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 Open-Label Extension Study of De-immunized DI-Leu16-IL2 Immunocytokine Administered in Participants With B-cell NHL (NCT02151903), a non-randomized phase 1, phase 2 study. The primary outcome is Number of Participants With Best Overall Response (BOR) Assessed Per International Workshop for Non-Hodgkin Lymphoma (NHL) Response Criteria.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT02151903 |
| Phase | Phase 1, Phase 2 |
| Condition | B-cell Non-Hodgkin Lymphoma |
| Allocation | Non-Randomized |
| Design model | Parallel |
| Masking | None (open label) |
| Enrollment | 5 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Alopexx Oncology, LLC |
| Results posted | Yes |
2. Clinical Question
Population
Participants with B-cell non-Hodgkin lymphoma who experienced clinical benefit after 6 cycles of DI-Leu16-IL2 in the Alopexx Oncology Dose-Escalation AO-101 study were eligible for this extension. The primary-outcome description defines the safety population as enrolled participants who received at least 1 dose of study drug.
Intervention
Participants continued DI-Leu16-IL2 at the dose, schedule, and route they had received in the main study. The registry describes dose groups of 1.0 mg/m^2 and 2.0 mg/m^2, administered subcutaneously for 3 consecutive days every 3 weeks.
Comparator
There was no randomized control group. The record describes a non-randomized, open-label, parallel design with the two DI-Leu16-IL2 dose groups. Because allocation was not randomized, these groups are not a like-for-like control comparison; differences between them cannot be interpreted as a randomized estimate of dose effect.
Primary question
The primary outcome was the number of participants with a best overall response classified using International Workshop for Non-Hodgkin Lymphoma response criteria. The registry gives the response categories and assessment timeframe, but does not report the response counts or an analysis result.
As an extension study, the central question is descriptive: what best overall response categories were recorded among participants continuing treatment after prior clinical benefit, and what safety events were recorded during the extension? This differs from asking whether DI-Leu16-IL2 is better than no treatment or another therapy. The record contains no randomized comparison that could answer such a question.
The study enrolled 5 participants and is listed as terminated. The reason for termination is not reported in the registry record. The extension’s eligibility depended on participation in the preceding AO-101 study and clinical benefit after its treatment cycles, so the enrolled group represents a selected population rather than an unselected group of people with B-cell non-Hodgkin lymphoma.
3. Trial Design
This was an open-label extension study of DI-Leu16-IL2 in participants with B-cell non-Hodgkin lymphoma. The registry lists phase 1 and phase 2, non-randomized allocation, no masking, and a parallel intervention model. The study enrolled 5 participants. It began on 2014-11-04, had primary completion on 2016-07-11, and is listed as terminated. The reason for termination is not reported in the registry record.
Eligibility for the extension centered on clinical benefit following 6 cycles of DI-Leu16-IL2 in the Alopexx Oncology Dose-Escalation AO-101 main study. Participants were to continue at the same dose, schedule, and route received in that study. The registry describes DI-Leu16-IL2 at 1.0 mg/m^2 and 2.0 mg/m^2, given subcutaneously for 3 consecutive days every 3 weeks, with each cycle described as 21 days. Prior pre-treatment, for example Rituximab, was to continue as before.
The design does not assign participants randomly to the dose groups, and neither participants nor study staff were masked. The groups therefore do not function as a randomized dose comparison. Prior treatment, selection into an extension after clinical benefit, and other differences between participants could affect outcomes; the registry does not report an adjustment strategy to account for such differences.
The primary outcome was the number of participants with best overall response under International Workshop for Non-Hodgkin Lymphoma response criteria. Its timeframe ran from first dose of study drug until first appearance of a response or disease-status category, up to 20 months. Listed secondary outcomes cover treatment-emergent adverse events, serious adverse events, clinically significant hematology or serum chemistry abnormalities considered related to a treatment-emergent event, and clinically significant physical examination abnormalities. The registry’s sample-size rationale and detailed statistical analysis plan are not reported.
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
| Stage | DI-Leu16-IL2 1.0 mg/m^2 | DI-Leu16-IL2 2.0 mg/m^2 |
|---|---|---|
| STARTED | 3 | 2 |
| Received at Least 1 Dose of Study Drug | 3 | 2 |
| COMPLETED | 0 | 1 |
| NOT COMPLETED | 3 | 1 |
Reasons for not completing this period:
| Reason | DI-Leu16-IL2 1.0 mg/m^2 | DI-Leu16-IL2 2.0 mg/m^2 |
|---|---|---|
| Withdrawal by Subject | 1 | 0 |
| Progressive disease | 2 | 1 |
Analysis population for the primary outcome, as defined in the registry: Safety population included all enrolled participants who received at least 1 dose of study drug.
