Vaccine Therapy Plus Interleukin-2 in Treating Patients With Stage III or Stage IV Melanoma: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Vaccine Therapy Plus Interleukin-2 in Treating Patients With Stage III or Stage IV Melanoma (NCT00003222), a randomized phase 2 study. The primary outcome is Evaluation of Objective Clinical Response (CR/PR/SD).

2. Clinical Question

This is a question about clinical response under two vaccine strategies in a Phase II trial, not a direct test of a single vaccine component in isolation. The strategies differ in how the peptides were administered: on dendritic cells in one arm, or with GM-CSF and adjuvant in the other. Because the registry describes both strategies in the context of interleukin-2 administration, the record does not establish a comparison of vaccination alone against vaccination plus interleukin-2. Nor does it describe a no-treatment or placebo group.

The trial enrolled 40 participants overall, while the stated primary-response analysis population was limited to Stage I, with 13 subjects in each arm. That population statement is important when interpreting any response estimate: the analysis is not described as covering every enrolled participant. The registry does not report why the response analysis used that subset, how participants were selected for it, or how participants outside it were handled.

3. Trial Design

This was a randomized, open-label, parallel-arm Phase II trial sponsored by the University of Virginia. The registry lists 40 participants as enrolled and marks the study completed. The two arms used distinct ways of administering four melanoma peptides: peptides pulsed on monocyte-derived dendritic cells, or peptides in an emulsion with GM-CSF and Montanide ISA-51 adjuvant. The study description also identifies interleukin-2 administration as part of the treatment approach.

Random allocation means the trial assigned participants to the arms by a randomized process, as recorded in the registry. The record does not state the allocation ratio, the method used to generate or conceal assignments, or whether any stratification factors were used. Masking is listed as none. In an unmasked trial, participants and study personnel are not described as blinded to assigned treatment; whether specific outcome assessors were blinded is not reported in the registry record.

The stated primary outcome was objective clinical response, assessed at Weeks 0-6,12; Months 6,12 and 24. The endpoint description says investigators measured assessable metastatic deposits using CT, MRI, or direct measurement of cutaneous deposits. It also describes multidisciplinary review of measurements and additional radiologist review of scans from clinical responders. These procedures provide context for response assessment, but the registry does not report how often each assessment occurred for each participant or how missing assessments were handled.

The primary-response analysis population is stated to include subjects enrolled in Stage I, with 13 subjects in each arm. The record does not explain how this analysis population relates to the overall enrollment of 40, or provide participant flow by arm. A sample-size justification, planned power calculation, interim-analysis plan, and detailed statistical analysis plan are not reported in the registry record. The registry also does not report the randomization procedures or whether the primary comparison was adjusted for any baseline characteristics.

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.

Before assignment: 13 participants were assigned to each arm in Stage I. 14 additional participants were assigned in Stage II to study arm 2. Data are reported for stage I. Reporting is planned for stage II when data are available.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: The analysis of this outcome measure was performed on subjects enrolled in Stage I of the trial, which included 13 subjects in each arm.

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 Evaluation of Objective Clinical Response (CR/PR/SD), measured over Weeks 0-6,12; Months 6,12 and 24.

The primary endpoint was clinical response, with the registry naming complete response, partial response, and stable disease. These categories describe whether measured tumor deposits met criteria for response or stability over assessment. The endpoint was based on measurements of assessable metastatic disease, obtained by CT, MRI, or direct measurement of cutaneous deposits. Baseline measurements were taken most immediately before the first vaccine administration and within 6 weeks of protocol entry.

Clinical response is used in trials because it translates serial measurements of disease into categories that can be compared across participants and treatment groups. In general, categorization can make complex changes in lesion measurements easier to report, but it also means that the classification depends on the criteria used and on how assessments are conducted. The registry says the original protocol defined response using changes in cross-sectional area calculated from two perpendicular measures. It further notes that the RECIST system was adopted during the study, with response based on changes in maximum cross-sectional dimensions.

