Modified Immune Cells (AFM13-NK) and A Monoclonal Antibody (AFM13) in Treating Patients With Recurrent or Refractory CD30 Positive Hodgkin or Non-Hodgkin Lymphomas: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Modified Immune Cells (AFM13-NK) and A Monoclonal Antibody (AFM13) in Treating Patients With Recurrent or Refractory CD30 Positive Hodgkin or Non-Hodgkin Lymphomas (NCT04074746), a na phase 1, phase 2 study. The primary outcome is Maximum Tolerate Dose of AFM13 Umbilical Cord Blood(UCB) Derived Natural Killer(NK) Cells Infused on D=0,D+7,D+14,D+21 for Each Cohort (1x10^6,1x10^7,1x10^8)..

2. Clinical Question

3. Trial Design

This is a phase I/II, single-group study sponsored by M.D. Anderson Cancer Center. The registry reports enrollment of 45 and a completed status. The recorded start date is 2020-07-18, and the primary completion date is 2025-09-23. Those dates describe the registry record; they do not by themselves establish when all analyses or reporting were finalized.

The treatment regimen includes fludarabine and cyclophosphamide on days -5 to -3, AFM13-NK by intravenous infusion on day 0, and AFM13 by intravenous infusion on days 7, 14, and 21. The registry describes the chemotherapy as standard of care and specifies infusion durations for the listed treatments. It also identifies genetically engineered lymphocyte therapy and AFM13 among the intervention categories. The treatment description does not establish that every enrolled participant received every scheduled dose.

The phase I portion identifies cohorts using cell doses of 1x10^6/kg, 1x10^7/kg, and 1x10^8/kg. The registry also lists a phase II cohort at 1x10^8/kg. It does not report the rules used to move participants between dose cohorts, whether dose changes were permitted, or how participants were assigned to cohorts. Allocation is recorded as NA, and masking is recorded as none. Consequently, cohort differences cannot be interpreted as randomized treatment effects.

The study’s primary outcome is a count of participants with dose-limiting toxicity during the specified 28-day period. A secondary outcome is the number achieving complete response after AFM13-NK cell infusions. The registry lists two outcome measures and zero analyses. Outcome results for the primary endpoint and the complete-response outcome are not reported in the registry record. The record also does not describe a comparison group or an analysis plan that would support comparative effectiveness conclusions.

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:

5. Baseline Characteristics

The table reproduces the baseline characteristics posted in the registry, which describe the participants analysed at baseline and help show whether the randomized groups were comparable.

6. Primary Endpoint

The registry lists the primary outcome as Maximum Tolerate Dose of AFM13 Umbilical Cord Blood(UCB) Derived Natural Killer(NK) Cells Infused on D=0,D+7,D+14,D+21 for Each Cohort (1x10^6,1x10^7,1x10^8)., measured over 28 days post AFM13-NK cells on D=0 for each Cohort..

The primary endpoint is the number of participants who experience dose-limiting toxicity during AFM13-NK cell infusions. The registry defines dose-limiting toxicity as a related grade 3 or greater non-hematologic toxicity occurring within 28 days of AFM13-NK infusion. The stated timeframe is 28 days post AFM13-NK cells on D=0 for each cohort. The measure is a participant count, rather than a continuous measurement or time-to-event summary.

In general, dose-limiting toxicity is used in early-phase treatment research to assess whether a dose is associated with unacceptable toxicity under a prespecified definition and observation window. Counting participants who meet the definition gives a direct description of how often that endpoint occurred in the observed cohort. It is not, by itself, a full account of all adverse events, their severity, or their timing beyond the defined window.

The endpoint’s definition includes an attribution requirement (related), a severity threshold, a toxicity category, and a time limit. These details matter because changing any of them could change which events count. The record does not report the number meeting the definition in each cohort or an estimated maximum tolerated dose. The serious adverse-event counts posted elsewhere in the record are not interchangeable with this endpoint: they do not establish that an event met the dose-limiting toxicity definition.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

Statistical methods for the trial’s outcome analyses are not reported in the registry record. The record lists two outcome measures and zero analyses. That absence matters: without an analysis description, it is not possible to know how outcomes were summarized, how missing observations were handled, or whether any adjusted estimates or formal comparisons were planned. The explanations below describe general statistical concepts relevant to the listed design and outcomes; they are not claims about methods used by this trial.

What does a single-group design allow?

