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 Study of Repeat Intranodal Injection of Memgen's Cancer Vaccine, Ad-ISF35, in Subjects With Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL) (NCT00849524), a na phase 2 study. The primary outcome is Determine and Monitor Clinical and Biological Responses in Patients Treated With Repeat Intranodal Injections of Ad-ISF35..
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT00849524 |
| Phase | Phase 2 |
| Condition | Chronic Lymphocytic Leukemia, Small Lymphocytic Lymphoma |
| Allocation | Not applicable (single group) |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 6 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Januario Castro, M.D. |
| Results posted | Yes |
2. Clinical Question
Population
The study concerned patients with chronic lymphocytic leukemia or small lymphocytic lymphoma. The registry record lists an enrollment of 6. Eligibility details beyond the conditions are not reported in the registry record, so the population’s clinical characteristics and the criteria used to select participants cannot be described from this record.
Intervention
The intervention was Ad-ISF35, described as repeat injections directly into a selected lymph node under ultrasound guidance. The intended schedule was every 2-4 weeks, for up to six total injections. The study was open label, and the registry describes it as a fixed-dose study. Whether each participant received any injections, and how many, is not reported in the registry record.
Comparator
There was no separate comparator group. The study used a single-group model, with allocation listed as not applicable. Consequently, the design does not make a randomized, like-for-like comparison between Ad-ISF35 and another treatment, placebo, or usual care. A comparison with a participant’s status before treatment is not reported as a formal control comparison.
Primary question
The stated primary objective was to determine and monitor clinical and biological responses during repeat intranodal Ad-ISF35 injections. The registry also listed safety and pharmacodynamic aims as secondary outcomes. The primary outcome timeframe was 2 years, with evaluation described as approximately 4 months per patient. The study was not completed because the study drug was unavailable, and primary-outcome data were not collected. Thus, the registry record states the question the study intended to address, but the posted results do not answer whether clinical or biological responses occurred.
3. Trial Design
This was a Phase II, open-label, single-group study of repeat intranodal Ad-ISF35 injections in patients with chronic lymphocytic leukemia or small lymphocytic lymphoma. The registry lists an enrollment of 6 and identifies the intervention as a biological product. There was no randomized allocation and no separate control arm. The sponsor is listed as Januario Castro, M.D.
The intervention description planned injections into a selected lymph node under ultrasound guidance. The intended fixed dose was administered every 2-4 weeks, up to six total injections. “Up to” describes the planned maximum; it does not establish how many injections participants actually received. Actual treatment exposure is not reported in the registry record. The study was described as single institution, but the institution’s name is not reported in the registry record.
The record lists a start date of 2009-01, a primary completion date of 2009-07, and a status of terminated. It also states that the study was not completed because the study drug was unavailable. The primary outcome timeframe was 2 years, with evaluation described as approximately 4 months per patient. These are the registry’s stated timeframes; they do not establish that participants completed follow-up over those periods.
As a general design principle, a single-group study can describe what was observed among enrolled participants, but without a concurrent comparison group it cannot separate a treatment-associated change from other explanations as a randomized comparison can. Open-label design means masking was not used. The registry does not report a detailed protocol, recruitment flow, reasons for termination beyond drug unavailability, or how many participants began treatment. These gaps limit interpretation of both the intended design and the amount of study activity completed.
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 | Ad-ISF35 |
|---|---|
| STARTED | 6 |
| COMPLETED | 3 |
| NOT COMPLETED | 3 |
Reasons for not completing this period:
| Reason | Ad-ISF35 |
|---|---|
| Lack of Efficacy | 3 |
Analysis population for the primary outcome, as defined in the registry: The study was not completed due to unavailability of the study drug, and therefore data were not collected for this Outcome Measure.
