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 Study of CAR T-cell Therapy in Acute Myeloid Leukemia and Multiple Myeloma (NCT04097301), a na phase 1, phase 2 study. The primary outcome is Phase I: Maximum Tolerated Dose (MTD) and the Recommended Phase IIa Dose of MLM-CAR44.1 T-cells in AML and MM.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT04097301 |
| Phase | Phase 1, Phase 2 |
| Condition | Acute Myeloid Leukemia, Multiple Myeloma |
| Allocation | Not applicable (single group) |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 8 |
| Arms in the primary outcome | n/a |
| Lead sponsor | AGC Biologics S.p.A. |
| Results posted | Yes |
2. Clinical Question
Population
Patients with acute myeloid leukemia (AML) or multiple myeloma (MM) expressing CD44v6 were the intended population. The registry record lists an enrollment of 8, but the primary outcome states that data were not collected because the trial ended early.
Intervention
The intervention was a single intravenous infusion of autologous MLM-CAR44.1 T-cells. In Phase I, dose levels were 0.5 x 10E6/Kg, 1 x 10E6/Kg, or 2 x10E6/Kg according to the BOIN design. Phase IIa was intended to use the maximum tolerated dose. The treatment description also mentions lymphodepleting chemotherapy before infusion, but the regimen description is incomplete in the registry record.
Comparator
There was no control group. The record describes a single-group study, with allocation listed as NA and masking as none. The study therefore does not make a randomized, like-for-like comparison between the CAR T-cell treatment and another treatment or control.
Primary question
The Phase I primary question was whether a maximum tolerated dose (MTD) could be established and a dose recommended for Phase IIa, based on dose-limiting toxicities (DLTs) occurring after infusion. The timeframe was within 30 days following CAR T-cell infusion, assessed as day 0. The registry states that data were not collected because the trial ended early, so it does not report an answer to this dose-selection question.
3. Trial Design
This was a Phase I–IIa, first-in-human study of autologous CD44v6 CAR T-cells in AML and MM. The registry record identifies AGC Biologics S.p.A. as the sponsor. The recorded start date was 2019-08-27, the primary completion date was 2021-06-18, and the status is terminated. The record lists an enrollment of 8.
The design was single-group, with no masking and no allocation to a concurrent comparator. Phase I was intended to examine dose safety and establish the MTD and a recommended Phase IIa dose. The specified Phase I dose levels were 0.5 x 10E6/Kg, 1 x 10E6/Kg, and 2 x10E6/Kg, assigned according to the BOIN design. Phase IIa was intended to use the MTD. The registry record does not report the dose assignments actually received by participants.
The intervention was one intravenous infusion of MLM-CAR44.1 T-cells. The arm description mentions lymphodepleting chemotherapy before infusion, but the description is cut off and the complete regimen is not reported in the registry record. Outcomes listed beyond the Phase I dose-selection endpoint include disease response in AML and MM, circulating CAR T-cell levels, activation of a suicide gene, and overall survival in Phase IIa.
Because the study had no comparator, its planned questions concern safety, dose selection, and antitumor activity within treated participants rather than a controlled estimate of a treatment difference. The registry record does not report the reason for termination or whether all planned phases or outcomes were reached.
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: The recruited patient population, due to the early termination of the clinical study, was made up only of patients affected by multiple myeloma (MM), whereas AML patients were not enrolled. Eight patients, 6 males and 2 females were enrolled in 2 centers. Two patients received the investigational product (MLM-CAR44.1 T-cells), while 6 patients did not. Age ranged from 41 to 66 years, with a median of 56 years.
Overall Study
| Stage | MLM-CAR44.1 T-cells Infusion |
|---|---|
| STARTED | 8 |
| Treated Patients | 2 |
| COMPLETED | 1 |
| NOT COMPLETED | 7 |
Reasons for not completing this period:
| Reason | MLM-CAR44.1 T-cells Infusion |
|---|---|
| Death | 1 |
| Withdrawal by Subject | 1 |
| Screening Failure | 5 |
Analysis population for the primary outcome, as defined in the registry: Data were not collected due to early end of trial
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.
