IL-15 Super Agonist ALT-803 to Treat Relapse Of Hematologic Malignancy After Allogeneic SCT: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for IL-15 Super Agonist ALT-803 to Treat Relapse Of Hematologic Malignancy After Allogeneic SCT (NCT01885897), a na phase 1, phase 2 study. The primary outcome is Number of Participants With Dose Limiting Toxicity (DLT) Events.

2. Clinical Question

This question combines safety-oriented dose finding with a later efficacy-oriented plan. These aims are related but distinct: identifying a dose using toxicity and efficacy considerations is not the same as estimating a comparative treatment effect. Because there is no control group, the registry record cannot establish how outcomes would have differed under another treatment or without ALT-803. The study enrolled 33 participants across its listed dose groups, but that enrollment figure alone does not indicate how many contributed to each endpoint analysis or what their outcomes were.

3. Trial Design

The registry describes a multicenter phase I/II study of ALT-803 in patients whose hematologic malignancy relapsed more than 60 day after allogeneic stem cell transplant. It lists the study as completed, with enrollment of 33, a start date of 2013-11-11, and primary completion in 2019-07. The sponsor is Masonic Cancer Center, University of Minnesota. No masking was used, allocation is listed as not applicable, and the model is single group.

The planned dose-finding phase was a modified phase I design. The brief summary describes a standard 3+3 dose-escalation design for toxicity, with an added provision to stop early if efficacy was confirmed. Six dose levels were planned: 1, 3, 6, 10, 20, and 30 mcg/kg. The stated dose-finding objective was to identify the maximum tolerated, minimum efficacious dose when ALT-803 was given once weekly for 4 weeks in the outpatient setting. The registry does not report which dose was selected or the dose-specific primary endpoint results.

The extended phase was described as a modified phase II study using an optimal Simon's two-stage design. Its stated goal was to study potential efficacy, measured using rates of remission induction. The plan called for Stage 1 enrollment of 14 patients, including 6 treated at the selected dose during dose finding. The plan specified proceeding to Stage 2, with an additional 23 patients, if 3 or more of the 14 responded; with 2 or fewer responses, enrollment would stop early. These are design rules, not reported outcomes. The registry record does not say whether the planned stages were completed or whether the stopping rule was triggered.

The treatment description specifies weekly ALT-803 for 4 weeks, with assigned doses ranging from 1mcg/kg to 30 mcg/kg and intravenous administration. The adverse-event listing also includes subcutaneous groups. The record does not explain how the subcutaneous groups relate to the planned efficacy phases, so they should be read as listed safety groups rather than assumed to be directly comparable arms.

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

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.

Only the first 6 of 7 groups are shown.

6. Primary Endpoint

The registry lists the primary outcome as Number of Participants With Dose Limiting Toxicity (DLT) Events, measured over 4 weeks.

The listed primary endpoint is the number of participants with dose-limiting toxicity (DLT) events, with a stated timeframe of 4 weeks. It is a count of participants meeting the DLT definition, not a measure of the severity of every event or a rate of remission. The registry defines DLT during the first treatment cycle as treatment-emergent grade 3 non-hematologic toxicity lasting more than 48 hours, any treatment-emergent grade 4 or 5 non-hematologic toxicity of any duration, or grade III or IV acute graft-versus-host disease within 6 weeks after the first ALT-803 dose. The description also defines the maximum tolerated dose as the dose level where ≤ 1 out of 6 patients has DLT during the first treatment cycle.

In general, a toxicity endpoint is used in dose finding to identify doses that can be carried forward while accounting for treatment-related safety concerns. The trial’s stated objective went beyond toxicity alone: it sought a maximum tolerated, minimum efficacious dose. However, the registry record does not report a DLT count by dose or identify a selected dose, and the primary endpoint entry does not provide remission-induction results.

The endpoint entry states a 4 weeks timeframe, while the DLT definition includes acute graft-versus-host disease within 6 weeks after the first dose. This difference in stated timing is important when interpreting the endpoint and does not by itself establish how the analysis handled events over those periods. That handling is not reported in the registry record. The primary endpoint population field is blank, so the analysis population definition is also not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does a single-group design imply?

In general, a single-group study observes participants receiving a study intervention without a concurrent control arm. It can describe outcomes within the treated group, but it does not by itself separate intervention effects from the course of disease, other care, participant selection, or other influences. Here, the registry lists no masking, allocation as not applicable, and a single-group model. The dose groups should not be interpreted as randomized controls. A comparison across doses may also reflect the planned escalation process and other differences between groups.

