Laboratory Treated T Cells in Treating Patients With Relapsed or Refractory Chronic Lymphocytic Leukemia, Non-Hodgkin Lymphoma, or Acute Lymphoblastic Leukemia: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Laboratory Treated T Cells in Treating Patients With Relapsed or Refractory Chronic Lymphocytic Leukemia, Non-Hodgkin Lymphoma, or Acute Lymphoblastic Leukemia (NCT01865617), a non-randomized phase 1, phase 2 study. The primary outcome is Death Within 8 Weeks of the Study Cell Infusion Thought to be Definitely or Probably Related to Chimeric Antigen Receptor (CAR) T Cell Therapy.

2. Clinical Question

3. Trial Design

This was a phase I/II, nonrandomized study with a single-group model. It evaluated engineered autologous T cells in patients with advanced CD19-positive chronic lymphocytic leukemia, acute lymphoblastic leukemia or lymphoma, and non-Hodgkin lymphoma. The listed arms organize participants into disease-specific and dose-level cohorts. Some cohorts also specify high or low tumor burden, ibrutinib treatment, or dose-dense treatment. These features describe the cohort labels; the registry record does not report enough detail to establish that all cohorts followed an identical treatment pathway.

The intervention was anti-CD19 CAR T cells. The arm descriptions state that cells were given intravenously over 20-30 minutes on day 0. They allow for treatment to be repeated no less than 21 days later when disease persisted and toxicity was not unacceptable, with or without additional lymphodepleting chemotherapy. The registry does not report the complete details of those treatment decisions in the material available for this analysis.

The study started on 2013-05-22, reached primary completion on 2021-03-26, and has a completed status. Fred Hutchinson Cancer Center is listed as the sponsor. The recorded enrollment was 204. The record does not report the allocation process beyond identifying the study as nonrandomized, and it identifies no masking.

Because there was no randomized control group, differences between the listed cohorts cannot be interpreted as randomized treatment effects. The groups differ by disease and other cohort characteristics, and the record does not establish that those differences are balanced. The primary endpoint is a safety outcome within a defined follow-up window; the registry record does not report a primary endpoint estimate or analysis.

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: 204 patients were enrolled on this study but only 197 met eligibility criteria and went on to be treated on study.

Only the first 6 of 13 groups are shown.

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.

Only the first 6 of 14 groups are shown.

6. Primary Endpoint

The registry lists the primary outcome as Death Within 8 Weeks of the Study Cell Infusion Thought to be Definitely or Probably Related to Chimeric Antigen Receptor (CAR) T Cell Therapy, measured over Within 8 weeks of the study cell infusion.

The primary endpoint is the count of participants who died within 8 weeks of study cell infusion and whose death was judged definitely or probably related to CAR T cell therapy. It is therefore a binary participant-level safety outcome: each participant either meets the endpoint definition or does not. The endpoint combines a defined time window with an attribution judgment about the relationship between the death and therapy.

A treatment-related death endpoint is used to describe a serious potential harm associated with study treatment. A defined follow-up window makes the observation period explicit, while the attribution categories distinguish deaths considered related to treatment from deaths not judged definitely or probably related. The endpoint definition does not itself establish how attribution was assessed, who made the judgment, or how disagreements were handled; those details are not reported in the registry record.

The registry record states the endpoint and its timeframe, but does not report a result for it. The death counts appearing in the adverse-event group information cannot be substituted for this endpoint: those counts are not identified there as deaths meeting the primary endpoint’s timing and relatedness criteria. Without a reported endpoint count and analysis, the primary safety question cannot be quantified from the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The study’s design determines what statistical conclusions are supportable. It was nonrandomized and used a single-group model, with disease-specific and dose-level cohorts rather than a randomized control arm. Randomization can help make comparison groups similar in expectation, whereas nonrandomized groups may differ in both measured and unmeasured characteristics. Because these cohorts are not like-for-like controls, an observed difference between them would not by itself establish that dose or treatment context caused the difference.

What does a participant count represent?

The primary endpoint is a count of participants meeting a specified event definition. For each participant, the relevant classification is whether a death occurred within the endpoint’s timeframe and was considered definitely or probably related to CAR T cell therapy. A count is descriptive. To understand its scale, readers would also need a clearly defined denominator and consistent outcome ascertainment. The registry record does not report the primary endpoint count or denominator as an outcome result.

What would a confidence interval add?

In general, a confidence interval describes the uncertainty around an estimated quantity under a statistical model. For an event proportion, it would help show how compatible the observed data are with a range of underlying event rates. A narrow interval indicates greater precision under the chosen model; a wide interval indicates less precision. An interval does not remove bias from nonrandomized selection, inconsistent follow-up, or outcome classification. No primary endpoint interval is reported in the registry record.

How should significance testing be read?

