Imexon for Relapsed Follicular and Aggressive Lymphomas: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Imexon for Relapsed Follicular and Aggressive Lymphomas (NCT01314014), a na phase 2 study. The primary outcome is Overall Response Rate of of Participants to Imexon in the Treatment of Relapsed/Refractory Indolent and Aggressive Lymphomas.

2. Clinical Question

The clinical question concerns whether tumor responses were observed after treatment in a population whose disease had progressed after standard therapies. The registry describes response assessment using CT, PET, or MRI scans at baseline, after cycle 2, and every 3 cycles thereafter until disease progression. Response classification followed standard response criteria from the International Harmonization Project on Lymphoma. The stated definition of partial response includes regression of measurable disease and no new sites; its criteria also refer to a decrease in the sum of products of lesion diameters and to imaging findings.

This is an activity question, not a comparison of imexon with another treatment. A single-group response estimate can describe outcomes among participants evaluated in the study, but by itself cannot establish how those outcomes compare with what would have occurred under another treatment or without the study intervention. The registry record states that 20 subjects were evaluable for response and that 2 discontinued therapy during cycle 1, one due to progressive disease and one due to grade 5 sepsis. It does not report the response count, an overall response estimate, or the confidence interval. Therefore, the clinical question is identifiable, but its numerical answer is not available in the registry record.

3. Trial Design

The registry describes a completed phase II study sponsored by the University of Rochester. It was a single-group trial with no masking and no randomized allocation. The enrollment listed is 22. The record gives a start of 2011-05 and a primary completion of 2013-03. These dates describe the trial record and do not, by themselves, explain the timing of individual assessments or analyses.

Participants received imexon by intravenous infusion over 60 minutes, following pre-treatment with anti-emetics. Treatment was scheduled on Days 1-5 of 21-day cycles and could continue for up to one year. The intervention description does not establish that every participant completed the planned treatment period. The primary endpoint refers to response over one year; the assessment schedule states that scans occurred at baseline, after cycle 2, and every 3 cycles thereafter until disease progression.

The single-group design means the trial describes outcomes among people treated with imexon, without a like-for-like control arm. It can document observed response and safety information, but it cannot separate treatment-associated outcomes from changes that might have happened because of disease course, participant characteristics, or other care. The registry specifically notes that this is not a randomized comparison and that arms are not a like-for-like control comparison; in this study there is only the imexon group.

The registry reports 22 enrolled and identifies 20 subjects as evaluable for response, with 2 discontinuing during cycle 1 for progressive disease and grade 5 sepsis, respectively. It does not report the full analysis plan, eligibility details beyond the listed disease context, or how all enrolled participants were handled for the primary endpoint. Those omissions limit reconstruction of the trial’s analysis from the registry record alone.

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

Analysis population for the primary outcome, as defined in the registry: 20 subjects were evaluable for response, 2 subjects discontinued therapy during cycle 1 due to progressive disease and grade 5 sepsis respectively.

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 Overall Response Rate of of Participants to Imexon in the Treatment of Relapsed/Refractory Indolent and Aggressive Lymphomas, measured over One year.

The primary endpoint is the overall response rate, expressed as a percentage of participants. It is intended to describe the proportion of participants classified as having an objective tumor response according to the stated lymphoma response criteria. Response was defined using imaging-based assessments and included partial response, which the registry describes in terms of regression of measurable disease and no new sites. The stated assessment methods were CT, PET, or MRI, with scans at baseline, after cycle 2, and every 3 cycles thereafter until disease progression.

Response rate is used in trials of this kind because it summarizes whether tumor shrinkage meeting prespecified classification criteria was observed. It is distinct from outcomes such as time to progression or survival: it classifies response at assessment rather than describing how long a response lasts or how long participants remain free of progression. The registry lists median time to progression free survival as a secondary outcome, but does not report a result for it.

The record gives the primary endpoint timeframe as one year and identifies the dispersion measure as a 95% confidence interval. However, it does not report the number of responders, the response percentage, or the confidence interval. Consequently, the endpoint’s definition and assessment approach can be described, but the observed response estimate and its precision cannot be interpreted from the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does an overall response rate represent?