How does the dose-finding plan work?

In general, a 3+3 dose-escalation design evaluates dose levels in small cohorts, with escalation decisions guided by observed toxicity. The registry describes this as a standard 3+3 design with an added early-stop provision if efficacy was confirmed. It lists dose levels of 1, 3, 6, 10, 20, and 30 mcg/kg. The maximum tolerated dose definition is stated as the dose level where ≤ 1 out of 6 patients has DLT during the first treatment cycle. This is a design definition, not a reported finding. No dose-level DLT outcomes or selected dose are reported in the registry record.

The stated objective uses the combined term maximum tolerated, minimum efficacious dose. In general, this signals that dose choice was intended to consider both toxicity and efficacy. The record describes the efficacy-based stopping feature but does not specify the detailed decision rule for minimum efficacy, the operational definition of efficacy in dose finding, or how that objective was applied. Those details are not reported in the registry record.

What does the two-stage plan contribute?

In general, a Simon's two-stage design allows an early decision about whether to continue enrollment, based on an initial group of responses. The registry describes Stage 1 enrollment of 14 patients, including 6 participants treated at the selected dose during dose finding. The plan was to proceed to Stage 2 and enroll an additional 23 patients if 3 or more of the 14 responded; if 2 or fewer responded, enrollment would terminate early. This is a planned screening rule for the remission-induction objective. It does not provide the observed response count, the final response estimate, or evidence about whether the study reached the second stage.

In general, a two-stage design can reduce further enrollment when early results do not meet a prespecified threshold, while retaining a path to further study when they do. Its interpretation depends on the response definition, analysis population, missing-response handling, and design assumptions. The registry record does not report these details beyond the stage thresholds and enrollment plan. It also does not report the final response findings.

How should the primary endpoint be read?

The primary outcome is a count of participants with DLT events. The event definition includes specified grades and durations of non-hematologic toxicity, as well as grade III or IV acute graft-versus-host disease within 6 weeks after the first dose. The endpoint timeframe is stated as 4 weeks. In general, an endpoint needs a clearly aligned observation window so that readers know which events are counted. The mismatch between the stated timeframe and one component of the definition warrants caution; how the analysis reconciled those periods is not reported in the registry record.

A count is not the same as an incidence rate unless the relevant denominator and observation period are specified. The registry gives group sizes for safety summaries, but it does not provide primary DLT counts by group. It also does not provide an analysis population or a statistical estimate of the DLT outcome. The maximum tolerated dose rule is a protocol criterion; the registry record does not establish which dose, if any, met it.

What do uncertainty and over-dispersion mean in general?

In general, a confidence interval describes a range of values compatible with the data under a statistical model and gives readers a sense of estimate precision. Wider intervals indicate less precision, while narrower intervals indicate greater precision under the model. No confidence interval for the primary endpoint or remission-induction outcome is reported in the registry record, so precision cannot be assessed from those results.

In general, over-dispersion occurs when outcome variability exceeds what a chosen statistical model expects. It can make standard errors too small if ignored, leading to intervals that appear more precise than warranted. This is a general statistical consideration, not a reported issue or analysis in this study. The registry record does not identify an over-dispersion assessment or a model for the primary outcome.

What can planning illustrations establish?

In general, sample-size calculations are planning tools based on assumptions about the effect to detect, significance level, allocation, and statistical method. The listed planning assumptions describe a two-sided significance level of 0.05, equal allocation, a normal approximation, and detection of a stated fraction of an observed effect. They are described as illustrations rather than the trial’s own design. Such calculations are not observed power and cannot establish whether a study found an effect. Numeric illustration results and the observed effect needed to anchor them are not reported in the registry record.

The registry separately describes the study’s actual planning as a dose-escalation phase and a two-stage response design. These plans should not be conflated with generic sample-size illustrations. In particular, an illustration based on hypothetical assumptions does not establish the achieved precision of this single-group study, and it cannot replace the missing outcome estimates.

