Study of Efficacy and Safety of Reinfusion of Tisagenlecleucel in Pediatric and Young Adult Patients With Acute Lymphoblastic Leukemia (ALL): Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Study of Efficacy and Safety of Reinfusion of Tisagenlecleucel in Pediatric and Young Adult Patients With Acute Lymphoblastic Leukemia (ALL) (NCT04225676), a na phase 2 study. The primary outcome is Percentage of Patients Who Establish B Cell Aplasia Within 9 Months of Reinfusion.

2. Clinical Question

3. Trial Design

This was a Phase II, open-label, multi-center, single-group trial of tisagenlecleucel reinfusion in pediatric and adolescent young adult patients with acute lymphoblastic leukemia. The study focused on patients who had previously received tisagenlecleucel and then experienced B-cell recovery. Tisagenlecleucel was given once during the study. The registry lists an enrollment of 5.

The registry lists the study start as 2020-10-19 and primary completion as 2021-10-19. Its status is terminated. The primary endpoint description says the planned timeframe was 12 months, but the actual timeframe was approximately 9 months due to early termination. The registry does not report why the trial was terminated beyond this explanation of the shortened follow-up.

Because this was a single-group study, there is no concurrent control group against which to compare outcomes. The study was open label, so masking was not used. These features describe the design; they do not establish why the design was selected or what analysis procedures were planned. Those details are not reported in the registry record.

The registry lists a primary endpoint concerning B-cell aplasia and names secondary outcomes concerning complete response or complete response with incomplete blood count recovery, participants with an event, and overall survival. It does not provide outcome results or analysis entries. The stated enrollment and study dates describe the registry record, but do not by themselves show how many participants contributed data to each endpoint.

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: There were 7 participants screened.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Full analysis set

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 Percentage of Patients Who Establish B Cell Aplasia Within 9 Months of Reinfusion, measured over Post-reinfusion up to 9 months (Day 1 is excluded).

The primary endpoint concerns the percentage of patients who establish B-cell aplasia following tisagenlecleucel reinfusion. The endpoint description defines B-cell aplasia using a peripheral blood absolute B lymphocyte count <50/μL. The timeframe is post-reinfusion up to 9 months, excluding Day 1. Day 1 is defined as after lymphodepleting chemotherapy and before tisagenlecleucel reinfusion.

This endpoint is used to describe whether a biological state was observed during follow-up after reinfusion. A defined threshold makes the outcome operational: patients can be classified according to whether the specified blood-cell criterion was met at a visit after reinfusion. The endpoint is expressed as a percentage in its title, while the registry describes the measure as a count of participants. Neither wording supplies the observed result.

The registry notes that the planned timeframe was 12 months and that the actual timeframe was approximately 9 months because the trial ended early. A shorter observation period can affect how much follow-up is available for assessing an endpoint over time. The registry record does not report the primary endpoint value, the number meeting the definition, or the timing of any observed cases. Therefore, the endpoint’s magnitude and precision cannot be assessed from the posted results.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry identifies a single-group design. In general, a single-group study describes outcomes in participants who receive the intervention, without a separate concurrent control group. It can report what occurred in the study population, but does not by itself show how outcomes would have differed under another treatment or no intervention. This distinction matters for the primary endpoint: a percentage of patients meeting the B-cell aplasia definition would be a description of the observed group, not a randomized treatment contrast.

What does the primary endpoint measure?

The endpoint is defined by a threshold in peripheral blood: absolute B lymphocyte count <50/μL. A threshold-based endpoint turns a laboratory observation into a classification, such as meeting or not meeting the definition at a post-reinfusion visit. The endpoint description specifies post-reinfusion follow-up up to 9 months and excludes Day 1, which is after lymphodepleting chemotherapy and before reinfusion. This timing definition is part of the outcome, not a statistical adjustment.

Although the endpoint title refers to a percentage, the registry describes the measure as a count of participants. A percentage ordinarily requires both a numerator and a denominator: the number meeting the criterion and the number included in the relevant analysis. The registry does not report those endpoint results or the full analysis set size. It is therefore not possible to recover the percentage or judge how many observations contributed.

How should uncertainty be understood?

In general, a confidence interval expresses the range of estimates compatible with the data under a specified method. It communicates uncertainty around an estimate; it is not a guarantee that the true value lies within the interval. For a binary outcome such as meeting a threshold, the observed proportion and its interval depend on the count of participants meeting the definition and the denominator analyzed. Neither an interval nor the required endpoint counts are reported in the registry record.

Small datasets generally provide limited information and can produce imprecise estimates. A single observation can have a substantial influence when the dataset is small. This is a general statistical point, not a calculation of precision for this trial. The record lists enrollment of 5, but that does not supply the endpoint denominator or permit a confidence interval to be calculated.

What does the record say about analysis?