In general, an overall response rate is a proportion: participants classified as having a response form the numerator, and the specified analysis population forms the denominator. The classification depends on the response rules and assessment schedule. It is not the same as a continuous measure of tumor size, a time-to-event outcome, or a statement about how long a response persists. The registry describes imaging-based assessment and criteria from the International Harmonization Project on Lymphoma, but does not post the response count or the resulting percentage.

The registry identifies 20 subjects as evaluable for response and reports that 2 discontinued treatment during cycle 1. It does not state whether the evaluable group was the denominator used for the primary endpoint, whether participants who discontinued were classified as nonresponders, or whether another rule was used. Such details matter because different analysis-population and missing-data rules can yield different response estimates. The actual rule is not reported in the registry record.

What would a confidence interval tell the reader?

In general, a confidence interval expresses uncertainty around an estimated quantity under a statistical model and its assumptions. For a response rate, it would indicate the range of values reasonably compatible with the observed data under the chosen interval procedure. A wider interval indicates less precision; a narrower interval indicates more precision. An interval does not remove bias from study design, incomplete outcome data, or an unsuitable analysis population.

The primary endpoint lists a 95% confidence interval as its dispersion measure. The registry record does not give the response estimate or interval bounds, and it does not identify the interval method. As a result, the interval’s width and the method used to calculate it cannot be assessed. No numerical interval can be reconstructed from the posted record without the responder count and the applicable denominator.

Why does the single-group design matter?

In general, a single-group study can estimate outcomes observed in participants receiving an intervention, subject to the endpoint definitions and data completeness. It lacks a concurrent comparison group, so it does not directly estimate a treatment contrast. A response observed during treatment cannot, from this design alone, distinguish the effect of treatment from other influences on the observed outcome. A randomized comparison is designed to support a different kind of inference by comparing groups assigned to different conditions.

This trial is identified as single group, with allocation recorded as not applicable and masking as none. The registry notes that it is not a randomized comparison and that arms are not a like-for-like control comparison. Therefore, any interpretation should remain descriptive of the study group and should not be framed as a comparative effect estimate.

What does the assessment schedule contribute?

In general, consistent imaging rules and an assessment schedule help define when response can be detected and classified. Assessment frequency can affect how soon a response or progression is recorded, while the criteria determine which observed changes qualify. The registry states that CT, PET, or MRI scans were performed at baseline, after cycle 2, and every 3 cycles thereafter until disease progression. It also states that standard response criteria from the International Harmonization Project on Lymphoma were used.

The stated partial-response criteria include regression of measurable disease and no new sites, with imaging-related conditions also described. These details identify the basis for classification, but the record does not provide participant-level assessment results, independent review information, or further detail about how different imaging modalities were handled. Those aspects are not reported in the registry record.

How should safety proportions be read?

In general, a safety percentage expresses the frequency of a recorded event relative to the relevant safety denominator. The interpretation depends on how events were defined, collected, and attributed, and on whether a percentage refers to participants or event episodes. The record describes adverse-event groups using participants at risk and affected, and lists serious terms with percentages. It does not report enough detail to establish whether participants could contribute to more than one listed term or how repeated episodes were counted.

Serious adverse events and other adverse events are separate categories in the record. The imexon group has 22 at risk and 9 affected for serious adverse events; the other-adverse-event entry has 22 at risk and 22 affected. The registry does not report death counts in this entry. These counts describe recorded safety outcomes; they do not establish causation, comparative risk, or the frequency of events outside the study’s observation and reporting process.

What analysis details are unavailable?

The registry indicates no analyses listed. The statistical analysis plan, endpoint calculation procedure, confidence interval method, handling of missing assessments, and any planned interim analyses are not reported in the registry record. It is therefore not possible to verify from the registry how the sponsor intended to conduct the primary analysis or whether the posted endpoint description captures every analysis decision.

General statistical interpretation also depends on prespecification, population definition, completeness of follow-up, and consistency of measurement. These are not substitutes for a documented analysis plan. In this record, the stated endpoint and assessment process can be explained, but the absent estimate and missing analysis details prevent a fuller statistical appraisal.

10. Exact Estimates for Each Arm

No two-arm comparison is shown for this trial, but each arm's result can still be summarized with exact interval estimates computed from the posted counts. The Clopper-Pearson interval is exact and conservative; the Wilson interval is a common closer-to-nominal alternative; the Bayesian credible interval uses a uniform Beta(1, 1) prior. For small groups the three can differ noticeably.

