CD3/CD19 Depleted or CD3 Depleted/CD56 Selected Haploidentical Donor Natural Killer (NK) Cell Based Therapy for AML Patients Not in CR: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for CD3/CD19 Depleted or CD3 Depleted/CD56 Selected Haploidentical Donor Natural Killer (NK) Cell Based Therapy for AML Patients Not in CR (NCT03152526), a na na study. The primary outcome is The Primary Endpoint of the Study is Complete Remission (±3 Days).

2. Clinical Question

The study summary describes adults with newly diagnosed acute myelogenous leukemia (AML) who had not achieved complete remission after one or two standard induction attempts. The treatment concept was to use natural killer (NK) cells from a related HLA-haploidentical donor after a preparative regimen, followed by interleukin-2 (IL-2). The registry record names two NK-cell products, but its design fields identify a single-group study and do not establish a randomized comparison between them.

Thus, the central question was whether this treatment approach could be evaluated for safety and complete remission in this population. The posted record does not establish an interpretable comparison between the two cell products or report a remission outcome. The planned assessment and the available evidence need to be distinguished: the endpoint is described, but the registry record does not report the outcome counts needed to assess it.

3. Trial Design

The registry record lists the study as terminated, with a start date of 2017-10-18 and a primary completion date of 2018-03-21. Enrollment is 1. Its design fields list allocation as NA, masking as NONE, and a single-group model. The arm description calls the study a multi-center, open-label, single-arm, phase I/II clinical trial. The phase field itself is NA, while the brief summary describes the study as phase II. These registry descriptions do not provide a consistent basis for assigning a single phase or a randomized comparative design.

The official title uses the words “A Randomized Trial” and compares CD3/CD19-depleted with CD3-depleted/CD56-selected haploidentical donor NK-cell therapy. However, the record lists allocation as NA and the model as single-group, and describes a single-arm study. It therefore does not establish that participants were randomly assigned to the two products or that the products were evaluated as a controlled comparison. The two product descriptions should not be treated as evidence of two randomized arms.

The study summary describes a regimen beginning with cyclophosphamide and fludarabine, followed by a single NK-cell infusion and a short course of IL-2. The stated treatment could use either CD3-/CD19- NK cells or CD3-/CD56+ NK cells. The intervention entry is broadly labeled “Interventions” and classified as a device. Specific treatment details beyond the summary are not reported in the registry record.

The primary completion date is recorded, but the trial status is terminated and accrual was poor. The primary endpoint description explicitly states that efficacy data cannot be defined statistically according to the protocol because enrollment was n=1. The registry record does not report a protocol, a sample-size justification, the reason for termination, or the actual method used to select a cell product for the enrolled participant. Consequently, the intended study question and its realized design must be kept separate.

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

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: As a result of poor subject accrual (n=1), statistically relevant efficacy data cannot be defined according to the protocol.

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: No participants were enrolled on the CD3-/CD19- NK cells arm. The study was closed due to poor enrollment.

6. Primary Endpoint

The registry lists the primary outcome as The Primary Endpoint of the Study is Complete Remission (±3 Days), measured over On Day+42 (+/- 3 days) after NK cell infusion.

The primary endpoint is complete remission, with assessment scheduled on Day+42 (+/- 3 days) after NK-cell infusion. The endpoint description says the report would distinguish patients with leukemia in complete remission from patients not in complete remission. Remission status was to be assessed according to the Revised Recommendations of The International Working Group (J Clin Oncol 21:4642-4649, 2003).

Complete remission is a binary clinical status for this endpoint: each assessed patient would be classified as in remission or not in remission. Counting patients in each category can describe whether the planned clinical response was observed in the study population. A prespecified assessment time is useful because it defines when the response is evaluated; it does not, by itself, establish the durability of remission or provide information beyond that assessment.

The endpoint is described, but an observed remission count is not reported in the registry record. The record states that poor accrual (n=1) meant statistically relevant efficacy data could not be defined according to the protocol. Therefore, the planned measure cannot be interpreted as an estimate of treatment response from the information recorded. In particular, the absence of a reported remission count is not equivalent to a reported count of zero patients in remission.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The methods that can be described are limited to the endpoint definition and the design information recorded. The primary outcome is complete remission, assessed on Day+42 (+/- 3 days) after NK-cell infusion. The endpoint description specifies classifying leukemia status as complete remission or not in complete remission, using the Revised Recommendations of The International Working Group. The registry record does not report the statistical method used to analyze this endpoint.

What does a binary endpoint mean?

In general, a binary endpoint assigns each assessed participant to one of two categories. A study can report the count in each category, and, when the analysis population and outcome data are available, may estimate the proportion in one category. The registry record says that both remission and non-remission counts would be reported, but it does not report those counts. Enrollment of 1 does not fill that gap: the outcome classification for the enrolled participant is not stated.

What can an estimate and confidence interval tell a reader?

