This page provides an independent statistical analysis and educational interpretation of publicly reported results. ClinicalTrials.gov provides the official trial registry record. Numerical trial results on this page are restricted to the results posted in the ClinicalTrials.gov record; calculations added by Clinical Biostats are labelled as such.
1. Trial at a Glance
This page covers the registry results for EGFRvIII CAR T Cells for Newly-Diagnosed WHO Grade IV Malignant Glioma (NCT02664363), a na phase 1 study. The primary outcome is Maximally Tolerated Dose.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT02664363 |
| Phase | Phase 1 |
| Condition | Glioblastoma, Gliosarcoma |
| Allocation | Not applicable (single group) |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 3 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Daniel Landi |
| Results posted | Yes |
2. Clinical Question
Population
Patients with newly diagnosed WHO grade IV malignant glioma who received EGFRvIII CAR T cells. The registry lists glioblastoma and gliosarcoma as conditions and defines the primary-outcome population as all patients who received the cells.
Intervention
A single intravenous infusion of EGFRvIII CAR T cells, with dose escalation across four planned dose levels. The study description places infusion after surgery, standard radiation therapy with temozolomide, and up to 3 cycles of dose-intensified temozolomide.
Comparator
There was no separate control group. This was a single-group study, so its primary objective was not a comparison of the CAR T cells with another treatment.
Primary question
What was the maximally tolerated dose of one intravenous infusion, using the study's dose-limiting toxicity rule? The registry defines the MTD as the highest dose level at which at most 1 of 3-6 patients experienced a dose-limiting toxicity during the 4 weeks after infusion. The registry record does not report the MTD result.
3. Trial Design
This was a phase 1, single-group, open-label dose-escalation study of EGFRvIII CAR T cells for patients with newly diagnosed WHO grade IV malignant glioma. The registry lists an enrollment of 3 and states that enrollment terminated early because grant funding ended. The listed start date is 2017-02-01 and the primary completion date is 2018-09-25.
The treatment sequence described in the registry began after surgery to remove the brain tumor. Eligible participants underwent leukapheresis to collect cells for generating the study treatment, then began standard radiation therapy with temozolomide. After radiation and temozolomide, participants returned for brain imaging; if their disease was stable, they began post-radiation temozolomide cycles. The description says participants received up to 3 cycles of dose-intensified temozolomide before the CAR T-cell infusion. After a one-month delay between cycles, they resumed post-radiation temozolomide and were monitored with blood work and brain imaging as part of standard care.
The planned dose-escalation approach was described as a 3+3 design. Four dose levels were to be considered: 4.5 x 10\^6/kg, 1.5 x 10\^7/kg, 4.5 x 10\^7/kg, and 1.5 x 10\^8/kg. Cohorts of 3-6 subjects were to be accrued at each dose level, starting at the lowest level. The MTD was defined by dose-limiting toxicity during the 4 weeks after infusion.
An expanded cohort of 12 subjects was originally planned after the MTD was reached. Its stated aims were to estimate the probability of unacceptable toxicity more precisely and to track CAR T cells using 111 Indium labeling, with CT planned on days 1, 2, and 3 after infusion to assess intracerebral localization. The record does not report whether the MTD was reached or whether any expanded-cohort activities occurred.
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
| Stage | EGFRvIII CAR T Cells |
|---|---|
| STARTED | 3 |
| COMPLETED | 3 |
| NOT COMPLETED | 0 |
Analysis population for the primary outcome, as defined in the registry: All patients who received EGFRvIII CAR T cells
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.
