This page provides an independent statistical analysis and educational interpretation of publicly reported results. ClinicalTrials.gov provides the official trial registry record. Numerical trial results on this page are restricted to the results posted in the ClinicalTrials.gov record; calculations added by Clinical Biostats are labelled as such.
1. Trial at a Glance
This page covers the registry results for Pembrolizumab, Standard Chemotherapy, Tumor Infiltrating Lymphocytes, and High- or Low-Dose Aldesleukin in Treating Patients With Metastatic Melanoma (NCT02500576), a randomized phase 2 study. The primary outcome is Overall Response Rate in Each Arm.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT02500576 |
| Phase | Phase 2 |
| Condition | Metastatic Melanoma, Stage IIIB Cutaneous Melanoma AJCC v7, Stage IIIC Cutaneous Melanoma AJCC v7 |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | None (open label) |
| Enrollment | 18 |
| Arms in the primary outcome | n/a |
| Lead sponsor | M.D. Anderson Cancer Center |
| Results posted | Yes |
2. Clinical Question
Population
Patients with metastatic melanoma, including the listed stage IIIB, stage IIIC, and stage IV cutaneous melanoma categories. The registry record does not report further eligibility details or a detailed description of the participants included in the primary analysis.
Intervention
Pembrolizumab with lymphodepleting chemotherapy, therapeutic tumor infiltrating lymphocytes (TIL), and high-dose aldesleukin in Arm I. The chemotherapy is described as cyclophosphamide and fludarabine phosphate. The detailed Arm I regimen in the registry record ends after the TIL infusion, so the remaining administration details are not reported in the registry record.
Comparator
Pembrolizumab with the same named chemotherapy and TIL components, followed by low-dose aldesleukin in Arm II. The record describes low-dose aldesleukin as subcutaneous treatment for 14 days, beginning approximately 6 hours after TIL. The two arms differ in the aldesleukin dose strategy.
Primary question
What is the overall response rate in each arm, and does the response rate differ between the high- and low-dose aldesleukin arms? The registry describes exact 95% confidence intervals for each arm and Fisher’s exact test for the between-arm comparison. It also describes logistic regression to assess associations between response and covariates.
This is a treatment comparison within a specific combination regimen: the intervention is not aldesleukin alone, and the record does not describe a group receiving pembrolizumab without TIL or lymphodepleting chemotherapy. The planned comparison therefore concerns the two regimen strategies named in the registry, rather than the separate contribution of each treatment component. Random allocation is stated, but the sequence-generation method and allocation concealment are not reported in the registry record.
The record identifies the primary endpoint as overall response rate, measured as a count of participants, with assessment up to 5 years. It does not report the observed response counts, arm-specific response rates, confidence intervals, or test result. Consequently, the statistical question is clear, but the posted information does not establish which arm had a higher response rate or how uncertain any difference would be.
3. Trial Design
The registry describes a randomized, parallel-group phase II trial with no masking. Its enrollment is recorded as 18. The study is marked completed; its start date is 2015-08-07, and its primary completion date is 2022-10-12. The sponsor is M.D. Anderson Cancer Center. These registry entries describe the trial’s status and design, not the completeness of its reported outcome data.
Both arms combine pembrolizumab with cyclophosphamide, fludarabine phosphate, and therapeutic TIL. Arm I is identified as the high-dose aldesleukin arm; Arm II is identified as the low-dose arm. For Arm II, the record describes subcutaneous low-dose aldesleukin for 14 days, starting approximately 6 hours after the TIL infusion. The Arm I description is incomplete after the TIL infusion, and the pembrolizumab administration details are not reported in the registry record. The two arms are therefore distinguishable by their assigned aldesleukin strategy, while the available description does not fully specify every administration detail.
The primary outcome is overall response rate in each arm, assessed up to 5 years. Planned methods named in the record are exact 95% confidence intervals for each arm, Fisher’s exact test for comparison between arms, and logistic regression for associations with covariates. The covariates are not identified in the registry record. Overall survival, progression-free survival, and change in blood and tumor biomarkers are listed as secondary outcomes.
The record states that the study is randomized but does not report the randomization procedure, allocation ratio, or method for concealing assignments. It identifies no masking. The registry lists an enrollment value, but the number analyzed for the primary endpoint and the analysis populations are not reported in the registry record. A primary response result and analysis are also not reported: the record lists 0 analyses. Thus, the design description supports understanding the intended comparison, but not an evaluation of the observed treatment effect.
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: 18 participants consented and off-study; 16 participants treated, 1-participant was not eligible and not assigned an arm, 1-participant withdrew due to denial of insurance.