The registry describes a multidisciplinary team making and reviewing measurements, and says scans of clinical responders were reviewed again by a senior faculty radiologist not otherwise involved in the study. These procedures are relevant to assessment consistency. However, the record does not report the number of participants in each response category, the response rate, or an arm-to-arm estimate. It therefore describes how the endpoint was assessed, but not the observed primary-response findings.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

Randomization and the parallel-arm design describe how this trial was structured. In general, randomization uses chance to assign participants to treatment groups, helping limit systematic differences between groups at the point of assignment. It does not guarantee that groups will be identical, particularly in a Phase II study. The registry does not report the allocation ratio, random-sequence method, concealment procedure, or any factors used to balance assignments. The design is listed as parallel, meaning participants were assigned to one of the treatment approaches rather than described as crossing between them.

What does an endpoint category represent?

The primary endpoint classifies clinical response as complete response, partial response, or stable disease. A categorical endpoint turns measurements into defined outcome groups. In general, this can simplify communication and support comparisons, but the classification depends on the definitions and measurement procedures. The registry describes an initial definition based on changes in cross-sectional area, using two perpendicular measurements. It also reports that RECIST was adopted during the study and uses changes in maximum cross-sectional dimensions. The record does not state how this transition was applied to the analysis or whether all assessments were evaluated using a consistent rule.

The response assessment involved measurable metastatic deposits, with CT, MRI, or direct measurement for cutaneous deposits. Baseline measurements were those obtained most immediately before the first vaccine and within 6 weeks of protocol entry. The registry describes multidisciplinary review and further review of clinical responders’ CT scans by a senior faculty radiologist not otherwise involved in the study. In general, independent or multidisciplinary review can help standardize interpretation, but the record does not state whether reviewers were blinded to treatment assignment, how disagreements were resolved, or whether measurement reliability was evaluated.

How should repeated assessments be understood?

The listed timeframe includes Weeks 0-6,12; Months 6,12 and 24. Repeated measurements can show whether response classifications change over follow-up. Statistical analysis must specify how these measurements contribute to the primary result. For example, a trial might analyze response at a particular assessment or use a defined rule to summarize response across visits. The registry does not report which approach was used, whether each time point was analyzed separately, or how multiple response observations from the same participant were handled. No additional analysis method should be assumed from the schedule alone.

What do the analysis populations tell us?

The registry states that the primary outcome analysis was performed on Stage I subjects, with 13 subjects in each arm. Overall enrollment was 40. An analysis population determines which participants contribute to an endpoint estimate. In general, a clearly defined population is needed to understand the denominator, assess possible exclusions, and interpret whether the analysis follows randomized assignment. The record does not explain the Stage I restriction, describe participant flow, or state how participants not included in that analysis were treated. It also does not report whether all Stage I participants had evaluable endpoint data.

What is the role of confidence intervals and significance tests?

In general, a confidence interval describes the range of values compatible with the data under a specified statistical model and gives a sense of precision. A significance test evaluates the data against a stated null hypothesis under its assumptions. Neither replaces consideration of the estimate itself, the endpoint definition, or the analysis population. The registry information available for the primary endpoint does not include an effect estimate, confidence interval, or significance test result. The record also does not state the test or model used for the response comparison. Therefore, no conclusion about statistical significance or precision for the primary endpoint can be drawn.

How should planning calculations be read?

Sample-size planning illustrations are calculations about what a future or hypothetical design might require under specified assumptions. The registry’s stated illustration assumptions are a two-sided significance level of 0.05, equal allocation between arms, and a normal approximation; the effect to detect is expressed as a stated fraction of the observed effect. These calculations are planning illustrations, not observed power and not evidence that the trial was adequately powered. In general, their interpretation depends on the effect used as a planning target, the outcome model, and whether the assumptions are appropriate. The registry does not report its own sample-size justification or design calculation.

For binary outcomes, event counts and denominators are central to interpreting estimates. A count alone does not describe uncertainty; the denominator and the way participants entered the analysis also matter. Here, the response category results are not reported, so no response estimate or uncertainty interval can be described. The adverse-event counts have denominators, but the record does not provide an inferential comparison or uncertainty interval for those outcomes. The serious-event terms listed with percentages should be read as descriptive registry entries, not as a comparative analysis.

What is not specified?