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: Safety population included all enrolled participants who received at least 1 dose of study drug.
| Characteristic | Unit | DI-Leu16-IL2 1.0 mg/m^2 | DI-Leu16-IL2 2.0 mg/m^2 | Total |
|---|---|---|---|---|
| Participants analysed | 3 | 2 | 5 | |
| Age, Categorical: <=18 years | Participants | 0 | 0 | 0 |
| Age, Categorical: Between 18 and 65 years | Participants | 2 | 0 | 2 |
| Age, Categorical: >=65 years | Participants | 1 | 2 | 3 |
| Sex: Female, Male: Female | Participants | 1 | 2 | 3 |
| Sex: Female, Male: Male | Participants | 2 | 0 | 2 |
6. Primary Endpoint
The registry lists the primary outcome as Number of Participants With Best Overall Response (BOR) Assessed Per International Workshop for Non-Hodgkin Lymphoma (NHL) Response Criteria, measured over First dose of study drug until first appearance of CR, CRu, PR, SD, or PD (up to 20 months).
| Element | Registry entry |
|---|---|
| Result type | Count Of Participants |
| Measure of spread | not applicable |
| Unit | Participants |
| Endpoint classification | Binary Endpoint |
The primary endpoint counts participants according to best overall response (BOR), assessed using International Workshop for Non-Hodgkin Lymphoma response criteria. The registry lists complete response (CR), unconfirmed complete response (CRu), partial response (PR), stable disease (SD), and progressive disease (PD) as the relevant categories. In broad terms, these classify whether disease findings disappear, shrink, remain stable, or progress according to specified clinical and imaging criteria. The full criteria in the record also refer to lymph nodes, other organs, bone marrow, and the appearance of new disease.
“Best overall” refers to the response category recorded as the best during the stated assessment period, rather than a single measurement at one fixed visit. The timeframe begins with the first dose of study drug and continues until first appearance of a listed category, up to 20 months. This endpoint can describe the range of disease statuses observed during follow-up, but it does not by itself measure how long a response lasted or compare treatment with an alternative.
The endpoint is expressed as a count of participants. The record identifies the safety population as enrolled participants who received at least 1 dose of study drug. However, it does not report the BOR counts, their denominators for each category, or an uncertainty interval. The stated endpoint and criteria therefore clarify what was intended to be assessed, but they do not establish the observed response distribution. The primary response result is not reported in the registry record.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry describes a small extension study rather than a randomized efficacy comparison. It enrolled 5 participants who had experienced clinical benefit after 6 cycles of treatment in the preceding AO-101 study. The selection of participants after prior benefit is important context: findings from this group would describe people who reached the extension eligibility stage, not all people with B-cell non-Hodgkin lymphoma or all people starting DI-Leu16-IL2.
The primary outcome is a count of participants by best overall response category. Although the registry defines those categories and the assessment timeframe, it does not report the number of participants in any category. No primary-outcome result or analysis is reported in the registry record. Consequently, the posted information does not allow a quantitative interpretation of the observed response distribution, and no estimate of response precision can be described.
The safety entries report serious adverse events for each dose group: in the 1.0 mg/m^2 group, 2 participants were affected among 3 at risk; in the 2.0 mg/m^2 group, 0 were affected among 2 at risk. The separate other-adverse-event counts were 3 affected among 3 at risk in the 1.0 mg/m^2 group and 1 affected among 2 at risk in the 2.0 mg/m^2 group. The registry lists 0 deaths in each group. Anaemia and Melena are listed among the top serious terms at 33.3% each. These counts describe the entries in the record; they do not establish that a dose caused an event or that one dose has a different safety profile.
General statistical interpretation: counts from a small group can change substantially when individual participants’ outcomes differ, and uncertainty is important when interpreting such estimates. No confidence intervals or formal comparisons are reported for these outcomes. The non-randomized allocation also means that any apparent difference between dose groups could reflect participant selection or other group differences, rather than dose alone.
The registry lists 6 outcome measures and no analyses. It does not report a statistical test, adjusted estimate, or inferential result for the primary endpoint. The record also does not explain why the study was terminated. Taken together, the available results support a description of the study design and recorded safety counts, but not a conclusion about treatment effect or a comparative assessment of the dose groups.