Population: Overall, 8 patients were enrolled in the study and underwent the screening phase to evaluate the compliance to the clinical inclusion / exclusion criteria as well as the CD44v6 expression by tumor cells (Table 10). Of the 8 enrolled patients, 2 were treated with MLM-CAR44.1 T-cell at the first dose level. Five patients were screening failures and 1 patient dropped-out before lymphocyte apheresis for fulminant disease progression.
| Characteristic | Unit | MLM-CAR44.1 T-cells Infusion |
|---|---|---|
| Participants analysed | 8 | |
| Age, Categorical: <=18 years | Participants | 0 |
| Age, Categorical: Between 18 and 65 years | Participants | 7 |
| Age, Categorical: >=65 years | Participants | 1 |
| Age, Continuous | years | 56 (41 to 66) |
| Sex: Female, Male: Female | Participants | 2 |
| Sex: Female, Male: Male | Participants | 6 |
| 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 | 8 |
| Race (NIH/OMB): More than one race | Participants | 0 |
| Race (NIH/OMB): Unknown or Not Reported | Participants | 0 |
| Region of Enrollment: Italy | participants | 5 |
| Region of Enrollment: Czechia | participants | 3 |
| Confirmed diagnosis of MM | Participants | 8 |
| Patients with relapse or refractory disease | Participants | 8 |
6. Primary Endpoint
The registry lists the primary outcome as Phase I: Maximum Tolerated Dose (MTD) and the Recommended Phase IIa Dose of MLM-CAR44.1 T-cells in AML and MM, measured over Within 30 days following CAR T-cell infusion, assessed as day 0.
| Element | Registry entry |
|---|---|
| Result type | N/A |
| Measure of spread | not applicable |
| Unit | not stated |
| Endpoint classification | not reduced to a single comparison |
The primary endpoint was the Phase I maximum tolerated dose and recommended Phase IIa dose of MLM-CAR44.1 T-cells in AML and MM. The record describes the MTD as established through the BOIN design and dose-limiting toxicities occurring following CAR T-cell infusion. The assessment timeframe was within 30 days following infusion, assessed as day 0.
This type of endpoint serves a dose-selection purpose in an early-phase study. Instead of estimating a comparative treatment effect, it uses observed toxicity at different dose levels to guide whether a dose can be selected for further study. A DLT is a protocol-defined toxicity used for that decision; the exact toxicity criteria and dose-decision rules are not reported in the registry record.
The endpoint is not a measure of antitumor activity itself. The registry lists disease-response outcomes separately, including responses in AML and MM. It also lists circulating CAR T-cell levels and other outcomes. The primary endpoint could have informed whether a dose was suitable for Phase IIa, but it cannot establish whether the treatment improves clinical outcomes relative to another option.
Crucially, the primary outcome states that data were not collected due to early end of trial. No MTD, recommended Phase IIa dose, DLT count, or endpoint estimate is reported in the registry record. Thus the endpoint’s intended role can be described, but its observed result cannot be interpreted.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The central statistical fact is that the primary endpoint has no collected data in the registry record. Although the trial was designed to establish an MTD and recommend a Phase IIa dose, the posted record reports neither a dose-selection result nor the DLT observations on which that result would depend. The primary question is therefore unanswered by the posted results.
The record lists an enrollment of 8, but that figure does not establish how many participants received an infusion, which dose each participant received, or which participants contributed to any particular outcome. The primary endpoint explicitly says data were not collected because the trial ended early. Enrollment should not be treated as an analyzed sample size for that endpoint.
The study was single-group and unmasked. Without a control group, any recorded changes in disease status would not, by themselves, provide a randomized estimate of how outcomes differed from an alternative. Here, the registry lists several secondary outcomes but does not post their numerical results or analyses. It lists 16 outcome measures and 0 analyses. Those counts do not supply evidence of a response or allow an estimate of its precision.
The safety record lists one intervention group. Serious adverse events were recorded for 2 participants at risk, with 2 affected; other adverse events were also recorded for 2 participants at risk, with 2 affected. The registry lists 1 death. It also lists pneumonia at 100.0% and disease progression at 50.0% among the top serious terms. These entries should be read as registry descriptions, not as a complete safety analysis: the record does not provide detailed event counts, timing, causal attribution, or a full account of the analysis population. The serious-event term percentages do not establish the treatment’s contribution to those events.
