Ixabepilone in Treating Patients With Relapsed or Refractory Aggressive Non-Hodgkin's Lymphoma: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Ixabepilone in Treating Patients With Relapsed or Refractory Aggressive Non-Hodgkin's Lymphoma (NCT00058019), a na phase 2 study. The primary outcome is Objective Overall Response Rate.

2. Clinical Question

3. Trial Design

This was a phase II, single-group study sponsored by the National Cancer Institute. The registry lists enrollment of 51 and describes a treatment arm receiving ixabepilone. Allocation is recorded as not applicable, and masking as none. With no concurrent control arm, the study can describe outcomes among participants in the treated group but cannot make a randomized comparison against another treatment or usual care.

The treatment schedule specified intravenous ixabepilone over 1 hour on days 1, 8, and 15, with courses repeating every 28 days. The schedule could end in the event of disease progression or unacceptable toxicity, or if a participant became a candidate for stem cell transplantation. The registry record does not report adherence, dose changes, treatment duration, or the number of participants who completed treatment.

The study start is recorded as 2003-02, primary completion as 2010-08, and status as completed. The primary outcome was objective overall response rate, with a timeframe of up to 3 years. Other listed outcomes were duration of response, overall survival, and time to progression. The record lists 5 outcome measures and 4 analyses, but does not identify all of their analysis details in the information available for this account.

The registered design supports a descriptive reading of response and safety within the study group. It does not, by itself, separate an intervention effect from the natural course of disease, participant selection, other care, or other factors that could influence outcomes. The registry record does not report a protocol-level statistical analysis plan, a sample-size justification, or details of how the analysis populations were defined.

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: One patient never received treatment and was excluded from analysis.

Overall Study

5. Baseline Characteristics

The table reproduces the baseline characteristics posted in the registry, which describe the participants analysed at baseline and help show whether the randomized groups were comparable.

6. Primary Endpoint

The registry lists the primary outcome as Objective Overall Response Rate, measured over up to 3 years.

The primary endpoint, objective overall response rate, is intended to capture whether participants experienced measurable tumor shrinkage that met specified response criteria. The registry describes use of the 1999 international response criteria attributed to Cheson, with target lesions defined under those criteria and response assessed using CT scans. Complete response and unconfirmed complete response require disappearance of all target lesions. Partial response requires at least 50% decrease in the sum of the products of the greatest diameters. Overall response combines complete response, unconfirmed complete response, and partial response.

Response is used in clinical trials because it gives a structured way to summarize tumor change over a specified assessment period. The endpoint is not the same as duration of response, time to progression, or overall survival: those outcomes address how long a response lasts, when progression occurs, or survival, respectively. They are listed as secondary outcomes in this study.

The registry gives a timeframe of up to 3 years for the primary endpoint and identifies its unit as participants, but does not report the primary response count or rate. Without that result, the endpoint definition can be described, but the magnitude and precision of the observed response cannot be evaluated from the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does a single-group design show?

In a single-group study, outcomes are observed among participants who receive the study intervention. Such a design can describe what happened in the enrolled group, provided the relevant outcome data are reported. It cannot create a concurrent estimate of what would have happened to comparable participants without the intervention. This is why a response count from a single group, even if available, would not be a randomized treatment contrast.

For this study, the registry lists a single group, allocation as not applicable, and masking as none. A comparison with an earlier study or a historical benchmark would require careful consideration of differences in eligibility, participant characteristics, assessment timing, and care. No such comparison is reported in the registry record. The design should therefore be read as descriptive rather than as a controlled estimate of relative treatment effect.

What does the response endpoint count?

Objective overall response is a categorical endpoint: participants are classified according to whether their tumor assessments meet the stated response criteria. The registry groups complete response, unconfirmed complete response, and partial response into overall response. A response endpoint can be clinically interpretable because it applies explicit imaging-based rules, but its numerical meaning depends on the observed count and the population included in the analysis.

The registry specifies CT scans and a response timeframe of up to 3 years. It does not report the number assessed, the number classified as responders, the denominator used for the primary analysis, or a confidence interval. It also does not report details such as the assessment schedule or how missing scans were handled. Thus, the operational definition is available, but the primary estimate and its reproducibility cannot be evaluated from this record.

How should uncertainty be understood?

In general, a confidence interval describes a range of values compatible with the observed data under a statistical model. It communicates uncertainty around an estimate; it is not a guarantee that the true value lies inside that particular interval. For an outcome such as a response proportion, the interval’s width depends in part on the number of observed participants and on the observed response count. Neither the response estimate nor its interval is reported in the registry record.

