Phase II Study of Metastatic Melanoma With Lymphodepleting Conditioning and Infusion of Anti-MART-1 F5 TCR-Gene-Engineered Lymphocytes: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Phase II Study of Metastatic Melanoma With Lymphodepleting Conditioning and Infusion of Anti-MART-1 F5 TCR-Gene-Engineered Lymphocytes (NCT00509288), a non-randomized phase 2 study. The primary outcome is Clinical Tumor Regression..

2. Clinical Question

3. Trial Design

This was a phase II study of an approach combining lymphodepleting conditioning with infusion of autologous, anti-MART-1 F5 T-cell receptor-engineered lymphocytes. The registry identifies the National Cancer Institute as sponsor and records the study as completed. Its recorded start was 2007-06, and primary completion was 2011-07.

The record classifies allocation as nonrandomized, masking as none, and the model as single-group. It also lists two treatment arms: anti-MART-1 F5 TCR PBL + HD IL-2 and anti-MART-1 F5 TCR TIL + HD IL-2. The PBL arm is described as treatment with peripheral blood lymphocytes; the TIL arm is described as treatment with tumor-infiltrating lymphocytes. The existence of these arms does not establish a randomized head-to-head comparison. The registry specifically cautions that the arms are not a like-for-like control comparison.

The brief description outlines collection of cells from patients, laboratory engineering of cells, lymphodepleting chemotherapy and subsequent cell infusion. Cyclophosphamide, fludarabine and aldesleukin appear among the listed interventions. Further details of the treatment schedule and how participants were assigned to the two cell approaches are not reported in the registry record.

Enrollment was 24. The primary outcome is clinical tumor regression assessed by RECIST, with a recorded timeframe of 7/5/07-4/23/09. Toxicity is listed as a secondary outcome. The record reports no analysis entries, and it does not provide an outcome-analysis plan, a sample-size justification or a description of interim monitoring. The trial design can therefore be described from its registration, but its planned statistical procedures cannot be reconstructed beyond the information explicitly recorded.

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.

6. Primary Endpoint

The registry lists the primary outcome as Clinical Tumor Regression., measured over 7/5/07-4/23/09.

The primary endpoint is clinical tumor regression, recorded as a participant-count outcome and assessed according to RECIST. It categorizes tumor response using measurements of target lesions and the appearance of new lesions. Complete response means disappearance of all target lesions. Partial response is defined as at least a 30% decrease in the sum of the longest diameters of target lesions relative to baseline. Progressive disease is defined as at least a 20% increase relative to the smallest recorded sum since treatment began, or the appearance of one or more new lesions. Stable disease falls between the stated criteria for partial response and progressive disease.

These categories provide a standardized way to describe changes in measurable disease. The endpoint is useful for organizing clinical response observations consistently, but the definition alone does not establish how many participants met each category or how response differed between treatment approaches. The registry record does not report the primary-outcome counts, the number assessed, or an estimate of uncertainty for the outcome. It also does not report an analysis population or explain how participants without an evaluable assessment were handled.

The recorded assessment timeframe is 7/5/07-4/23/09. The registry does not describe additional details of assessment timing or the handling of measurements beyond the stated RECIST definitions. Thus, the record specifies what tumor regression meant for this endpoint, while leaving the numerical results and some implementation details unreported.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

Clinical trial results are easiest to interpret when the outcome definition, analysis population, estimate and uncertainty are all available. In this record, the outcome definition is described, but the primary-outcome results and analysis are not. The explanations below distinguish general statistical principles from what the registry records for this study.

What does a confidence interval add?

General: A confidence interval describes the statistical uncertainty around an estimate. It gives a range of values that are compatible with the observed data under the method's assumptions. A narrow interval generally indicates more precise estimation than a wide interval. A point estimate without an interval can conceal substantial uncertainty, particularly when data are limited.

For this study: The registry record does not report an estimate or confidence interval for the primary tumor-regression endpoint. Precision therefore cannot be assessed from the primary-outcome information recorded. The arm-specific adverse-event counts do not substitute for an interval around the tumor-response outcome.

What does a hypothesis test tell the reader?

General: A hypothesis test evaluates how compatible observed data are with a specified null hypothesis under a statistical model. A p-value is not the probability that a treatment works, nor is it a measure of the size or clinical importance of an effect. Tests also depend on the analysis plan, assumptions and data included.

For this study: No primary-outcome test result or analysis entry is reported in the registry record. There is also no reported statistical plan specifying a primary comparison or inferential procedure. It is not possible to infer a p-value or recreate a sponsor analysis from the endpoint definition alone.

Why does the design matter for comparisons?

General: Random allocation can balance measured and unmeasured baseline factors in expectation, supporting a causal interpretation of between-group differences when the trial is otherwise appropriately conducted. In a nonrandomized study, treatment groups may differ for reasons associated with both treatment choice and outcome. An unadjusted difference between groups can therefore reflect selection or other differences rather than a treatment effect.