| Characteristic | Unit | EGFRvIII CAR T Cells |
|---|---|---|
| Participants analysed | 3 | |
| Age, Continuous | years | 58.33 (SD 3.79) |
| Sex: Female, Male: Female | Participants | 1 |
| Sex: Female, Male: Male | Participants | 2 |
| Ethnicity (NIH/OMB): Hispanic or Latino | Participants | 1 |
| Ethnicity (NIH/OMB): Not Hispanic or Latino | Participants | 2 |
| Ethnicity (NIH/OMB): Unknown or Not Reported | Participants | 0 |
| Race (NIH/OMB): American Indian or Alaska Native | Participants | 0 |
| Race (NIH/OMB): Asian | Participants | 0 |
| Race (NIH/OMB): Native Hawaiian or Other Pacific Islander | Participants | 0 |
| Race (NIH/OMB): Black or African American | Participants | 0 |
| Race (NIH/OMB): White | Participants | 3 |
| Race (NIH/OMB): More than one race | Participants | 0 |
| Race (NIH/OMB): Unknown or Not Reported | Participants | 0 |
6. Primary Endpoint
The registry lists the primary outcome as Maximally Tolerated Dose, measured over 12-18 months.
| Element | Registry entry |
|---|---|
| Result type | Number |
| Measure of spread | not applicable |
| Unit | Cells/kg |
| Endpoint classification | not reduced to a single comparison |
The primary endpoint is the maximally tolerated dose (MTD), expressed as cells per kilogram. It concerns the tolerability of a single intravenous infusion of EGFRvIII CAR T cells in patients with newly diagnosed WHO grade IV malignant glioma. The registry defines the MTD as the highest of the planned dose levels at which at most 1 of 3-6 patients experiences a dose-limiting toxicity during the 4 weeks after infusion.
The MTD is used in early dose-escalation research to identify a dose level that meets a prespecified toxicity rule. It is not a measure of tumor response or survival. In general, a toxicity-based endpoint describes what happened under the study's dose and observation conditions; it does not by itself establish how a treatment compares with another option.
The primary outcome description gives a timeframe of 12-18 months, while its operational definition specifies that dose-limiting toxicity is assessed during the 4 weeks after infusion. These are distinct registry entries; the record does not explain how they relate. It also does not report a numeric MTD, dose-level enrollment, dose-limiting toxicity counts by dose, or the result of the primary endpoint. Consequently, the stated endpoint can be described, but its observed value cannot be established from the registry record.
The registry lists a secondary outcome concerning the number of patients who experienced a dose-limiting toxicity. A numerical result for that outcome is not reported in the registry record.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry describes a dose-escalation study designed to determine an MTD, but it does not post the primary endpoint result. It therefore does not establish which dose level, if any, met the protocol's toxicity criterion. The planned dose levels and decision rule describe the study's intended method; they are not evidence that every level was reached or that a particular level was selected.
The record lists enrollment of 3 and says the study terminated early because grant funding ended. That information places the posted results in context: the observed enrollment was limited, and the registry does not describe completion of the planned dose-escalation process. It also does not report the number treated at each dose level, the dose-limiting toxicity evaluations, or an analysis of the primary endpoint. Without those details, it is not possible to assess how much information the study generated about tolerability at each planned dose.
The registry's adverse-event figures are separate from a reported MTD determination. It lists 3 participants at risk for the adverse-event group, 1 with a serious adverse event, 3 with other adverse events, and 3 deaths. Generalized muscle weakness and confusion are listed among the serious adverse-event terms, each with a reported percentage of 33.3%. These are descriptive safety entries. The record does not state the causes of the deaths or whether the events were attributed to the CAR T cells, the underlying disease, or other care.
There is no randomized comparator, and the design is single-group. Thus, even if an endpoint result were posted, this design would not estimate a treatment difference against a concurrent control group. The primary question is about dose selection under the stated toxicity rule, not comparative efficacy.
The registry reports no statistical analyses. It does not report an estimate with a confidence interval for the MTD, a precision measure, or an inferential test. A confidence interval, in general, expresses uncertainty around an estimated quantity; no such interval for the primary endpoint is reported in this record. The planned expanded cohort was intended to obtain a more precise estimate of unacceptable toxicity, but the record does not report that cohort's results. Overall, the posted information describes the design and some safety counts, while leaving the primary dose-finding result and its uncertainty unreported.