9. Statistical Methods Explained
What kind of outcome is the primary endpoint? The primary outcome is a count of participants classified by best overall response. This is a categorical outcome: each participant’s disease status is assigned to a response category under the stated criteria. The categories are CR, CRu, PR, SD, and PD. The endpoint is not a continuous measurement such as a laboratory value, nor is it a time-to-event estimate. The registry does not report the category counts, so the response distribution cannot be reconstructed from this record.
Why use a best overall response measure? General explanation: response categories provide a structured way to describe the most favorable disease status recorded during a specified follow-up period. They can summarize several kinds of clinical and imaging findings in a clinically interpretable classification. They do not, by themselves, convey how long a response lasted, how outcomes changed at each visit, or whether treatment caused the observed status. Those questions require other outcomes or a suitable comparison and analysis.
How should the assessment window be understood? The registry defines the timeframe as beginning at first dose of study drug and continuing until first appearance of CR, CRu, PR, SD, or PD, up to 20 months. This gives the stated observation period for the endpoint. The record does not report visit schedules, the number of assessments per participant, or the handling of assessments that were unavailable or difficult to classify. It is therefore not possible to assess how those operational details may have affected the endpoint.
What do the safety counts represent? The adverse-event entries give counts of affected participants and participants at risk within each dose group. These are descriptive counts, not adjusted comparisons. General explanation: a count should be interpreted in relation to the population being observed and the event definition. Counts alone do not convey uncertainty, and they cannot show whether an event was caused by treatment. The registry also reports serious-event terms and deaths, but does not provide a comparative statistical analysis of those outcomes.
Why does the design matter for interpretation? General explanation: random allocation can help balance both known and unknown participant characteristics across groups, making a treatment comparison more interpretable. This study is explicitly non-randomized and open-label. The registry further describes enrollment after participants experienced clinical benefit in the main study. As a result, the dose groups may differ in ways that are not measured or adjusted for in the posted record. A simple difference between their event counts would not isolate a dose effect.
What can be said about statistical testing? The record lists no analyses. It does not report a test statistic, p-value, confidence interval, adjusted estimate, or model for the primary outcome. General explanation: a confidence interval describes a range of values compatible with an estimate under a statistical model; it helps communicate precision, but does not remove design limitations. Without a reported estimate and interval, precision cannot be assessed for the primary outcome. No uncertainty interval is reported for the safety counts either.
How should sample-size illustrations be read? The stated planning approach is an illustration based on the observed effect, not the trial’s own design. It assumes a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation; the effect to detect is a stated fraction of the observed effect. For time-to-event outcomes the described output is a total number of events, while other outcomes are expressed as participants per arm. These assumptions describe planning calculations, not observed results. Any resulting sample-size estimate is not observed power. The registry does not report a sample-size justification for the trial itself, and the primary response result needed to interpret an illustration based on the observed effect is not reported.
Why does over-dispersion matter in general? General explanation: over-dispersion occurs when observed variability in count data exceeds what a chosen statistical model assumes. If ignored, standard errors and resulting uncertainty estimates can be misleading. The posted primary endpoint is a participant count by category, and no model or inferential analysis is reported. It would therefore be inappropriate to infer that an over-dispersion assessment was performed or that a particular count model was used.
What about multiple outcomes? The registry lists 6 outcome measures, including the primary response endpoint and safety outcomes. General explanation: when multiple outcomes or tests are assessed, the chance of at least one apparently notable finding can increase if no multiplicity strategy is used. The registry record does not report a multiplicity adjustment or an outcome hierarchy beyond identifying the primary and secondary outcomes. Since no analyses are listed, the impact of multiplicity on any inferential results cannot be evaluated.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists 6 outcome measures: a primary best overall response measure and secondary safety measures covering treatment-emergent adverse events, serious adverse events, clinically significant hematology or serum chemistry abnormalities considered related to a treatment-emergent event, and clinically significant physical examination abnormalities. It lists no analyses. A multiplicity adjustment, testing hierarchy, or other approach to interpreting results across outcomes is not reported in the registry record. Without reported inferential tests, there is no basis to assess how multiplicity was handled in practice.
The primary-outcome description defines the safety population as enrolled participants who received at least 1 dose of study drug. The record does not describe other analysis populations, such as an intention-to-treat or per-protocol population, and does not explain how participants were assigned to analysis sets. The adverse-event entries give group-specific counts at risk and affected, but the broader analysis-population definitions are not reported.