In general, a single-group study describes outcomes among people receiving the study regimen. It can provide information about events observed during treatment and follow-up, subject to the quality of measurement and completeness of reporting. Without a concurrent control group, it does not directly estimate what would have happened to the same population under another treatment or no study treatment. Differences from an external population or historical experience can be affected by patient selection, disease characteristics, follow-up, and event ascertainment.

This distinction is especially important for the dose cohorts. A dose-labelled cohort is not automatically a randomized comparator. Cohort membership may be related to the way a dose-escalation study is conducted, but the registry does not report assignment rules. General comparisons across cohorts can therefore be descriptive, while a causal interpretation requires additional design and analysis support that is not reported.

How should a participant count be read?

The primary endpoint is a count of participants who experienced an event meeting a specified definition. A count is not a rate unless a denominator and relevant observation period are incorporated into the summary. In general, reporting both the number with the event and the number assessed helps readers understand the scale of the observed frequency. The registry’s primary outcome result by cohort is not reported, so no endpoint frequency or estimate of its precision can be interpreted.

Counts also depend on outcome ascertainment. For this endpoint, an event must be related, non-hematologic, at least grade 3, and within the stated 28-day period. Events that do not meet one or more parts of that definition would not qualify as dose-limiting toxicity under the registry definition, though they could still be clinically relevant adverse events. A clearly specified endpoint avoids conflating this measure with broader safety summaries.

What is the role of the toxicity window?

In general, a prespecified observation window defines the period during which events are counted for a particular endpoint. A bounded window can make dose evaluation more consistent, but it does not describe events outside that interval. Interpretation also depends on complete follow-up during the window and consistent event review. The registry states the window for the primary endpoint but does not report details of endpoint adjudication, follow-up completeness, or handling of participants who did not complete the window.

Severity and attribution are further judgment-based components. A severity grade classifies the intensity of an event under an established grading approach, while attribution assesses whether it is considered related to treatment. The registry gives the threshold and attribution condition but does not report the detailed grading or attribution procedures. General statistical summaries cannot eliminate uncertainty arising from differences in event assessment.

What does precision mean?

In general, an estimate from a sample is subject to sampling variation. A confidence interval describes uncertainty around an estimate under the assumptions of the chosen statistical method. Narrower intervals generally indicate greater statistical precision, while wider intervals indicate more uncertainty. Such intervals do not account automatically for selection bias, missing observations, or outcome misclassification. No confidence intervals for the primary endpoint or response outcome are reported in the registry record, so their precision cannot be assessed.

For uncommon outcomes, small cohort counts can be especially imprecise; observed counts may change substantially with additional observations. This general point does not establish the precision of any cohort result in this trial, because the primary outcome counts are not posted. The safety counts should likewise be read as descriptive entries rather than as precise comparative estimates.

What can planning illustrations tell readers?

In general, sample-size planning asks how many participants may be needed under chosen assumptions to detect a specified effect with a chosen statistical procedure. The registry’s planning assumptions describe a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. They also state that the effect to detect is a specified fraction of the observed effect. These are planning assumptions, not a description of the actual single-group design, and they do not establish observed power.

The record does not report the numeric planning estimates or an observed effect from which to assess those illustrations. Because the study has no like-for-like randomized arms, assumptions involving equal allocation between two arms do not describe the trial’s recorded allocation. Planning estimates should not be mistaken for observed sample sizes, results, or evidence that the study could detect a particular effect. Any interpretation of an estimate would also depend on the underlying effect assumption and the suitability of the approximation.

Over-dispersion is a general concern when count outcomes vary more than a model assumes; ignoring it can make uncertainty estimates too optimistic. This endpoint, however, is specified as a participant count, and the registry does not report a count model or any fitted analysis. It would not be appropriate to assume a particular distribution or infer that over-dispersion was assessed. The key statistical limitation is that the record does not provide outcome estimates or analysis methods needed to evaluate the primary endpoint quantitatively.

10. Exact Estimates for Each Arm

No two-arm comparison is shown for this trial, but each arm's result can still be summarized with exact interval estimates computed from the posted counts. The Clopper-Pearson interval is exact and conservative; the Wilson interval is a common closer-to-nominal alternative; the Bayesian credible interval uses a uniform Beta(1, 1) prior. For small groups the three can differ noticeably.