Overall Study
| Stage | Arm 1-High Dose IL2 | Arm 2- Low Dose IL2 |
|---|---|---|
| STARTED | 8 | 8 |
| COMPLETED | 0 | 0 |
| NOT COMPLETED | 8 | 8 |
Reasons for not completing this period:
| Reason | Arm 1-High Dose IL2 | Arm 2- Low Dose IL2 |
|---|---|---|
| Adverse Event | 0 | 1 |
| Death | 2 | 1 |
| Lack of Efficacy | 5 | 5 |
| Withdrawal by Subject | 1 | 1 |
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.
Population: Those who were randomized
| Characteristic | Unit | Arm 1- High Dose IL2 | Arm 2- High Dose IL2 | Total |
|---|---|---|---|---|
| Participants analysed | 8 | 8 | 16 | |
| Age, Categorical: <=18 years | Participants | 0 | 0 | 0 |
| Age, Categorical: Between 18 and 65 years | Participants | 8 | 8 | 16 |
| Age, Categorical: >=65 years | Participants | 0 | 0 | 0 |
| Sex: Female, Male: Female | Participants | 3 | 4 | 7 |
| Sex: Female, Male: Male | Participants | 5 | 4 | 9 |
| Ethnicity (NIH/OMB): Hispanic or Latino | Participants | 0 | 0 | 0 |
| Ethnicity (NIH/OMB): Not Hispanic or Latino | Participants | 7 | 7 | 14 |
| Ethnicity (NIH/OMB): Unknown or Not Reported | Participants | 1 | 1 | 2 |
| Race (NIH/OMB): American Indian or Alaska Native | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): Asian | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): Native Hawaiian or Other Pacific Islander | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): Black or African American | Participants | 0 | 1 | 1 |
| Race (NIH/OMB): White | Participants | 7 | 7 | 14 |
| Race (NIH/OMB): More than one race | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): Unknown or Not Reported | Participants | 1 | 0 | 1 |
| Region of Enrollment: United States | participants | 8 | 8 | 16 |
6. Primary Endpoint
The registry lists the primary outcome as Overall Response Rate in Each Arm, measured over Up to 5 years.
| Element | Registry entry |
|---|---|
| Result type | Count Of Participants |
| Measure of spread | not applicable |
| Unit | Participants |
| Endpoint classification | Binary Endpoint |
Overall response rate describes the proportion of participants who meet the study’s definition of an overall response during the specified assessment period. The registry records the primary outcome as a participant count and states that response will be summarized separately by arm, with exact 95% confidence intervals. The response criteria used to classify participants are not reported in the registry record, so the operational definition of response cannot be assessed from the posted details.
Response is used as an endpoint because it captures whether tumors meet a prespecified response category, rather than tracking only survival duration or a biomarker change. As a binary outcome for each participant, it can be summarized as the number classified as responders relative to the number assessed. The registry proposes Fisher’s exact test to compare the arms and logistic regression to examine associations between response and covariates. These are methods described for the endpoint, not evidence that the analyses were completed.
The stated timeframe is up to 5 years. No arm-specific response counts, response rates, confidence limits, or comparison result are reported in the registry record. Nor does the record identify the response criteria, assessment schedule, handling of unevaluable participants, or analysis population. Without those details and observed outcome data, the endpoint’s planned meaning is identifiable, but its result and precision cannot be interpreted.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record defines a randomized comparison of two combination strategies for metastatic melanoma. Both include pembrolizumab, lymphodepleting chemotherapy, and TIL; the named arm distinction is high- versus low-dose aldesleukin. The primary question concerns overall response rate, with separate arm summaries and a planned between-arm comparison. However, the record does not report response counts or rates, confidence intervals, or a test result. It therefore does not support a conclusion about the direction, size, or statistical uncertainty of a response difference.
The record lists enrollment as 18, but it does not report how many participants contributed to the primary outcome analysis in either arm. The planned endpoint timeframe is up to 5 years; this does not establish that every participant had that duration of follow-up. Follow-up completeness, outcome assessment timing, and the handling of missing response information are not reported in the registry record. These omissions matter because a response estimate depends on who was assessed and how missing or unevaluable cases were handled.
The registry names exact 95% confidence intervals, Fisher’s exact test, and logistic regression as methods for response. A confidence interval would convey the range of values compatible with the observed data under the method’s assumptions; its width would indicate precision. But no interval is posted, so precision cannot be judged. A test result is also absent, and statistical significance cannot be inferred from the design description, enrollment value, or adverse-event counts.
