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 High Dose Interleukin-2 Followed by Intermittent Low Dose Temozolomide in Patients With Melanoma (NCT01124734), a na phase 2 study. The primary outcome is Clinical Response to High-Dose Interleukin-2 (H-D IL-2) Followed by Low Dose Temozolomide.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT01124734 |
| Phase | Phase 2 |
| Condition | Malignant Melanoma |
| Allocation | Not applicable (single group) |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 17 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Milton S. Hershey Medical Center |
| Results posted | Yes |
2. Clinical Question
Population
Participants with metastatic malignant melanoma were eligible for the treatment sequence under study. The registry record lists an enrollment of 17. It does not report further details about participant characteristics or eligibility criteria in the outcome description, so the population’s clinical profile cannot be characterized more fully from this record.
Intervention
The sequence was high-dose interleukin-2 (IL-2) followed by low-dose temozolomide. The trial description identifies the temozolomide schedule as intermittent. For Course 1 Cycle 1 and Cycle 2, the record describes high-dose IL-2 at 600,000 IU/kg, up to 14 doses at 8-hour intervals.
Comparator
There was no separate comparison group: the trial is described as single-group, with allocation recorded as not applicable. The registry background discusses other treatment experiences, but those are not a concurrent control arm in this trial. Comparisons with those experiences cannot replace a randomized, like-for-like comparison.
Primary question
The primary outcome asks how many participants had a clinical response to high-dose IL-2 followed by low-dose temozolomide, assessed using RECIST categories. The outcome timeframe is 2 years. The registry record does not report the response counts, so the observed distribution across complete response, partial response, minor response, stable disease, and progressive disease cannot be described.
3. Trial Design
This is a phase II, completed, single-group clinical trial sponsored by Milton S. Hershey Medical Center. The registry record lists enrollment of 17 and identifies malignant melanoma as the condition. The study began in 2010-05, and its primary completion date is 2017-07-18. Allocation is recorded as not applicable and masking as none. There is no concurrent randomized comparator, and the trial arms therefore do not provide a like-for-like control comparison.
The treatment sequence was high-dose interleukin-2 followed by low-dose temozolomide. The intervention description identifies intermittent temozolomide. For Course 1 Cycle 1 and Cycle 2, the registry record specifies high-dose IL-2 at 600,000 IU/kg, up to 14 doses at 8-hour intervals. The cycle description also begins to describe what happens after discharge, but the full schedule is not reported in the registry record. Further details of the temozolomide dose and timing are not reported in the registry record.
The primary outcome is clinical response, measured using RECIST categories, with a stated timeframe of 2 years. The registry record also lists a secondary outcome concerning the effect of the sequence on lymphocyte subsets, described as autoimmune biomarkers. It lists four outcome measures, but the record does not provide the primary response counts or statistical analyses. This limits what can be concluded about efficacy and precision from the registry information.
The registry summary explains that the investigators were interested in the sequence after observing responses in earlier patients. Those observations are part of the rationale described in the record, not a concurrent control group or the reported primary result of this trial. The study design can describe outcomes among participants receiving the sequence, but by itself cannot separate treatment effects from other explanations for observed outcomes.
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: Participants were excluded if they received any chemotherapy, hormonal therapy, immunotherapy, or radiation therapy within 1 month of entry to the study.
Overall Study
| Stage | Course 1 Cycle 1 and Cycle 2 |
|---|---|
| STARTED | 17 |
| Completion of Course 1 Cycle 1 | 17 |
| Initiation of Course 1 Cycle 2 | 17 |
| COMPLETED | 0 |
| NOT COMPLETED | 17 |
Reasons for not completing this period:
| Reason | Course 1 Cycle 1 and Cycle 2 |
|---|---|
| Disease progression | 13 |
| Adverse Event | 1 |
| Withdrawal by Subject | 1 |
| Elected for alternative treatment | 2 |
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: All participants had melanoma.