In general, an estimate summarizes the observed data, while a confidence interval indicates the uncertainty associated with that estimate under a specified statistical method. A narrow interval would indicate greater precision than a wide interval, all else being equal. No remission estimate or confidence interval is reported in the registry record, and the endpoint counts required to calculate one are absent. No precision claim can therefore be made about the efficacy endpoint.

What is the role of a p-value?

In general, a p-value is calculated under a specified statistical model and addresses how compatible the observed data are with a stated null hypothesis. Its interpretation depends on the design, the analysis plan, the outcome data, and the assumptions of the method. The registry record reports zero analyses and no p-value for remission. A p-value should not be inferred from enrollment, the endpoint definition, or the fact that the trial was intended to study efficacy.

Why does the design description matter?

A randomized comparison requires a documented allocation process and groups that can be interpreted according to that process. Here, the title says “A Randomized Trial,” but allocation is NA; the model is single-group; and the arm description calls the study single-arm. The record does not reconcile those descriptions. Without documented allocation and outcome data by assigned group, an analysis comparing the two cell products is not established. The adverse-event groups do not change this: group-specific safety counts alone do not establish randomization or a valid comparative efficacy analysis.

What should be made of the sample-size illustrations?

In general, a planning sample size depends on assumptions about the endpoint, the effect to detect, the statistical method, and the desired error rates or power. The record describes a planning illustration based on a stated fraction of an observed effect, with two-sided significance level 0.05, equal allocation, and a normal approximation; it distinguishes between participants per arm for most outcomes and total events for time-to-event outcomes. These are planning assumptions, not evidence that the trial enrolled enough participants or had a particular probability of detecting an effect. The record does not report a protocol-based sample-size justification. Because it also states that efficacy data cannot be defined statistically from the accrual of n=1, a planning illustration should not be read as observed power or as confirmation of an efficacy result.

Why are estimates especially difficult with limited accrual?

In general, estimates based on very little information are highly sensitive to the observations available and can be imprecise. For a binary outcome, the number of participants with each outcome category is central. With the remission classification unreported and enrollment of 1, neither an outcome proportion nor its uncertainty can be determined from the registry record. This is distinct from saying that the result is statistically non-significant: no such test result is reported.

The registry record does not report an interim analysis plan, a statistical analysis plan, an adjustment method, or an efficacy analysis. It also does not report methods for handling missing outcome data. These omissions mean that the analysis cannot be reconstructed or checked against a prespecified approach. General statistical principles can explain what an analysis might do, but they cannot substitute for the unreported design and analysis details.

10. Multiplicity, Missing Data and Analysis Populations

Multiplicity concerns arise when a study tests or estimates several outcomes, groups, time points, or treatment contrasts. In general, repeated testing can increase the chance of an apparently notable result arising by chance, so an analysis plan may specify which outcomes are primary and how multiple comparisons will be addressed. The registry record identifies complete remission as the primary endpoint and lists expansion and persistence of NK cells as a secondary endpoint. It does not report a multiplicity strategy or describe statistical tests for these outcomes.

The record also does not establish a randomized comparison between the two NK-cell products. Although both product descriptions appear in the record, allocation is NA and the model is single-group. It is therefore not possible to identify a planned treatment contrast or determine whether any adjustment for comparisons was intended. The record reports zero analyses, so it contains no analysis results from which multiplicity handling could be assessed.

Missing-data methods and analysis populations are not reported in the registry record. The outcome classification for the enrolled participant is also not reported. That absence should be distinguished from a documented missing-data event: the record does not say whether the assessment was not performed, not submitted, or unavailable for another reason. It does not specify an intention-to-treat, per-protocol, safety, or other analysis population.

In general, an analysis population defines which participants contribute to a particular result, and a missing-data approach describes how unavailable measurements are handled. Those choices can affect interpretation, especially in a small study. Here, the record does not provide enough information to determine either the population used for efficacy or how any missing outcome information was treated.

11. 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: serious adverse event (100.0%).

The adverse-event record lists two product-labeled groups. For CD3-/CD19- NK Cells Followed by IL-2, it reports 0 participants at risk and 0 affected by serious adverse events, 0 at risk and 0 affected by other adverse events, and 0 deaths. For CD3-/CD56+ NK Cells Followed by IL-2, it reports 1 participant at risk and 1 affected by serious adverse events, 1 at risk and 1 affected by other adverse events, and 1 death. The top serious-event term is “Serious adverse event” at 100.0%.

These are small descriptive counts, not estimates of comparative risk. In particular, a group with 0 participants at risk provides no observed participant experience from which to characterize safety. The record does not identify the serious adverse event, clarify whether the serious and other-event entries refer to distinct events, or describe the timing, severity details, or relationship to treatment. It also does not state the context of the death.

The listed groups do not establish randomized treatment arms: the record’s allocation is NA and its model is single-group. The counts therefore should not be read as evidence that one product caused more or fewer events than the other. They document the posted safety figures for the recorded group labels, with substantial limits on what can be inferred.

