Evaluation of CD19-Specific CAR Engineered Autologous T-Cells for Treatment of Relapsed/Refractory CD19+ Acute Lymphoblastic Leukemia: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Evaluation of CD19-Specific CAR Engineered Autologous T-Cells for Treatment of Relapsed/Refractory CD19+ Acute Lymphoblastic Leukemia (NCT03573700), a na phase 1, phase 2 study. The primary outcome is Maximum Tolerated Dose and Dose-limiting Toxicities.

2. Clinical Question

3. Trial Design

The registry describes SJCAR19 as a Phase I/II study of CD19-specific CAR engineered autologous T cells in pediatric and young adult patients ≤ 21 years of age with relapsed or refractory CD19+ acute lymphoblastic leukemia. The listed conditions are acute lymphoblastic leukemia in relapse and acute lymphoblastic leukemia that is refractory. St. Jude Children's Research Hospital is the sponsor.

The study is classified as single-group. Allocation is recorded as NA and masking as NONE, so the design does not provide a randomized, masked comparison with a separate control group. The safety results are organized by Dose Level 1 and Dose Level 2, but the registry does not describe those groups as like-for-like comparison arms. A difference between their reported counts would not, on its own, establish a causal dose effect.

The intervention list includes cyclophosphamide, fludarabine, mesna, CliniMACS, and the SJCAR19 biological product. The arm description says participants receive lymphodepleting chemotherapy unless the principal investigator determines it is not necessary, followed by a single infusion of the patient-derived cellular product. The description of the chemotherapy is incomplete in the registry record, so additional regimen details are not reported in the registry record.

Enrollment is listed as 24. The recorded study start is 2018-07-24, and the primary completion date is 2023-07-01. The current status is active, not recruiting. These design and status details describe the registry entry; they do not establish that all planned analyses have been posted or that the study has reached a final interpretation.

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

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 Maximum Tolerated Dose and Dose-limiting Toxicities, measured over 4 weeks post-SJCAR19 infusion.

The primary endpoint is the proportion of participants with dose-limiting toxicities (DLTs), measured over 4 weeks post-SJCAR19 infusion. The registry specifies participants as the unit and describes the outcome as a count of participants. A proportion expresses how many participants in the relevant group experienced the defined event relative to the group assessed.

In the Phase I portion, this endpoint is used alongside safety characterization to inform the objective of determining the maximum tolerated dose. DLTs are relevant to that objective because the dose decision concerns treatment-limiting toxicity, rather than simply whether any adverse event occurred. The registry record does not provide the operational definition of a DLT, the rules for attributing an event to treatment, or the method used to determine the maximum tolerated dose. Those details are not reported in the registry record.

The posted adverse-event counts should not be treated as the primary endpoint result. Serious adverse events and DLTs are not interchangeable categories: the registry does not say that every serious event qualifies as a DLT, or that every DLT must be classified as serious. The number of participants with DLTs and the corresponding primary endpoint analysis are not reported in the registry record. Accordingly, the endpoint's intended measurement can be described, but its observed result cannot be interpreted from the posted information.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

Statistical methods help distinguish the quantity a study intends to measure from what its posted results can establish. In this study, the primary outcome is binary at the participant level: a participant is counted as having a DLT or not having a DLT during the specified follow-up window. The registry describes the result as the proportion of participants with DLTs. A proportion is a descriptive summary of event occurrence in the group assessed; it is not, by itself, a causal comparison.

What does a confidence interval add?

General statistical explanation: an estimate from a study is subject to sampling uncertainty. A confidence interval communicates a range of values compatible with the observed data under a specified statistical procedure. It helps readers judge precision: a narrower interval conveys more precision than a wider interval. An interval does not correct for bias, missing observations, or an unsuitable design, and it does not establish that a treatment caused an outcome.

No confidence interval for the DLT proportion is reported in the registry record. The record also does not provide the DLT event count needed to describe the observed primary outcome. Consequently, neither the point estimate nor its precision can be assessed from the posted primary endpoint information.

Why does the design matter?

General statistical explanation: a single-group study can describe outcomes among participants receiving the study intervention. It cannot isolate an intervention effect by comparing outcomes with a concurrent control group when no such group is present. A comparison between groups formed by dose level may be useful descriptively, but treatment assignment, participant characteristics, and other design details matter when interpreting differences. The registry does not describe random allocation between dose levels, and allocation is recorded as NA.

For this reason, dose-level safety counts should be read as descriptions of the recorded groups, not as estimates from a randomized dose comparison. The record does not report an adjusted analysis or a method for controlling differences between groups. Any such method is not reported in the registry record.

How should counts and percentages be read?

General statistical explanation: counts show how many participants are recorded with an event; proportions put that count in context of the participants assessed. The denominator and the event definition both matter. In particular, a serious adverse event, a DLT, a death, and an efficacy outcome are separate categories unless the registry explicitly defines them as equivalent. This record does not equate them.

