates why outcome definitions and reporting completeness are essential. The primary outcome is named and its timeframe is stated, but the DLT definition, primary counts, selected dose, and analysis are not reported. The phase II outcome titles are present, but their estimates and precision are not. Without these elements, readers cannot judge how much information the trial provides about dose selection or clinical outcomes.

The listed adverse-event data also show why denominators and attribution matter. Counts occur in groups of different sizes, and the record does not say whether events or deaths were considered treatment-related. Descriptive safety data can identify what was recorded, but they cannot establish comparative risk or causality without appropriate context and analysis.

Finally, the record lists multiple outcomes but does not report a multiplicity strategy, missing-data approach, or sample-size justification. These are not minor technical details: they shape how estimates should be interpreted and how confidently results can be generalized. The study is statistically informative as an example of early-phase dose and cohort questions, but the posted registry information is insufficient to evaluate its primary result or draw comparative conclusions.

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 most consequential limitation for interpretation is that no primary or secondary outcome analyses are reported in the registry information available for this analysis. The primary outcome’s count without DLT is not given, and neither a maximum tolerated dose nor its supporting dose-level evidence is reported. The DLT definition and dose-selection method are also absent. These omissions prevent assessment of the study’s central phase I question.

The two treatment arms are not described as randomized, allocation is listed as NA, and the registry warns against treating them as a like-for-like comparison. The arm titles differ with respect to surgery, but the record does not support attributing any outcome difference to that component. Participant-level comparability and adjustment for potential differences are not reported.

Although the registry lists 65 participants enrolled, the number contributing to each outcome is not reported. Analysis populations, exclusions, missing-data handling, follow-up completeness, and censoring methods are not described in the registry record. These details are especially relevant to response and time-to-event outcomes, which are listed but have no reported estimates.

The adverse-event record gives counts by group, but group sizes vary and causal attribution is not reported. It is not clear from the registry information whether the events or deaths were judged related to treatment. The listed serious-event percentages also lack accompanying denominators in the available information.

Finally, the registry does not report the statistical analysis plan, sample-size justification, interim analyses, or a multiplicity strategy. Some arm descriptions are truncated, so the full treatment schedules are not reported in the registry record. These limits concern what can be concluded from the registered information; they do not establish whether additional information exists elsewhere.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Autologous CMV-Specific Cytotoxic T Cells and Temozolomide in Treating Patients With Glioblastoma — NCT02661282.
• Registry record last updated 2023-06-18; status last verified 2023-05.
• Results first posted 2023-06-18.
• 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 is a completed phase I/II parallel-design trial sponsored by M.D. Anderson Cancer Center, with enrollment of 65. It evaluated autologous CMV-specific cytotoxic T cells given with temozolomide in glioblastoma cohorts. The registry describes two arms, including one titled with surgery, and records no masking and allocation as NA. It cautions that the arms are not a like-for-like control comparison.

The primary outcome is the number of participants in the recurrent-glioblastoma phase I cohort treated at a respective dose level without DLT, assessed for up to 42 days. Secondary outcomes include time to progression, objective response rate, duration of response, and progression-free survival in specified cohorts. The registry information available for this analysis does not report outcome analyses or the primary result. It does list adverse-event counts and serious-event terms, but does not report event attribution. Statistical methods, analysis populations, missing-data procedures, and sample-size justification are not reported in the registry record.