Missing-data methods are not reported in the registry record. It does not state how missing response assessments, incomplete follow-up, withdrawal, or unevaluable response classifications were handled. Nor does it report the completeness of outcome assessments for each participant. As a result, the potential effect of missing observations on the response count cannot be assessed.
General statistical explanation: missing observations can affect an outcome summary when the likelihood of missingness is related to participants’ health status, treatment experience, or outcome. Methods for addressing missing data depend on the outcome and the reasons observations are unavailable. No such method should be attributed to this study without documentation. The registry also does not report a sensitivity analysis to test whether conclusions would change under different assumptions about missing outcomes. Since the primary response counts themselves are not reported, even a descriptive evaluation of missingness and completeness is not possible from this record.
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 |
|---|---|---|---|
| DI-Leu16-IL2 1.0 mg/m^2 | 2 | 3 | 66.7% |
| DI-Leu16-IL2 2.0 mg/m^2 | 0 | 2 | 0.0% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| DI-Leu16-IL2 1.0 mg/m^2 | 0 of 3 |
| DI-Leu16-IL2 2.0 mg/m^2 | 0 of 2 |
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 |
|---|---|
| DI-Leu16-IL2 1.0 mg/m^2 | 3 of 3 |
| DI-Leu16-IL2 2.0 mg/m^2 | 1 of 2 |
Most frequent serious adverse event terms
| Event term | Organ system | DI-Leu16-IL2 1.0 mg/m^2 | DI-Leu16-IL2 2.0 mg/m^2 |
|---|---|---|---|
| Anaemia | Blood and lymphatic system disorders | 1 of 3 | 0 of 2 |
| Melena | Gastrointestinal disorders | 1 of 3 | 0 of 2 |
Most frequent non-serious adverse event terms
| Event term | Organ system | DI-Leu16-IL2 1.0 mg/m^2 | DI-Leu16-IL2 2.0 mg/m^2 |
|---|---|---|---|
| Dry mouth | Gastrointestinal disorders | 1 of 3 | 1 of 2 |
| Injection site erythema | General disorders | 1 of 3 | 1 of 2 |
| Injection site induration | General disorders | 1 of 3 | 1 of 2 |
| Fall | Injury, poisoning and procedural complications | 2 of 3 | 0 of 2 |
| Insomnia | Psychiatric disorders | 1 of 3 | 1 of 2 |
| Hypotension | Vascular disorders | 1 of 3 | 1 of 2 |
| Injection site pruritus | General disorders | 1 of 3 | 1 of 2 |
| Injection site swelling | General disorders | 1 of 3 | 1 of 2 |
| Upper respiratory tract infection | Infections and infestations | 1 of 3 | 1 of 2 |
| Anaemia | Blood and lymphatic system disorders | 1 of 3 | 0 of 2 |
Serious events with the highest arm-level rate: anaemia (33.3%), melena (33.3%).
The serious adverse-event entries are counts within each dose group. For DI-Leu16-IL2 1.0 mg/m^2, 2 participants were affected among 3 at risk. For DI-Leu16-IL2 2.0 mg/m^2, 0 participants were affected among 2 at risk. The registry lists 0 deaths in each group. The separate other-adverse-event counts are 3 affected among 3 at risk in the 1.0 mg/m^2 group and 1 affected among 2 at risk in the 2.0 mg/m^2 group.
Anaemia and Melena are listed as top serious terms, each at 33.3%. The registry record does not provide additional detail in these entries about timing, duration, severity beyond the serious-event classification, or a causal assessment for these terms. The entries should therefore be read as recorded safety information, not as proof that treatment caused an event.
General statistical explanation: counts from small groups are descriptive and can be imprecise. A difference in counts across non-randomized groups does not establish a difference in underlying risk, particularly when participant characteristics and follow-up may not be comparable. No formal safety comparison or uncertainty interval is reported in the registry record. The listed counts should not be converted into a comparative conclusion.
12. What the Result Does, and Does Not, Mean
The record documents an open-label, non-randomized extension of DI-Leu16-IL2 among participants with B-cell non-Hodgkin lymphoma who had clinical benefit after 6 cycles in the main study. It identifies best overall response as the primary endpoint, gives the response criteria and assessment timeframe, and reports group-level safety counts. These details establish what the study set out to observe and what safety entries appear in the registry.
