QUILT-3.033: Haplo NK With SQ ALT-803 for Adults With Relapsed or Refractory AML: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for QUILT-3.033: Haplo NK With SQ ALT-803 for Adults With Relapsed or Refractory AML (NCT03050216), a na phase 2 study. The primary outcome is Number of Participants With Complete Remission With or Without Incomplete Platelet Recovery.

2. Clinical Question

The clinical question is whether the described treatment approach was followed by remission by the specified assessment time in this selected group. Because there is no concurrent control group, the study is not structured to isolate the treatment’s effect from other influences on outcomes. The registry record also does not report the clinical characteristics of the analyzed participants in enough detail to assess how closely they represent other people with AML.

3. Trial Design

QUILT-3.033 (NCT03050216) is listed as a phase II, single-group study sponsored by Masonic Cancer Center, University of Minnesota. Its title describes haploidentical donor natural killer (NK) cell infusion with subcutaneous ALT-803 for adults with relapsed or refractory AML. The registry lists the study as completed. The recorded start date is 2017-05-16, and the primary completion date is 2019-12-15.

The treatment description includes fludarabine and cyclophosphamide as a preparative regimen, donor NK cell activation with ALT-803, and ALT-803 intended to facilitate NK cell survival and expansion. The brief summary characterizes the study as a multi-institutional Simon's optimal two-stage phase II trial. Although that design description is recorded, the registry record does not report stage-specific enrollment targets, stopping boundaries, or the rules used to move between stages.

There was no masking recorded, and allocation is listed as not applicable. Since this is a single-group study, it has no randomized control arm. Its results can describe outcomes observed among participants receiving the study regimen, but cannot make a direct randomized comparison against another regimen.

The registry lists enrollment as 8. For the primary endpoint, the record states that 7 participants' data were analyzed because one participant died after receiving 2 days of chemotherapy and never received any research treatment, NK cells, or ALT-803. These are different populations: the enrollment figure describes the study record's enrollment, while the endpoint description identifies the participants included in that analysis. No further account of participant flow or the analysis populations is reported in the registry record.

The primary endpoint was assessed at Day 42 post NK cell infusion. The record also lists secondary outcomes concerning donor-derived NK cell expansion, ALT-803-associated toxicity, and treatment-related mortality. The detailed results for those outcomes 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

Analysis population for the primary outcome, as defined in the registry: One patient died after receiving 2 days of chemotherapy and never received any elements of research, NK cells or ALT-803. So only 7 participants' data were analyzed

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 Number of Participants With Complete Remission With or Without Incomplete Platelet Recovery, measured over Day 42 post NK cell infusion.

The primary endpoint is recorded as the number of participants with complete remission with or without incomplete platelet recovery, with assessment at Day 42 post NK cell infusion. The endpoint description states that the objective was to estimate the rate of complete remission with incomplete platelet recovery (CRp). It defines CRp as leukemic clearance and neutrophil recovery without platelet recovery. The title and description thus do not use exactly the same phrasing: the title includes complete remission with or without incomplete platelet recovery, while the description specifies CRp.

A remission endpoint is clinically relevant to a study of relapsed or refractory AML because it records whether participants meet a defined disease-response state at a specified assessment time. The stated time point also makes clear when the response is being evaluated; it does not describe response at other times or its duration.

The record describes this endpoint as a count of participants, but does not report the remission count or an estimated rate. It also does not report a confidence interval for the rate. The endpoint definition and analysis population are described, but the available record does not allow readers to determine how many participants met the response criteria or how precisely a response rate was estimated.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary outcome is a binary response concept: for each participant included in the analysis, the endpoint concerns whether remission criteria were met by the specified assessment time. A count of participants with the event is a direct way to report such an outcome. An estimated rate expresses that count relative to the analysis population, while an uncertainty interval communicates how much statistical uncertainty remains around the estimate. The registry record identifies the count-type endpoint and the analysis population, but does not report the count, rate, or interval.

What does a single-group estimate describe?

In a single-group study, an outcome estimate describes the participants who received the study regimen and were included in the analysis. It does not automatically estimate what would have happened to the same participants under another regimen. A concurrent comparison group can help separate treatment differences from other influences, but no such group is reported for this study. The registry lists allocation as not applicable and identifies the model as single group.

This distinction matters even if a response count is available. A response proportion could be interpreted as a description of observed outcomes in the analyzed group, subject to the endpoint definition, follow-up, and analysis population. Without a control group, it would not establish that the regimen caused those outcomes or that its outcomes differ from another treatment.

Why does the endpoint definition matter?

The primary endpoint title refers to complete remission with or without incomplete platelet recovery. The accompanying description focuses on CRp and defines it as leukemic clearance and neutrophil recovery without platelet recovery. A reader should retain that wording distinction rather than assume that all possible remission categories were combined in a particular way. The registry does not provide further adjudication rules or operational details for classifying responses.

