Autologous T Cells With or Without Cyclophosphamide and Fludarabine in Treating Patients With Recurrent or Persistent Advanced Ovarian Epithelial Cancer, Primary Peritoneal Cavity Cancer, or Fallopian Tube Cancer (Fludarabine Treatment Closed as of 12/01/2009): Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Autologous T Cells With or Without Cyclophosphamide and Fludarabine in Treating Patients With Recurrent or Persistent Advanced Ovarian Epithelial Cancer, Primary Peritoneal Cavity Cancer, or Fallopian Tube Cancer (Fludarabine Treatment Closed as of 12/01/2009) (NCT00562640), a na phase 1 study. The primary outcome is Number of Participants Assessed for Safety and Tolerability as Assessed by NCI CTCAE v3.0.

2. Clinical Question

This is a safety-focused early-phase question, rather than a confirmatory test of whether treatment improves a clinical outcome. The registry record identifies an intended dose-escalation purpose: to identify tolerable, clinically active doses of WT1 peptide-sensitized T cells. It does not report a numerical clinical-activity result. The information available therefore supports describing the study's purpose and structure, but not deciding whether a dose was tolerable or clinically active.

3. Trial Design

The registry record describes a phase I, sequential dose-escalation study with no masking and allocation listed as not applicable. Enrollment was 12. The study started on 2007-10-16, its primary completion date is listed as 2021-08-03, and its status is completed. These dates describe the registry record; they do not establish how long each participant was followed.

The listed WT1-specific T-cell groups were 5 x 10^6/m2, 2 x 10^7/m2, 5 x 10^7/m2, and 1 x 10^8/m2. Their recorded group sizes were 3, 3, 4, and 2, respectively. In a sequential dose-escalation study, cohorts are considered in an ordered dose context. Such cohorts are not randomized parallel groups, and the record does not describe a concurrent control group. The small, unequal cohort sizes also mean that a numerical contrast across dose groups would not, by itself, establish a dose effect.

The study title and summary describe autologous T cells with or without cyclophosphamide and fludarabine. The interventions list includes filgrastim, therapeutic autologous lymphocytes, cyclophosphamide, and laboratory biomarker analysis. The record notes that fludarabine treatment closed as of 12/01/2009. It does not report the participant-level treatment assignments, the precise sequence of interventions, or whether each listed intervention was received by all participants.

The registry record lists four outcome measures, but the available outcome detail identifies the primary safety and tolerability measure. The number of analysis entries is 0. A full protocol, dose-escalation decision rules, and the statistical analysis plan are not reported in the registry record. Consequently, the design can be described as sequential and dose-escalating, but its operating rules should not be inferred.

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:

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 Participants Assessed for Safety and Tolerability as Assessed by NCI CTCAE v3.0, measured over 2 years.

The primary outcome is the number of participants assessed for safety and tolerability using NCI CTCAE v3.0, with a timeframe of 2 years. The measure is a count of participants, not a continuous measurement or a time-to-event estimate. The description says participant toxicity will be evaluated using that grading system; it does not report a count of participants assessed, toxicity grades, or a numerical outcome result.

In general, safety and tolerability outcomes are central to early-phase dose-escalation research because they characterize toxicities observed during treatment and can inform decisions about doses for further study. A toxicity grading system offers a structured way to classify adverse events. However, the outcome label alone does not give the event definitions, rules for attributing an event to treatment, or the threshold used to call a dose tolerable. Those details are not reported in the registry record.

The two-year timeframe describes the stated assessment window; it should not be read as confirmation that every participant completed that duration of follow-up. The record does not report individual follow-up, handling of participants with incomplete assessment, or whether the safety count includes every enrolled participant. Without the primary outcome result and its analysis population, the endpoint's stated purpose can be explained, but its observed value and precision cannot be evaluated.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does a sequential dose-escalation design mean?

In general, a sequential dose-escalation study examines dose levels in an ordered process, with early-phase attention commonly placed on safety and tolerability. It differs from a randomized comparison: participants are not assigned at random to treatment groups for a balanced estimate of a treatment contrast. In this study, the registry record lists allocation as not applicable, masking as none, and the model as sequential. It identifies four WT1-specific T-cell dose groups. The exact rules for moving from one dose to another, pausing escalation, or selecting a dose are not reported in the registry record.