9. Statistical Methods Explained
The design is described as a 3+3 phase 1 dose-escalation study. General explanation: a dose-escalation design studies successive dose levels and uses observed toxicities to guide whether escalation, continuation, or stopping is appropriate. The registry states that cohorts of 3-6 subjects were planned at each dose level, beginning at the lowest level. It defines the MTD as the highest dose level at which at most 1 of 3-6 patients experiences a dose-limiting toxicity during the 4 weeks after infusion. The record does not report the actual dose assignments, cohort decisions, or MTD determination.
What does the MTD rule measure?
The rule combines a dose level with a defined toxicity window and a threshold for the number of affected participants. It is a decision rule for selecting a dose in the study, not a direct measure of clinical benefit. A participant's toxicity status, how dose-limiting toxicity was defined in practice, and the evaluability rules would be relevant to applying the rule. Details of those operational rules beyond the registry's stated definition are not reported in the registry record.
What can a single-group design establish?
General explanation: a single-group study can describe outcomes among participants who receive the intervention, but it does not provide a concurrent control group for estimating a between-group treatment effect. Here, the registry identifies no comparator and lists the design as single group. The primary objective is dose finding, rather than a randomized comparison. Differences that might be observed in another setting cannot be inferred from this design alone.
How should the sample-size information be understood?
The planned cohorts of 3-6 subjects at each dose level are part of the described dose-escalation approach. The registry also describes an expanded cohort of 12 subjects as originally planned after reaching the MTD, with the aim of obtaining a more precise estimate of unacceptable toxicity and tracking labeled cells. These are planned design features, not observed enrollment or outcome results. The registry lists overall enrollment of 3 and early termination due to the end of grant funding; it does not say that the planned expanded cohort was enrolled.
General explanation: planning calculations based on an assumed effect or precision are not the same as observed evidence. A post hoc sample-size illustration cannot show that the study had a specified probability of detecting an effect, and it cannot replace reporting the outcomes and their uncertainty. The record does not report a sample-size justification, the assumptions behind the original design, or a statistical power calculation.
What does absence of a reported analysis imply?
The registry record reports no statistical analyses. That means no inferential analysis of the primary endpoint is posted in this record; it does not establish what analyses may have been undertaken outside the record. There is no reported estimate of the MTD, confidence interval, or statistical test. General explanation: uncertainty should be evaluated using the analysis and data appropriate to the endpoint, and a numerical point estimate alone would not convey its precision. Since the endpoint result is not reported, its precision cannot be assessed.
The primary outcome population is defined as all patients who received EGFRvIII CAR T cells. The record does not report the number included in an analysis of that endpoint or how missing observations, unevaluable participants, or deviations from the planned treatment sequence were handled. The enrollment count should not be treated as proof that every enrolled participant received the infusion or contributed to the primary endpoint.
How do the outcome timeframes fit together?
The primary outcome entry gives a timeframe of 12-18 months, whereas the endpoint definition places the dose-limiting toxicity assessment within the 4 weeks after infusion. The registry does not explain the relationship between these entries. The study description also refers to ongoing blood work and brain imaging during post-radiation temozolomide. Those monitoring activities do not, by themselves, supply a posted result for the MTD endpoint.
In general, over-dispersion matters when outcome variability exceeds what a statistical model assumes; ignoring it can make uncertainty appear smaller than it is. The registry record does not report a model for the primary endpoint, a dispersion estimate, or an analysis that would permit assessing over-dispersion. No additional model-based interpretation is warranted from the posted information.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists a primary MTD endpoint and a secondary outcome concerning the number of patients who experienced dose-limiting toxicity. It does not report statistical analyses or a plan for handling multiple outcomes. A multiplicity adjustment or other strategy for controlling the interpretation of several statistical tests is not reported in the registry record. Since no analyses are posted, there are no reported test results to evaluate for multiplicity.
The primary endpoint population is specified as all patients who received EGFRvIII CAR T cells. The registry does not report the number of participants who received the infusion, the number included in the primary endpoint assessment, or whether the analysis followed another population definition. Overall enrollment is listed as 3, but enrollment alone does not establish the analysis population.