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("ALT-803, IV, 1 mcg/kg", "ALT-803, IV, 3 mcg/kg", "ALT-803, IV, 6 mcg/kg", "ALT-803, IV, 10 mcg/kg", "ALT-803, SQ, 6 mcg/kg", "ALT-803, SQ, 10 mcg/kg")
n      <- c(6, 3, 4, 3, 8, 9)
events <- c(0, 0, 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  ALT-803, IV, 1 mcg/kg  6  0  0.0  0.0  45.9  0.0  39.0  0.4  41.0
ARM  ALT-803, IV, 3 mcg/kg  3  0  0.0  0.0  70.8  0.0  56.1  0.6  60.2
ARM  ALT-803, IV, 6 mcg/kg  4  0  0.0  0.0  60.2  0.0  49.0  0.5  52.2
ARM  ALT-803, IV, 10 mcg/kg  3  0  0.0  0.0  70.8  0.0  56.1  0.6  60.2
ARM  ALT-803, SQ, 6 mcg/kg  8  0  0.0  0.0  36.9  0.0  32.4  0.3  33.6
ARM  ALT-803, SQ, 10 mcg/kg  9  0  0.0  0.0  33.6  -0.0  29.9  0.3  30.8

11. Multiplicity, Missing Data and Analysis Populations

The registry record lists a primary DLT endpoint and secondary outcomes concerning excessive toxicity, acute graft-versus-host disease, and chronic graft-versus-host disease. The extended phase also had a remission-induction objective. Evaluating several outcomes can raise multiplicity concerns: in general, when many hypotheses are tested, the chance of at least one apparently notable result can increase. Appropriate interpretation depends on which outcomes were prespecified as primary, how many analyses were conducted, and whether any adjustment or hierarchy was used. An adjustment strategy and detailed statistical analysis plan are not reported in the registry record.

The record lists zero analyses. It does not report endpoint estimates, hypothesis tests, confidence intervals, or a multiplicity adjustment. The presence of multiple planned outcomes does not establish that statistical tests were performed, and no claim about control of false-positive findings can be made from the posted information.

Missing-data methods and analysis populations are also not reported in the registry record. The primary endpoint population field is blank. It is therefore unclear from the record how participants who did not complete the first treatment cycle, had incomplete follow-up, or had an unevaluable response would have been handled. In general, excluding participants with missing outcomes can bias results if missingness is related to prognosis or treatment experience; treating missing outcomes as failures or using another approach also requires a stated rationale. No such approach is reported.

Enrollment of 33 is a registry study-level count, not a statement that all participants were included in every endpoint analysis. The record does not provide the participant flow, numbers analyzed for each outcome, or reasons for exclusions or missing observations. These omissions limit assessment of whether the reported safety groups and any future efficacy findings represent all enrolled participants.

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: febrile neutropenia (55.6%), sepsis (33.3%), generalized muscle weakness (25.0%), catheter related infection (16.7%), fever (12.5%).

The safety listing gives separate ALT-803 groups by route and dose. For intravenous groups, the serious-event counts are 1 of 6 at 1 mcg/kg, 1 of 3 at 3 mcg/kg, 0 of 4 at 6 mcg/kg, and 0 of 3 at 10 mcg/kg. For subcutaneous groups, the counts are 6 of 8 at 6 mcg/kg and 6 of 9 at 10 mcg/kg. The listed counts for participants with other events are 4 of 6, 2 of 3, 2 of 4, 2 of 3, 8 of 8, and 9 of 9 in those same groups. These are descriptive counts, not randomized comparisons.

The record lists selected serious-event terms with percentages: febrile neutropenia, 55.6%; sepsis, 33.3%; generalized muscle weakness, 25.0%; catheter related infection, 16.7%; fever, 12.5%; and hypoxia, 12.5%. The denominator used for these percentages is not reported in the registry record. The terms should not be assumed to be mutually exclusive or to represent all serious events.

Death counts are listed by group, but the record does not establish their timing or causal relationship to ALT-803. Serious events, other events, and deaths are distinct summaries and should not be combined or interpreted as proof of treatment causation. Small group counts and differing routes and doses further limit direct comparison.

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

The registry record establishes that a phase I/II study was designed to evaluate ALT-803 after relapse of hematologic malignancy following allogeneic stem cell transplantation. It reports the planned dose-escalation approach, a dose-selection objective, and a two-stage remission-induction plan. It also provides safety-group counts for serious events, other events, and deaths. These features allow readers to understand the study’s structure and the kinds of outcomes it intended to examine.

However, a design objective is not a result. The record does not report the primary endpoint count of participants with DLT, a selected maximum tolerated, minimum efficacious dose, or remission-induction results. It therefore does not support a conclusion about the frequency of DLT in the study or the observed remission rate. Nor does the absence of a posted result indicate that no events or responses occurred.

The group-specific adverse-event counts are not evidence of comparative safety. There is no randomized control group, and the listed groups vary by route and dose. The record does not supply an adjusted comparison, uncertainty estimates, or causal attribution for the adverse events and deaths. The figures describe what is recorded for those groups; they do not show what would have happened to the same participants under another intervention.