| Characteristic | Unit | Course 1 Cycles 1 and 2 |
|---|---|---|
| Participants analysed | 17 | |
| Age, Categorical: <=18 years | Participants | 0 |
| Age, Categorical: Between 18 and 65 years | Participants | 15 |
| Age, Categorical: >=65 years | Participants | 2 |
| Sex: Female, Male: Female | Participants | 6 |
| Sex: Female, Male: Male | Participants | 11 |
| Ethnicity (NIH/OMB): Hispanic or Latino | Participants | 0 |
| Ethnicity (NIH/OMB): Not Hispanic or Latino | Participants | 17 |
| Ethnicity (NIH/OMB): Unknown or Not Reported | Participants | 0 |
| Race (NIH/OMB): American Indian or Alaska Native | Participants | 0 |
| Race (NIH/OMB): Asian | Participants | 0 |
| Race (NIH/OMB): Native Hawaiian or Other Pacific Islander | Participants | 0 |
| Race (NIH/OMB): Black or African American | Participants | 0 |
| Race (NIH/OMB): White | Participants | 17 |
| Race (NIH/OMB): More than one race | Participants | 0 |
| Race (NIH/OMB): Unknown or Not Reported | Participants | 0 |
| Region of Enrollment: United States | Participants | 17 |
6. Primary Endpoint
The registry lists the primary outcome as Clinical Response to High-Dose Interleukin-2 (H-D IL-2) Followed by Low Dose Temozolomide, measured over 2 years.
| Element | Registry entry |
|---|---|
| Result type | Count Of Participants |
| Measure of spread | not applicable |
| Unit | Participants |
| Endpoint classification | Binary Endpoint |
The primary endpoint is clinical response to high-dose interleukin-2 followed by low-dose temozolomide. It is expressed as a count of participants and classified using Response Evaluation Criteria in Solid Tumors (RECIST): complete response, partial response, minor response, stable disease, or progressive disease. The stated timeframe is 2 years.
Response categories provide a structured way to describe changes in tumor status using predefined criteria. Separating complete and partial responses from minor response, stable disease, and progressive disease preserves clinically relevant distinctions that a single undifferentiated count could obscure. A count in each category can show the pattern of outcomes among participants assessed, if those counts and the analysis population are reported.
The registry record does not report the observed counts in these categories, the number assessed at the endpoint, or how missing assessments were handled. It therefore does not establish the frequency or distribution of clinical responses. The record also does not report additional detail on assessment timing or procedures beyond the stated 2-year timeframe and use of RECIST. The endpoint definition identifies what the study intended to measure; it does not substitute for the missing outcome data.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record establishes the study’s design and the intended clinical response outcome, but it does not report the primary response results. In particular, the record gives no count of participants in the RECIST categories and no statistical analysis of the primary endpoint. Consequently, the observed response pattern, its precision, and the extent of missing outcome data cannot be assessed from the registry information. The study’s title and rationale do not establish its results.
The design is single-group. Without a concurrent control group, outcomes among treated participants cannot by themselves show what would have happened under another treatment or without this sequence. The registry summary describes earlier observations that motivated the study, including responses after treatment, but those observations are not a control arm for the trial. Differences between historical experiences may reflect differences in participants, assessment, follow-up, or other factors that cannot be evaluated from the registry record.
The endpoint’s categories matter for interpretation. A complete response and a partial response are distinct categories, as are minor response, stable disease, and progressive disease. If counts were available, they would describe the reported RECIST outcomes in the assessed population; they would not alone establish a causal effect of the sequence. Here, even that descriptive distribution is not reported in the registry record.
The registry lists serious adverse event information for Course 1 Cycle 1 and Course 1 Cycle 2, including one affected participant among 17 at risk in each cycle and a death count of 0 in Cycle 1 and 9 in Cycle 2. These are reported cycle-specific counts. The record does not establish whether the deaths were attributed to treatment, nor does it explain the circumstances or timing. The counts should not be interpreted as proof of causation. The record also lists Stroke and Arrhythmia among the top serious event terms, each at 5.9%.
Overall, the available registry information supports a description of the design, endpoint definition, treatment sequence, and listed safety counts. It does not support a conclusion about the primary response outcome or a comparative treatment effect. Any interpretation should keep the distinction between the investigators’ motivating observations and this trial’s unreported primary results clear.