The record lists overall survival, progression-free survival, and biomarker change as secondary outcomes. It does not provide their results in the registry record described for this trial. These outcomes cannot be used to corroborate or qualify a response comparison on the available record. Nor can the safety summaries substitute for the missing efficacy endpoint: adverse-event counts describe a different aspect of the study.
There is also a discrepancy between the endpoint methods described and the availability of results: the primary outcome description specifies an analysis approach, while the record lists 0 analyses and supplies no outcome comparison. This means there is no sponsor-reported response estimate to prioritize over a recalculation. No recalculated response result is available either. The appropriate statistical reading is therefore limited to the intended design and analysis plan, together with the reported safety counts; the trial’s response effect remains unreported in the registry record.
9. Statistical Methods Explained
The registry describes an arm-specific summary of overall response rate using exact 95% confidence intervals, a Fisher’s exact test for the comparison between arms, and logistic regression for covariate associations. These are methods stated for the planned primary outcome. The record does not provide the resulting estimates or test output, so the descriptions below explain what the methods are intended to do, not what this trial’s data showed.
What does an exact confidence interval convey?
General: A confidence interval expresses uncertainty around an estimated quantity. For a response proportion, an interval reflects the range of values reasonably compatible with the observed response count under the method’s assumptions. A narrow interval indicates greater precision than a wide interval. Exact methods use the discrete probability structure of binary counts rather than relying only on a large-sample approximation. This can be useful when counts are limited, although an exact interval can still be wide when the available information is sparse.
The registry specifies exact 95% confidence intervals for the response rate in each arm. Those intervals would describe uncertainty around each arm’s response estimate. Separate arm intervals are not, by themselves, a direct test of the difference between arms: overlap or non-overlap is not a substitute for the prespecified comparison method. The registry does not report the intervals, so neither the estimates nor their precision can be assessed.
Why use Fisher’s exact test?
General: Fisher’s exact test evaluates whether the observed distribution of a binary outcome across treatment groups is compatible with a null hypothesis of no association between assigned group and outcome. It calculates probabilities conditional on the observed margins of a two-by-two count table. This approach does not depend on the large-sample approximation used by some other tests and is often considered for small or sparse categorical data.
The registry names Fisher’s exact test for comparing overall response between the two arms. The record does not report whether the test was performed, its result, its sidedness, or any associated effect estimate. A p-value, even if available, would address compatibility with a null model under the test’s assumptions; it would not itself quantify the size or clinical importance of a difference. The absent response counts and uncertainty estimates prevent those aspects from being evaluated.
What role would logistic regression play?
General: Logistic regression models the probability of a binary outcome in relation to explanatory variables. It can estimate associations adjusted for specified covariates and can examine whether outcome patterns vary with participant or disease characteristics. Results depend on the variables included, their coding, the number of outcome events, and model assumptions. With limited data, complex adjustment may produce unstable estimates; interpretation requires the model specification and uncertainty measures.
The registry says that the association between overall response and the same covariates will be assessed using logistic regression, but it does not identify those covariates or report a fitted model. It does not state whether the treatment comparison itself was intended to be adjusted in that model, how variables would be selected, or how model adequacy would be assessed. No adjusted estimates or confidence intervals are reported in the registry record.
What do the planning assumptions mean?
General: A sample-size calculation uses design assumptions to illustrate how much information might be needed to detect a specified effect under a chosen error rate and allocation plan. Such an illustration is not a summary of observed evidence and does not measure the probability that a completed study found a true effect. The registry’s planning assumptions specify a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation; the target effect is stated as a fraction of the observed effect. The registry also distinguishes planning quantities for binary outcomes from quantities for time-to-event outcomes.
These assumptions are described as a planning illustration computed from the observed effect, not as the trial’s own design. The registry record does not report a numerical sample-size illustration in the registry record for this analysis. Such planning assumptions cannot replace an observed treatment estimate, and they should not be described as observed power. No power calculation can establish whether this trial’s actual response comparison was statistically significant.
10. Multiplicity, Missing Data and Analysis Populations
The record names multiple outcomes: overall response rate as the primary outcome, and overall survival, progression-free survival, and changes in blood and tumor biomarkers as secondary outcomes. It does not report a multiplicity adjustment, a hierarchy for interpreting secondary outcomes, or a prespecified strategy for controlling the chance of false-positive findings across multiple comparisons. Those details are not reported in the registry record. General: When several outcomes or tests are examined, multiplicity can increase the chance that at least one result appears statistically unusual by chance; a prespecified strategy helps clarify how results should be interpreted.