R code and output

arm    <- c("Phase I_ Cohort 1(1x10^6/kg)", "Phase I_ Cohort 2(1x10^7/kg)", "Phase I_ Cohort 3(1x10^8/kg)", "Phase II_ Cohort 3(1x10^8/kg)")
n      <- c(3, 3, 4, 35)
events <- c(0, 0, 0, 0)
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  Phase I_ Cohort 1(1x10^6/kg)  3  0  0.0  0.0  70.8  0.0  56.1  0.6  60.2
ARM  Phase I_ Cohort 2(1x10^7/kg)  3  0  0.0  0.0  70.8  0.0  56.1  0.6  60.2
ARM  Phase I_ Cohort 3(1x10^8/kg)  4  0  0.0  0.0  60.2  0.0  49.0  0.5  52.2
ARM  Phase II_ Cohort 3(1x10^8/kg)  35  0  0.0  0.0  10.0  0.0  9.9  0.1  9.7

11. Multiplicity, Missing Data and Analysis Populations

The registry lists two outcome measures: the primary dose-limiting toxicity count and the secondary complete-response count after AFM13-NK cell infusions. It does not report an analysis plan describing how these outcomes were prioritized beyond the primary and secondary labels, whether multiple comparisons were intended, or whether any adjustment for multiplicity was planned. A multiplicity strategy is not reported in the registry record.

In general, when several outcomes or comparisons are examined, the chance of at least one apparently notable result can increase if each is assessed separately. Methods to address multiplicity depend on the goals and structure of the analyses. No such method can be attributed to this study from the available record. Further, the registry lists zero analyses, and results for the primary and secondary outcomes are not reported, so there are no posted outcome tests to interpret in relation to multiplicity.

Missing-data methods and analysis populations are also not reported in the registry record. It is not stated how participants with incomplete follow-up, unavailable outcome assessments, treatment discontinuation, or missing safety information were handled. The record does not define an intention-to-treat, per-protocol, or safety analysis population. These omissions matter because the population included in a summary and the handling of absent measurements can affect its interpretation.

In general, a complete account of missingness explains how much information was unavailable, why it was missing, and what assumptions or methods were used to address it. Without those details, the degree to which posted counts represent all enrolled participants cannot be assessed. No imputation method or sensitivity analysis is reported in the registry record.

12. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Deaths

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 0% reporting threshold.

Most frequent non-serious adverse event terms

The registry lists serious adverse-event figures by four groups. The number at risk is 3 in Phase I Cohort 1, 3 in Phase I Cohort 2, 4 in Phase I Cohort 3, and 35 in Phase II Cohort 3. Serious adverse events affected 0 participants in each listed group. The other adverse-event counts are 2, 3, 1, and 9 in those same groups, respectively. Death counts are 2, 2, 2, and 14, respectively.

These figures are counts, not evidence of a causal relationship. The record does not report whether deaths were related to treatment, their causes, or their timing. It also does not give the detailed definitions and observation periods for the safety categories in the posted entries. The zero serious adverse-event counts therefore should not be read as meaning that no adverse events occurred: the record separately lists other adverse events and deaths.

The groups are phase and dose cohorts within a single-group study, not randomized comparator arms. Their counts should not be compared as if participants had been assigned to equivalent groups under controlled conditions. The serious adverse-event counts also do not substitute for the primary dose-limiting toxicity endpoint, which has a specific definition and a stated 28-day timeframe. The endpoint counts are not reported in the registry record.

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

The registry record establishes the broad study question and treatment structure: a phase I/II, single-group evaluation of AFM13-NK and AFM13 in patients with recurrent or refractory CD30-positive Hodgkin or non-Hodgkin lymphomas. It identifies dose cohorts, specifies the primary toxicity endpoint, and posts selected safety counts. These details help describe what the study was intended to examine and what information is available for statistical interpretation.

The record does not report the primary dose-limiting toxicity counts by cohort, a maximum tolerated dose result, or the complete-response result. It therefore does not support a quantitative conclusion about those outcomes. The safety counts are descriptive and do not establish that the regimen caused or prevented any event. In particular, the listed deaths cannot be attributed to treatment based on the information reported.

Because there is no separate comparator and allocation is recorded as NA, the trial does not provide a randomized estimate of the effect of the regimen relative to another treatment. Even a complete outcome count in a single group would describe observed outcomes rather than isolate treatment effects from other influences. Statistical significance, if reported for some result, would not by itself resolve that design limitation.