R code and output

arm    <- c("Imexon")
n      <- c(20)
events <- c(6)
for (i in seq_along(n)) {
  ci <- binom.test(events[i], n[i])$conf.int          # Clopper-Pearson exact interval
  cr <- qbeta(c(0.025, 0.975), 1 + events[i], 1 + n[i] - events[i])   # Bayesian, uniform Beta(1,1) prior
  wi <- (function(x, n) { p <- x / n; z <- qnorm(0.975); d <- 1 + z^2 / n
    c((p + z^2 / (2 * n) - z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d, (p + z^2 / (2 * n) + z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d) })(events[i], n[i])
  cat(sprintf("ARM|%s|%d|%d|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f\n", arm[i], n[i], events[i], 100 * events[i] / n[i],
              100 * ci[1], 100 * ci[2], 100 * wi[1], 100 * wi[2], 100 * cr[1], 100 * cr[2]))
}

ARM  Imexon  20  6  30.0  11.9  54.3  14.5  51.9  14.6  52.2

11. Multiplicity, Missing Data and Analysis Populations

The registry lists an overall response rate as the primary outcome and median time to progression free survival as a secondary outcome. It also states that there are 2 outcome measures and no analyses listed. No multiplicity strategy, testing hierarchy, adjustment procedure, or distinction between confirmatory and exploratory analyses is reported in the registry record.

In general, multiplicity arises when multiple outcomes or analyses are examined. Without a stated plan, readers cannot determine whether any reported statistical claims were intended to control the chance of false-positive findings across analyses. The absence of listed analyses also means that no analysis-specific methods or inferential results can be evaluated from this record. No claim about whether multiplicity adjustment was needed or applied can be made.

For the primary outcome, the record identifies 20 subjects as evaluable for response and reports 2 early discontinuations, due to progressive disease and grade 5 sepsis, respectively. It does not report how these participants were incorporated into the endpoint analysis, how missing scans or unevaluable responses were handled, or whether the analysis used an intention-to-treat, evaluable, or other population. Those rules are not reported in the registry record.

In general, missing-data handling matters because excluding participants or assigning an outcome can change the estimate and its interpretation. Here, the posted evaluable count alone does not reveal the analysis denominator or the reasons for any other missing measurements. The record does not provide participant flow beyond the stated discontinuations or explain follow-up completeness. Consequently, the impact of missing data on the response estimate cannot be assessed, and no sensitivity analysis is reported.

12. 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 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: vomiting (9.1%), sepsis (9.1%), bronchial infection (4.5%), creatinine increased (4.5%), dehydration (4.5%).

The registry’s serious adverse event entry lists the imexon group as having 22 participants at risk and 9 affected. The listed serious terms are vomiting and sepsis, each at 9.1%, and bronchial infection, creatinine increased, dehydration, and hyperuricemia, each at 4.5%. These are registry-recorded safety figures, not a comparison with another treatment group.

The entry separately records other adverse events, with 22 at risk and 22 affected. That category should not be conflated with serious adverse events: the figures represent different event classifications in the record. The list of serious terms does not establish that each term affected a separate participant, and the registry record does not explain whether a participant could have more than one listed event or how repeat events were handled.

In general, adverse-event counts describe what was recorded under a study’s reporting procedures. They do not, without a suitable comparison and attribution information, establish that the intervention caused an event or quantify a comparative risk. Death counts are not reported in the registry record’s adverse-event entry. These safety data should therefore be read as descriptive counts and percentages rather than as a causal or comparative estimate.

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

The registry record documents a phase II, single-group study of imexon in adults with previously treated indolent and aggressive lymphomas. It specifies an imaging-based overall response endpoint, the response-assessment schedule, and the treatment schedule. It also records safety counts and a secondary outcome of median time to progression free survival. These details establish what the study set out to assess and what categories of outcomes the registry lists.

The most important limitation for interpreting efficacy is that the primary endpoint result is absent. The registry does not report the responder count, response percentage, or 95% confidence interval. It therefore cannot establish from the posted results how many evaluable participants met the response criteria or how precise any response estimate was. The secondary time-to-progression-free-survival result is also not reported.

