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 Clinical Trial of Expanded and Activated Autologous NK Cells to Treat Multiple Myeloma (NCT02481934), a na phase 1 study. The primary outcome is Number of Participants With Adverse Events During NKAE Treatment.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT02481934 |
| Phase | Phase 1 |
| Condition | Multiple Myeloma |
| Allocation | Not applicable (single group) |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 5 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Joaquín Martínez López, MD, PhD |
| Results posted | Yes |
2. Clinical Question
Population
The study enrolled patients with multiple myeloma on second or later relapse who were receiving consolidation treatment. The registry lists an enrollment of 5. The primary endpoint population is described as analysis per protocol; further eligibility details and the number included in that analysis are not reported in the registry record.
Intervention
The intervention was an infusion of expanded and activated autologous natural killer cells, called NKAE cells in the registry. The infusion was combined with chemotherapy: lenalidomide or bortezomib. The record does not report how the choice between those drugs was made or how many participants received each one.
Comparator
This was a single-group study with no randomized allocation and no like-for-like control group. The registry does not describe a separate comparator treatment. Consequently, the posted results can describe events observed during the treatment regimen, but they cannot directly compare that regimen with another treatment or with no NKAE infusion.
Primary question
The listed primary outcome is the number of participants with adverse events during NKAE treatment, assessed over a timeframe of 16 months. The registry’s study summary also describes an interest in effectiveness, and lists peripheral blood monoclonal protein reduction or stabilization as a secondary outcome. The posted record does not include a reported result for that secondary outcome or a primary endpoint analysis. The central answerable question from the available outcome details is therefore descriptive: what adverse-event information was recorded for this small, single-group treatment experience?
3. Trial Design
This is a completed Phase 1 clinical trial, listed with a single-group model and no masking. The registry records enrollment of 5 and identifies multiple myeloma as the condition. The study ran from 2013-03 to primary completion in 2016-07, and its status is COMPLETED. Those dates describe the registry’s recorded study timeline; they do not supply the timing of each participant’s treatment or follow-up.
The treatment regimen combined expanded and activated autologous NK cells with chemotherapy. The chemotherapy options named in the registry are lenalidomide or bortezomib. The record does not report participant counts by chemotherapy option, dose schedules, or the rules used to select between options. It describes the intended population as patients on second or later relapse receiving consolidation treatment.
With a single group and no masking, the design is suited to recording experience with the regimen, including adverse events, rather than producing a randomized treatment contrast. There is no concurrent control arm described in the registry record. A before-and-after or external comparison is also not reported as part of the posted results. This matters because events observed during treatment cannot, by themselves, establish whether the regimen caused an event or whether outcomes differ from those under another approach.
The registry specifies a primary endpoint population of analysis per protocol. It does not report a fuller analysis-population definition, such as the rules for remaining in the per-protocol population, or whether every enrolled participant contributed to each outcome. Protocol details beyond those listed, including the planned statistical analysis, are not reported in the registry record.
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 | NKAE Cells Infusion + Chemotherapy |
|---|---|
| STARTED | 5 |
| COMPLETED | 3 |
| NOT COMPLETED | 2 |
Reasons for not completing this period:
| Reason | NKAE Cells Infusion + Chemotherapy |
|---|---|
| Death | 2 |
Analysis population for the primary outcome, as defined in the registry: Analysis per 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: The number of participants was directly related with the cost of expanded and activated NK cells production.
| Characteristic | Unit | NKAE Cells Infusion + Chemotherapy |
|---|---|---|
| Participants analysed | 5 | |
| Age, Continuous | years | 62 (61 to 72) |
| Sex: Female, Male: Female | Participants | 3 |
| Sex: Female, Male: Male | Participants | 2 |
| Region of Enrollment: Spain | participants | 5 |
6. Primary Endpoint
The registry lists the primary outcome as Number of Participants With Adverse Events During NKAE Treatment, measured over 16 months.
| Element | Registry entry |
|---|---|
| Result type | Number |
| Measure of spread | not applicable |
| Unit | participants |
| Endpoint classification | Binary Endpoint |
The primary endpoint is the number of participants with adverse events during NKAE treatment. It is expressed in participants, so it concerns whether participants experienced an adverse event rather than the total number of event episodes. The endpoint timeframe is 16 months. The accompanying description says toxicity was assessed using adverse-event counts and monitoring of peripheral blood absolute neutrophil count, with evaluation based on Common Toxicity Criteria for Adverse Events of the National Cancer Institute, version 4.03.