The registry lists no analysis entries. It does not report a statistical model, hypothesis test, adjustment method, or confidence-interval method for the primary endpoint. The analysis plan, including any prespecified handling of incomplete observations, is not reported in the registry record. No method should be inferred from the endpoint title or study phase.

In general, an analysis plan can specify which participants are included, how an endpoint is classified, and how missing or incomplete observations are handled. These choices affect the interpretation of an estimate. Here, the record names the full analysis set as the primary endpoint population but does not state its size or describe how membership was determined. It also does not report whether observations were missing, how missingness was assessed, or how such observations were handled.

Why does the shortened follow-up matter?

The endpoint description says that the planned timeframe was 12 months and the actual timeframe was approximately 9 months because the trial ended early. In general, shorter follow-up can limit the opportunity to observe outcomes that may occur later. For a result framed as occurring within a follow-up window, the actual observation period and the completeness of follow-up are important context. The record does not provide participant-level follow-up or endpoint timing, so the effect of the shortened period on the observed result cannot be quantified.

The registry also lists a planning illustration based on an observed effect, with assumptions of a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. Such an illustration is a planning calculation, not observed power and not evidence that this single-group trial made a two-arm comparison. The stated assumptions do not describe the trial’s actual design. The record does not report the trial’s own sample-size justification or a statistical plan that connects the illustration to its objectives.

In general, planning calculations estimate the sample size needed under specified assumptions about an effect and analysis. Their outputs depend on those assumptions and are not a summary of the information actually observed. A planning estimate cannot substitute for the trial’s endpoint counts, uncertainty interval, or analysis results. The registry record does not provide the primary endpoint estimate needed to interpret any illustration as a scale for this trial’s observed result.

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("Tisagenlecleucel")
n      <- c(5)
events <- c(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  Tisagenlecleucel  5  2  40.0  5.3  85.3  11.8  76.9  11.8  77.7

11. Multiplicity, Missing Data and Analysis Populations

The registry names a primary endpoint and lists secondary outcomes concerning complete response or complete response with incomplete blood count recovery, participants with an event, and overall survival. It also reports four outcome measures overall. The registry record does not provide results for those outcomes or explain how the primary and secondary outcomes were ordered for statistical testing.

When a study examines multiple outcomes, the chance of obtaining at least one apparently notable result can increase if each is tested separately. In general, multiplicity procedures can control or describe this issue by specifying how tests are interpreted or adjusted. The registry record does not report whether any multiplicity procedure was planned or used. No adjustment should be assumed.

The record lists no analysis entries and does not report p-values or confidence intervals for the primary or secondary outcomes. It also does not report whether interim analyses were planned or conducted. These details are not reported in the registry record, so the statistical status of any outcome cannot be reconstructed from the listed endpoint names alone.

The primary endpoint population is identified as the full analysis set, but the record does not give its size or define inclusion in that set. It does not describe missing-data patterns, exclusions, or methods for handling participants without complete follow-up. In general, missing outcome data can affect both the denominator and the interpretation of an estimate, particularly when follow-up is shortened. The record does not establish whether missingness occurred or how it was handled.

The endpoint description notes that follow-up was approximately 9 months rather than the planned 12 months because of early termination. It does not state whether every participant had the same observation window or whether incomplete follow-up affected endpoint classification. Consequently, neither multiplicity nor missing-data handling can be evaluated from the registry record.

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: pyrexia (20.0%), cytokine release syndrome (20.0%), headache (20.0%), paraesthesia (20.0%).

The registry reports safety tallies for the tisagenlecleucel group. For serious adverse events, 5 were listed as at risk and 3 as affected. For other adverse events, 5 were listed as at risk and 4 as affected. The registry lists 0 deaths. These are the recorded counts; they do not provide a comparison with another group.

The listed serious adverse-event terms are pyrexia, cytokine release syndrome, headache, and paraesthesia, each reported as 20.0%. The registry record does not provide further detail in these entries about event timing, duration, severity beyond the serious classification, or attribution. The terms and percentages should be read as the registry’s reported safety information, not as a complete narrative of each participant’s experience.

In general, safety counts describe events recorded under the definitions and observation procedures used by a study. They do not establish that an event was caused by the intervention. With no control group, the tallies cannot show whether event occurrence differed from what would have been observed under another treatment. The registry does not report comparative safety estimates or uncertainty intervals for these counts.

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

The record establishes that a Phase II, open-label, multi-center, single-group study was conducted to investigate tisagenlecleucel reinfusion after B-cell recovery in pediatric and young adult patients with acute lymphoblastic leukemia. It specifies a primary endpoint based on B-cell aplasia, defined by a peripheral blood absolute B lymphocyte count <50/μL, and notes that follow-up was approximately 9 months rather than the planned 12 months because of early termination.

