Natural Killer Cells Plus IL-2 Following Chemotherapy to Treat Advanced Melanoma or Kidney Cancer: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Natural Killer Cells Plus IL-2 Following Chemotherapy to Treat Advanced Melanoma or Kidney Cancer (NCT00328861), a randomized phase 2 study. The primary outcome is Objective Response.

2. Clinical Question

The central clinical research question was whether the regimen could produce an objective tumor response in people with metastatic melanoma or kidney cancer previously treated with high-dose IL-2, while also evaluating safety. This is a question about a complex treatment sequence, not the effect of NK cells in isolation: the listed intervention includes chemotherapy, NK-cell infusion, and IL-2. The registry record does not report results that would establish how often a response occurred or how response differed between the cancer groups.

3. Trial Design

The registry record describes a completed phase II study with randomized allocation, no masking, and a parallel model. Enrollment was 8. The listed groups were “NK Cells + IL-2: Melanoma” and “NK Cells + IL-2: Renal Cell”; 7 participants were listed in the melanoma group and 1 in the renal-cell group. The record does not explain what was randomized, how allocation was carried out, or whether participants were randomized between treatment options. It also does not describe a separate control arm.

The treatment sequence included leukapheresis to collect white blood cells and obtain NK cells, followed by cyclophosphamide and fludarabine, infusion of the treated NK cells, and IL-2 therapy. The group descriptions list cyclophosphamide at 60 mg/kg/day intravenously on days -8 and -7, fludarabine at 25 mg/m^2/day intravenously on days -6 through -2, and IL-2 at 720,000 IU/kg/intravenously every 8 hours for up to 5 days. NK cells were infused after chemotherapy. The detailed description in the registry record is truncated, so further treatment details are not reported in the registry record.

The primary outcome was objective response, assessed by RECIST. The record gives a schedule of every 4-6 weeks for up to 1 year, and then every 6 months for up to 5 years. Safety was listed as a secondary outcome. The study began in 2006-05, reached primary completion in 2007-07, and has a completed status. The planned sample-size justification, allocation details, and any analysis plan are not reported in the registry record.

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 Objective Response, measured over very 4-6 weeks for up to 1 year, and then every 6 months for up to 5 years..

The primary endpoint was objective response, recorded as the number of participants with a complete response or partial response under RECIST. In the registry description, complete response means disappearance of all target lesions. Partial response means at least a 30% decrease in the sum of the longest diameters of target lesions, using the baseline sum as the reference.

Objective response is used to describe whether measurable tumors meet predefined criteria for substantial shrinkage or disappearance. Because the criteria are specified in advance, response assessment can be expressed as a count of participants who meet them rather than as an informal impression. The registry record gives repeated assessment time points: every 4-6 weeks for up to 1 year, and then every 6 months for up to 5 years. That schedule indicates that response status was intended to be assessed over time, but the record does not report how response categories were handled across assessments or which time point defined the reported primary result.

The posted record does not include the number of complete responses, partial responses, or participants with no objective response. It also does not provide a response estimate, confidence interval, or statistical comparison. Consequently, the endpoint definition is available, but the primary outcome result cannot be interpreted from the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

Statistical methods are difficult to evaluate when a registry record gives an endpoint definition but no outcome analysis. The study lists objective response as its primary outcome and safety as a secondary outcome. It records 0 analyses. The registry record does not report the statistical analysis plan, the method used to summarize responses, or the method used to compare groups. No response estimate, confidence interval, or p-value is reported.

What an objective-response analysis would describe

For a binary endpoint such as whether a participant met the objective-response definition, a basic summary can count participants with a response and participants without one. An estimated response proportion describes the share of the analyzed group meeting the criterion. A confidence interval describes uncertainty around an estimate; it is not a guarantee that the true value lies within a particular interval. With small groups, estimates can be imprecise, and the possible values compatible with the data can remain broad. These are general statistical principles, not analyses reported for this study.

Here, the registry record does not report response counts, so a response proportion or confidence interval cannot be described. The endpoint is assessed repeatedly according to the stated schedule, but the registry record does not say whether the primary result was based on a particular assessment, the best response over follow-up, or another rule. It also does not report how participants who stopped follow-up or had missing assessments were handled.