The registry describes monthly toxicity evaluation during NKAE treatment (4 months), monthly assessment during the first 6 months of follow-up, and quarterly assessment until one year of follow-up. These details indicate that the endpoint was intended to capture safety over treatment and follow-up, rather than only an immediate infusion reaction. The record does not state the exact operational rule for classifying a participant as having an adverse event for the primary endpoint, nor does it provide a primary endpoint result.
In general, a participant-level safety endpoint can give a direct account of how many people experienced an event, while an event-count endpoint can reflect repeated events in the same person. Those measures answer different questions. The primary endpoint is specified as participants with events, but the registry’s posted safety summary does not substitute for a complete endpoint analysis.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry describes a very small, completed, single-group study. Its enrollment was 5. The adverse-event information lists 5 participants at risk for serious adverse events and 2 affected, and 5 at risk for other adverse events and 2 affected. These are descriptive counts for the group receiving NKAE cells infusion plus chemotherapy. They should not be read as a comparison against another treatment, because no control group is described.
The registry also names gastrointestinal bleeding and vertebral compression among the top serious adverse-event terms, each listed at 20.0%. The record does not provide event-level narratives, timing, severity grades for these terms, or participant-level attribution. Nor does it establish whether the participants associated with one term were also associated with another. The term percentages should therefore be read as registry-reported summaries, not as enough information to reconstruct individual clinical histories.
Most importantly, the posted details do not include a result for the stated primary endpoint, the number of participants with adverse events during NKAE treatment. The adverse-event figures are useful descriptive information, but the registry does not say that they are the complete primary endpoint result or explain how their categories map to that endpoint. A primary endpoint estimate, its uncertainty, and a formal comparison are not reported in the registry record. The analysis count is listed as 0.
In general, an estimate from a small study is likely to be imprecise: the observed experience can change substantially if only a small number of participants have different outcomes. A confidence interval, if reported, would show a range of values compatible with the data under its statistical assumptions. No confidence interval for the primary endpoint or the adverse-event summaries is reported in the registry record. The counts alone do not show how precisely the underlying event frequency is known.
These results can document that serious adverse events and other adverse events were recorded in the treated group. They cannot establish that NKAE cells caused any particular event, quantify a comparative safety difference, or establish effectiveness. The record lists a secondary outcome concerning peripheral blood monoclonal protein reduction or stabilization, but does not report a result for it. The study’s stated interest in effectiveness should not be confused with evidence of an efficacy outcome in the posted results.
9. Statistical Methods Explained
The statistical information in the registry is limited. It identifies a single-group design, a primary outcome measured as participants with an event, a per-protocol primary analysis population, and an analysis count of 0. It does not report an inferential analysis for the primary endpoint, a confidence interval, or a statistical comparison. The registry also contains a description of planning assumptions for a sample-size illustration. Such assumptions describe a hypothetical calculation and should not be treated as the trial’s registered design or as observed power.
What does a participant count measure?
For a binary safety outcome, each participant is classified according to whether the specified event occurred during the defined observation period. The result is a count of participants with the event, paired with the number of participants assessed or at risk. This is different from counting every event episode: a participant who experiences repeated episodes may still contribute once to a participant-level outcome. The registry’s primary endpoint is worded at the participant level, while its description also refers to adverse-event counts. Without a detailed endpoint definition or a reported endpoint result, it is not possible to determine exactly how those descriptions were combined in the analysis.
The posted safety summary gives group-level counts for serious adverse events and other adverse events. Those category summaries should be kept separate unless the registry explicitly establishes how categories overlap. The same participant may potentially contribute to more than one category, and the record does not provide the participant-level data needed to assess overlap. Adding category counts would therefore not produce a justified total number of participants with any adverse event.
Why does uncertainty matter?