This distinction matters when interpreting group counts. Dose cohorts may be small and may have been enrolled at different stages of the study. A higher or lower count in one group would not, on its own, show that the dose caused the difference. Differences may also reflect chance, participant characteristics, follow-up, or other aspects of the treatment context. Without randomization, a specified comparative analysis, and participant-level information, the registry counts are descriptive rather than a controlled dose-effect estimate.

What does the primary outcome count?

The primary outcome is the number of participants assessed for safety and tolerability with NCI CTCAE v3.0 over 2 years. A count answers how many participants were assessed; it is not itself a rate unless the relevant denominator and definition are also available. The record does not report the primary count or the number of participants included in its analysis. The separate safety listing gives counts by group, but that listing does not supply the missing primary outcome result or explain whether its population is the same.

In general, a confidence interval describes uncertainty around an estimated quantity under specified statistical assumptions. It can help distinguish a relatively precise estimate from one compatible with a broad range of values. No confidence interval for the primary safety outcome is reported in the registry record. With small cohorts, uncertainty is often substantial; without the analysis result and its method, that uncertainty cannot be quantified from the registry entries.

How should adverse-event counts be understood?

The serious and other adverse-event entries report numbers at risk and numbers affected for each group. The listed counts match within each group: 3 of 3 for the first dose group, 3 of 3 for the second, 4 of 4 for the third, and 2 of 2 for the fourth, for each of the serious-event, other-event, and death entries. These are descriptive counts. They do not identify the number of distinct events, their severity beyond the listed category, their timing, or whether a participant had multiple events. The registry record does not report definitions or attribution rules for these entries.

Likewise, the serious-event terms and their percentages summarize terms listed in the record, but their denominator and method of calculation are not reported in the registry record. An adverse-event term can describe an event without establishing that treatment caused it. General safety interpretation therefore separates the occurrence of an event from its attribution to treatment. The listed “Death not assoc with CTCAE term - Death NOS” wording specifically indicates that the term is not associated with a CTCAE term; it does not provide a full cause-of-death assessment.

Why can event counts be difficult to compare?

In general, adverse events may be counted as participants affected or as total events. These are different quantities: one participant may experience multiple events, while a participant count records whether an event occurred for that person. A comparison also depends on the time each participant was observed and the definition of the population at risk. If follow-up varies, raw counts may not represent comparable exposure periods. The registry record does not report event-level data, person-time, or participant-level follow-up, so these issues cannot be resolved from the listed counts.

Over-dispersion is a general statistical concern when counts vary more than a simple count model would expect. It can arise, for example, when some participants experience many events and others experience few. Aggregate counts cannot show whether such clustering occurred. No event-count model or over-dispersion adjustment is reported in the registry record, so no such analysis should be assumed.

What do the planning illustrations mean?

In general, a sample-size calculation describes the amount of information a hypothetical study might need under chosen assumptions. The planning framework associated with the record describes two-sided significance level 0.05, equal allocation, and a normal approximation, with the detectable effect expressed as a stated fraction of an observed effect. It also distinguishes participants per arm from total event counts for time-to-event calculations. These are planning conventions, not evidence that the trial used that design or achieved a particular probability of detecting an effect.

The present study is described as sequential, has no randomized allocation, and has no like-for-like control comparison. Its cohort sizes are not equal. Therefore, equal-allocation planning illustrations should not be read as a reconstruction of this trial's design or as observed power. The trial's own sample-size justification and power calculation are not reported in the registry record. Moreover, the numerical primary outcome result needed to evaluate an observed effect is not reported in the registry record. Any planning illustration is consequently hypothetical and cannot fill in the missing clinical results.

What inferential analysis is available?

No analysis entries are listed in the registry record. No model, hypothesis test, confidence interval, adjustment method, or prespecified dose comparison is reported. This absence does not prove that no analyses were conducted outside the registry; it means their methods and results are not reported in the registry record. Without those details, interpretation should remain descriptive and should not add formal statistical conclusions to the listed counts.