9. Statistical Methods Explained
Statistical methods determine how outcomes are summarized and how uncertainty is represented. For this trial, the registry record identifies a count-based primary outcome: participants categorized by RECIST response. However, it reports no analysis for the primary endpoint. The number of analyses listed is 0. The registry record does not report a statistical analysis plan, confidence intervals, hypothesis tests, adjustment methods, or a model for the response categories. Those methods cannot be inferred from the phase II designation or from the study’s stated objective.
What does a response count describe?
A count describes how many participants fall into a specified category in the population being assessed. For a multi-category endpoint, each category should be interpreted separately and alongside information about who was assessed and who was not. A count alone does not express uncertainty about the underlying response frequency. A confidence interval, when reported, describes a range of values compatible with the data and the method used; it is not a guarantee that the true value lies within that range. No confidence interval for the primary outcome is reported in the registry record.
Why does the single-group design matter?
In a single-group study, the observed outcomes are described among participants who receive the treatment sequence. A treatment contrast requires a comparison with an appropriate alternative. Without a concurrent control group, an observed outcome cannot isolate the effect of the treatment from other influences, such as participant characteristics or the natural course of illness. This is a general design principle, not a claim about what caused any individual outcome in this trial. The registry summary mentions earlier experiences as context, but it does not report a randomized comparison based on those experiences.
What does precision mean?
Precision concerns how much uncertainty surrounds an estimate. In general, estimates based on limited information tend to be less precise than estimates based on more information, but precision should be evaluated using the actual data and an appropriate method. The enrollment entry alone is not enough to establish how many participants contributed to the primary outcome, whether all were assessed, or how precise an outcome estimate would be. Those details are not reported in the registry record. No precision estimate should therefore be inferred.
What can be said about sample-size planning?
The registry record does not report the trial’s sample-size justification, target effect, or statistical plan for enrollment. Any sample-size illustration based on an observed effect would be a planning calculation, not observed power and not evidence that the trial was adequately powered. In this case, the primary effect estimate is not reported in the registry record, so there is no reported primary result from which to assess such a calculation. The design assumptions for any planning illustration should not be mistaken for the trial’s own protocol or analysis.
How should adverse-event counts be handled?
Safety counts are descriptive unless the record supplies a defined comparison and analysis. The registry reports event information separately for Course 1 Cycle 1 and Course 1 Cycle 2. These are cycle-level entries; the record does not specify whether a participant could contribute to both entries or how recurrent events were handled. Counts across cycles should not be added to infer a number of distinct participants. The record also does not describe attribution procedures, exposure-adjusted rates, or statistical comparisons for safety outcomes.
In general, a statistical analysis should specify the population analyzed, outcome definitions, handling of missing observations, and methods for estimating uncertainty. Those details are important because different choices can change what a reported estimate represents. The registry record identifies the primary outcome and timeframe, but does not report these analysis details. The most defensible reading is therefore descriptive and limited to the registry entries that are explicitly recorded.
10. Multiplicity, Missing Data and Analysis Populations
Multiplicity arises when a study assesses several outcomes, categories, time points, or statistical tests. In general, testing many hypotheses can increase the chance of finding an apparently noteworthy result by chance, so a statistical plan may specify which outcome is primary and how other analyses will be interpreted. The registry record identifies clinical response as the primary outcome and lists a secondary outcome concerning lymphocyte subsets (autoimmune biomarkers). It also states that there are four outcome measures, but the record does not report a multiplicity adjustment or a plan for interpreting multiple tests. No such approach should be assumed.
The registry record does not report the primary response counts, the number assessed, or the handling of missing outcome assessments. It also does not report an analysis population definition, such as whether the endpoint was analyzed among all enrolled participants or only those with an assessment. These omissions prevent evaluation of whether the reported outcome—if available elsewhere—would represent all enrolled participants or a subset. The record does not report reasons for missing assessments or how those reasons were addressed.