A point estimate describes the observed data, but it does not alone show the range of plausible values beyond those observations. In general, a confidence interval represents uncertainty in an estimate under a specified statistical model and sampling assumptions. For a binary outcome, intervals can be especially wide when the number of observations is small or when events are uncommon or frequent. Different interval methods can also produce different results, particularly in small samples. The registry does not report a confidence interval or identify an interval method for the primary endpoint.
With no control group, there is no randomized contrast from which to estimate a treatment difference. A within-group event count is not a substitute for a comparison: it does not separate treatment effects from the underlying condition, concurrent chemotherapy, prior treatment, or other influences. General statistical methods for comparative trials, including tests of differences between groups, do not create a valid comparison when the design does not include such groups.
How should the planning assumptions be read?
The registry’s planning-illustration description specifies a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. It describes the effect to detect as a stated fraction of an observed effect. These are assumptions for a planning illustration, not evidence that the trial itself randomized participants, used that allocation, or followed that design. In particular, the actual study is registered as single-group with allocation listed as NA.
Sample-size calculations are planning tools. They depend on the target effect, variability or event rate, analysis method, and design assumptions. They do not tell whether a study’s observed results are statistically significant, and a planning calculation should not be interpreted as observed power. The registry record does not report a trial-specific sample-size justification, and no numerical planning estimate is included in the outcome details available for interpretation. The posted planning description therefore cannot be used to infer the study’s original recruitment target or rationale.
For a binary outcome, a normal approximation is a general approach that uses an approximate sampling distribution for an estimate. Its adequacy depends on the data and assumptions. With a small enrolled group, approximate methods may be less reliable than methods designed for sparse data; however, the registry does not identify a method used to analyze the primary outcome. It would be inappropriate to attribute a particular method, model, or inferential result to the investigators.
Overall, the methodologically defensible reading is descriptive. The record provides adverse-event counts and term percentages, but does not provide a primary endpoint estimate with uncertainty, an analysis plan, or a comparison. These omissions limit both precision assessment and causal interpretation.
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.
| Arm | Participants | Events | Observed % | Clopper-Pearson 95% CI | Wilson 95% CI | Bayesian 95% credible interval |
|---|---|---|---|---|---|---|
| NKAE Cells Infusion + Chemotherapy | 5 | 2 | 40.0% | 5.3% to 85.3% | 11.8% to 76.9% | 11.8% to 77.7% |
R code and output
arm <- c("NKAE Cells Infusion + Chemotherapy")
n <- c(5)
events <- c(2)
for (i in seq_along(n)) {
ci <- binom.test(events[i], n[i])$conf.int # Clopper-Pearson exact interval
cr <- qbeta(c(0.025, 0.975), 1 + events[i], 1 + n[i] - events[i]) # Bayesian, uniform Beta(1,1) prior
wi <- (function(x, n) { p <- x / n; z <- qnorm(0.975); d <- 1 + z^2 / n
c((p + z^2 / (2 * n) - z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d, (p + z^2 / (2 * n) + z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d) })(events[i], n[i])
cat(sprintf("ARM|%s|%d|%d|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f\n", arm[i], n[i], events[i], 100 * events[i] / n[i],
100 * ci[1], 100 * ci[2], 100 * wi[1], 100 * wi[2], 100 * cr[1], 100 * cr[2]))
}
ARM NKAE Cells Infusion + Chemotherapy 5 2 40.0 5.3 85.3 11.8 76.9 11.8 77.711. Multiplicity, Missing Data and Analysis Populations
The registry lists a primary safety outcome and a secondary outcome concerning the number of participants with peripheral blood monoclonal protein reduction or stabilization. It reports 2 outcome measures and 0 analyses, but does not provide a statistical analysis plan describing how outcomes were to be tested or interpreted. The planned hierarchy among outcomes, any adjustment for multiple comparisons, and any rules for prioritizing analyses are not reported in the registry record.
Multiplicity arises when several outcomes, time points, groups, or analyses are considered. In general, testing many hypotheses without an appropriate strategy can increase the chance of chance-positive findings. The registry record does not say whether any multiplicity adjustment was planned or used. Because no analysis results are listed, there are no reported p-values to interpret as confirmatory evidence. The absence of a reported adjustment does not prove that none was conducted; the relevant plan is not reported in the registry record.