The timing is also part of the endpoint: Day 42 post NK cell infusion. This identifies the intended response assessment time, but does not tell readers about response after that time, the duration of remission, or outcomes at other time points. The record does not report those results.

What does an uncertainty interval contribute?

In general, a confidence interval gives a range of values compatible with the observed data under a statistical method and its assumptions. For an event rate, a narrow interval usually indicates greater precision than a wide interval. The interval does not remove limitations in study design, and it cannot correct for the lack of a concurrent control group. No confidence interval for the primary endpoint is reported in the registry record, so its precision cannot be evaluated from the posted results.

General statistical tests and intervals can also depend on the number of observations and the analysis method. With a small analysis population, estimates can be sensitive to each participant's outcome. This is a general consideration, not a calculation of precision for this trial; the registry does not provide the remission count or an interval with which to quantify it.

How should the design label be read?

The brief summary calls the study a Simon's optimal two-stage phase II trial. In general, two-stage designs can use information collected in an initial stage to inform whether enrollment should continue, according to prespecified rules. The registry record does not state the decision thresholds, stage enrollment targets, stopping rules, or whether any interim decision was made. Those details should not be inferred from the design label alone.

The sample-size planning illustrations associated with the posted results are described as calculations based on the observed effect, rather than the trial's own design. They assume a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation; the effect to detect is a stated fraction of the observed effect. Such calculations are planning illustrations, not observed power, and the hypothetical two-arm allocation does not match this single-group trial. No calculated planning values are reported in the registry record.

In general, power is a design-stage probability of detecting a specified effect under assumptions about the outcome and analysis. It is not a measure of the probability that a result is true, and it should not be inferred after the fact from whether a result appears statistically significant. The registry record does not report a statistical analysis plan or the assumptions used to design the trial.

What can the posted analyses establish?

The registry lists zero analyses. This means there are no posted analysis results in the record for assessing the primary endpoint or the listed secondary outcomes. It does not establish whether analyses were conducted outside the registry or whether results were reported elsewhere. No p-value, adjusted estimate, or sponsor analysis is reported in the registry record, so none can be compared with a recalculation.

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("Cy, FLU, Haplo NK and ALT-803")
n      <- c(7)
events <- c(1)
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  Cy, FLU, Haplo NK and ALT-803  7  1  14.3  0.4  57.9  2.6  51.3  3.2  52.7

11. Multiplicity, Missing Data and Analysis Populations

The registry lists 7 outcome measures, including the primary remission outcome and secondary outcomes concerning in vivo expansion of donor-derived NK cells, ALT-803-associated toxicity, and treatment-related mortality. The secondary outcome list repeats the ALT-803-associated toxicity wording. The record does not report a multiplicity adjustment, a hierarchy among secondary outcomes, or a statistical analysis plan describing how multiple outcomes would be handled.

Multiplicity is a general statistical concern when several outcomes or comparisons are examined: the chance of at least one apparently unusual finding can increase as more tests are considered. Whether and how that concern was addressed in this trial is not reported in the registry record. The record lists zero analyses, so there are no posted outcome-specific analysis results or p-values to assess for multiplicity.

The endpoint description states that 7 participants' data were analyzed and explains that one participant died after 2 days of chemotherapy without receiving research treatment, NK cells, or ALT-803. Enrollment is listed as 8. This identifies an exclusion from the primary endpoint analysis, but the registry record does not describe a broader missing-data approach, imputation, sensitivity analysis, or analysis population definition beyond that statement.

It is therefore not possible to assess how missing or unavailable outcome data were handled beyond the stated exclusion. The record also does not report an intention-to-treat analysis or other population-specific analysis. These details should not be inferred from the study's phase or design label.

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 serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: neoplasms benign, malignant and unspecified (incl cysts and polyps) - other (62.5%), febrile neutropenia (25.0%), febrile neutropenia - changed to levaquin and micafungin (12.5%), heart failure (12.5%), lung infection (12.5%).

The registry safety entry lists 8 participants at risk for both serious and other adverse events. It lists 7 participants affected under serious adverse events and 8 affected under other adverse events. These are safety summaries, separate from the primary remission endpoint. The record also lists deaths as 8; the timing, cause, and relationship to study treatment are not described in the registry entries, so that count should not be interpreted as treatment-related mortality.

The serious event terms include neoplasms benign, malignant and unspecified (incl cysts and polyps) at 62.5%, febrile neutropenia at 25.0%, and febrile neutropenia - Changed to levaquin and micafungin, heart failure, lung infection, and tumor lysis syndrome at 12.5% each. These registry labels and percentages describe reported serious adverse event entries. They do not establish that ALT-803 or the overall regimen caused an event. The record does not provide event-level timing, severity details, or causal attribution for these terms.

The secondary outcomes include ALT-803-associated toxicity and treatment-related mortality, but their outcome results are not reported in the registry record. The serious-event listing should therefore be read as a descriptive safety summary, not as a comparative estimate or a complete account of treatment-related harm.