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.
| Characteristic | Unit | Ad-ISF35 |
|---|---|---|
| Participants analysed | 6 | |
| Age, Categorical: <=18 years | Participants | 0 |
| Age, Categorical: Between 18 and 65 years | Participants | 2 |
| Age, Categorical: >=65 years | Participants | 4 |
| Sex: Female, Male: Female | Participants | 1 |
| Sex: Female, Male: Male | Participants | 5 |
| Region of Enrollment: United States | participants | 6 |
6. Primary Endpoint
The registry lists the primary outcome as Determine and Monitor Clinical and Biological Responses in Patients Treated With Repeat Intranodal Injections of Ad-ISF35., measured over 2 years (evaluation will be approx. 4 months per patient).
| Element | Registry entry |
|---|---|
| Result type | N/A |
| Measure of spread | not applicable |
| Unit | not stated |
| Endpoint classification | not reduced to a single comparison |
The primary outcome was described broadly as determining and monitoring clinical and biological responses among patients treated with repeat intranodal Ad-ISF35 injections. The stated timeframe was 2 years, with evaluation approximately 4 months per patient. The outcome record does not specify a particular response definition, measurement scale, laboratory marker, assessment schedule, or rule for deciding whether a response occurred. Those details are not reported in the registry record.
In general, a primary outcome gives a trial a principal target for assessing the question it was designed to address. Clinical and biological measures can capture different kinds of change: a clinical measure concerns patient or disease status, while a biological measure concerns a biological process or marker. That distinction is general; the registry does not identify which particular measures would have been used in this study.
The record says the study was not completed because the study drug was unavailable and that data were not collected for this outcome measure. Therefore, there is no posted primary-outcome result to estimate or interpret. The stated purpose and timeframe describe what investigators intended to assess, not an observed response. No response rate, change estimate, uncertainty interval, or statistical test result for the primary outcome is reported in the registry record.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The main statistical fact is that the planned primary clinical and biological response outcome has no collected data in the registry record. The record explicitly attributes this to the study not being completed because the study drug was unavailable. Without primary-outcome observations, there is no estimate of the size, direction, or variability of a response in the enrolled group. The registry therefore offers no basis for quantifying a treatment effect from this primary outcome.
The study enrolled 6 participants, but enrollment alone does not show that all participants received Ad-ISF35, completed the planned injection schedule, or contributed follow-up measurements. Those details are not reported in the registry record. The intervention was planned as repeat injections every 2-4 weeks, up to six total injections, but a planned schedule should not be read as observed exposure.
The single-group, open-label design also matters to interpretation. In general, without a concurrent control group, changes observed in participants cannot be compared with changes that might have occurred without the intervention under the same study conditions. This design does not provide the randomized, like-for-like treatment contrast that would support a direct comparative estimate. In this case, the absence of primary outcome data means even a descriptive estimate of change is unavailable.
The posted safety figures are distinct from the uncollected primary outcome. The registry lists 6 participants at risk and 0 affected for serious adverse events, and 6 at risk and 6 affected for other adverse events. These counts describe the categories recorded in the registry; they do not establish which event types occurred, their severity within the non-serious category, their timing, or whether they were attributed to treatment. Deaths are not reported in the registry record. The small enrolled group and absence of detailed event terms constrain how much can be inferred from these figures.
No statistical analyses are listed in the posted results. There are no reported primary-outcome estimates, confidence intervals, or p-values to assess. The study status and missing endpoint data should therefore be kept separate from a conclusion about efficacy: the record documents an incomplete study with unavailable primary results, not evidence that the intervention did or did not produce a response.
9. Statistical Methods Explained
The registry describes the study’s structure but does not report a statistical analysis plan. In particular, it does not state how clinical or biological responses would have been defined, how repeated measurements would have been summarized, or what model or test would have been used. The posted results list no analyses. The methods discussion below explains general statistical concepts relevant to this design; it does not attribute unreported methods to the investigators.
What does a single-group design estimate?