Statistical significance and clinical importance are different questions. A statistical test evaluates data against a specified null hypothesis and assumptions. Clinical importance requires judging the size and relevance of an outcome in context. The registry record does not report the primary response result, its test, a confidence interval, or a stated null hypothesis. No significance claim can therefore be drawn from the listed endpoint definition alone.

What do the planning illustrations represent?

The planning illustrations are described as calculations based on the observed effect, with a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. They consider planning for a stated fraction of the observed effect. For time-to-event outcomes, the illustration is based on the total number of events; for other outcomes, it is expressed as participants per arm.

These are planning illustrations, not a report of the study’s design rationale or its achieved statistical power. The registry record does not report that the trial itself was designed using those assumptions, nor does it report a sample-size justification or interim analyses. A planning calculation based on an observed effect is not observed power: it does not indicate the probability that the completed study would detect an effect after the results are known. The registry record does not report the numerical planning outputs in the information, so no such values can be interpreted in this account.

What analysis details remain unknown?

The registry lists 4 analyses and 5 outcome measures, but does not report a full statistical analysis plan. It does not report whether the primary endpoint was analyzed using a particular test, whether any adjustment or stratification was used, or how multiple testing was addressed. The analysis population, handling of participants with unevaluable response assessments, and approach to missing data are also not reported in the registry record. These omissions do not show that the study lacked such procedures; they mean the procedures cannot be established from the registry entry.

Over-dispersion is a general concern for count outcomes when variability exceeds what a simple model assumes. In general, ignoring over-dispersion can make uncertainty appear too small and tests too optimistic. The primary endpoint is described as a participant count for a binary response classification, not as an event-rate model, and the record does not report an over-dispersion model. The distinction is useful when reading statistical methods, but no such method should be attributed to this trial without documentation.

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("Cohort 1 (Chemosensitive)", "Cohort 2 (Chmoresistant)")
n      <- c(39, 12)
events <- c(14, 0)
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  Cohort 1 (Chemosensitive)  39  14  35.9  21.2  52.8  22.7  51.6  22.7  51.7
ARM  Cohort 2 (Chmoresistant)  12  0  0.0  0.0  26.5  0.0  24.2  0.2  24.7

11. Multiplicity, Missing Data and Analysis Populations

The registry lists objective overall response rate as the primary outcome and names duration of response, overall survival, and time to progression as secondary outcomes. It also lists 5 outcome measures and 4 analyses. A collection of outcomes and analyses can create a multiplicity issue: when several hypotheses are tested, the chance of at least one apparently unusual result can increase if no adjustment or hierarchy is used. The registry record does not report a multiplicity strategy, a testing hierarchy, or which analyses were confirmatory versus exploratory.

The primary outcome timeframe is stated as up to 3 years. The registry record does not explain how incomplete follow-up, unevaluable scans, or missing outcome assessments were handled. It also does not report the analysis population definition, such as whether the response analysis included all enrolled participants or only those with an assessment. These details affect the interpretation of an endpoint count and its denominator.

The record does not report imputation methods, sensitivity analyses for missing data, or a plan for participants who stopped treatment or began other care. This does not establish that such methods were absent from the study; it means they are not reported in the registry record. Without the methods and analysis populations, readers cannot determine how missing assessments may have influenced reported endpoint results. In this case, the primary response result is itself not reported, further limiting interpretation.

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: dehydration (3.9%), infections and infestations - other, specify (3.9%), neutrophil count decreased (3.9%), diarrhea (2.0%), hypokalemia (2.0%).

The registry lists 51 participants at risk for serious adverse events and 11 affected. For other adverse events, it lists 51 at risk and 48 affected. These are registry counts, and the record does not provide a control group for comparison. The counts should be read as descriptions of the recorded study experience, not as comparative risk estimates or proof that the intervention caused an event.

The listed serious adverse event terms and percentages are dehydration, 3.9%; infections and infestations - Other, specify, 3.9%; neutrophil count decreased, 3.9%; diarrhea, 2.0%; hypokalemia, 2.0%; and lung infection, 2.0%. The registry record does not explain whether participants could be counted under more than one term, nor does it provide additional detail on severity, timing, duration, or attribution for these terms. The listed percentages should therefore be quoted as registry-reported values rather than treated as a complete causal safety analysis.

Serious adverse events and other adverse events are separate categories in the record. The counts do not describe treatment discontinuations, dose changes, or deaths; a death count is not reported in the registry record. These data can identify events recorded during the study, but they cannot establish comparative safety in the absence of a like-for-like control group and fuller event-level context.