The record does not report the primary endpoint result. It therefore cannot show how many participants met the endpoint, what percentage met it, or how precise an estimate would be. The absence of an outcome result should not be interpreted as evidence that the endpoint was or was not achieved. The endpoint is simply not reported in the registry record.

The registry’s safety entries provide descriptive counts and selected serious adverse-event terms. They do not establish comparative safety, and the single-group design offers no randomized comparison. Likewise, enrollment and study status do not demonstrate an efficacy result or explain the reason for termination.

In general, trial results are best interpreted with the outcome estimate, the analysis population, and a measure of uncertainty, alongside information about follow-up and missing data. Those details are not reported for the primary endpoint. The record also does not provide a statistical analysis result that could support a claim about statistical significance. A planning illustration, if considered, would address hypothetical sample-size requirements under stated assumptions, not observed treatment benefit or observed power.

The appropriate conclusion is limited: the registry describes the study question and design, reports shortened follow-up and selected safety information, but does not report the primary efficacy result. It cannot support a quantitative conclusion about the primary endpoint or a comparison with another treatment.

14. Why This Trial Matters Statistically

This trial is statistically notable because its design and reporting illustrate the difference between a clearly defined outcome and an available outcome result. The registry specifies a biological threshold for B-cell aplasia and a post-reinfusion follow-up window. Those details define what the endpoint would measure. However, the endpoint result itself is not reported, so the definition alone cannot establish what happened in the study.

The single-group, open-label design also shapes what can be learned. In general, a single-group study can describe outcomes among participants who receive an intervention, but it lacks a concurrent comparator for estimating a between-group difference. The registry does not report an adjusted or unadjusted comparative effect. Readers should therefore distinguish the study’s clinical question from a comparative treatment-effect question.

The registry lists enrollment of 5 and explains that the actual endpoint timeframe was approximately 9 months rather than the planned 12 months because the trial ended early. These details make the analysis population, endpoint denominator, and completeness of follow-up particularly important. Yet the record does not report the primary endpoint counts, analysis-set size, or participant-level follow-up. Without them, neither the estimate nor its precision can be evaluated.

The record also shows why planning calculations and observed results serve different purposes. A sample-size planning illustration uses assumptions to explore what a future design might require; it is not observed power and cannot replace an outcome estimate. The stated planning assumptions describe a two-arm illustration, whereas the trial itself is listed as single group. Keeping those roles separate prevents a planning scenario from being mistaken for evidence generated by this trial.

Overall, the statistical importance lies in the limits of interpretation: a defined endpoint, a small listed enrollment, shortened follow-up, and selected safety counts do not substitute for the missing primary result and its uncertainty.

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 primary endpoint result is not reported in the registry record. There is no endpoint count, percentage, or uncertainty interval to assess. The primary analysis population is named as the full analysis set, but its size is not stated, and the registry does not give the endpoint-specific denominator.

The trial was terminated, and the endpoint description says actual follow-up was approximately 9 months rather than the planned 12 months. The registry does not report the reason for termination beyond linking it to the shortened timeframe, nor does it provide participant-level follow-up, endpoint timing, or information about incomplete observations.

The single-group, open-label design has no separate control group. The record does not provide a comparative estimate, so outcomes cannot be interpreted as a randomized contrast. Allocation is listed as not applicable and masking as none.

The registry provides no analysis entries. It does not report the statistical analysis plan, outcome analysis methods, multiplicity procedures, interim analyses, missing-data methods, or a sample-size justification for the trial. These features are not reported in the registry record and should not be inferred.

Safety reporting is also limited: the record includes selected counts and serious adverse-event terms, but does not provide detailed event narratives, timing, attribution, or comparative estimates. The enrollment entry should not be assumed to equal the analysis population for every outcome.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Study of Efficacy and Safety of Reinfusion of Tisagenlecleucel in Pediatric and Young Adult Patients With Acute Lymphoblastic Leukemia (ALL) — NCT04225676.
• Registry record last updated 2023-01-30; status last verified 2023-01.
• Results first posted 2022-07-15.
• 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

NCT04225676 is a terminated Phase II, open-label, multi-center, single-group study of tisagenlecleucel reinfusion in pediatric and adolescent young adult patients with acute lymphoblastic leukemia experiencing B-cell recovery after prior tisagenlecleucel treatment. The registry lists enrollment of 5, a start date of 2020-10-19, and primary completion on 2021-10-19.

The primary endpoint was the percentage of patients establishing B-cell aplasia after reinfusion, using a peripheral blood absolute B lymphocyte count <50/μL. The endpoint description states that follow-up was approximately 9 months rather than the planned 12 months because the trial ended early. The primary endpoint result and analysis details are not reported in the registry record.

The registry lists selected adverse-event counts, serious adverse-event terms, and 0 deaths. There is no separate control group, and no statistical analysis entries are listed. The record therefore describes the trial design and selected safety information but does not permit a quantitative assessment of the primary endpoint or a comparative treatment effect.