In general, confidence in an estimated outcome depends on details such as a defined analysis population, complete outcome ascertainment, and uncertainty estimates. Those are not reported for the primary endpoint. The total enrollment of 33 should not be treated as a measure of statistical power or as proof that the planned analyses were completed. The Simon's two-stage thresholds likewise state how enrollment was planned to proceed, not whether the observed response findings satisfied the rule.

The appropriate interpretation is therefore limited: the registry outlines an early-phase safety and efficacy study and posts descriptive safety figures, while key efficacy and primary endpoint results are not reported in the registry record. No claim that ALT-803 works or does not work follows from these posted details alone.

14. Why This Trial Matters Statistically

This trial is statistically notable because its objectives span dose finding and a planned efficacy assessment within one phase I/II study. The dose-finding phase was intended to use toxicity information, with an added early-stop feature for confirmed efficacy. The extended phase was intended to use a two-stage design for remission induction. These are different statistical tasks: one concerns selecting a dose under safety and efficacy considerations, while the other concerns evaluating a response outcome against a staged continuation rule.

The registry makes the planned decision structure unusually concrete by listing dose levels and the Stage 1 response threshold for proceeding to Stage 2. That detail helps distinguish protocol rules from results. It also highlights why readers should not infer that a stage was reached or a dose selected simply because the plan is described. Those outcomes are not reported in the registry record.

The single-group structure is another important feature. In general, early-phase studies often focus on dose and safety characterization, but a single-group design does not provide a concurrent estimate of what would have occurred under a comparator. The posted safety counts can describe the groups, but the groups are not randomized control arms. That distinction is essential when comparing different dose or route groups.

Finally, the registry record illustrates a common limitation of interpreting trial records: a clear protocol summary can coexist with sparse outcome reporting. The count of enrolled participants and listed adverse events do not replace endpoint estimates, analysis populations, or measures of uncertainty. Without the primary endpoint and remission-induction results, readers can assess the intended statistical framework but cannot judge the resulting evidence for the study’s central objectives.

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 endpoint entry does not report the number of participants with DLT, and the record lists zero analyses. The efficacy results for remission induction are also not reported. This prevents assessment of the study’s principal safety and efficacy objectives, including dose selection and whether the planned two-stage continuation rule was met.

The endpoint timing is not fully aligned in the registry description: the stated timeframe is 4 weeks, while the DLT definition includes acute graft-versus-host disease within 6 weeks after the first dose. The analysis approach to this timing difference is not reported. The primary endpoint population field is blank, and the record does not describe missing-data handling, participant flow, or numbers analyzed for each outcome.

The safety groups include different doses and both intravenous and subcutaneous administration. The record does not describe these groups as randomized comparisons, and allocation is listed as not applicable. Differences among their event counts cannot be attributed to dose or route from these data alone. Serious-event term percentages are listed without a reported denominator. Death counts are reported, but timing and causal attribution are not.

The registry identifies secondary safety outcomes and a remission-induction objective but does not report a detailed analysis plan, multiplicity approach, estimates of uncertainty, or outcome definitions for all endpoints. The sample-size assumptions describe planning illustrations, but numeric illustration results and the observed effect used for them are not reported. Enrollment of 33 does not resolve these limitations or establish the precision of an unreported outcome.

These constraints are specific to interpreting this registry record. They do not establish that analyses were not conducted elsewhere; they mean that the results needed to evaluate them are not reported in the registry record.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: IL-15 Super Agonist ALT-803 to Treat Relapse Of Hematologic Malignancy After Allogeneic SCT — NCT01885897.
• Registry record last updated 2020-08-12; status last verified 2020-07.
• Results first posted 2020-08-12.
• 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

NCT01885897 is a completed, single-group phase I/II study sponsored by Masonic Cancer Center, University of Minnesota. The registry lists enrollment of 33, a start date of 2013-11-11, and primary completion in 2019-07. It studied ALT-803 in patients with relapse of hematologic malignancy after allogeneic stem cell transplantation.

The planned dose-finding phase used dose escalation, with an objective of determining a maximum tolerated, minimum efficacious dose. The extended phase was intended to assess remission induction using a Simon's two-stage design. The listed primary endpoint is the number of participants with DLT events.

The record includes safety counts by dose and route, but does not report primary endpoint analyses, remission-induction results, confidence intervals, or the selected dose. Participant-level analysis details, missing-data methods, and a multiplicity strategy are not reported in the registry record.