High-Dose Interleukin-2 (HDIL-2), Combined With recMAGE-A3 + AS15 ASCI: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for High-Dose Interleukin-2 (HDIL-2), Combined With recMAGE-A3 + AS15 ASCI (NCT01266603), a na phase 2 study. The primary outcome is Objective Response Rate.

2. Clinical Question

The study asks whether the combination can produce objective tumor responses in a selected melanoma population, while also examining safety. Its primary endpoint classifies response as complete or partial. A complete response means disappearance of all target lesions; a partial response means a decrease of >=30% in the sum of the longest diameters of target lesions. Overall response is defined as complete response plus partial response.

This is a descriptive question about outcomes among participants receiving the combination, not a randomized comparison of the combination against another treatment. Without a concurrent control group, the response rate cannot by itself identify what would have happened to similar patients without the study combination or under a different treatment. The registry also describes exploratory study of tumor-tissue genes in relation to response, but does not report a result for that work.

The primary endpoint timeframe is until disease progression or up to 3 years & 9 months. The registry lists progression-free survival and rate of serious adverse events as secondary outcomes. Numerical results for these outcomes are not reported in the registry record.

3. Trial Design

This is a phase II, completed, single-group study sponsored by M.D. Anderson Cancer Center. The registry lists melanoma as the condition and enrollment as 44. That enrollment figure is a registry characteristic; the number included in any particular endpoint analysis is not reported in the registry record. The study start is listed as 2011-02-22 and primary completion as 2018-11-01.

The intervention combines HDIL-2 with recMAGE-A3 + AS15 ASCI. The arm description specifies HDIL-2 at 720,000 IU/kg by vein over an approximate 15 minute period every eight hours, for a maximum of 14 doses per cycle. It describes recMAGE-A3 300 μg plus 420 μg of CpG7909, a part of the Adjuvant System AS15, by intermuscular injection within 24 hours from the first dose of HDIL-2.

The record lists no masking and records allocation as NA. It identifies the model as single-group, so the design does not include a randomized control group for a like-for-like comparison. The record’s planning assumptions refer to equal allocation between two arms; those assumptions are not the design of this trial and should not be read as evidence that the trial had two arms.

Objective response rate is the primary outcome, assessed by RECIST v1.0 for target lesions using MRI, until disease progression or up to 3 years & 9 months. The listed secondary outcomes are rate of SAEs and progression-free survival. The registry identifies 3 outcome measures, but the endpoint-specific numerical results and analysis details are not reported in the registry record. No analysis is listed.

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 Objective Response Rate, measured over Until disease progression or up to 3 years & 9 months.

Objective response rate is the proportion of participants classified as having an overall response. In this study, overall response is defined as complete response plus partial response, assessed using RECIST v1.0 for target lesions by MRI. A complete response is disappearance of all target lesions. A partial response is a decrease of >=30% in the sum of the longest diameters of target lesions.

This endpoint is used to describe whether measurable target lesions meet prespecified response categories during the stated assessment period. Combining complete and partial responses into an overall response rate gives a single summary of participants meeting either category. The endpoint is not the same as a time-to-event outcome: it records response classification rather than the length of time until progression or another event.

The timeframe is until disease progression or up to 3 years & 9 months. The registry record does not report the number of participants assessed, the number classified as complete or partial responses, or the resulting response rate. It also does not report the assessment schedule or how participants without an evaluable assessment were handled. Consequently, the endpoint definition is available, but the observed result and its precision cannot be described from the registry record.

In general, a response rate is interpretable only alongside its denominator and a clear account of who was assessed. Those details help distinguish the fraction among all enrolled participants from the fraction among participants with evaluable assessments. The relevant denominator for this reported outcome is not stated in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary outcome is binary at the participant level: each assessed participant is classified as having an overall response or not, according to the endpoint definition. In general, a binary outcome can be summarized as the number meeting the definition divided by the number assessed. The registry gives neither of those primary-outcome counts nor a response percentage, so an observed rate cannot be interpreted from this record.

RECIST v1.0 supplies the response categories used in the registry description. Complete response means disappearance of all target lesions. Partial response requires a decrease of >=30% in the sum of the longest diameters of target lesions. The overall response definition combines those categories. This operational definition matters because a response estimate depends on how the endpoint is classified, which lesions are evaluated, and which participants contribute assessments. The registry record states the criteria and MRI assessment, but not the assessment schedule, the handling of missing scans, or the evaluable analysis population.

In general, the uncertainty around a binary rate is often expressed with a confidence interval. The interval conveys how much uncertainty remains about the underlying response proportion given the observed data and the method used. An interval cannot be reconstructed from the endpoint definition alone. The registry does not report the primary response numerator, denominator, rate, or confidence interval. Accordingly, there is no posted primary estimate whose precision can be assessed.