Missing-data handling is also not reported in the registry record. The primary outcome population is identified as analysis per protocol, but the record does not explain how participants with incomplete follow-up, missing assessments, or deviations from treatment were handled. It does not state whether all enrolled participants contributed to each outcome or whether any imputation or sensitivity analysis was used.
These gaps matter because safety observation depends on follow-up and outcome ascertainment. In general, incomplete observation can make event counts difficult to interpret if participants differ in how long or how completely they were monitored. The registry gives an assessment schedule and a timeframe, but does not provide participant-level follow-up completeness or a missing-data analysis. As a result, the posted counts should be understood as registry summaries, without assuming complete ascertainment or a particular analysis population beyond the stated per-protocol label.
12. 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 |
|---|---|---|---|
| NKAE Cells Infusion + Chemotherapy | 2 | 5 | 40.0% |
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 |
|---|---|
| NKAE Cells Infusion + Chemotherapy | 2 of 5 |
Most frequent serious adverse event terms
| Event term | Organ system | NKAE Cells Infusion + Chemotherapy |
|---|---|---|
| Gastrointestinal bleeding | Gastrointestinal disorders | 1 of 5 |
| Vertebral compression | Musculoskeletal and connective tissue disorders | 1 of 5 |
Most frequent non-serious adverse event terms
| Event term | Organ system | NKAE Cells Infusion + Chemotherapy |
|---|---|---|
| Neutropenia | Immune system disorders | 2 of 5 |
Serious events with the highest arm-level rate: gastrointestinal bleeding (20.0%), vertebral compression (20.0%).
The registry’s adverse-event summary lists 5 participants at risk for serious adverse events, with 2 affected. It also lists 5 at risk for other adverse events, with 2 affected. These are separate category summaries for the NKAE cells infusion plus chemotherapy group. The record does not state whether the participants in the categories overlap, so the counts should not be added to derive a total number of participants with any adverse event.
Gastrointestinal bleeding and vertebral compression are listed among the top serious adverse-event terms, each at 20.0%. The posted information does not give event timing, duration, severity grade, relatedness assessment, or participant-level detail for these terms. It also does not establish whether a listed term occurred once or more than once. The percentages should be treated as the registry’s reported term summaries, not as a complete description of the clinical course.
These figures describe events recorded in a small treated group. They do not establish that the infusion or chemotherapy caused an event, and they do not estimate comparative risk. The primary endpoint result itself is not reported in the registry record.
13. What the Result Does, and Does Not, Mean
The posted record offers a limited descriptive account of a Phase 1 treatment experience in patients with multiple myeloma on second or later relapse. It records a single-group regimen combining expanded and activated autologous NK cells with lenalidomide or bortezomib, and reports adverse-event summaries for the treated group. The serious-event and other-event counts, along with the listed serious-event terms, are part of the available safety information.
The record does not report the primary endpoint result as defined: the number of participants with adverse events during NKAE treatment. It also does not report results for the secondary outcome concerning peripheral blood monoclonal protein reduction or stabilization. Therefore, the stated interest in effectiveness cannot be answered from these posted outcome details. No treatment-effect estimate, uncertainty interval, or formal statistical analysis is reported.
Even if a primary endpoint count were available, an uncontrolled single-group study would not establish what would have happened under a different treatment. In general, outcomes observed during a regimen can reflect the disease, prior treatment, concurrent therapies, follow-up intensity, and other factors, as well as any contribution from the intervention. A comparison group and a prespecified analysis are needed to support a treatment contrast; neither is described in this record.
The small enrollment also limits how broadly the observed experience can be generalized. The counts document what the registry reports for this group, not a precise estimate of event frequency in a broader population. The record’s omissions—particularly the lack of a primary outcome result, uncertainty estimates, and missing-data details—further constrain interpretation. The appropriate conclusion is about the content and limits of the posted record, not a clinical recommendation or a claim that the treatment is effective or ineffective.