In general, a single-group study can describe outcomes among participants who receive an intervention. If outcome measurements are collected before and after treatment, a within-participant change can be calculated, but such a change is not the same as a controlled treatment effect. Changes could also reflect the natural course of disease, other care, measurement variation, or factors associated with who was enrolled. A concurrent comparison group helps distinguish these explanations, especially when allocation is randomized. This study had no separate comparator arm, so a between-group treatment contrast was not part of its design.
Even descriptive estimates require observed data. Here, the registry says primary-outcome data were not collected because the study was not completed due to unavailability of the study drug. The planned single-group design cannot produce a primary response estimate when the outcome observations are absent. Enrollment and intervention plans do not substitute for those observations.
What would an estimate and confidence interval convey?
In general, an estimate summarizes the observed outcome, while a confidence interval conveys the uncertainty associated with that estimate under the statistical model used. The interval’s width depends on factors such as the amount and variability of the data and the analysis method. A confidence interval does not repair missing observations or account automatically for bias from a non-comparative design. Since no primary result is reported, there is no estimate or confidence interval for the primary clinical or biological response to interpret in this study.
Why can small samples be imprecise?
As a general principle, estimates from small groups can be sensitive to the outcomes of individual participants and often have substantial uncertainty. A small group may also provide limited information about uncommon events or variation across patients. The registry lists enrollment of 6, but the number who received treatment or contributed particular outcome data is not reported. More importantly, the primary outcome is explicitly described as having no collected data, so no precision estimate can be obtained for it. This is not a case where a result is merely imprecise; the primary result is unavailable.
Why do repeated measurements require an analysis plan?
The intervention was planned as repeat injections, and the primary objective was to determine and monitor responses. In general, repeated measurements from the same participant are related rather than independent. An analysis of such data may need to account for within-participant correlation, the timing of assessments, incomplete follow-up, and the definition of change or response. These choices can affect both the estimate and its uncertainty. The registry record does not report the schedule of outcome assessments beyond the stated timeframe, the statistical handling of repeated observations, or a response algorithm. It would be inappropriate to assume a particular longitudinal model or analysis method.
What is the role of over-dispersion?
As a general statistical concept, over-dispersion occurs when observed variability is greater than a model assumes. For count outcomes, for example, a simple model may underestimate uncertainty if the data vary more than expected under its assumptions. Analysts may then consider a model that allows additional variability. Whether over-dispersion is relevant depends on the outcome type and observed data. The registry does not identify the primary outcome’s measurement scale or report collected primary data, so no assessment of over-dispersion can be made for this study.
What can be said about statistical significance?
A p-value is a measure calculated under a specified statistical model and null hypothesis; it is not a measure of the size or clinical importance of an effect. In general, interpretation requires knowing the analysis, assumptions, and outcome being tested. No primary analyses or p-values are listed in the posted results. There is consequently no statistical significance claim to evaluate, and none should be inferred from the study’s Phase II label or its stated objectives.
The registry record also does not report a sample-size justification, planned power, interim analyses, or a detailed statistical plan. Those omissions mean the intended precision and decision framework cannot be reconstructed from the record. Any general discussion of statistical methods should therefore remain conceptual rather than being presented as the methods actually used in this trial.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists a primary objective concerning clinical and biological responses, along with secondary aims concerning safety and pharmacodynamic parameters. Multiple outcomes can raise a general multiplicity issue: when several hypotheses are tested, the chance of at least one apparently notable result can increase unless the analysis plan addresses that possibility. The registry record does not report a multiplicity strategy, a hierarchy among specific measures, or analyses for these outcomes. Since no analyses are listed, there are no reported inferential findings whose multiplicity adjustment can be assessed.
Missing outcome data are central to interpreting this study. The registry explicitly states that primary-outcome data were not collected because the study was not completed due to unavailability of the study drug. This is not a reported set of missing measurements among otherwise completed follow-up; the record says the outcome data were not collected. The reasons individual participants may or may not have received injections or completed follow-up are not reported in the registry record.