The registry record does not report the detailed statistical analysis plan, missing-data method, interim analyses, multiplicity strategy, or adjustment for baseline characteristics. It does not report the primary response category counts, effect estimates, confidence intervals, or p-values. These omissions limit reconstruction of the efficacy analysis. General statistical principles can explain why these details matter, but they cannot establish which methods this trial actually used.

10. Multiplicity, Missing Data and Analysis Populations

The primary endpoint was assessed across a timeframe that includes Weeks 0-6,12; Months 6,12 and 24, and it has multiple response categories. When several outcomes, time points, or comparisons are evaluated, the chance of obtaining a statistically notable result by chance can increase. In general, a multiplicity strategy specifies which comparisons are primary and whether any adjustment or hierarchical testing is planned. The registry does not report a multiplicity plan or clarify how the several listed assessment times contributed to one primary analysis.

The endpoint description notes that RECIST was adopted during the study after the original protocol had defined response using cross-sectional area based on two perpendicular measures. The registry does not report how results under these approaches were reconciled, whether measurements were reclassified, or whether the analysis method was changed in response. This makes the endpoint’s operational definition important when evaluating reproducibility.

Missing-data handling is not reported in the registry record. In general, incomplete outcome assessments can affect estimates if the participants with missing results differ systematically from those with observed results. The record does not specify how missed visits, unevaluable lesions, withdrawal, or other incomplete response data were handled. It also does not describe whether the primary analysis included all randomized participants, all participants who received treatment, or only participants with assessable response data.

The registry identifies a Stage I analysis population of 13 subjects in each arm, while overall enrollment was 40. It does not explain the relationship between those populations or provide participant flow by arm. A detailed definition of the analysis population and accounting for participants excluded from it are therefore not available. Interim analyses and any associated stopping rules are not reported in the registry record.

11. Safety Results

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

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: dyspnea (7.4%), other (7.4%), alkaline phosphatase (3.7%), creatinine (3.7%), fever (3.7%).

The registry reports serious adverse events and other adverse events separately for the two treatment groups. In the dendritic-cell arm, 10 participants were listed as at risk for serious adverse events, with 0 affected; 10 were listed as at risk for other adverse events, with 9 affected. In the GM-CSF-in-adjuvant arm, 27 were listed as at risk for serious adverse events, with 5 affected; 27 were listed as at risk for other adverse events, with 27 affected. These are descriptive counts and denominators, not adjusted comparisons between the arms.

The record also lists serious adverse-event terms with percentages: Dyspnea, 7.4%; Other, 7.4%; Alkaline Phosphatase, 3.7%; Creatinine, 3.7%; Fever, 3.7%; and General- Other, 3.7%. The registry does not provide further detail in these entries about event timing, duration, recurrence, attribution to treatment, or whether one participant experienced more than one event. Death counts are not reported in the registry record.

In general, adverse-event counts should be interpreted alongside the population at risk, follow-up duration, event definitions, and data-collection procedures. Those details are not fully. The counts do not establish a causal relationship with treatment, and differences in the listed counts alone do not provide a measure of statistical uncertainty or a complete safety comparison.

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

The registry record establishes that a randomized Phase II trial compared two peptide-vaccine approaches in patients with Stage III or Stage IV melanoma, in the context of interleukin-2 administration. It describes the primary endpoint as clinical response and gives the measurement approach, assessment timeframe, and response categories. It also reports adverse-event counts for the two groups. These details allow readers to understand the trial question and some aspects of outcome assessment.

The record does not report the primary response results. There are no response-category counts, response estimate, confidence interval, or p-value in the information recorded for this endpoint. Consequently, the posted record does not establish which arm had more responses, whether the arms differed, or how precisely any difference was estimated. The absence of a reported result is not itself evidence that there was no response or no difference.

The enrollment total of 40 should be distinguished from the stated response-analysis population of 13 subjects in each arm. The registry does not explain this distinction, so the total enrollment cannot be used as the primary-response denominator. It also does not report participant flow, missing-data handling, or the precise rule used to combine or select among assessments over time.

The serious and other adverse-event counts are descriptive. They do not, by themselves, show that treatment caused an event or support a complete comparison of safety. The registry does not report the full context needed to interpret event timing, attribution, duration, or statistical uncertainty, and deaths are not reported in the registry record.