The record lists 0 analyses. This does not establish that no analysis was conducted; it means that statistical analyses are not reported in the registry record. Details about interim analyses, missing-data methods, and population definitions are likewise not reported in the registry record. Without these details, the primary endpoint’s statistical interpretation and vulnerability to missing-data assumptions cannot be assessed. The absence of reported methods should not be filled by guessing what investigators may have planned or done.
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 |
|---|---|---|---|
| Course 1 Cycle 1 | 1 | 17 | 5.9% |
| Course 1 Cycle 2 | 1 | 17 | 5.9% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Course 1 Cycle 1 | 0 of 17 |
| Course 1 Cycle 2 | 9 of 17 |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 5% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Course 1 Cycle 1 | 17 of 17 |
| Course 1 Cycle 2 | 17 of 17 |
Most frequent serious adverse event terms
| Event term | Organ system | Course 1 Cycle 1 | Course 1 Cycle 2 |
|---|---|---|---|
| Stroke | Nervous system disorders | 0 of 17 | 1 of 17 |
| Arrhythmia | Cardiac disorders | 1 of 17 | 0 of 17 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Course 1 Cycle 1 | Course 1 Cycle 2 |
|---|---|---|---|
| Capillary leak syndrome | Vascular disorders | 10 of 17 | 4 of 17 |
| Diarrhea | Gastrointestinal disorders | 9 of 17 | 4 of 17 |
| Flu like symptoms | General disorders | 9 of 17 | 3 of 17 |
| Hypocalcemia | Metabolism and nutrition disorders | 9 of 17 | 3 of 17 |
| Hypophosphatemia | Metabolism and nutrition disorders | 8 of 17 | 4 of 17 |
| Nausea | Gastrointestinal disorders | 9 of 17 | 3 of 17 |
| Thrombocytopenia | Blood and lymphatic system disorders | 9 of 17 | 3 of 17 |
| Fatigue | General disorders | 9 of 17 | 2 of 17 |
| Dry Skin | Skin and subcutaneous tissue disorders | 8 of 17 | 3 of 17 |
| Anemia | Blood and lymphatic system disorders | 7 of 17 | 3 of 17 |
Serious events with the highest arm-level rate: stroke (5.9%), arrhythmia (5.9%).
The registry reports adverse-event entries separately for Course 1 Cycle 1 and Course 1 Cycle 2. In each cycle, 17 participants are listed as at risk for serious adverse events, and 1 as affected. For other adverse events, 17 are listed as at risk and 17 as affected in each cycle. The death count is listed as 0 for Cycle 1 and 9 for Cycle 2. These are the counts recorded for the separate course cycles; they should not be added to estimate distinct participants because overlap between cycle entries is not described.
Stroke and Arrhythmia are each listed among the top serious event terms at 5.9%. The record does not provide additional details about timing, severity grading, event recurrence, or whether the events were judged related to treatment. The cycle-specific death entries also do not establish that deaths were caused by treatment. The counts describe what the registry records, not an attribution or comparative safety analysis.
Adverse-event figures are most informative when definitions, exposure, follow-up, and attribution are clear. Those details are not reported in the registry record. Accordingly, these entries should be read as descriptive safety counts rather than as estimates of comparative risk.
12. What the Result Does, and Does Not, Mean
The record describes a phase II evaluation of a treatment sequence and defines clinical response using RECIST categories over a 2-year timeframe. It also records adverse-event counts by treatment cycle. These details establish what the study set out to evaluate and provide a limited account of safety reporting. They do not reveal the primary outcome distribution because response counts are not reported in the registry record.
The investigators’ rationale refers to earlier patients treated with the sequence and compares their experience with other treatment experiences. That narrative explains why the sequence was of interest, but it is not the primary result of this trial and does not supply a concurrent control group. Observations from different treatment settings cannot be treated as a randomized comparison based on the information in the registry record.
The trial’s single-group design also limits causal interpretation. Even if response results were available, outcomes in a single treated group would describe what occurred among participants, but would not on their own establish what would have occurred under a different treatment. A comparison group and a suitable design are important for estimating relative treatment effects.