The primary response outcome itself is not reported in the registry record. There are no response-category counts, effect estimates, confidence intervals, or listed analyses. The record therefore cannot show the observed distribution of best overall response or quantify the precision of a response estimate. It also cannot support a conclusion about whether treatment changed disease status.
The adverse-event counts are descriptive. They do not determine whether an event was caused by DI-Leu16-IL2, and the difference in counts across the dose groups is not a randomized comparison. The groups were not randomly allocated, the study was open-label, and enrollment followed clinical benefit in the preceding study. Those design features limit causal and comparative interpretation.
General statistical explanation: an observed outcome in a treated group is not by itself an estimate of what would have happened to the same participants under a different treatment or no treatment. A suitable comparison is needed to separate treatment effects from other influences. This record does not provide such a randomized control comparison.
The record also does not report why the study was terminated, how missing response data were handled, or what analysis plan was followed. Accordingly, the strongest interpretation is limited to the design and reported safety counts. The registry does not establish efficacy, a dose-response relationship, or a comparative safety profile.
13. Why This Trial Matters Statistically
This trial is statistically notable because it illustrates the difference between an extension study and a randomized treatment comparison. Participants entered after clinical benefit in the main study, and the registry describes continued treatment at the dose and schedule already received. Such a design can document subsequent observations in a selected group, but it does not provide a randomized estimate of what would have happened under another treatment or without continued treatment.
The stated primary endpoint is a categorical participant count rather than a time-to-event effect or a direct between-group contrast. Naming the endpoint and its response criteria is useful because it clarifies what the investigators intended to classify. However, the registry does not report the resulting response counts or analyses. This distinction matters: endpoint definitions are not outcome results.
The study also demonstrates why safety counts need context. Counts are presented by dose group, but allocation was non-randomized and the groups are not like-for-like controls. The recorded counts can describe what was observed in the registry, while leaving causal attribution and comparative risk unresolved. The small enrolled cohort further limits how precisely these counts can characterize uncommon outcomes.
Finally, the record lists sample-size planning assumptions separately from evidence about outcomes. General statistical explanation: planning calculations depend on assumptions about the effect to detect, variability, allocation, and the test design. They are not a substitute for observed data and do not reveal the strength of evidence from a completed study. In this record, the primary response result and the trial’s own statistical plan are not reported. The example therefore highlights how transparent endpoint reporting, analysis methods, missing-data handling, and uncertainty estimates are all needed to interpret a clinical study fully.
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 primary limitation for interpretation is that the registry does not report the primary best overall response counts or a statistical analysis. The endpoint’s categories and timeframe are described, but the actual distribution of outcomes and its precision cannot be assessed.
The study enrolled 5 participants, and the record describes a non-randomized, open-label design. Participants were eligible after clinical benefit in the preceding AO-101 study. This selection and the lack of random allocation constrain generalizability and make between-dose comparisons vulnerable to differences among participants. The registry does not report an adjustment method that would address those differences.
The reason for termination is not reported in the registry record. The record also does not describe the statistical analysis plan, sample-size justification, missing-data methods, outcome completeness, or a multiplicity strategy. No confidence intervals or formal comparisons are reported. These omissions limit assessment of both the reliability of observed counts and the way outcome analyses were intended to be interpreted.
The registry’s safety information is also limited to counts and listed serious-event terms. Details such as event timing, duration, and causal assessment are not reported in these entries. The group-specific counts should not be treated as a randomized comparison or as evidence that a particular dose caused or prevented an event. These limitations apply to interpretation of the registry record and do not establish what may have been documented elsewhere.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Open-Label Extension Study of De-immunized DI-Leu16-IL2 Immunocytokine Administered in Participants With B-cell NHL — NCT02151903.
- Registry record last updated 2020-11-27; status last verified 2020-11.
- Results first posted 2020-11-27.
- 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
NCT02151903 is an open-label extension study of DI-Leu16-IL2 in participants with B-cell non-Hodgkin lymphoma who had clinical benefit after 6 cycles in the Alopexx Oncology Dose-Escalation AO-101 study. It is listed as phase 1 and phase 2, non-randomized, with no masking and a parallel model. The record lists enrollment of 5, a start date of 2014-11-04, primary completion on 2016-07-11, and terminated status.
The primary outcome was the number of participants with best overall response under International Workshop for Non-Hodgkin Lymphoma response criteria. The primary response counts and analyses are not reported in the registry record. Safety entries give serious and other adverse-event counts by dose group and list 0 deaths in each group. The reason for termination, statistical analysis plan, and missing-data methods are not reported.