In general, a trial’s interpretation depends on its endpoint definition, analysis population, measurement procedures, and statistical plan as well as on the numerical results. The record supplies useful design and assessment details, but without the primary response results and analysis specifications, the efficacy question cannot be resolved from the registry record. This is a limitation of what is reported, not a conclusion about what the trial investigators may have observed.

13. Why This Trial Matters Statistically

This trial raises several statistical issues that are important in clinical research. First, it illustrates why a registry’s enrollment total and its endpoint analysis population must be distinguished. The record lists 40 enrolled overall but says the primary response analysis was performed on Stage I subjects, with 13 subjects in each arm. Without participant flow or an explanation of the population definition, readers cannot determine how the endpoint denominator relates to enrollment.

Second, the endpoint description records a change in measurement approach during the study. The original protocol used changes in cross-sectional area calculated from two perpendicular measures, while the record says RECIST was later employed, using changes in maximum cross-sectional dimensions. In general, changes in outcome definitions can affect comparability and reproducibility. Reporting how a transition was handled is therefore important to interpreting response results.

Third, the assessment schedule includes multiple time points, and the primary endpoint includes multiple response categories. Clear specification of the primary time point, response summary, and multiplicity approach helps distinguish a planned primary analysis from exploratory comparisons. Those details are not reported in the registry record.

Finally, reporting the endpoint’s numerical findings is essential. A description of measurement procedures cannot establish the observed response pattern, the size of a treatment contrast, or its precision. The registry’s adverse-event counts likewise need context and should not be mistaken for a complete comparative safety analysis. These features make transparent reporting of populations, outcomes, analysis methods, and uncertainty central to interpreting a clinical trial.

14. 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 most consequential limitation of the registry record for interpretation is that it does not report the primary clinical-response results. Although the endpoint is described in detail, the response counts by category and arm, an effect estimate, confidence interval, and significance test are not reported in the registry record. The direction, magnitude, and precision of the response comparison therefore cannot be assessed.

The stated primary-response population is Stage I subjects, with 13 subjects in each arm, while overall enrollment was 40. The registry does not explain why the primary analysis was restricted to that population, how it was defined, or how participants outside it were accounted for. There is no participant-flow description or report of missing and unevaluable response assessments.

The endpoint timeframe includes multiple assessments, and the registry describes a change from the original response definition to RECIST. It does not clarify which assessment or summary determined the primary result, how repeated assessments were handled, or how the criteria transition was applied. The record also does not state whether response assessors were blinded to treatment assignment.

Important design and analysis details are not reported in the registry record, including the randomization method, allocation ratio, sample-size justification, interim-analysis plan, multiplicity strategy, and detailed statistical analysis plan. The serious and other adverse-event counts do not include a full account of event timing, duration, attribution, or uncertainty. Death counts are not reported in the registry record. These limitations restrict assessment of both the efficacy findings and the completeness of the safety comparison.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Vaccine Therapy Plus Interleukin-2 in Treating Patients With Stage III or Stage IV Melanoma — NCT00003222.
• Registry record last updated 2014-12-19; status last verified 2014-12.
• Results first posted 2014-12-19.
• 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.

18. Record Summary

This completed Phase II trial was a randomized, open-label, parallel-arm study sponsored by the University of Virginia. It enrolled 40 participants with Stage III or Stage IV melanoma and compared four melanoma peptides pulsed on monocyte-derived dendritic cells with four peptides administered in an emulsion with GM-CSF and Montanide ISA-51 adjuvant. The study description includes interleukin-2 administration.

The primary endpoint was clinical response, categorized as complete response, partial response, or stable disease, with assessments listed at Weeks 0-6,12; Months 6,12 and 24. The registry says the response analysis used Stage I subjects, with 13 subjects in each arm. It describes imaging and direct measurement, multidisciplinary review, and adoption of RECIST during the study. Primary response results and the detailed statistical analysis plan are not reported in the registry record.

Serious and other adverse-event counts are reported by arm, but the registry does not provide the full context needed for a causal or comparative safety interpretation. Death counts are not reported in the registry record.