The design further limits what can be inferred. With a single group and no randomized comparator, the study does not estimate a treatment difference against another intervention. Even if a response estimate were available, it would describe outcomes in the study group and would not by itself establish what caused those outcomes or how they compare with outcomes under another approach.

The safety entry reports serious adverse events in 9 of 22 at risk and gives percentages for listed serious terms. Those data describe recorded events within the registry entry. They do not provide a controlled comparison, establish causality, or indicate the full safety experience beyond the reporting information recorded. The registry does not report death counts in that entry.

Accordingly, the record supports a careful account of study design, planned endpoint definition, assessment schedule, and recorded safety data. It does not support a numerical conclusion about the primary response outcome, its precision, a comparative effect, or the secondary progression-free outcome. Those missing results and methods should remain explicit rather than being inferred from the study’s purpose or design.

14. Why This Trial Matters Statistically

This trial is statistically informative as an example of the distinction between a clearly described research question and an interpretable posted result. The registry names an overall response rate, defines an imaging-based response framework, and states a timeframe and confidence-interval measure. Yet the record does not include the response estimate or its interval. A defined endpoint is not itself an outcome result, and the absence of the numerical result prevents assessment of both magnitude and precision.

The design also illustrates the inferential limits of single-group evidence. Such a study can document outcomes among treated participants, but a concurrent randomized comparison is needed for a direct estimate of difference between treatment groups. The registry itself flags the absence of a randomized comparison. That distinction is essential when describing what the evidence can support: observed outcomes and comparative effects answer different questions.

The record additionally shows why analysis populations and missing-data rules matter. It distinguishes enrollment from the response-evaluable count and notes early discontinuations, but does not explain how those participants entered the primary analysis or how missing response assessments were handled. A reader cannot assess the influence of those choices without a documented rule and the relevant results.

Finally, the safety information is descriptive. The serious adverse event counts and listed terms can be reported as recorded, but they cannot establish comparative risk or causation without a suitable design and additional analytical detail. This case underscores the value of complete outcome reporting, explicit analysis methods, and clear separation between descriptive findings and causal conclusions.

15. 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 in the registry record is the absence of the primary response result. Although the endpoint, timeframe, confidence-interval measure, and assessment criteria are described, the response count, percentage, and interval are not reported. The secondary outcome of median time to progression free survival is named but has no result listed. This prevents quantitative interpretation of either efficacy endpoint.

The single-group design has no concurrent control, and masking is recorded as none. The study therefore cannot provide a randomized comparison or an estimate of the difference between imexon and another treatment. The registry notes that it is not a randomized comparison. These design features limit causal and comparative interpretation independently of whether an outcome estimate is available.

The registry identifies 20 subjects as evaluable for response and reports that 2 discontinued during cycle 1, because of progressive disease and grade 5 sepsis, respectively. It does not state how those discontinuations were treated in the primary endpoint analysis, what denominator was used, or how other missing assessments were handled. The analysis population and missing-data rules are not reported in the registry record.

Further statistical details are also absent: no analyses are listed, and the record does not state the confidence-interval method, statistical analysis plan, or multiplicity approach. The adverse-event entry provides counts and term percentages, but does not report death counts there or explain event attribution and repeat-event handling. These limitations are specific to what the registry records and should not be filled by assumptions about trial conduct.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Imexon for Relapsed Follicular and Aggressive Lymphomas — NCT01314014.
• Registry record last updated 2016-01-06; status last verified 2015-12.
• Results first posted 2014-07-01.
• 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.

19. Record Summary

The registry describes a completed phase II, single-group study of imexon in adults with previously treated follicular and aggressive lymphomas. The intervention was given by intravenous infusion on Days 1-5 of 21-day cycles for up to one year. Enrollment was 22, and the record identifies 20 subjects as evaluable for response; 2 discontinued during cycle 1 for progressive disease and grade 5 sepsis, respectively.

The primary endpoint was overall response rate over one year, assessed with imaging and lymphoma response criteria. The response count, percentage, and 95% confidence interval are not reported in the registry record. Median time to progression free survival is listed as a secondary outcome, without a posted result. The serious adverse event entry records 9 affected among 22 at risk and lists serious event terms with percentages. The single-group design provides no randomized comparator, and analysis and missing-data details are not reported.