For this study: Allocation is recorded as nonrandomized, and the registry warns that the PBL and TIL arms are not like-for-like controls. The record does not report a randomized comparison or an adjusted analysis. The arms should not be interpreted as if they were exchangeable groups created by random assignment.

How should the RECIST categories be understood?

General: A categorical endpoint translates measurements into clinically interpretable response classes. Classification can make results easier to communicate, but it also means that the definition and timing of assessments matter. A category count does not, by itself, show the range of individual measurement changes or uncertainty in the estimated response frequency.

For this study: The record defines complete response, partial response, progressive disease and stable disease using RECIST criteria. The specified partial-response and progression thresholds are part of the endpoint definition, not results observed in the participants. The registry does not report the number assigned to each category or details on how missing or unevaluable assessments were treated.

What do the planning assumptions mean?

General: A sample-size calculation is a planning exercise that estimates how much information may be needed to detect a chosen effect under stated assumptions. Its output depends on the target effect, significance level, allocation, statistical approximation and outcome type. A planning calculation is not an observed result and does not show the probability that the completed trial detected an effect.

For this study: The record describes a planning illustration based on the observed effect, with a two-sided significance level of 0.05, equal allocation, a normal approximation and effects expressed as fractions of the observed effect. It characterizes these as planning illustrations, not as the trial's own design. No numerical planning outputs or specific effect fractions are reported in the registry information available for this analysis. These assumptions should not be mistaken for a documented prospective sample-size rationale.

Why can over-dispersion matter?

General: Over-dispersion occurs when variability in count data exceeds what a chosen model assumes. If ignored, standard errors may be too small and confidence intervals or tests may give an overly optimistic impression of precision. Appropriate modeling depends on the outcome structure and the available data.

For this study: The primary outcome is recorded as participants with an event, a binary count outcome. The registry does not report a dispersion estimate or statistical model for the primary analysis. There is therefore no basis in the record for describing whether over-dispersion was assessed or how it would have been handled.

These distinctions matter because outcome definitions and design descriptions are not substitutes for reported results. Without the primary counts, estimates, uncertainty measures and analysis details, the statistical evidence for tumor regression cannot be quantified from the registry record.

10. Multiplicity, Missing Data and Analysis Populations

Multiplicity arises when a study evaluates multiple outcomes, groups, time points or statistical comparisons. If many tests are conducted, the chance of at least one apparently unusual result can increase unless the analysis plan accounts for this. A registry can help readers understand whether outcomes and analyses were prespecified, but interpretation also requires the actual analysis plan and results.

The record identifies clinical tumor regression as the primary outcome and toxicity as a secondary outcome. It reports two treatment arms, but does not provide analysis entries or a statistical plan describing any comparisons, multiple testing strategy or hierarchy among outcomes. Whether multiplicity adjustments were planned or used is not reported in the registry record. No interim analyses or stopping rules are described in the available record, so their use should not be inferred.

Missing-data methods are also not reported. The primary endpoint description does not state how participants without an evaluable tumor assessment, missing measurements or withdrawals were handled. The number included in a primary analysis and the definition of an analysis population are not reported in the registry record. The enrollment figure alone does not establish how many participants contributed data to the endpoint.

These omissions limit reproducibility and interpretation. Without a stated analysis population and missing-data approach, it is not possible to determine whether the reported endpoint—if results were available elsewhere—would represent all enrolled participants or a subset. Without the analysis plan, readers cannot assess whether the reported outcome and testing choices followed prespecified procedures. The registry record does not resolve these questions.

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 0% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: somnolence/depressed level of consciousness (33.3%), rash/desquamation (4.8%), infection (documented clinically or microbiologically) (4.8%), infection with unknown anc (4.8%), creatinine (4.8%).

The registry reports serious adverse-event figures by arm. In the anti-MART-1 F5 TCR PBL + HD IL-2 arm, 3 participants with serious adverse events are recorded among 21 at risk. In the anti-MART-1 F5 TCR TIL + HD IL-2 arm, 1 participant with serious adverse events is recorded among 3 at risk. These are the registry's arm-specific counts; they should not be treated as a randomized comparison or as evidence that one approach is safer.

The listed serious-event terms include somnolence/depressed level of consciousness at 33.3%, and rash/desquamation, infection documented clinically or microbiologically, infection with unknown ANC, creatinine and renal failure at 4.8% each. The record excerpt does not identify which arm or denominator is associated with each term, so those percentages should not be assigned to an arm. They are also not a substitute for a full account of event severity, timing, duration or relationship to treatment.

Because the study is nonrandomized and the arm sizes differ, raw safety counts do not support a fair comparative risk assessment. The registry record does not report a statistical comparison, adjustment or uncertainty interval for serious events. A count of participants with at least one event should also be distinguished from a count of all event occurrences; the record does not provide enough detail to characterize recurrent events.