In general, missingness can affect estimates when the likelihood of having an observed outcome is related to participant characteristics or outcomes. Statistical methods can sometimes address incomplete data, but they require observed information and assumptions about why data are missing. They cannot create the uncollected primary endpoint observations or establish the response that would have been observed. No imputation method or missing-data sensitivity analysis is reported.
The analysis populations are also not described. The registry does not report an intention-to-treat population, a treated population, or a per-protocol population, nor does it provide participant-level disposition. Enrollment of 6 should not be taken to mean that 6 participants were analyzed for the primary endpoint. The available record therefore does not support reconstruction of an analysis denominator for that outcome.
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 |
|---|---|---|---|
| Ad-ISF35 | 0 | 6 | 0.0% |
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 |
|---|---|
| Ad-ISF35 | 6 of 6 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Ad-ISF35 |
|---|---|---|
| Flu like syndrome | Immune system disorders | 6 of 6 |
| Fever | General disorders | 6 of 6 |
| Injection site reaction | Immune system disorders | 6 of 6 |
| Sweating | General disorders | 6 of 6 |
| Fatigue | General disorders | 6 of 6 |
| Nausea | Gastrointestinal disorders | 4 of 6 |
| Arthritis (non-septic) | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | 3 of 6 |
| Anorexia | General disorders | 3 of 6 |
| Vomiting | Gastrointestinal disorders | 2 of 6 |
| Dyspnea-Shortness of breath | Respiratory, thoracic and mediastinal disorders | 2 of 6 |
The registry’s serious adverse event figures list 6 participants at risk and 0 affected. For other adverse events, it lists 6 at risk and 6 affected. These are counts in distinct registry categories. “At risk” is the denominator recorded for the category; “affected” is the number recorded as having an event in that category. The counts do not identify event types or show the number of events per participant.
The registry does not list top serious adverse event terms. Deaths are not reported in the registry record. The absence of listed serious-event terms is consistent with the serious-event count of 0 affected, but it does not add detail about the other adverse events. The record does not report the nature, timing, duration, severity, outcome, or treatment attribution of the other events. It also does not describe how adverse events were collected or whether all participants had the same observation period.
These counts should be read as the safety information posted in the registry, not as a complete characterization of safety. In general, a small study group provides limited information about uncommon events, and an event count alone does not establish causation. The safety figures do not answer the primary clinical and biological response question, for which the registry states that data were not collected.
12. What the Result Does, and Does Not, Mean
The record establishes that a Phase II, open-label, single-group study of repeat intranodal Ad-ISF35 injections was registered for patients with chronic lymphocytic leukemia or small lymphocytic lymphoma. It also establishes that the study was terminated and not completed because the study drug was unavailable. The registry reports enrollment of 6, a planned injection schedule, and safety counts. Those details describe the study and its posted results, but they do not establish a primary treatment response.
The primary outcome was intended to monitor clinical and biological responses, yet the registry states that no data were collected for it. Therefore, the posted results do not show whether participants experienced a response, how large any response may have been, or how much uncertainty would surround an estimate. There is no reported comparison with another treatment or control group, and no primary statistical analysis is listed.
The safety counts show 0 of 6 affected in the serious adverse event category and 6 of 6 affected in the other adverse event category as recorded. They do not disclose event details, treatment attribution, or deaths. They should not be expanded into claims about the type or clinical importance of events.
In general, a trial can be informative even when it does not yield an efficacy estimate: its record may clarify what was planned, what was completed, and where evidence is absent. For this study, the key limitation is that the intended primary outcome was not measured. The record cannot support a conclusion that Ad-ISF35 did or did not produce clinical or biological effects. It likewise cannot support a reliable comparative conclusion, since the design had no control arm and the primary outcome data are unavailable.