The record does not report the primary response counts, statistical analyses, uncertainty estimates, or analysis population. It therefore cannot establish the frequency of response, the precision of any effect estimate, or whether results apply beyond the participants assessed. Safety counts are similarly descriptive; the record does not establish treatment attribution for the reported events or deaths.
The appropriate conclusion is narrow: the registry documents the treatment sequence, the intended response measure, and selected safety counts, while leaving the central primary outcome results and their analysis unreported. This does not show that the sequence did or did not produce a particular response. It means the registry information is insufficient to make that judgment.
13. Why This Trial Matters Statistically
This trial is statistically notable for the gap between a clearly stated clinical question and the results available in the registry record. The question concerns response after a particular treatment sequence in metastatic malignant melanoma, with response categorized using RECIST. Yet the response counts and statistical analyses are not reported. Without them, readers cannot assess the observed category distribution, quantify uncertainty, or judge how the outcome relates to the motivating observations in the registry summary.
The single-group structure is central to interpretation. It can describe outcomes among participants receiving the sequence, but it does not provide a concurrent counterfactual for comparison. This distinction matters especially when the rationale rests on comparisons with experiences from other settings. Historical observations may motivate a trial, but they do not remove confounding or other differences between groups.
The record also illustrates why endpoint definitions, analysis populations, missing-data handling, and statistical methods should be reported alongside outcomes. A stated endpoint alone does not reveal who contributed data or how uncertainty was handled. Similarly, cycle-level safety counts need context about exposure, overlap, event definitions, and attribution to support meaningful comparisons.
These limitations do not diminish the value of a registered research question; they define what can be learned from the record. Clear reporting of the primary results and analysis methods would be necessary to evaluate the response findings statistically. On the current registry information, the sound approach is to distinguish the planned endpoint and study rationale from results that are not reported.
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 important trial-specific limitation in the registry record is that the primary clinical response results are not reported. There are no counts for complete response, partial response, minor response, stable disease, or progressive disease, and no statistical analysis is listed. Consequently, the primary outcome cannot be evaluated for magnitude, distribution, or precision using the registry record.
The design is single-group, with no concurrent comparator. This prevents a direct randomized estimate of how outcomes differ from another treatment or alternative course. The background narrative describes earlier observations, but the record does not establish them as a comparable control group. The trial design therefore cannot determine from the registry data whether outcomes are attributable to the treatment sequence.
Further details needed to interpret outcomes are not reported in the registry record. These include the primary analysis population, the number assessed at the endpoint, missing-data handling, and the statistical plan. The record’s treatment description gives the high-dose IL-2 dosing for the first two cycles, but the full temozolomide dosing and schedule are not reported in the registry record. The record also does not detail response assessment procedures beyond RECIST categories and the 2-year timeframe.
Safety information is reported by cycle, but the registry record does not describe overlap between cycle entries, event attribution, recurrence handling, or the circumstances of the reported deaths. These limitations mean the safety counts should not be treated as causal or comparative estimates. Taken together, the registry information supports a description of the registered design and selected counts, but not a complete assessment of efficacy or safety.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: High Dose Interleukin-2 Followed by Intermittent Low Dose Temozolomide in Patients With Melanoma — NCT01124734.
- Registry record last updated 2019-02-12; status last verified 2019-01.
- Results first posted 2019-02-12.
- 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
The registry describes a completed phase II, single-group trial of high-dose interleukin-2 followed by intermittent low-dose temozolomide in malignant melanoma. Enrollment is listed as 17. The primary endpoint is clinical response assessed with RECIST categories over 2 years. For Course 1 Cycle 1 and Cycle 2, the record specifies high-dose IL-2 at 600,000 IU/kg, up to 14 doses at 8-hour intervals.
The primary response counts and statistical analyses are not reported in the registry record. The registry does list a secondary outcome concerning lymphocyte subsets and cycle-specific adverse-event counts, including deaths recorded as 0 in Cycle 1 and 9 in Cycle 2. The single-group design does not provide a concurrent control comparison. The record therefore defines the study question and reports selected safety information, but does not allow assessment of the primary response result or a comparative treatment effect.