The trial status is terminated, but the reason for termination is not reported in the registry record. The available information therefore supports a description of the design, intended endpoints, and limited posted safety figures. It does not support a conclusion about the selected dose, treatment activity, comparative benefit, or the overall balance of potential benefits and harms.
Any planning illustrations based on an observed effect must be distinguished from observed trial evidence. The primary endpoint has no collected data, and the record does not post analyses for the outcome measures. Planning calculations are not observed power, and they cannot replace missing estimates or make the underlying clinical question answerable.
9. Statistical Methods Explained
What does the BOIN design contribute?
The record says that Phase I dose levels were assigned according to the BOIN design. In general, BOIN is a model-assisted approach for dose escalation in early-phase studies. It uses observed toxicity information to guide whether the next participants should receive a lower dose, the same dose, or a higher dose, with the aim of identifying a dose suitable for further study. This general description does not establish the exact rules used in this trial. The specific toxicity target, decision boundaries, cohort structure, and rules for stopping or selecting a dose are not reported in the registry record.
The intended decision depended on DLTs after infusion. In general, DLT criteria define which toxicities count toward dose decisions and during what assessment window. The registry specifies a primary endpoint timeframe within 30 days following CAR T-cell infusion, assessed as day 0, but does not list the detailed DLT definitions or how events were attributed to dose levels. Without those details and the participant-level observations, the BOIN decisions cannot be reconstructed.
Why is the primary endpoint not an effect estimate?
The MTD and recommended Phase IIa dose are dose-selection outputs, not estimates of a treatment-versus-control difference. In general, early dose-finding designs focus on the relationship between dose and toxicity. The result is meant to inform a dose choice for later evaluation. It does not, on its own, show antitumor activity or establish whether treatment outcomes differ from those under another approach.
The registry reports that primary endpoint data were not collected because the study ended early. Consequently, there is no reported MTD, recommended dose, toxicity rate by dose, or uncertainty interval for a dose-selection result. A confidence interval, in general, describes the range of values compatible with an estimate under a statistical procedure. No such primary endpoint estimate is available in the registry record to interpret.
What can a single-group design establish?
The study had a single group, no masking, and no randomized allocation. In general, observations in one group can describe what happened among participants who received an intervention, if outcomes are collected and reported. They do not provide the same protection against differences in participant characteristics, disease course, or other influences as a randomized comparison. Without a concurrent control, a change in an outcome cannot be separated cleanly from those other influences.
This limitation is especially relevant to secondary outcomes such as hematologic disease response and overall survival. The registry lists those outcomes but posts no analyses. There is therefore no numerical response estimate or survival analysis to assess. The absence of posted analyses does not mean that an outcome had no events or that an effect was absent; it means the registry record does not provide an analysis result.
How should the planning assumptions be understood?
General sample-size planning uses assumptions about the effect to be detected, the significance level, allocation, and statistical method. The planning illustration associated with this record is described as using a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. It is described as targeting a stated fraction of an observed effect. These are planning assumptions, not a description of the actual single-group trial design.
The planning description also distinguishes between participant counts per arm for non-time-to-event outcomes and total event counts for time-to-event outcomes. Those calculations are illustrations rather than evidence from this trial. Sample-size illustrations are not observed power; they do not establish what the trial could reliably detect in practice. In this record, the primary outcome was not collected, and no outcome analyses are posted. The registry does not report the trial’s own sample-size justification.
In general, small studies produce imprecise estimates, and toxicity rates can be particularly uncertain when few participants contribute data. The enrollment listed in the record does not tell how many people were treated or analyzed for any outcome. It would therefore be inappropriate to infer precision or power from the enrollment figure alone.
What analysis details remain unknown?
The registry record reports 0 analyses. It does not report a statistical analysis plan, interim analyses, a method for handling missing outcomes, analysis populations, or adjustment for multiple outcomes. It also does not give numerical results for the listed disease-response, cell-level, suicide-gene, or survival outcomes. These omissions prevent an assessment of model choice, covariate adjustment, adherence to a prespecified analysis, or robustness checks.