Although the primary outcome description names exact confidence intervals, Fisher’s exact test, and logistic regression, the record lists 0 analyses and reports no primary outcome result. It does not state whether the endpoint was changed, whether an interim analysis was conducted, or how any such analysis would affect interpretation. These matters are not reported in the registry record.
Missing-data handling is also not described. The record does not state how participants without an evaluable response, with incomplete follow-up, or with unavailable biomarker measurements would be treated. The analysis population for each endpoint is not reported in the registry record, nor are reasons for exclusion or withdrawal. The enrollment value alone does not establish how many participants contributed data to an outcome analysis.
Without outcome-specific denominators and missing-data rules, it is not possible to assess whether the reported safety summaries and intended efficacy analysis refer to the same population. The posted information does not establish whether an intention-to-treat or another analysis population was used. These gaps limit reproducibility and make it difficult to judge how sensitive an eventual estimate would be to missing observations or analysis choices.
11. Safety Results
The registry reports serious adverse events as affected participants divided by participants at risk.
| Arm | Participants with serious adverse events | Participants at risk | Percentage |
|---|---|---|---|
| Arm 1- High Dose IL2 | 0 | 8 | 0.0% |
| Arm 2- Low Dose IL2 | 1 | 8 | 12.5% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Arm 1- High Dose IL2 | 2 of 8 |
| Arm 2- Low Dose IL2 | 1 of 8 |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 0% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Arm 1- High Dose IL2 | 8 of 8 |
| Arm 2- Low Dose IL2 | 8 of 8 |
Most frequent serious adverse event terms
| Event term | Organ system | Arm 1- High Dose IL2 | Arm 2- Low Dose IL2 |
|---|---|---|---|
| Death | Investigations | 0 of 8 | 1 of 8 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Arm 1- High Dose IL2 | Arm 2- Low Dose IL2 |
|---|---|---|---|
| Neutrophil Count decreased | Investigations | 7 of 8 | 7 of 8 |
| Anemia | Blood and lymphatic system disorders | 7 of 8 | 6 of 8 |
| Hypoalbuminemia | Metabolism and nutrition disorders | 7 of 8 | 6 of 8 |
| Hypocalcemia | Metabolism and nutrition disorders | 7 of 8 | 6 of 8 |
| Platelete Count Decreased | Investigations | 7 of 8 | 6 of 8 |
| Alopecia | Skin and subcutaneous tissue disorders | 7 of 8 | 5 of 8 |
| Anorexia | Metabolism and nutrition disorders | 7 of 8 | 5 of 8 |
| Generalized muscle weakness | General disorders | 6 of 8 | 6 of 8 |
| Chills | Respiratory, thoracic and mediastinal disorders | 7 of 8 | 4 of 8 |
| Constipation | Gastrointestinal disorders | 6 of 8 | 5 of 8 |
Serious events with the highest arm-level rate: death (12.5%).
The adverse-event summaries report serious events and other events separately for the two named arms. In Arm 1- High Dose IL2, 0 of 8 participants at risk are listed as affected by a serious event, while 8 of 8 are listed as affected by an other event. In Arm 2- Low Dose IL2, 1 of 8 participants at risk is listed as affected by a serious event, and 8 of 8 are listed as affected by an other event. These are participant counts in the registry summary; they do not describe the number of separate event episodes.
The registry lists deaths as the top serious term, at 12.5%. The death counts are 2 in the high-dose arm and 1 in the low-dose arm. The record does not provide enough context in these summaries to determine whether each death was classified as treatment-related, when it occurred, or how the listed death term relates to the serious-event count. No causal attribution should be inferred from the counts alone.
These summaries are descriptive. They do not establish a comparative safety effect, especially without fuller definitions, follow-up details, event-level descriptions, or information about attribution and timing. The figures should also be kept separate from the primary response endpoint: they do not indicate whether participants met response criteria.
12. What the Result Does, and Does Not, Mean
The registry record gives a clear outline of the trial’s central comparison: two randomized combination-regimen arms, distinguished by high- or low-dose aldesleukin, with overall response rate named as the primary outcome. It also states the intended summary and comparison methods. That information explains what investigators planned to assess, but it is not evidence of the observed response results.
No response counts, response rates, confidence intervals, or Fisher’s exact test result are reported in the registry record. The listed count of 0 analyses reinforces that the record does not contain a reported primary analysis. The trial’s response effect, its direction, its magnitude, and its precision therefore cannot be determined from the posted results. The absence of a reported result should not be interpreted as evidence of no effect or as evidence favoring either arm.