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

The registry record documents a phase II, single-group study of haploidentical donor NK cell infusion with subcutaneous ALT-803 for adults with relapsed or refractory AML. It specifies a Day 42 remission endpoint and states that 7 participants' data were analyzed for that endpoint. It also explains why one enrolled participant was not included in that analysis. These registry entries clarify the study question and analysis population, but they do not provide the primary remission result.

Without the remission count or rate, the record cannot show how often the endpoint occurred or how precise an estimate would be. No conclusion about the frequency of remission in the analyzed group can be drawn from the endpoint definition alone. The missing result should not be treated as a zero response or as a favorable response.

Even if a response result were reported, the single-group design would limit causal interpretation. An outcome observed among participants receiving the regimen would not by itself show what would have occurred with a different treatment. The study has no concurrent control arm reported in the registry, and no randomized comparison is described.

The safety entries give counts of participants affected and list several serious adverse event terms. They are descriptive registry reports, not proof that treatment caused the events. The record also lists deaths, but does not report the context needed to interpret that count or connect it to treatment. Results for the secondary outcomes are not reported in the registry record.

The most defensible reading is therefore narrow: the registry describes the treatment approach, study design, endpoint, analysis population, and selected safety reporting. It does not report a primary efficacy estimate or the detailed analyses needed to assess its statistical uncertainty. No claim about treatment benefit, lack of benefit, or comparative safety follows from the available results.

14. Why This Trial Matters Statistically

This trial is statistically notable because its design and reporting make the distinction between an outcome definition and an outcome result especially important. The registry specifies a primary remission endpoint and an assessment time, but does not report the remission count or rate. Naming a clinically meaningful endpoint is not equivalent to reporting the observed result; without the result, neither its size nor its precision can be evaluated.

The single-group structure is also central to interpretation. It permits descriptive reporting of outcomes among participants treated in the study, but it does not provide a randomized contrast. A reader cannot use a single-group result to establish how outcomes compare with a different treatment or to isolate the effect of the regimen from other factors.

The record identifies a Simon's optimal two-stage phase II design, which signals a staged design approach, but omits the rules and thresholds needed to understand its operation. Reporting those elements would help readers evaluate the relationship between the design and the study's decisions. The registry also lists no analyses, leaving the primary and secondary outcomes without posted statistical results.

Finally, the record distinguishes enrollment from the primary endpoint analysis population: enrollment is listed as 8, while 7 participants' data were analyzed after one participant died before receiving any research treatment. Clear reporting of who is included in each analysis is essential for interpreting event counts and missing outcomes. The record gives a reason for this particular exclusion but does not describe a broader missing-data strategy.

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 primary limitation for interpreting efficacy is that the registry record does not report the remission count, estimated rate, or confidence interval. The endpoint is described, but the result needed to assess its frequency and precision is absent. The record lists zero analyses, and it does not report detailed results for the secondary outcomes.

The study is single group, with no concurrent comparator reported. Thus, even a descriptive remission result would not establish a treatment effect relative to another regimen. No random allocation is reported; allocation is listed as not applicable. The brief summary identifies a two-stage design, but the stage-specific thresholds, enrollment targets, and stopping decisions are not reported.

The analysis population differs from the enrollment figure: 7 participants' data were analyzed for the primary endpoint, while enrollment is listed as 8. The record explains that one participant died after 2 days of chemotherapy and did not receive research treatment, NK cells, or ALT-803. It does not report a broader account of participant flow, missing-data methods, or sensitivity analyses.

The endpoint title refers to remission with or without incomplete platelet recovery, while the description specifically defines CRp as leukemic clearance and neutrophil recovery without platelet recovery. Further operational criteria for response classification are not reported. Safety information is also limited: the record lists affected counts, event terms, percentages, and deaths, but the detailed timing, attribution, and clinical context are not reported. These constraints limit interpretation of both efficacy and safety.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: QUILT-3.033: Haplo NK With SQ ALT-803 for Adults With Relapsed or Refractory AML — NCT03050216.
• Registry record last updated 2023-07-18; status last verified 2023-07.
• Results first posted 2020-11-27.
• 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

QUILT-3.033 (NCT03050216) is listed as a completed phase II, single-group study sponsored by Masonic Cancer Center, University of Minnesota. It evaluated haploidentical donor NK cell infusion with subcutaneous ALT-803 after fludarabine and cyclophosphamide in adults with relapsed or refractory AML. The registry lists enrollment as 8 and reports that 7 participants' data were analyzed for the primary endpoint after one participant died before receiving any research treatment.

The primary endpoint was remission at Day 42 post NK cell infusion. Its outcome count and rate are not reported in the registry record. The registry lists safety counts and serious adverse event terms, but does not report detailed outcome analyses, causal attribution, or the results for the listed secondary outcomes. No comparator group or randomized comparison is reported.