The study’s single-group structure is central to interpretation. A one-group response estimate describes outcomes in the treated group; it does not provide a randomized estimate of the difference between treatments. In general, random allocation helps balance prognostic factors across comparison groups, while a single-group study lacks that direct concurrent contrast. The registry marks allocation as NA and the model as single-group, so the combination’s effect relative to a control cannot be estimated from this design alone.

The registry’s sample-size assumptions are explicitly planning illustrations based on an observed effect, not the trial’s own design. They specify a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation; the effect to detect is stated as a fraction of the observed effect. For time-to-event outcomes, the planning quantities are total events using the Schoenfeld approach; for other outcomes, they are participants per arm. Those assumptions describe an illustrative calculation and do not turn this single-group study into a two-arm trial. The record does not report a trial-specific sample-size justification, and the illustrations are not observed power.

In general, planning calculations answer a design question: how much information might be needed to detect a specified effect under stated assumptions. They do not measure the probability that a completed study’s finding is true, and they do not replace confidence intervals around observed results. The assumptions also matter: changing the target effect, allocation, significance level, or statistical approximation can change a planning result. No calculated planning values are stated in the registry record, so no numeric sample-size interpretation is possible from it.

Progression-free survival is listed as a secondary outcome. In general, time-to-event analyses use both event information and follow-up time, and may need to account for participants whose event has not occurred by the end of observation. The registry does not provide a survival estimate, event count for this outcome, censoring details, or analysis method. It is therefore not possible to assess the progression-free survival result or its uncertainty from the record.

Rate of SAEs is also listed as a secondary outcome. In general, a rate requires a clear definition of what qualifies as an event and a stated population and observation period. The adverse-event fields give counts and a list of serious terms, but the record does not explain their analysis population, follow-up window, or event attribution. The listed terms should not be treated as a complete estimate of the safety profile without that context.

The registry records no analyses. The method used for the primary endpoint, any adjustment or stratification, and any prespecified handling of missing outcome data are not reported in the registry record. Statistical significance, multiplicity adjustment, and the analysis populations are also not reported. Those absences prevent a reader from checking whether analyses followed a prespecified plan or whether uncertainty was quantified using an appropriate method.

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("High-dose Interleukin-2 (HDIL-2) + recMAGE-A3 Prot")
n      <- c(16)
events <- c(4)
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  High-dose Interleukin-2 (HDIL-2) + recMAGE-A3 Prot  16  4  25.0  7.3  52.4  10.2  49.5  10.3  49.9

11. Multiplicity, Missing Data and Analysis Populations

The registry lists 3 outcome measures, including objective response rate, rate of SAEs, and progression-free survival. It does not report a multiplicity strategy or explain whether additional outcomes were treated as exploratory. When several outcomes are examined, multiplicity matters in general because repeated statistical testing can increase the chance of at least one apparently notable finding. The registry does not report tests or p-values for these outcomes, so the effect of any multiplicity adjustment cannot be assessed.

Missing-data methods are not reported in the registry record. In general, missing assessments can affect an endpoint if participants without an evaluable assessment differ from those with one. Interpretation requires knowing how missing scans, withdrawals, or other unavailable outcome information were handled. The record does not describe those procedures for objective response rate or the secondary outcomes.

The analysis populations are also not reported. The enrollment figure is 44, but the registry does not say how many participants were included in each outcome analysis or provide the primary endpoint denominator. It is therefore not possible to determine whether the reported population, if an outcome estimate were available, would include all enrolled participants or a subset with evaluable data.

The record lists no analyses and does not report a statistical analysis plan, interim analyses, or endpoint-specific methods. These details are not reported in the registry record; their absence should not be filled by assuming a conventional method or a particular protocol decision.

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: renal insufficiency (5.9%), hyperuricemia (5.9%), diarrhea (5.9%), hypothyroidism (5.9%), hypotension (5.9%).

The registry lists a serious-adverse-event record for the HDIL-2 and recMAGE-A3 combination. The recorded fields show 17 at risk and 1 serious-event affected; the other-event fields show 17 at risk and 17 affected, and the death field lists 5. The record does not explain the relationship among these fields, their observation period, or whether the listed deaths were attributed to treatment.

The listed serious terms are renal insufficiency, hyperuricemia, diarrhea, hypothyroidism, hypotension, and acute kidney injury. Each is accompanied by 5.9%. These percentages are registry entries; the record does not give further detail about event timing, recurrence, seriousness criteria, or causal assessment for each term.