In general, a p-value describes how surprising data would be under a specified null model, if that model and its assumptions were appropriate. It is not the probability that a treatment works, nor does it measure the size or clinical importance of an effect. A p-value also does not correct for biased comparisons or incomplete reporting. The registry record does not report primary endpoint analyses or p-values, so significance testing cannot be interpreted for this endpoint.

Why do event definitions and follow-up matter?

For a time-bounded safety endpoint, both the event definition and observation window matter. A death outside the specified window is not counted by the stated endpoint, and a death not attributed as definitely or probably related does not meet its stated definition. Interpretation also depends on whether participants were followed consistently and how missing follow-up was handled. Those details are not reported in the registry record. The adverse-event death counts cannot be assumed to follow the primary endpoint’s specific rules.

What do the cohort labels permit?

The listed groups identify disease types, dose levels, tumor-burden categories, and certain treatment contexts. They permit a descriptive reading of the registry entries by group. They do not establish a controlled dose-response analysis or a comparative effect. Cohort sizes and characteristics may differ, and no adjusted statistical comparison is reported. General statistical methods can account for measured differences only when the relevant data and model are available; they cannot guarantee removal of unmeasured confounding.

What about sample-size illustrations?

Any sample-size illustrations associated with the posted results are planning calculations, not evidence about what the trial was powered to detect. The stated illustration assumptions use a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation, with the effect expressed as a fraction of an observed effect. Such calculations are hypothetical planning tools and do not turn this nonrandomized study into a two-arm trial. Sample sizes are planning illustrations, never observed power. The registry record does not report a trial-specific sample-size justification or the analysis results needed to assess those illustrations for the primary endpoint.

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("CLL Dose Level 1", "CLL Dose Level 2", "CLL Dose Level 3", "CLL (Ibrutinib) Dose Level 2", "NHL Dose Level 1", "NHL Dose Level 2")
n      <- c(5, 22, 1, 20, 5, 49)
events <- c(0, 1, 0, 1, 0, 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  CLL Dose Level 1  5  0  0.0  0.0  52.2  0.0  43.4  0.4  45.9
ARM  CLL Dose Level 2  22  1  4.5  0.1  22.8  0.8  21.8  1.1  21.9
ARM  CLL Dose Level 3  1  0  0.0  0.0  97.5  0.0  79.3  1.3  84.2
ARM  CLL (Ibrutinib) Dose Level 2  20  1  5.0  0.1  24.9  0.9  23.6  1.2  23.8
ARM  NHL Dose Level 1  5  0  0.0  0.0  52.2  0.0  43.4  0.4  45.9
ARM  NHL Dose Level 2  49  0  0.0  0.0  7.3  0.0  7.3  0.1  7.1

11. Multiplicity, Missing Data and Analysis Populations

The registry record lists seven outcome measures and identifies secondary outcomes concerning the duration of persistence and migration of adoptively transferred CD19 CAR T cells. It reports zero outcome analyses. It does not report which outcomes were analyzed, how many comparisons were planned, or whether any multiplicity adjustment was used. The statistical plan for handling multiple outcomes or repeated analyses is not reported in the registry record.

Multiplicity matters because testing many outcomes or comparisons can increase the chance of apparently unusual results even when no underlying effect exists. Adjustments or a prespecified hierarchy can address that issue, but the record does not say whether either approach was used. With no posted outcome analyses, there are no reported inferential findings to evaluate for multiplicity.

Missing-data handling is also not reported in the registry record. For a safety endpoint, readers would need to know how participants with incomplete follow-up were treated, whether outcome status was available for everyone, and how deaths were classified when attribution or timing was uncertain. The record does not report those details or an analysis population for the primary endpoint.

The recorded enrollment of 204 does not establish how many participants contributed to any specific outcome analysis. The registry record does not report endpoint denominators, exclusions, or analysis-population definitions. These omissions limit interpretation of both the completeness and precision of any outcome estimate; no primary endpoint estimate is posted to resolve those questions.

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: febrile neutropenia (100.0%), cytokine release syndrome (100.0%), lung infection (100.0%), hypotension (100.0%), fever (60.0%).

The adverse-event information is arranged by disease and dose-level group and distinguishes serious-event entries from other event entries. Read each group as a descriptive registry listing, not as a randomized comparison. The number at risk and number affected are group-specific entries; they should not be added across groups or treated as a study-wide total. The registry record does not explain whether any participant could appear in more than one group or provide further context for combining these entries.

The serious-event terms include febrile neutropenia, cytokine release syndrome, lung infection, and hypotension, each listed at 100.0%; fever and depressed level of consciousness are listed at 60.0%. The denominators underlying these term percentages are not reported in the registry record. Therefore, those percentages cannot be interpreted as the fraction of all participants who experienced each event.