General interpretation also depends on the denominator, follow-up completeness, outcome definitions, and analysis population. Some of those details are stated for the primary endpoint, while the procedures for missing data and participant inclusion are not reported in the registry record. The posted data therefore support a bounded description of trial design and safety entries, but not claims about comparative benefit, efficacy, or causal safety effects.

14. Why This Trial Matters Statistically

This trial is statistically notable because it combines early-phase dose evaluation with a subsequent phase II cohort, while remaining a single-group study. The dose cohorts are relevant to the primary question about dose-limiting toxicity, but they are not randomized treatment arms. That distinction is central: dose cohorts can inform a descriptive dose evaluation, yet they do not provide the same protection against confounding as randomized allocation.

The primary endpoint is narrowly defined by event relationship, toxicity category, severity threshold, and a 28-day observation period. In general, such precision in outcome definition is important when evaluating tolerability, because readers need to know which events contribute to the endpoint and when they count. Here, however, the registry does not report the resulting cohort counts. The carefully stated endpoint cannot be interpreted as a result without those data.

The record also illustrates why safety counts need context. Serious adverse events, other adverse events, deaths, and dose-limiting toxicity are not interchangeable categories. Their interpretation depends on definitions, timing, denominators, and attribution. The posted counts provide some descriptive information, but do not include enough detail to establish causation or permit a fair comparison across cohorts.

Finally, the record lists a complete-response outcome but does not report its result or analysis methods. It also does not describe missing-data procedures, analysis populations, or multiplicity handling. Statistically, these omissions limit assessment of both the magnitude and precision of any treatment-related outcome. The trial’s record is therefore informative about design and endpoint intent, while leaving key numerical efficacy and dose-evaluation conclusions unreported.

15. Limitations

• The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
• Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.

The main trial-specific limitation is the absence of reported primary and secondary outcome results. Although the primary endpoint definition is detailed, the number of participants meeting it in each cohort is not reported in the registry record. The complete-response result is also not reported. No maximum tolerated dose determination or outcome estimate can be assessed from the posted information.

The single-group design and lack of a comparator restrict causal interpretation. Dose cohorts do not constitute randomized controls, and the registry does not report the rules for cohort assignment or movement between doses. Cohort differences may therefore reflect factors other than dose. The record also provides no comparative analysis that could separate treatment effects from natural disease course or other influences.

Safety interpretation is limited by missing context. The registry posts serious adverse-event, other adverse-event, and death counts, but does not report causes of death, treatment attribution, detailed event definitions, or follow-up periods for those entries. The serious adverse-event counts cannot be substituted for the dose-limiting toxicity endpoint because the endpoint has its own definition and window.

Further limitations include the absence of reported analysis methods, missing-data handling, analysis populations, and multiplicity procedures. The record does not provide confidence intervals or other measures of precision for the outcome estimates. It also does not report details of participant characteristics by cohort or completeness of follow-up. These limitations constrain interpretation to the trial design, endpoint definitions, and posted counts rather than conclusions about comparative effectiveness, treatment causality, or the precision of outcome estimates.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Modified Immune Cells (AFM13-NK) and A Monoclonal Antibody (AFM13) in Treating Patients With Recurrent or Refractory CD30 Positive Hodgkin or Non-Hodgkin Lymphomas — NCT04074746.
• Registry record last updated 2026-09-30; status last verified 2026-09.
• Results first posted 2026-09-30.
• Data retrieved from ClinicalTrials.gov on 2026-11-09.
• Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.

19. Record Summary

The registry describes a completed phase I/II, single-group study sponsored by M.D. Anderson Cancer Center, with enrollment of 45. The treatment combined AFM13-NK with AFM13 and included fludarabine and cyclophosphamide. Dose cohorts are listed at 1x10^6/kg, 1x10^7/kg, and 1x10^8/kg, with a phase II cohort also identified at 1x10^8/kg.

The primary outcome is the number of participants with related grade 3 or greater non-hematologic toxicity within 28 days of AFM13-NK infusion. Complete response after cell infusions is listed as a secondary outcome. Neither outcome result is reported in the registry record. The posted safety entries include zero serious adverse events in each listed group, counts of other adverse events, and death counts, but do not establish treatment causality. With no comparator and no reported outcome analyses, the record supports descriptive interpretation of design and posted safety counts, not comparative treatment conclusions.