In general, adverse-event percentages need a defined denominator and observation period to be interpreted as risks. The record’s fields should be read as recorded, without inferring treatment causality or assuming that the listed terms capture every safety event. A fuller safety interpretation would require the missing analysis population, follow-up details, event definitions, and attribution information.

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

The record establishes the study’s clinical question and design: a phase II, single-group evaluation of HDIL-2 with recMAGE-A3 + AS15 in MAGE-A3-positive, unresectable or metastatic melanoma. It specifies objective response rate as the primary endpoint and describes how complete and partial responses are defined. It also identifies progression-free survival and rate of SAEs as secondary outcomes.

It does not report the observed objective response rate, the response count, or the denominator. It therefore does not show how often the defined response occurred or how precise an estimate would be. The registry also does not report numerical results for the secondary outcomes. The absence of these results is not evidence that an outcome did or did not occur; it means the outcome result is not reported in the registry record.

Even if a response rate were reported, the single-group design would make it a description of outcomes in the treated group, not a randomized comparison against another treatment. The record does not support attributing an outcome to the combination alone or estimating its relative effect against a control group.

The adverse-event entries provide limited safety information, including recorded serious-event fields, listed terms, and deaths. They do not, by themselves, establish causation or provide a complete safety profile. Event attribution, follow-up, and analysis-population details are not reported in the registry record.

In general, a complete interpretation of trial outcomes considers the endpoint definition, denominator, uncertainty, missing-data handling, and design. Here, the endpoint definition and broad design are available, but the primary and secondary outcome results and important analysis details are not. The record can therefore inform readers about what was intended to be evaluated, but not the magnitude or precision of the resulting outcomes.

14. Why This Trial Matters Statistically

This study is statistically informative as an example of the distinction between an outcome definition and an outcome result. The registry describes objective response rate in concrete terms, including RECIST v1.0 categories and MRI assessment. Yet without the response count, denominator, or rate, the endpoint description alone cannot answer how frequently participants met the response criteria.

Its single-group design also illustrates why a treatment outcome and a treatment comparison are different quantities. A response estimate from participants receiving the combination would describe that group. A comparative effect requires a credible comparator, and the registry does not describe one. The planning assumptions referring to equal allocation between two arms are illustrative assumptions, not evidence of a randomized comparison in this trial.

The record also highlights the importance of reporting uncertainty and analysis populations. A rate needs a denominator, while an uncertainty interval helps readers judge its precision. The registry does not report either for the primary outcome. Enrollment of 44 is not a substitute for the endpoint-specific denominator.

Finally, secondary outcomes and adverse-event entries require context: definitions, follow-up, attribution, and analytic handling. Their mention in a registry does not itself establish a result. These distinctions help readers separate what the study intended to assess from what the posted record permits them to conclude.

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 of the registry record for statistical interpretation is that it does not report the observed objective response rate, response count, denominator, or uncertainty interval. As a result, the primary outcome cannot be quantified or assessed for precision using the record.

The single-group design has no concurrent control group, so the record cannot provide a randomized comparison. The study description also does not report a statistical analysis plan, analysis populations, interim analyses, or methods for missing data. These details are not reported in the registry record and should not be inferred from common practice.

The registry lists 44 participants for enrollment, but does not state the endpoint-specific numbers assessed or analyzed. Its adverse-event fields list 17 at risk and 1 serious-event affected, as well as 17 at risk and 17 other-event affected, with 5 deaths. The record does not explain the populations, follow-up window, event attribution, or the relationship among these fields. Serious terms are listed with percentages, but the accompanying context needed to interpret them is limited.

The timeframe for the primary endpoint is until disease progression or up to 3 years & 9 months, but the assessment schedule and handling of participants without an evaluable assessment are not described. Results for the listed secondary outcomes and the tumor-gene work described in the summary are not reported in the registry record. Together, these omissions limit assessment of both outcome magnitude and the methods used to produce any estimates.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: High-Dose Interleukin-2 (HDIL-2), Combined With recMAGE-A3 + AS15 ASCI — NCT01266603.
• Registry record last updated 2020-02-19; status last verified 2020-02.
• Results first posted 2020-02-19.
• 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 II, single-group study of HDIL-2 with recMAGE-A3 + AS15 ASCI in patients with MAGE-A3-positive, unresectable or metastatic melanoma. Enrollment is listed as 44. The primary outcome is objective response rate by RECIST v1.0 for target lesions assessed by MRI, until disease progression or up to 3 years & 9 months.

The listed secondary outcomes are rate of SAEs and progression-free survival. The record gives intervention dosing and limited adverse-event fields, but does not report the primary response result, secondary outcome results, analysis populations, or statistical methods. Therefore, the endpoint and design are described, while the magnitude and precision of the clinical outcomes are not reported in the registry record.