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("WT1 Specific T Cells 5 x 10^6/m2", "WT1 Specific T Cells 2 x 10^7/m2", "WT1 Specific T Cells 5 x 10^7/m2", "WT1 Specific T Cells 1 x 10^8/m2")
n      <- c(3, 3, 4, 2)
events <- c(3, 3, 4, 2)
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  WT1 Specific T Cells 5 x 10^6/m2  3  3  100.0  29.2  100.0  43.9  100.0  39.8  99.4
ARM  WT1 Specific T Cells 2 x 10^7/m2  3  3  100.0  29.2  100.0  43.9  100.0  39.8  99.4
ARM  WT1 Specific T Cells 5 x 10^7/m2  4  4  100.0  39.8  100.0  51.0  100.0  47.8  99.5
ARM  WT1 Specific T Cells 1 x 10^8/m2  2  2  100.0  15.8  100.0  34.2  100.0  29.2  99.2

11. Multiplicity, Missing Data and Analysis Populations

The registry record lists four outcome measures, but the available outcome detail identifies the primary safety and tolerability measure. The other outcome definitions, their status as primary or secondary, and any hierarchy for testing them are not reported in the registry record. The number of analysis entries is 0. No multiplicity strategy, such as a prespecified order of tests or adjustment for multiple comparisons, is reported.

In general, multiplicity arises when several outcomes, time points, subgroups, or comparisons are examined. Without a prespecified analysis plan, it can be difficult to distinguish confirmatory tests from exploratory summaries. This is especially relevant in a dose-escalation study with multiple dose groups and several safety terms. The registry record does not describe which comparisons, if any, were planned, so no adjustment or testing strategy should be assumed.

The primary outcome is described as a count of participants assessed, but the numerical result, analysis population, and missing-data handling are not reported in the registry record. The record does not explain whether participants with incomplete follow-up were included, how incomplete safety assessments were handled, or whether analysis was based on enrollment, treatment received, or another population. The timing and completeness of assessments for individual participants are also not reported.

In general, missing-data methods depend on why observations are missing and on the outcome definition. A missing assessment should not automatically be interpreted as either absence of toxicity or evidence of toxicity. Since the registry record does not describe the extent or handling of missing data, the direction or size of any resulting bias cannot be assessed. The completion status of the study does not resolve these analysis details.

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: death not assoc with ctcae term - death nos (100.0%), pelvic pain (66.7%), fatigue (33.3%), inf norm anc/gr1/2 neut-cellulitis(skin) (33.3%), hypomagnesemia (33.3%).

The registry lists serious adverse events, other adverse events, and deaths by T-cell dose group. For each category, the counts at risk and affected are 3 and 3 in the 5 x 10^6/m2 group, 3 and 3 in the 2 x 10^7/m2 group, 4 and 4 in the 5 x 10^7/m2 group, and 2 and 2 in the 1 x 10^8/m2 group. These are group-level counts; the record does not provide participant-level event histories or the time period covered by these entries.

The serious-event terms listed include “Death not assoc with CTCAE term - Death NOS” at 100.0%, “Pelvic pain” at 66.7%, and four terms at 33.3%: fatigue, an infection/neutropenia-related term, hypomagnesemia, and small bowel obstruction. The denominator for these percentages is not reported in the registry record. The terms may overlap, and the percentages should not be added or interpreted as distinct participant groups.

Counts of deaths do not, by themselves, show that treatment caused the deaths. The record does not report cause, timing, or a treatment-attribution assessment for the death counts. The listed death term is explicitly described as not associated with a CTCAE term. These safety entries are descriptive and should not be read as a causal comparison between dose groups.

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

The record documents a phase I investigation of WT1-specific autologous T cells in recurrent or persistent advanced ovarian, primary peritoneal, and fallopian tube cancer. Its sequential dose-escalation design and stated safety and tolerability endpoint place the study in an early-phase, descriptive context. The posted group counts and adverse-event terms communicate what the registry lists, but the primary safety outcome result is not reported in the registry record.

The data do not establish whether a particular dose was tolerable under the study's criteria, because those criteria and the primary outcome result are not reported. Nor do the counts establish a dose-response relationship. The cohorts were not randomized comparators, and the record does not provide an inferential analysis or a controlled estimate of differences between doses. The safety entries also do not establish whether an event or death was caused by treatment.

The study's stated purpose includes identifying clinically active doses, but a numerical clinical-activity result is not reported in the registry record. No conclusion about tumor response, disease control, or survival can be drawn from the information. Likewise, the listed safety terms do not indicate how often each event occurred across all observed time or how severe it was for an individual participant.

In general, a registry entry is most informative when outcomes, analysis populations, follow-up, and statistical methods are reported in enough detail to interpret estimates and their uncertainty. Those elements are incomplete in this record. The best-supported reading is therefore narrow: a small sequential phase I study was registered, with four dose groups and descriptive safety listings, but the primary endpoint result and key analysis details are not reported in the registry record.