The group information also includes death counts, but it does not identify them as deaths meeting the primary endpoint definition. That endpoint requires death within 8 weeks and attribution as definitely or probably related to CAR T cell therapy. The adverse-event listing should not be used to infer that endpoint’s result or to estimate comparative safety.

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

The registry record establishes that a phase I/II study of engineered autologous anti-CD19 CAR T cells was completed in patients with relapsed or refractory leukemia or lymphoma. It records enrollment of 204 and describes several disease and dose-level cohorts. Its primary endpoint was a treatment-related death outcome within 8 weeks of infusion. These details identify the study question and the broad structure of the investigation.

The posted information does not provide a primary endpoint result, an efficacy estimate, or an analysis comparing the treatment with a control. The study was nonrandomized, and the listed cohorts are not a randomized comparator. Even if group outcomes were available, differences between cohorts would need cautious interpretation because disease type, tumor burden, dose level, and treatment context could differ. The registry record does not report an adjusted analysis that addresses those differences.

The adverse-event term percentages and group counts provide descriptive information, but missing denominators and outcome details limit their interpretation. In particular, neither the term percentages nor the death counts can be taken as the primary endpoint result. No conclusion about the magnitude or precision of that endpoint is possible from the posted registry information.

This does not mean that no analyses or additional results exist outside the registry record. It means those analyses and results are not reported in the registry record. A complete assessment would require the endpoint results, definitions and denominators for adverse events, follow-up and missing-data information, and a prespecified statistical analysis approach. Without these, the appropriate interpretation is limited to the design and descriptive entries that are recorded, rather than a judgment about treatment benefit or comparative safety.

14. Why This Trial Matters Statistically

This study raises statistical issues common to early-phase investigations that include multiple diseases and dose-level cohorts. A single-group, nonrandomized design can describe treatment exposure and observed events, but it does not provide the protection against confounding that random assignment can offer. The cohort labels make clear why a simple comparison across groups would be difficult: disease, tumor burden, dose level, and treatment context may vary together.

The primary endpoint also illustrates the importance of a precise event definition. It is not simply a count of all deaths; it is limited by a follow-up window and a judgment that the death was definitely or probably related to therapy. Without a reported endpoint count, denominator, and attribution process, readers cannot assess either the observed frequency or its precision. The separate adverse-event death entries do not substitute for those details.

Finally, the record lists multiple outcomes but no outcome analyses. That makes transparent reporting of prespecified outcomes, analysis populations, missing-data handling, and multiplicity especially important. Those methods determine how descriptive counts and any inferential estimates should be understood. In this record, their absence prevents a statistical appraisal of the primary endpoint beyond its stated definition. The study is therefore informative about the planned clinical question and broad design, while the posted results do not support a quantitative conclusion about that question.

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 direct limitation is that no primary endpoint result is reported in the registry record. There is no endpoint count, denominator, estimate, or confidence interval with which to describe the frequency or precision of treatment-related deaths within 8 weeks. The registry record also reports zero outcome analyses.

The nonrandomized, single-group design does not support a randomized comparison with another treatment. The listed disease and dose-level cohorts have different labels and may represent clinically different groups. The record does not report an adjusted comparison or sufficient participant-level detail to assess how cohort characteristics relate to outcomes.

Important reporting details are absent, including the analysis population, completeness of follow-up, handling of missing data, statistical plan, and multiplicity approach. The method for deciding whether a death was definitely or probably related to CAR T cell therapy is not reported in the registry record. The adverse-event term percentages lack reported denominators, and the death counts are not identified as meeting the primary endpoint definition.

The arm descriptions include possible repeat treatment and possible lymphodepleting chemotherapy, but the registry record does not provide complete treatment exposure details for interpreting outcomes. These limitations mean that the posted information can describe the design and listed adverse-event entries, but cannot establish the primary endpoint’s observed rate, its precision, or comparative treatment effects.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Laboratory Treated T Cells in Treating Patients With Relapsed or Refractory Chronic Lymphocytic Leukemia, Non-Hodgkin Lymphoma, or Acute Lymphoblastic Leukemia — NCT01865617.
• Registry record last updated 2022-05-25; status last verified 2022-05.
• Results first posted 2022-05-25.
• 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 completed phase I/II study evaluated autologous T cells engineered to express a CD19-specific CAR in patients with relapsed or refractory chronic lymphocytic leukemia, non-Hodgkin lymphoma, or acute lymphoblastic leukemia. The registry records enrollment of 204, a nonrandomized allocation, and a single-group model. It lists multiple disease and dose-level cohorts.

The primary endpoint was death within 8 weeks of infusion considered definitely or probably related to CAR T cell therapy. The registry record does not report a result or analysis for this endpoint. It lists serious adverse-event terms and group-level event information, but the term denominators and the relationship between death counts and the primary endpoint are not reported. The record supports description of the design, not a quantitative conclusion about the primary endpoint or a controlled treatment comparison.