14. Why This Trial Matters Statistically
This trial is statistically notable because it illustrates the difference between a study’s scientific motivation and the outcome information available for analysis. The brief summary describes an interest in whether activated and expanded autologous natural killer cells are effective in relapsed multiple myeloma, in combination with anti-myeloma drugs. The registered primary endpoint, however, concerns participants with adverse events during NKAE treatment. The record also lists a secondary outcome related to monoclonal protein reduction or stabilization, but does not report its result.
That distinction matters when interpreting clinical evidence. A safety endpoint can describe tolerability-related observations, while an efficacy outcome addresses a different question. Neither endpoint can be substituted for the other, and a study’s stated purpose does not itself provide an outcome result. Clear separation of the research question, endpoint definition, analysis population, and reported findings helps readers avoid attributing evidence to the wrong outcome.
The single-group design also makes the limits of descriptive evidence visible. The adverse-event counts document observations during the regimen, but without a comparator they do not quantify a treatment-related increase or decrease. The small enrollment of 5 means the record is a limited safety experience rather than a precise comparative estimate. In general, descriptive early-phase information can help characterize what was observed and identify questions for further study; it does not establish a causal treatment effect.
Finally, the record shows why reporting the analysis itself is important. A defined primary outcome is most informative when accompanied by its result, denominator, uncertainty, and explanation of missing observations. Here, the endpoint definition and some adverse-event summaries are available, but a primary endpoint analysis and uncertainty measures are not reported. That gap should shape the strength of any statistical interpretation.
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.
Several limitations are specific to the information registered for this trial. The enrollment is 5, and the design is single-group with allocation listed as NA and no masking. The absence of a like-for-like control group prevents a direct comparative interpretation of safety or efficacy. The record does not report a comparison with another regimen or a separate control condition.
The registered primary endpoint is the number of participants with adverse events during NKAE treatment, but a corresponding primary endpoint result is not reported. Although the safety summary includes serious and other adverse-event counts, the record does not explain whether these summaries fully represent the primary endpoint, how their categories overlap, or how event-level records were grouped. The listed serious-event terms do not include participant-level narratives or relatedness assessments.
The registry identifies the primary analysis population as per protocol, but does not report the criteria for inclusion in that population or the handling of deviations. Missing-data methods, follow-up completeness, and the number assessed for each outcome are not reported in the registry record. The record also does not provide a statistical analysis plan, confidence intervals, or inferential analyses. These omissions prevent an assessment of precision and make it difficult to evaluate the sensitivity of the findings to analysis choices.
Additional details that would help interpret the regimen—such as the numbers receiving lenalidomide versus bortezomib, treatment doses, and selection rules—are not reported in the registry record. Nor are a trial-specific sample-size justification or interim-analysis details reported. These limitations concern what can be established from the registry entry; they should not be replaced with assumptions about procedures or analyses that are not documented.
16. Related Tutorials
17. Related Statistical Calculators
18. Sources
- ClinicalTrials.gov: Clinical Trial of Expanded and Activated Autologous NK Cells to Treat Multiple Myeloma — NCT02481934.
- Registry record last updated 2021-08-20; status last verified 2021-08.
- Results first posted 2016-12-05.
- 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.
Continue through the Clinical Biostats statistical pathway
Use this trial's endpoint as a starting point for deeper study of effect measures, confidence intervals, and sample-size planning.
19. Record Summary
The registry identifies NCT02481934 as a completed Phase 1, single-group study of expanded and activated autologous NK cells in multiple myeloma. The regimen combined NKAE cell infusion with lenalidomide or bortezomib. Enrollment was 5, and the listed study period runs from 2013-03 to primary completion in 2016-07.
The primary endpoint is the number of participants with adverse events during NKAE treatment, with a timeframe of 16 months and a per-protocol analysis population. The posted safety summary lists 2 affected among 5 at risk for serious adverse events and 2 affected among 5 at risk for other adverse events. Gastrointestinal bleeding and vertebral compression are each listed at 20.0% among the top serious-event terms.
A primary endpoint result, secondary outcome result, uncertainty estimates, and inferential analyses are not reported in the registry record. Because the design has no control group, the posted counts are descriptive and do not establish a comparative effect or causation.