This distinction is important because absence of a reported result is not evidence that an outcome did or did not occur. It also does not establish that no analysis was conducted. It means the registry record does not provide the information needed to assess the endpoint quantitatively or to make comparative claims. The posted material should be interpreted as a limited record of study structure and safety listings, not as a complete account of treatment effects.

14. Why This Trial Matters Statistically

This study illustrates how early-phase clinical research poses a different statistical question from a randomized efficacy trial. The focus is safety and tolerability during sequential dose escalation, not an unbiased estimate of benefit relative to a control group. Recognizing that distinction prevents dose cohorts from being treated as if they were randomized arms.

The registry record also illustrates why counts need context. The dose groups contain 3, 3, 4, and 2 participants, and the safety listings report affected counts that equal the listed at-risk counts. Those observations are useful descriptions of the registry entries, but without a defined analysis population, follow-up information, event attribution, and uncertainty estimates they cannot yield a precise safety rate or a causal dose comparison.

For biostatisticians and clinical researchers, the gap between a stated endpoint and a reported result is consequential. The primary endpoint is clearly described as a count of participants assessed for toxicity over 2 years using NCI CTCAE v3.0, yet its numerical result is not reported in the registry record. This limits reproducibility and makes it impossible to evaluate how the study's stated safety question was answered from the posted information.

The study also shows why planning calculations must be separated from observed evidence. A hypothetical calculation based on assumptions such as equal allocation does not describe the operating characteristics of a sequential, nonrandomized study. Planning illustrations are not observed power and do not substitute for an analysis result, a confidence interval, or a documented dose-escalation rule.

Finally, safety terms require careful interpretation. Their presence describes reported events, but does not by itself establish treatment causation. Explicitly distinguishing occurrence, severity, attribution, and statistical uncertainty is essential when translating early-phase registry data into a scientific account.

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 important limitation is that the numerical primary outcome result is not reported in the registry record. The endpoint is defined as the number of participants assessed for safety and tolerability, but the record does not state that count or describe the analysis population. This prevents a direct evaluation of the primary question.

The study enrolled 12 participants across four sequential dose groups. The groups were not randomized comparators, and no control group is listed. The record does not provide the dose-escalation rules, stopping criteria, or threshold for identifying a tolerable dose. Accordingly, the group counts cannot be treated as a causal dose comparison or as a formal dose-selection result.

The adverse-event listings lack event-level details, timing, follow-up duration by participant, and attribution to treatment. The denominator and calculation method for the listed serious-event percentages are not reported in the registry record. The death counts and terms therefore cannot establish cause, treatment relationship, or comparative mortality risk.

The registry lists four outcome measures, but detail for the remaining outcomes is not available in the record. No analysis entries are listed, and the statistical plan, multiplicity handling, missing-data rules, confidence intervals, and sample-size justification are not reported in the registry record. The stated 2-year timeframe does not establish that each participant was observed for that duration.

The record describes treatment with or without chemotherapy and notes that fludarabine treatment closed as of 12/01/2009, but does not report participant-level exposure to the listed interventions. This limits interpretation of safety findings in relation to specific treatment components. Overall, the registry information supports a description of study structure and posted safety counts, but leaves substantial uncertainty about outcome ascertainment, analysis, attribution, and interpretation.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Autologous T Cells With or Without Cyclophosphamide and Fludarabine in Treating Patients With Recurrent or Persistent Advanced Ovarian Epithelial Cancer, Primary Peritoneal Cavity Cancer, or Fallopian Tube Cancer (Fludarabine Treatment Closed as of 12/01/2009) — NCT00562640.
• Registry record last updated 2023-09-15; status last verified 2021-08.
• Results first posted 2023-09-15.
• 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

NCT00562640 is a completed phase I study sponsored by Memorial Sloan Kettering Cancer Center. It enrolled 12 participants and used a sequential, unmasked dose-escalation design without randomized allocation. The study examined WT1-specific autologous T cells in advanced ovarian, primary peritoneal, or fallopian tube cancer.

The primary outcome was the number of participants assessed for safety and tolerability using NCI CTCAE v3.0 over 2 years. Four T-cell dose groups are listed, with group sizes of 3, 3, 4, and 2. The safety listings report serious adverse events, other adverse events, and deaths by group, alongside serious-event terms and percentages.

The numerical primary outcome result, detailed analysis methods, missing-data handling, and participant-level treatment exposures are not reported in the registry record. The posted information supports descriptive interpretation only; it does not establish a treatment effect, a causal dose comparison, or treatment attribution for deaths.