Rules for missing endpoint data, incomplete toxicity follow-up, unevaluable participants, and protocol deviations are not reported in the registry record. The description states that the dose-limiting toxicity window was the 4 weeks after infusion, but it does not say how incomplete observation during that window would be handled. There is also no reported imputation approach or sensitivity analysis.
These omissions limit assessment of how the planned dose-finding rule was applied and how robust any result might be to incomplete data. The record's early termination due to the end of grant funding is relevant context, but it does not reveal the reason for each participant's follow-up status or establish whether missing data occurred.
11. Safety Results
The registry reports serious adverse events as affected participants divided by participants at risk.
| Arm | Participants with serious adverse events | Participants at risk | Percentage |
|---|---|---|---|
| EGFRvIII CAR T Cells | 1 | 3 | 33.3% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| EGFRvIII CAR T Cells | 3 of 3 |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 5% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| EGFRvIII CAR T Cells | 3 of 3 |
Most frequent serious adverse event terms
| Event term | Organ system | EGFRvIII CAR T Cells |
|---|---|---|
| Generalized muscle weakness | Musculoskeletal and connective tissue disorders | 1 of 3 |
| Confusion | Psychiatric disorders | 1 of 3 |
Most frequent non-serious adverse event terms
| Event term | Organ system | EGFRvIII CAR T Cells |
|---|---|---|
| Hypertension | Vascular disorders | 3 of 3 |
| Gait disturbance | General disorders | 2 of 3 |
| Anemia | Blood and lymphatic system disorders | 1 of 3 |
| Eye disorders - Other, Specify: DOUBLE VISION, INTERMITTENT | Eye disorders | 1 of 3 |
| Vitreous hemorrhage | Eye disorders | 1 of 3 |
| Nausea | Gastrointestinal disorders | 1 of 3 |
| Vomiting | Gastrointestinal disorders | 1 of 3 |
| Edema limbs | General disorders | 1 of 3 |
| Infections and infestations - Other, Specify: FUNGUS FEET AND GROIN | Infections and infestations | 1 of 3 |
| Infections and infestations - Other, Specify: RING WORM | Infections and infestations | 1 of 3 |
Serious events with the highest arm-level rate: generalized muscle weakness (33.3%), confusion (33.3%).
The adverse-event record lists 3 participants at risk in the EGFRvIII CAR T Cells group. It reports 1 participant with a serious adverse event and 3 with other adverse events. The record also lists 3 deaths. Generalized muscle weakness and confusion are among the serious adverse-event terms, each reported at 33.3%.
These entries are counts and percentages in a small enrolled group, not estimates of risk that can be generalized reliably to other populations. The serious and other adverse-event categories are registry reporting categories; the record does not provide event-level details, timing, duration, severity grading, or a causal assessment for these terms. It also does not identify the causes of the deaths or state whether they were considered related to study treatment.
Counts of participants with an event do not necessarily describe the total number of events, because a participant may experience more than one event. The posted figures should therefore be read as descriptive safety information, not as a complete account of each participant's clinical course. The registry record does not report enough detail to attribute these events to the CAR T cells or distinguish their contribution from the disease and other treatments.
12. What the Result Does, and Does Not, Mean
The posted information establishes that the study was planned as a phase 1, single-group dose-escalation study and that the registry lists enrollment of 3. It also records early termination because grant funding ended. The study's primary objective was to determine the MTD of a single infusion of EGFRvIII CAR T cells under a stated dose-limiting toxicity rule.
The record does not report the primary MTD result, dose-level-specific toxicity counts, or statistical analyses. It therefore cannot establish which dose level met the rule, whether a dose level was selected, or how precisely any dose-finding conclusion was estimated. The adverse-event counts offer limited descriptive information, but do not identify event causes or treatment attribution.