In general, over-dispersion occurs when observed variability is greater than a statistical model expects. It can make uncertainty estimates too narrow if a model assumes less variability than the data contain. No outcome model or dispersion estimate is reported for this study, so over-dispersion cannot be assessed as a trial-specific issue. More broadly, no numerical outcome analysis is available to evaluate whether statistical assumptions were appropriate.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists multiple outcome measures, including dose selection, disease response in AML and MM, circulating CAR T-cell levels, suicide-gene activation, and overall survival. It reports 16 outcome measures and 0 analyses. The primary endpoint is identifiable as Phase I dose selection, but numerical results for it were not collected because the trial ended early. Results for the listed secondary outcomes are not reported in the registry record.
When a study assesses multiple outcomes, the chance of finding an apparently noteworthy result can increase if each is tested separately. In general, multiplicity procedures can address that issue, but the appropriate approach depends on the study’s goals and analysis plan. A multiplicity adjustment or hierarchy is not reported in the registry record. With no outcome analyses posted, it is not possible to assess whether multiplicity was handled or how it might affect any reported inference.
The record does not describe the analysis populations or how missing outcome data were handled. It also does not state whether all enrolled participants received an infusion, whether participants withdrew, or whether any outcomes were collected before termination. The reason for early termination is not reported in the registry record. These gaps mean the extent and pattern of missingness cannot be evaluated. Because the primary outcome explicitly says data were not collected, no primary endpoint estimate can be reconstructed from the posted record.
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 |
|---|---|---|---|
| MLM-CAR44.1 T-cells Infusion | 2 | 2 | 100.0% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| MLM-CAR44.1 T-cells Infusion | 1 of 2 |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 0% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| MLM-CAR44.1 T-cells Infusion | 2 of 2 |
Most frequent serious adverse event terms
| Event term | Organ system | MLM-CAR44.1 T-cells Infusion |
|---|---|---|
| Pneumonia | Infections and infestations | 2 of 2 |
| Disease progression | General disorders | 1 of 2 |
Most frequent non-serious adverse event terms
| Event term | Organ system | MLM-CAR44.1 T-cells Infusion |
|---|---|---|
| Pyrexia | Immune system disorders | 2 of 2 |
| Neutropenia | Blood and lymphatic system disorders | 2 of 2 |
| Anemia | Blood and lymphatic system disorders | 2 of 2 |
Serious events with the highest arm-level rate: pneumonia (100.0%), disease progression (50.0%).
The registry lists one group, “MLM-CAR44.1 T-cells Infusion.” For serious adverse events, it records 2 participants at risk and 2 affected. For other adverse events, it also records 2 participants at risk and 2 affected. The record lists 1 death. These figures describe the registry entries; they should not be treated as a complete account of all participants enrolled or as a comparison with an untreated or control group.
The top serious-event terms are pneumonia at 100.0% and disease progression at 50.0%. The registry does not supply enough detail to determine the event counts behind each percentage, their timing, whether an individual had more than one event, or how the percentages were defined. It also does not report a causal assessment linking these events or the death to the intervention. The listed terms and percentages are therefore descriptive entries, not estimates of treatment-attributable risk.
Because there is no comparator and the primary data were not collected, these safety figures cannot establish how event frequency compares with another treatment or with the expected course of disease. The reason for termination and the full safety follow-up are not reported in the registry record.
12. What the Result Does, and Does Not, Mean
The registry record documents a planned early-phase investigation of autologous CD44v6 CAR T-cells in AML and MM, with Phase I dose selection intended to guide Phase IIa. It identifies the intervention, dose levels considered in Phase I, the BOIN design, and the primary endpoint’s toxicity-assessment window. It also records that the study was terminated and that primary endpoint data were not collected due to early end of trial.
Those details do not establish an MTD or a recommended Phase IIa dose. They do not show how many participants received each dose, what toxicities occurred at each dose, or whether a Phase IIa dose was selected. Nor do they establish antitumor activity: although disease response and other outcomes are listed, no outcome analyses are posted in the registry record.
The enrollment of 8 is not a substitute for outcome data. It does not show how many participants were treated or analyzed, and it does not make the missing primary endpoint interpretable. Likewise, the safety entries are descriptive and lack a comparator. They cannot show whether events were caused by the intervention or whether their frequency differs from what would have occurred otherwise.