Interpreting the study structure

Randomized allocation can support a fair comparison when participants are assigned to distinct alternatives and outcomes are analyzed according to a stated plan. The registry record labels this study randomized, parallel, and unmasked, but lists groups by cancer type and does not identify a distinct comparator treatment. It does not explain the allocation procedure, what assignment meant, or whether the groups were intended to be compared. Therefore, a randomized treatment contrast cannot be reconstructed from the record.

Even if a comparison had been intended, the group sizes recorded—7 in the melanoma group and 1 in the renal-cell group—would make estimates for the renal-cell group especially uncertain. This is a general consequence of having very few observations: each participant's outcome has a large influence on a group summary. It is not a substitute for a reported analysis, and it does not establish what the investigators planned to do.

Planning calculations and power

The registry record's sample-size assumptions describe a planning illustration based on an observed effect, not the trial's own design. The stated assumptions are a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation, with the effect to detect expressed as a fraction of the observed effect. For non-time-to-event outcomes, the illustration is defined in participants per arm for 80% or 90% power; time-to-event illustrations are defined in total events. These assumptions do not establish that the study was originally designed with those targets, and no planning results should be read as observed power. The trial's sample-size justification is not reported in the registry record.

Power is a design-stage probability tied to a specific effect, analysis, and set of assumptions. It is not a measure of how likely a result is true after data have been observed. A calculation that uses an observed effect for planning is especially illustrative: it shows what a future design might require under those assumptions, not what this study had power to detect or whether its treatment was effective. No new sample-size calculation or power estimate is reported for the study outcomes.

Multiplicity and repeated assessments

Multiple outcomes, comparisons, or time points can create multiplicity: the more opportunities there are to detect a result, the more difficult it can be to interpret isolated statistical findings. The registry describes repeated assessment of objective response and lists safety as a secondary outcome, but does not report any multiplicity strategy or identify which analyses were planned. General methods for addressing multiplicity include defining a primary time point in advance, controlling error across planned tests, or treating secondary analyses as exploratory. Which, if any, was used is not reported in the registry record.

The record therefore supports an explanation of the endpoint and broad statistical concepts, but not a reconstruction of the investigators' statistical methods. In particular, the analysis population, handling of missing response assessments, confidence-interval method, and treatment of repeated measurements are not reported in the registry record. Without those details and without outcome analyses, statistical conclusions about response or comparative effects cannot be drawn.

10. Multiplicity, Missing Data and Analysis Populations

The registry identifies objective response as the primary outcome and safety as a secondary outcome. Objective response was scheduled for assessment every 4-6 weeks for up to 1 year, and then every 6 months for up to 5 years. The record does not state which assessment or summary across assessments defined the primary analysis. It also does not describe a plan for handling multiple outcomes, repeated assessments, or multiple statistical tests. Whether any multiplicity adjustment was used is not reported in the registry record.

The analysis population is not reported in the registry record. In particular, the record does not say whether all enrolled participants were included in the primary analysis, how participants who did not receive the full regimen were handled, or how follow-up loss affected outcome summaries. The number of analyses is 0, and no response counts or analysis results are posted.

Missing outcome data can affect interpretation if participants with unavailable assessments differ from those whose outcomes are observed. General approaches include describing missingness, specifying the analysis population, and conducting sensitivity analyses under stated assumptions. Those details are not reported in the registry record, so the impact of missing or unrecorded assessments cannot be evaluated. The absence of such information does not establish that outcome data were missing; it means the registry record does not describe their status or handling.

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 non-serious adverse event terms

The posted safety counts distinguish serious adverse events from other adverse events. In the melanoma group, 0 of 7 participants are listed with a serious adverse event, and 7 of 7 are listed with other adverse events. In the renal-cell group, 0 of 1 participant is listed with a serious adverse event, and 1 of 1 is listed with other adverse events. The registry record lists no serious-event terms. Death counts are not reported in the registry record.

These counts describe participants recorded in each category; they do not show the number of individual events, their types, severity, timing, duration, or relationship to treatment. The registry record does not provide definitions for the serious and other adverse-event categories. In particular, an “other adverse event” count should not be interpreted as a count of distinct events or as a measure of clinical importance.

The groups are small, especially the renal-cell group, so the counts provide limited information about how often adverse events might occur in a broader population. A count of zero serious adverse events in the listed participants does not establish that serious harms are absent. These descriptive results also do not compare the regimen with another treatment, since a separate comparator is not reported in the registry record.