The safety figures provide limited descriptive information about serious and other events and deaths. They do not establish that the regimens caused or prevented those events, and they do not answer the response question. The secondary outcomes are named, but their results are not reported in the registry record. A full interpretation would require outcome results together with analysis denominators, endpoint definitions, follow-up completeness, and details of how missing information was handled.
More generally, a trial design and a completed status do not by themselves establish a treatment benefit or lack of benefit. Randomization describes how a comparison was intended to reduce systematic differences between groups, but interpretation still depends on the conduct and results of the study. In this case, the posted record supports a description of the planned comparison and selected safety counts, not a conclusion about efficacy or a definitive comparison of harms.
13. Why This Trial Matters Statistically
This trial is statistically notable for the structure of its intended comparison. It evaluates two complex regimens that share pembrolizumab, lymphodepleting chemotherapy, and TIL, while differing by the named high- or low-dose aldesleukin strategy. That structure focuses the primary comparison on the assigned regimen arms, rather than isolating the effect of each treatment component individually.
The record also illustrates why the design description and outcome results must be read separately. It specifies an arm-specific response summary with exact 95% confidence intervals, Fisher’s exact test for the comparison, and logistic regression for covariate associations. Those methods describe how data could be analyzed, but they do not provide estimates in the absence of reported results. With the response counts and intervals unreported, neither the estimated response pattern nor its precision can be evaluated.
For clinical researchers and biostatisticians, the record highlights the importance of outcome denominators, response criteria, analysis populations, missing-data rules, and the handling of multiple outcomes. These details help readers assess how an endpoint was constructed and how robust an estimate may be. They are not reported in the registry record for the primary response analysis. The listed secondary outcomes likewise have no results in the information.
The record is therefore useful for understanding the trial question and planned methods, while also showing the limits of registry-based interpretation when results are absent. Its value is statistical transparency about the intended comparison; it cannot stand in for a completed outcome analysis or resolve the treatment comparison.
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 principal limitation is the absence of reported primary outcome results. Although the registry identifies overall response rate and describes planned statistical methods, it reports no response counts, rates, confidence intervals, or comparison result. The record lists 0 analyses. Thus, the primary endpoint cannot be interpreted quantitatively.
The endpoint’s operational definition is not reported. Response criteria, assessment schedule, rules for unevaluable participants, and the primary analysis population are also not reported in the registry record. Without these details, it is not possible to determine precisely how participants would be classified or how missing assessments would affect the response estimate. The stated timeframe of up to 5 years does not establish the follow-up actually achieved for each participant.
The treatment descriptions are incomplete. The Arm I description ends after the TIL infusion, and administration details for pembrolizumab are not reported in the registry record. The record does not describe randomization sequence generation, allocation concealment, or a full analysis plan. It also does not identify the logistic-regression covariates or describe missing-data procedures, interim analyses, or multiplicity handling.
The safety summaries provide counts but do not include event timing, participant-level context, or causal attribution. The death term is listed, but the available information does not explain how those deaths relate to serious-event classifications. These limits mean the safety counts are descriptive and should not be treated as a complete comparison of harms.
Finally, the named secondary outcomes have no reported results in the registry record. With the primary and secondary findings unavailable, there is no basis for assessing consistency across outcomes or for drawing a broad efficacy conclusion from the posted information.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Pembrolizumab, Standard Chemotherapy, Tumor Infiltrating Lymphocytes, and High- or Low-Dose Aldesleukin in Treating Patients With Metastatic Melanoma — NCT02500576.
- Registry record last updated 2025-01-15; status last verified 2025-01.
- Results first posted 2025-01-15.
- 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.
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18. Record Summary
NCT02500576 is a completed randomized phase II trial sponsored by M.D. Anderson Cancer Center. The registry lists an enrollment of 18 and compares pembrolizumab, lymphodepleting chemotherapy, and TIL with high- or low-dose aldesleukin in metastatic melanoma. The study started on 2015-08-07 and has a primary completion date of 2022-10-12.
Overall response rate is the primary outcome, with a stated timeframe of up to 5 years. The planned methods are exact 95% confidence intervals for each arm, Fisher’s exact test between arms, and logistic regression for covariate associations. The record lists overall survival, progression-free survival, and blood and tumor biomarker change as secondary outcomes.
Arm-specific response results and the primary analysis are not reported in the registry record, which lists 0 analyses. Safety summaries give serious-event, other-event, and death counts by arm, but do not establish causation. The registry supports a description of the planned question and selected safety information, not a conclusion about the response comparison.