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

The registry record documents a phase II investigation of ixabepilone in patients with relapsed or refractory aggressive non-Hodgkin’s lymphoma. It specifies a single-group design, a treatment schedule, a response definition, and selected safety counts. It also lists duration of response, overall survival, and time to progression as secondary outcomes. These details help explain what the study set out to assess and what kinds of outcomes were registered.

The record does not report the primary objective response result. It therefore cannot establish the observed response frequency, its precision, or whether response differed from a comparator. There is no randomized comparison group in the registered design. Even if a response estimate were reported, a single-group result would describe outcomes in the study group rather than directly identify what would have happened under another treatment.

The listed safety counts describe adverse events recorded among participants at risk. They do not establish causation, comparative risk, or a complete safety profile. The registry does not report the event timing, attribution, or the context required to interpret each term fully. Secondary outcome results and their uncertainty are also not reported in the registry record.

Accordingly, the posted information supports a description of the trial and its registered endpoint definitions, but not a conclusion about the magnitude of response, survival, progression outcomes, or treatment effect. Absence of a reported result is not evidence that the outcome did or did not occur. It means the registry entry, as recorded, does not permit that result to be evaluated.

14. Why This Trial Matters Statistically

This study is statistically informative as an example of the distinction between a registered question and a reported result. The registry specifies objective overall response rate, the response criteria, and an assessment timeframe. Yet the primary endpoint result is not reported in the registry record. Endpoint definitions are essential for interpreting a result, but they cannot substitute for the estimate, denominator, and uncertainty measure needed to evaluate it.

The single-group design is another important statistical feature. It can provide a descriptive account of outcomes in a treated group, but it does not supply a concurrent control for estimating a comparative effect. This distinction is especially important when readers encounter response or adverse-event counts: the counts describe what was recorded in the study, while causal or comparative claims require a design and analysis that support those claims.

The record also shows why outcome-specific details matter. Response, duration of response, overall survival, and time to progression address different questions. A response assessment is not a substitute for a survival result, and the results of the listed secondary outcomes are not reported in the registry record. Likewise, a safety count cannot by itself characterize the timing, attribution, or relative frequency of an event.

Finally, the registry lists multiple outcomes and analyses but does not report the full analysis plan, handling of missing data, or multiplicity approach. These are not minor technicalities: they inform how estimates should be interpreted and how much confidence to place in them. The record allows readers to see the design and some reporting gaps clearly, while leaving the central efficacy estimate unavailable.

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.

Several limitations specific to this registry entry constrain interpretation. Most importantly, the primary objective response result is not reported. The record therefore lacks the response count or rate and an uncertainty estimate. It also does not report the denominator used for that analysis, which prevents assessment of how the analysis population relates to the enrollment figure.

The study is single-group, with allocation listed as not applicable and masking as none. There is no concurrent comparator in the registry record, so the design cannot provide a like-for-like estimate of relative effect. The record also does not report participant-level characteristics, the number who received treatment, treatment completion, dose changes, or the number assessed for response.

Details needed to assess outcome ascertainment and analysis are not reported in the registry record. These include the response assessment schedule, handling of missing or unevaluable assessments, analysis populations, statistical tests, confidence intervals, and a multiplicity plan. Although multiple secondary outcomes are listed, their results are not reported in the record.

The safety information is limited to selected counts and serious adverse event terms. The registry does not report a control group, event attribution, timing, duration, or a death count. These limitations mean the reported safety figures should be treated as descriptive registry information rather than a complete comparative safety assessment. The record’s completed status does not fill these reporting gaps.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Ixabepilone in Treating Patients With Relapsed or Refractory Aggressive Non-Hodgkin's Lymphoma — NCT00058019.
• Registry record last updated 2014-05-23; status last verified 2011-10.
• Results first posted 2014-02-27.
• 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.

19. Record Summary

The registry identifies NCT00058019 as a completed phase II study sponsored by the National Cancer Institute. It enrolled 51 participants with relapsed or refractory aggressive non-Hodgkin’s lymphoma and evaluated ixabepilone in a single-group design. The primary endpoint was objective overall response rate, assessed for up to 3 years using the response criteria described in the record.

The treatment schedule called for intravenous ixabepilone over 1 hour on days 1, 8, and 15, with courses repeating every 28 days subject to specified stopping conditions. Secondary outcomes included duration of response, overall survival, and time to progression. The primary response result and the results for those secondary outcomes are not reported in the registry record.

The safety entry lists serious and other adverse event counts and selected serious event terms. With no concurrent comparator and limited analysis details, those figures are descriptive. The record does not report the full statistical plan, missing-data approach, or multiplicity handling.