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

The registry record establishes that a phase II study of autologous NK cells plus IL-2 after chemotherapy was completed, with 8 participants enrolled across metastatic melanoma and renal-cell cancer groups. It specifies an objective-response endpoint based on RECIST and records safety as a secondary outcome. The posted adverse-event counts are also available, including zero serious adverse events recorded in each listed group and other adverse events recorded for all participants in each group.

Those details do not provide the primary efficacy result. The registry record does not report complete-response or partial-response counts, a response estimate, or an analysis comparing groups. Without those results, the effect of the regimen on objective response cannot be quantified from the posted record. The absence of a reported result does not mean that no participant responded, just as the study's completion status does not itself establish that the treatment was effective.

The study is labeled randomized, but the record does not identify a separate control treatment or explain the allocation. The two groups are described by cancer type. Therefore, the available information does not support a randomized comparison of this regimen against another treatment, or a conclusion that any difference between the listed groups was caused by treatment.

The small enrolled groups also limit how much can be inferred from the safety counts. The record does not report adverse-event terms or deaths, and zero recorded serious adverse events in a small study cannot establish that serious events do not occur. The most defensible reading is descriptive: the registry documents the study's intended endpoint, its enrollment, and selected safety counts, while leaving the primary response findings and important analysis details unreported.

13. Why This Trial Matters Statistically

This study is statistically notable because it combines a clearly defined response endpoint with a registry record that contains no primary-outcome analysis. RECIST gives explicit criteria for complete and partial response, which can make an endpoint more reproducible than an unstructured clinical judgment. However, an endpoint definition alone does not show how many participants met the criteria. Without response counts or an analysis, the central statistical question remains unanswered in the posted record.

The small enrollment and the imbalance in group sizes are also important context for interpreting any descriptive results. The record lists 7 participants with melanoma and 1 with renal-cell cancer. A single outcome in a group of that size can strongly shape its apparent pattern, and uncertainty would be substantial. These registry entries argue for caution in reading the safety counts and make clear why estimates and uncertainty intervals matter; no such primary-outcome estimates are reported.

Finally, the record labels the study randomized but does not identify a distinct comparator or explain the allocation. That gap illustrates a basic principle of trial interpretation: design labels do not, by themselves, establish what contrast was tested. A treatment effect requires a defined comparison and an analysis that matches the design. Here, the available record supports description of the regimen and enrollment, but does not permit an estimate of comparative effect.

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 registry record has several limitations for statistical interpretation. It reports enrollment of 8 and lists group sizes of 7 for melanoma and 1 for renal-cell cancer, but provides no primary response counts or analyses. Consequently, response frequency and uncertainty cannot be assessed. The record also does not include confidence intervals or test results.

Although the study is labeled randomized, the allocation procedure and meaning of randomization are not described. The listed groups are organized by cancer type, and a distinct comparator treatment is not reported in the registry record. This prevents reconstruction of a treatment contrast and leaves the role of randomization unclear.

The primary endpoint was assessed repeatedly, but the record does not specify which time point or response summary was used in the primary analysis. It does not report the analysis population, handling of missing assessments, or methods for repeated measurements. The statistical analysis plan and sample-size justification are also not reported in the registry record.

Safety information is limited to counts of participants with serious and other adverse events. Event terms, definitions, grades, timing, and deaths are not reported in the registry record. The small groups further limit the descriptive value of these counts. In addition, the brief treatment description is truncated, so details beyond the listed regimen are not available. These limitations do not establish that information was absent from the full study; they describe what is not reported in the registry record.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Natural Killer Cells Plus IL-2 Following Chemotherapy to Treat Advanced Melanoma or Kidney Cancer — NCT00328861.
• Registry record last updated 2012-11-05; status last verified 2012-10.
• Results first posted 2012-11-05.
• 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

NCT00328861 is a completed phase II study titled “Natural Killer Cells Plus IL-2 Following Chemotherapy to Treat Advanced Melanoma or Kidney Cancer.” The study began in 2006-05, reached primary completion in 2007-07, and enrolled 8 participants. It is recorded as randomized, unmasked, and parallel, with groups listed for melanoma and renal-cell cancer.

The treatment combined autologous NK cells and IL-2 after cyclophosphamide and fludarabine chemotherapy. The primary outcome was objective response by RECIST, with safety listed as a secondary outcome. The registry record does not report primary response counts or analyses. It records 0 serious adverse events among 7 participants in the melanoma group and among 1 participant in the renal-cell group; other adverse events are recorded for all participants in both groups. Death counts are not reported in the registry record.