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

The study record describes a phase II investigation of autologous anti-MART-1 F5 T-cell receptor-engineered lymphocytes for adults with metastatic melanoma and HLA-A 0201. It identifies a RECIST-based primary endpoint and records PBL and TIL treatment approaches. This information establishes what the study set out to assess and how tumor-response categories were defined.

It does not, however, report the primary endpoint results. There are no recorded counts for response categories and no primary-outcome estimate, confidence interval or test result. The registry information therefore cannot show the observed frequency or precision of tumor regression. Completion status and enrollment do not fill this gap.

The record also does not establish whether PBL treatment differed from TIL treatment. The design is nonrandomized, and the record warns that the arms are not like-for-like controls. Any between-arm difference would need careful consideration of participant selection and other potential differences; the available record does not report an adjusted comparative analysis.

General statistical interpretation requires separating a study's question from the evidence it reports. A prespecified endpoint can be meaningful while its results remain unavailable in the registry record. Likewise, a planning illustration based on an observed effect is not an observed treatment effect, nor does it demonstrate that a study had adequate power. The record's stated planning assumptions cannot be used to reconstruct an efficacy result.

Accordingly, the posted information supports a description of the trial's population, interventions, design and endpoint, together with limited serious adverse-event counts. It does not support a quantitative conclusion about tumor response, the comparative effects of the two cell approaches, or a complete safety profile. Those conclusions require outcome and analysis details not reported in the registry record.

13. Why This Trial Matters Statistically

This trial illustrates why a registry entry needs to be read at two levels: the clinical question and the results actually reported. The record describes a specific cell-engineering strategy, a target population and a standardized tumor-response definition. Those details clarify the intended investigation, but they do not independently provide evidence about the observed response.

Its design also highlights the importance of distinguishing treatment arms from valid controls. The registry lists both PBL and TIL approaches but identifies nonrandomized allocation and cautions against treating the arms as like-for-like. Statistical comparisons depend on the way groups were formed, not simply on whether separate arm labels appear in a record.

The endpoint shows how a clinical concept becomes an operational statistical outcome. RECIST criteria convert lesion measurements into response categories, which can support consistent reporting. Yet readers still need counts, analysis populations and uncertainty estimates to understand the resulting evidence. A definition without results cannot answer how often each response occurred or how precisely it was estimated.

Finally, the record underscores the value of transparent reporting on missing data, analysis plans and safety denominators. Those details allow readers to judge how outcomes were collected, who contributed to each analysis and how robust an inference may be. Where such information is absent, careful interpretation means identifying the limits rather than filling them with assumptions.

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.

Several limitations are specific to what is recorded for this study. The primary endpoint is defined, but its outcome counts and statistical analysis are not reported in the registry record. This prevents estimation of the response frequency and its uncertainty, and leaves the endpoint's observed distribution unknown.

The design is nonrandomized, with a single-group classification and two listed cell-treatment arms. The record cautions that the arms are not like-for-like controls. It does not describe how assignment to PBL or TIL occurred or provide an adjusted comparison. Therefore, a causal interpretation of any apparent difference between approaches would not be justified from these registry entries.

The registry does not report primary-analysis population details, assessment completeness or the treatment of missing or unevaluable RECIST results. It also does not report the statistical analysis plan, multiplicity procedures, interim monitoring or a prospective sample-size justification. The planning assumptions noted in the record are explicitly illustrations based on an observed effect, rather than the trial's own design.

For safety, arm-specific serious-event counts are recorded, but the listed event-term percentages are not linked to arms in the information available. A comparative analysis, uncertainty estimates and fuller event detail are not reported. These gaps limit interpretation of both safety patterns and differences between cell approaches. The registry information is therefore useful for describing the study framework, but insufficient for a complete efficacy or comparative safety assessment.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Phase II Study of Metastatic Melanoma With Lymphodepleting Conditioning and Infusion of Anti-MART-1 F5 TCR-Gene-Engineered Lymphocytes — NCT00509288.
• Registry record last updated 2012-12-28; status last verified 2012-12.
• Results first posted 2012-12-18.
• 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

The registry describes a completed phase II, nonrandomized study of autologous anti-MART-1 F5 T-cell receptor-engineered lymphocytes in metastatic melanoma. Enrollment was 24, and the record identifies the National Cancer Institute as sponsor. The listed treatment approaches were engineered PBL and TIL, with high-dose IL-2 in the arm labels; cyclophosphamide and fludarabine are also listed among the interventions.

The primary outcome was clinical tumor regression assessed using RECIST, with an outcome timeframe of 7/5/07-4/23/09. Toxicity was listed as a secondary outcome. The record includes serious adverse-event counts by arm but does not report the primary tumor-response counts, analysis results or a statistical analysis plan. It cautions that the nonrandomized arms are not like-for-like controls. Thus, the trial question and endpoint are described, while the primary efficacy result and comparative interpretation remain unreported in the registry record.