The serious-event counts are reported by dose level and overall. The listed serious adverse-event terms also have percentages, but the record does not specify whether these terms can overlap within participants or provide an event-level accounting in the results described. They should therefore be read as term-specific summaries, not added together or treated as mutually exclusive categories. No new total or derived percentage is needed to interpret them.

What can planning calculations establish?

General statistical explanation: sample-size planning calculations describe how a future study might be designed under stated assumptions. They are not observed results, and they do not show the probability that a completed study has detected a real effect. The registry's planning description refers to a two-sided significance level of 0.05, equal allocation between two arms, a normal approximation, and an effect defined as a stated fraction of the observed effect. It also distinguishes participants per arm for ordinary outcomes from a total number of events for time-to-event outcomes.

Those planning assumptions are not the same as the design of this single-group study. The registry record does not include values for a planning illustration in the results described, and no observed effect estimate is posted for interpreting such an illustration. Any planning calculation would therefore be hypothetical, not an observed power result or a result of the SJCAR19 trial.

The registry lists 0 analyses. It does not report which statistical test or interval method was used for the primary endpoint, how the maximum tolerated dose was selected, or whether any model was fitted. Those methods are not reported in the registry record. Statistical methods should not be inferred from a study's phase or its stated objectives.

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("Dose Escalation Level 1 (N = 6)", "Dose Escalation Level 2 (MTD) (N=18)")
n      <- c(6, 18)
events <- c(1, 1)
for (i in seq_along(n)) {
  ci <- binom.test(events[i], n[i])$conf.int          # Clopper-Pearson exact interval
  cr <- qbeta(c(0.025, 0.975), 1 + events[i], 1 + n[i] - events[i])   # Bayesian, uniform Beta(1,1) prior
  wi <- (function(x, n) { p <- x / n; z <- qnorm(0.975); d <- 1 + z^2 / n
    c((p + z^2 / (2 * n) - z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d, (p + z^2 / (2 * n) + z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d) })(events[i], n[i])
  cat(sprintf("ARM|%s|%d|%d|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f\n", arm[i], n[i], events[i], 100 * events[i] / n[i],
              100 * ci[1], 100 * ci[2], 100 * wi[1], 100 * wi[2], 100 * cr[1], 100 * cr[2]))
}

ARM  Dose Escalation Level 1 (N = 6)  6  1  16.7  0.4  64.1  3.0  56.4  3.7  57.9
ARM  Dose Escalation Level 2 (MTD) (N=18)  18  1  5.6  0.1  27.3  1.0  25.8  1.3  26.0

11. Multiplicity, Missing Data and Analysis Populations

The registry lists 2 outcome measures and 0 analyses. It does not report an analysis plan describing which outcomes were designated for formal hypothesis testing, how multiple outcomes or comparisons would be handled, or whether any adjustment for multiplicity was planned. Multiplicity refers generally to the interpretive problem that arises when several hypotheses are examined; the registry entry does not state how that issue was addressed.

Handling of missing outcome data is not reported in the registry record. The record does not state how participants without a complete DLT assessment were handled, whether follow-up could be incomplete, or what assumptions would be used for missing observations. The primary endpoint has a defined follow-up period of 4 weeks post-SJCAR19 infusion, but that alone does not specify a missing-data method.

Analysis populations are also not reported in the registry record. There is no description of whether the primary analysis included all treated participants, only participants meeting specified assessment criteria, or another defined group. The registry's enrollment entry and the adverse-event counts do not establish which population would be used for each outcome analysis.

These omissions limit reproducibility and interpretation. Without a statistical plan, population definitions, and missing-data procedures, readers cannot determine whether an eventual endpoint analysis followed prespecified methods or how sensitive it might be to alternative assumptions. No analysis result is posted for the primary endpoint, so these issues cannot be resolved by examining an outcome estimate.

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 (16.7%), immune system disorders - other (16.7%), acute kidney injury (16.7%), cytokine release syndrome (11.1%), fever (11.1%).

The safety entry reports serious adverse events for Dose Level 1, Dose Level 2, and overall. The affected-participant counts are 2, 7, and 9, respectively. It also records other adverse events in 6, 18, and 24 participants, respectively. These are counts as recorded in the registry; they do not identify whether an individual experienced multiple events.

The listed serious adverse-event terms and percentages are febrile neutropenia, immune system disorders - Other, and acute kidney injury at 16.7% each; cytokine release syndrome and fever at 11.1% each; and hepatitis viral at 5.6%. The registry does not describe the event-term denominator or whether the terms overlap, so the percentages should not be summed or interpreted as separate participant groups.

Deaths are recorded as 3 at Dose Level 1, 9 at Dose Level 2, and 12 overall. Cause, timing, and relationship to study treatment are not reported in the registry record. The counts do not establish that the deaths were caused by SJCAR19. Serious adverse events, deaths, and DLTs are distinct measures; the registry does not report the DLT endpoint result alongside these safety figures.