Because the design has no control group, it does not estimate a comparative effect against another treatment. It also does not provide a basis for conclusions about comparative efficacy. The registry describes a treatment sequence that included surgery, radiation therapy, temozolomide, and CAR T-cell infusion; outcomes in this context could not be attributed to the CAR T cells alone from the posted information.
General explanation: a study's planned objective and its observed result are different kinds of information. A design can specify how a result would be determined, while the registry may not post enough outcome data to show what happened. Likewise, lack of a posted result is not evidence that a particular dose was safe or unsafe. The record supports a description of the planned dose-finding question and the reported safety counts, but not a treatment-effect conclusion or a definitive MTD determination.
13. Why This Trial Matters Statistically
This study illustrates why early-phase dose-finding questions need to be kept distinct from comparative treatment questions. The registry's primary objective was to identify an MTD using a toxicity rule across planned dose levels. That goal differs from estimating whether an intervention changes an outcome compared with a control group. Since this was a single-group study, its design did not include a concurrent comparator.
The record also shows the importance of reporting the pathway from design to result. A dose-escalation plan describes intended cohorts and a decision rule, but interpretation requires the number treated at each dose, the dose-limiting toxicity observations, and the resulting dose decision. Those primary endpoint results are not reported in the registry record. The planned expanded cohort was intended to improve precision for estimating unacceptable toxicity, but the record does not report its results.
Early termination due to the end of grant funding is important context for interpreting the listed enrollment and the unreported endpoint. It does not, by itself, indicate how participants fared or what the MTD would have been. Likewise, the safety counts should be interpreted descriptively and with attention to the lack of reported event attribution and detail.
For statistical readers, the central lesson is that a protocol-defined estimand or decision rule is not a substitute for the observed data and its uncertainty. When endpoint results, analysis populations, and missing-data handling are not reported, the strength and precision of a dose-finding conclusion cannot be evaluated. This distinction helps prevent a planned method from being mistaken for an observed finding.
14. 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 this study is that the registry record does not report the primary MTD result or the dose-limiting toxicity counts at the planned dose levels. It also does not provide the number of participants treated at each level, whether escalation reached all planned levels, or whether the MTD decision rule was applied to evaluable participants.
Overall enrollment is listed as 3, and the study terminated early because grant funding ended. The record does not explain the participant-level course, follow-up completeness, or whether the planned expanded cohort was initiated. Although an expanded cohort of 12 subjects was described as planned after reaching the MTD, its conduct and results are not reported.
The registry gives a primary-outcome timeframe of 12-18 months and describes dose-limiting toxicity assessment during the 4 weeks after infusion, without explaining the relation between those entries. Definitions and procedures beyond the stated MTD rule, including how incomplete assessments were handled, are not reported in the registry record. No statistical analyses, confidence intervals, or precision estimates are posted.
The single-group design has no comparator, so it cannot estimate a between-group treatment effect. The adverse-event entries are limited counts and selected terms; causes of death, event-level detail, and attribution to treatment are not reported. These limitations mean that the record supports description of the study plan and posted safety information, but not a firm conclusion about the selected dose, treatment effects, or causal safety profile.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: EGFRvIII CAR T Cells for Newly-Diagnosed WHO Grade IV Malignant Glioma — NCT02664363.
- Registry record last updated 2023-02-17; status last verified 2023-02.
- Results first posted 2020-07-24.
- 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.
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18. Record Summary
NCT02664363 is a phase 1, single-group study of EGFRvIII CAR T cells for newly diagnosed WHO grade IV malignant glioma. The planned objective was to determine the MTD of a single intravenous infusion using a 3+3 dose-escalation design and a dose-limiting toxicity window of 4 weeks after infusion. The registry lists four planned dose levels and an enrollment of 3.
The study is marked terminated; the description attributes early termination to the end of grant funding. The registry reports 1 participant with a serious adverse event, 3 with other adverse events, and 3 deaths in the adverse-event group. It does not report the primary MTD result, statistical analyses, or causes and treatment attribution for the adverse events or deaths. The planned expanded cohort and its results are not reported.