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

The registry record establishes that a study was planned to evaluate haploidentical donor NK-cell therapy in adults with AML who had not achieved complete remission after one or two induction attempts. It describes the treatment sequence and defines complete remission at Day+42 (+/- 3 days) after infusion as the primary endpoint. It also records termination, enrollment of 1, and the statement that poor accrual prevented statistically relevant efficacy data from being defined according to the protocol.

Those details do not establish whether the enrolled participant achieved complete remission. The primary outcome count is not reported in the registry record. Accordingly, the posted information cannot support a response estimate, a precision statement, or a conclusion about efficacy. No result for the secondary endpoint of NK-cell expansion and persistence is reported either.

The trial title uses randomized-comparison language, but the registry design entries do not document random allocation. The model is single-group, allocation is NA, and the arm description says single-arm. The record therefore does not support a causal comparison between CD3-/CD19- and CD3-/CD56+ NK-cell products. The safety counts also do not supply such a comparison, particularly because one listed group has no participants at risk.

In general, a terminated study with very limited accrual can still describe its intended question and the information it managed to collect. It cannot answer the intended efficacy question when the outcome classification is not reported and the record itself says relevant efficacy data cannot be defined. This distinction matters: an unreported result is not the same as a negative result, and a planned endpoint is not an observed finding.

The appropriate interpretation is narrow. The registry documents a treatment concept, an endpoint, and limited enrollment and adverse-event counts. It does not establish a remission outcome, treatment effect, or comparative safety conclusion. These limitations apply to what can be learned from this record and do not determine what would have been observed in a larger or differently conducted study.

13. Why This Trial Matters Statistically

This record illustrates the difference between a clinical question and an answerable statistical comparison. The title presents the study as randomized, but the design fields list allocation as NA and a single-group model, while the arm description calls it single-arm. A title can communicate the intended question, but an interpretable comparison depends on the recorded design and analyzable outcome data.

Accrual is also central to what the study can establish. The registry record reports enrollment of 1 and explicitly states that statistically relevant efficacy data cannot be defined according to the protocol because of poor accrual. Even a clearly specified endpoint cannot yield a useful study-level efficacy estimate when the outcome information needed for that estimate is not reported. Statistical interpretation must account for both the planned design and the amount of information actually available.

The record also demonstrates why a missing result should not be converted into a zero result. Complete remission was the primary endpoint, but remission and non-remission counts are not reported. Without those classifications, there is no observed efficacy result to interpret. This distinction protects against drawing conclusions from the absence of a registry result.

Finally, safety counts require their denominators and design context. One listed product group has no participants at risk, and the other has one. Such counts can document what the registry records, but they cannot support a meaningful product comparison or a general safety estimate. Read carefully, the record is informative about study conduct and the limits of its evidence, while leaving the intended treatment question unresolved.

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.

Accrual is the most consequential limitation specific to this study. The registry reports enrollment of 1 and directly states that poor accrual meant statistically relevant efficacy data could not be defined according to the protocol. The primary remission outcome is not reported, so the record does not permit even a descriptive account of whether the enrolled participant was in remission at the planned assessment.

The design descriptions do not align. The title calls the study randomized and names two cell products, but allocation is NA, the model is single-group, and the arm description is single-arm. The record does not explain this discrepancy, document a randomization procedure, or establish a comparative control group. Any interpretation treating the product labels as randomized arms would go beyond the record.

The phase descriptions also differ: the phase field is NA, the brief summary describes phase II, and the arm description calls the study phase I/II. The record does not explain the difference. It also does not report the reason for termination, a protocol-based sample-size justification, an analysis plan, interim analyses, an efficacy analysis population, or methods for missing data.

Safety interpretation is limited by the very small recorded groups and lack of clinical detail. The record does not identify the serious adverse event, explain its relationship to treatment, or provide context for the death count. The group with zero participants at risk cannot inform safety occurrence in that group. Together, these limitations mean that the record is most useful for describing the intended study and the extent of reported information, not for estimating efficacy or comparing safety.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: CD3/CD19 Depleted or CD3 Depleted/CD56 Selected Haploidentical Donor Natural Killer (NK) Cell Based Therapy for AML Patients Not in CR — NCT03152526.
• Registry record last updated 2020-07-09; status last verified 2020-02.
• Results first posted 2019-05-07.
• 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.

18. Record Summary

The registry record describes haploidentical donor NK-cell therapy for adults with AML who had not achieved complete remission after one or two induction attempts. The planned primary endpoint was complete remission on Day+42 (+/- 3 days) after infusion, assessed using the Revised Recommendations of The International Working Group. The study summary describes preparative cyclophosphamide and fludarabine, a single NK-cell infusion, and a short course of IL-2.

The record lists the study as terminated, with enrollment of 1, and states that statistically relevant efficacy data could not be defined because of poor accrual. It does not report the remission classification or analyses. Although the title says randomized, the design entries list allocation as NA and a single-group model, and the arm description calls the study single-arm. The adverse-event record reports limited group counts, including 1 serious adverse event-affected participant and 1 death in the CD3-/CD56+ group. These data do not establish comparative efficacy or safety.