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

The posted information establishes the study's purpose and design, and gives descriptive safety counts. It does not provide an analyzed result for the primary endpoint. The Phase I objective is to determine the maximum tolerated dose and characterize safety and DLTs, but the registry record does not report how many participants experienced a DLT or an estimate of the DLT proportion. The central dose-finding result therefore cannot be read from the posted analyses.

The adverse-event counts show that serious and other adverse events were recorded among participants in both listed dose-level groups. They do not by themselves compare the risks that would have occurred under another treatment or no treatment. The groups are not described as randomized, there is no separate control group, and the record does not provide adjusted comparisons. Counts also do not convey the timing, duration, severity distribution, or clinical context of each event.

The listed deaths are an important part of the reported safety information, but the record does not provide their causes or relationships to study treatment. They cannot be attributed to the intervention on the basis of these counts alone. Likewise, the serious-event terms and percentages should not be treated as the primary DLT result because the record does not define them as equivalent.

The brief summary states that the study seeks to assess whether SJCAR19 is effective, but the results described do not include an efficacy analysis. The record lists 0 analyses. It therefore does not establish an efficacy estimate, its precision, or a comparison with another treatment. This is a statement about what is reported in the registry, not a conclusion about outcomes that may be available elsewhere.

Overall, the entry supports a description of a single-group Phase I/II study and its recorded safety summaries. It does not support a quantified conclusion about the primary endpoint, a causal claim, or a treatment-effect estimate.

14. Why This Trial Matters Statistically

This trial raises a statistical question common to early-phase clinical research: how to describe safety while evaluating dose in a study without a randomized control group. The registry identifies the Phase I objectives as determining the maximum tolerated dose and characterizing safety and DLTs. Those aims require clear outcome definitions and transparent reporting of the assessed population, follow-up, and dose-decision method. The registry record does not report several of those analysis details.

The study's single-group design makes the distinction between description and comparison especially important. Counts by dose level can summarize what was recorded in each group, but they do not alone show that dose level caused a difference. Participant selection, treatment details, and the way dose levels were assigned can affect interpretation. Random allocation is recorded as NA, and no separate control group is described.

Precision matters as well as the event count. A primary endpoint estimate would be more informative when accompanied by uncertainty and a clearly stated denominator. Neither an estimate nor a confidence interval for the DLT proportion is reported in the registry record. The absence of posted analyses means that the stated primary objective cannot be evaluated from the registry results described.

The safety entry also illustrates why event categories should remain distinct. Serious adverse events, other adverse events, deaths, and DLTs answer different questions unless the record supplies definitions connecting them. The reported counts are useful descriptive information, but cannot replace endpoint-specific analysis or attribution details.

For statistical readers, the central issue is not whether the registry states an important research question, but whether the posted results permit that question to be assessed with appropriate precision and context. In this record, the study design and safety counts are described, while the primary endpoint analysis and several supporting methods are not reported in the registry record.

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 main limitation for interpreting the primary objective is that the registry lists 0 analyses and does not report the DLT count, proportion, or uncertainty. The endpoint is specified as the proportion of participants with DLTs during 4 weeks post-SJCAR19 infusion, but the DLT definition and dose-decision rules are not reported in the registry record.

The design is single-group, with allocation recorded as NA and masking as NONE. There is no separate control group described. The dose-level safety summaries are therefore descriptive and cannot be treated as randomized comparisons. The registry does not report adjustment for differences between dose-level groups or other statistical analyses that might address them.

The adverse-event entry does not explain the cause, timing, or treatment relationship of the recorded deaths. It also does not provide sufficient event-level detail to determine whether listed serious adverse-event terms overlap within participants. The relationship between these categories and the primary DLT endpoint is not reported in the registry record.

Other limitations include the absence of reported missing-data procedures, analysis-population definitions, and a statistical plan addressing multiplicity. The arm description notes that lymphodepleting chemotherapy may be omitted when the principal investigator determines it is not necessary, but the registry does not provide further details about how that decision affected analysis. The chemotherapy description itself is incomplete. These gaps limit assessment of reproducibility and the context needed to interpret safety summaries.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Evaluation of CD19-Specific CAR Engineered Autologous T-Cells for Treatment of Relapsed/Refractory CD19+ Acute Lymphoblastic Leukemia — NCT03573700.
• Registry record last updated 2026-08-11; status last verified 2026-07.
• Results first posted 2024-10-30.
• 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

The registry describes a Phase I/II, single-group study of SJCAR19 in pediatric and young adult patients ≤ 21 years of age with relapsed or refractory CD19+ acute lymphoblastic leukemia. Enrollment is listed as 24; the study is sponsored by St. Jude Children's Research Hospital and is marked active, not recruiting. The primary endpoint concerns the proportion of participants with dose-limiting toxicities during 4 weeks post-SJCAR19 infusion.

Safety results are reported for Dose Level 1, Dose Level 2, and overall, including serious adverse events, other adverse events, deaths, and selected serious-event terms. The registry lists 2 outcome measures and 0 analyses. It does not report the primary endpoint result, a statistical analysis of efficacy, or several methods needed to interpret the findings, including missing-data procedures and analysis-population definitions.