More generally, a single-group early-phase study can provide information about dose and observed safety when those data are collected and reported. It is not designed as a randomized comparison in this record, so it cannot by itself provide a controlled estimate of treatment effect. Here, the registry’s missing primary results and lack of posted outcome analyses further limit what can be concluded.
The statistically accurate conclusion is narrow: the registry reports the intended design and endpoints, a terminated status, an enrollment of 8, and limited adverse-event entries, but it does not report the primary dose-selection result or analyses of antitumor outcomes. The absence of those results should not be interpreted as evidence that the treatment succeeded or failed.
13. Why This Trial Matters Statistically
This record illustrates how an early-phase study can have a clear dose-selection objective while still leaving that objective unresolved in the registry. The Phase I endpoint was intended to identify an MTD and recommend a Phase IIa dose using DLT observations and a BOIN design. Because the registry says primary data were not collected, the dose-finding question cannot be answered from the posted record.
It also shows why enrollment and analysis counts must be kept distinct. The record lists an enrollment of 8, but it reports 0 analyses and no collected primary endpoint data. Enrollment alone does not tell readers which participants received treatment, contributed to outcomes, or were included in any analysis. Statistical interpretation depends on the data available for the specific endpoint, not just the overall enrollment entry.
The single-group design is another important feature. It can be suitable for studying dose and toxicity in an early-phase setting, but it does not create a randomized comparison. Any later interpretation of response or survival would require attention to the absence of a control group and to other influences on outcomes. In this registry record, those outcomes have no posted analyses to evaluate.
Finally, the record separates planned outcomes from reported evidence. Listing disease response, circulating cell levels, suicide-gene activation, or overall survival does not mean results were observed or analyzed. The termination status, missing primary data, and limited safety reporting all matter when deciding what the registry can support. These distinctions prevent planned questions from being mistaken for answered questions.
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 most consequential limitation is explicit: the primary endpoint says data were not collected due to early end of trial. The registry therefore provides no DLT observations, MTD, recommended Phase IIa dose, or estimate of uncertainty for the primary question. It does not report why the trial ended early.
The record lists enrollment of 8, but it does not report the number treated, dose received by each participant, or analysis population for the posted safety figures. The treatment description mentions lymphodepleting chemotherapy but is incomplete, and the detailed DLT criteria and BOIN decision rules are not reported in the registry record. These missing details limit interpretation and prevent reconstruction of the planned dose-selection process.
The design was single-group and unmasked, with no concurrent control. That limits comparative interpretation even if outcome data are available. In this case, the registry lists multiple secondary outcomes but reports 0 analyses, so there are no posted numerical results for disease response, circulating CAR T-cell levels, suicide-gene activation, or overall survival.
The safety entries are limited: the record gives participant counts at risk and affected, a death count, and percentages for top serious-event terms, but not the event timing, detailed counts by term, causal attribution, or full follow-up. The registry record does not report the statistical analysis plan, handling of missing data, multiplicity approach, interim analyses, or sample-size justification. These gaps, together with early termination and absent primary data, constrain any statistical conclusions to the design and limited descriptive information recorded.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Study of CAR T-cell Therapy in Acute Myeloid Leukemia and Multiple Myeloma — NCT04097301.
- Registry record last updated 2022-01-19; status last verified 2021-12.
- Results first posted 2022-01-19.
- 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
NCT04097301 is a terminated, single-group Phase I–IIa study of autologous CD44v6 CAR T-cells in AML and MM. The registry lists AGC Biologics S.p.A. as sponsor, an enrollment of 8, and no masking. Phase I was intended to establish an MTD and recommend a Phase IIa dose using the BOIN design and DLTs after infusion. The primary endpoint timeframe was within 30 days following CAR T-cell infusion, assessed as day 0.
The registry states that primary endpoint data were not collected because the trial ended early. It reports 0 analyses and does not provide numerical results for the listed secondary outcomes. Safety entries include 2 participants at risk and 2 affected for serious adverse events, 2 at risk and 2 affected for other adverse events, and 1 death. The record does not establish a dose-selection result or comparative treatment effect.