13. Why This Trial Matters Statistically
This study illustrates an important distinction in clinical-trial interpretation: a stated research objective is not itself an outcome result. The registry defines an intended question about clinical and biological responses to repeated intranodal Ad-ISF35 injections, but also records that the study was not completed because the study drug was unavailable and that primary-outcome data were not collected. Readers therefore need to distinguish the protocol’s aim from evidence generated by the study.
The record also shows why trial status and data availability matter statistically. Enrollment was 6, but enrollment is not the same as outcome completion, and the record does not describe treatment exposure or participant-level follow-up. When primary measurements are absent, statistical modeling cannot produce a defensible estimate of the primary response. A design description, planned dose schedule, or Phase II designation cannot replace outcome data.
Its single-group, open-label structure is another useful teaching point. In general, such a design may describe observed outcomes but does not offer the controlled comparison that randomization is intended to support. Here, the absence of primary outcome data means that even a descriptive response summary is not available in the registry.
The study record also separates safety reporting from the primary efficacy objective. Serious and other adverse event counts are posted, but event details and attribution are not. Statistical interpretation must match the level of detail recorded: counts can be described as counts, while unsupported claims about causation, event types, or treatment effects should be avoided.
For clinical researchers and biostatisticians, the case emphasizes transparent reporting of completion, outcome collection, analysis populations, and analysis methods. The registry makes the primary-data gap explicit, while leaving many design and analytic details unreported. Recognizing both what the record documents and what it cannot establish is essential for a balanced reading.
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 main trial-specific limitation is that the planned primary clinical and biological response outcome has no collected data. The registry attributes this to the study not being completed because the study drug was unavailable. No primary estimate, variability measure, confidence interval, or test result is available. The posted results therefore cannot quantify response.
The single-group design offers no randomized comparator. Even if outcome measurements had been collected, observed changes would not by themselves provide a controlled contrast against another treatment or a control condition. The open-label design also means masking was not used; the record does not describe whether this affected outcome assessment.
The planned intervention was repeat dosing, but actual treatment exposure is not reported. The registry does not say how many participants received injections, how many doses were administered, or whether participants completed follow-up. Although enrollment is listed as 6, it cannot be assumed that all 6 contributed to any specific outcome analysis. The stated primary timeframe and per-patient evaluation period do not establish completed observation.
The primary outcome is broadly described, without a specified response definition, measurement scale, assessment schedule, or statistical method. A detailed protocol, sample-size justification, interim analysis plan, analysis populations, and missing-data strategy are not reported in the registry record. No statistical analyses are listed. These omissions prevent assessment of the intended inferential framework as well as reconstruction of how any outcome would have been analyzed.
Safety reporting is also limited. The registry provides affected and at-risk counts but does not list event terms, details, timing, attribution, or deaths. The small enrollment further limits the amount of safety information the study could provide. These limitations are distinct from the primary-outcome data gap, but both constrain interpretation of the posted results.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Study of Repeat Intranodal Injection of Memgen's Cancer Vaccine, Ad-ISF35, in Subjects With Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL) — NCT00849524.
- Registry record last updated 2015-12-30; status last verified 2015-11.
- Results first posted 2015-11-20.
- 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 Phase II, open-label, single-group study of repeat intranodal Ad-ISF35 injections for chronic lymphocytic leukemia or small lymphocytic lymphoma. Enrollment is listed as 6. The planned intervention was given every 2-4 weeks, up to six injections. The record lists a start date of 2009-01, primary completion of 2009-07, and status as terminated.
The stated primary objective was to determine and monitor clinical and biological responses, with a 2-year timeframe and evaluation described as approximately 4 months per patient. The study was not completed because the study drug was unavailable, and primary-outcome data were not collected. No statistical analyses are listed in the posted results.
For safety, the registry lists 0 affected among 6 at risk for serious adverse events and 6 affected among 6 at risk for other adverse events. Serious event terms are not listed, and deaths are not reported. The record does not provide a comparator group, treatment exposure details, primary outcome estimates, or a detailed statistical analysis plan.