Gemcitabine Hydrochloride, Carboplatin, Dexamethasone, and Rituximab in Treating Patients With Previously Treated Lymphoid Malignancies: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Gemcitabine Hydrochloride, Carboplatin, Dexamethasone, and Rituximab in Treating Patients With Previously Treated Lymphoid Malignancies (NCT00072514), a na phase 2 study. The primary outcome is Ability to Successfully Deliver the Investigational Therapy Without Incurring the Protocol Suspension Rules.

2. Clinical Question

The primary question concerns whether the regimen could be administered under the study’s safety stopping rule. It is not framed as a comparison of the combination with another treatment, nor as a direct estimate of comparative benefit. The primary outcome is a count of participants who received the therapy without incurring the protocol suspension rules, assessed at 3-4 weeks after completion of study treatment.

The record also lists overall and complete response rates, hematologic and non-hematologic adverse events, and peripheral blood stem cell collection as secondary outcomes. These outcome names indicate areas of interest, but numerical results for them are not reported in the registry record. The primary endpoint result is also not reported in the registry record. Consequently, the registered question can be described, but the available record does not establish how many participants met the primary endpoint or provide response estimates.

3. Trial Design

This is a completed phase II study sponsored by Fred Hutchinson Cancer Center. Its recorded enrollment is 55, and its listed start and primary-completion dates are 2003-08 and 2008-07. The study is categorized as single-group, with no masking and allocation recorded as not applicable. It therefore does not provide a randomized treatment-versus-control comparison.

The treatment group received a combination of gemcitabine hydrochloride, carboplatin, dexamethasone, and rituximab. The registry description gives administration details for the drugs and says treatment repeats every 21 days for up to 4 courses, subject to disease progression or unacceptable toxicity. The available treatment description is incomplete, so further regimen details are not reported in the registry record.

The condition list covers a wide range of previously treated lymphoid malignancies, including recurrent lymphoma diagnoses and other specified lymphoma types. That breadth is relevant to interpretation: the enrolled group was not described as a single narrowly defined diagnosis in the registry record. The record does not report the number of participants in each diagnostic subgroup or their baseline characteristics.

The primary endpoint is a safety-related delivery count, with assessment at 3-4 weeks after completion of study treatment. A stopping rule specified suspension if sufficient evidence indicated that the true grade 4-5 non-hematologic toxicity rate exceeded 10%. This rule describes the safety monitoring criterion, not the observed toxicity rate. The registry record does not report whether the stopping rule was triggered or the primary endpoint result.

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

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 Ability to Successfully Deliver the Investigational Therapy Without Incurring the Protocol Suspension Rules, measured over At 3-4 weeks after completion of study treatment.

The primary endpoint counts participants who received the investigational therapy without incurring the protocol suspension rules. It is assessed at 3-4 weeks after completion of study treatment. The endpoint therefore focuses on whether treatment delivery could proceed under the study’s predefined safety conditions, rather than directly measuring a comparative treatment effect.

The record specifies a safety stopping rule: the study would be suspended if sufficient evidence indicated that the true rate of grade 4-5 non-hematologic toxicity exceeded 10%. This is a threshold for a decision about continuing the study. It should not be mistaken for a reported toxicity rate or for a finding that suspension did or did not occur.

As a count, the endpoint is straightforward to describe when its result and analysis population are available. Its interpretation still depends on the exact operational definition of “received” therapy and how the suspension rules were applied. Those details are not reported in the registry record. Nor is the observed primary endpoint count reported in the registry record. Without that result, the endpoint’s intended role can be explained, but its observed value and precision cannot be assessed.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The record identifies a single-group phase II study, rather than a randomized comparison. The primary outcome is a participant count related to successful treatment delivery under the protocol’s suspension rules. The registry also lists secondary outcomes covering response, adverse events, and stem cell collection. It does not report numerical results for the primary endpoint or those secondary outcomes.

What does a single-group design estimate?

In general, a single-group study describes outcomes among participants treated in that study. If a binary outcome is reported, its observed proportion summarizes how often the outcome occurred in that group. Such a description does not itself estimate what would have happened to the same participants under a different treatment. A concurrent comparison group, preferably assigned in a way that supports a fair comparison, is needed to estimate a between-treatment contrast with fewer concerns about differences in patient mix and other influences.

Here, the treatment group is the only group specified. Allocation is recorded as not applicable, and masking as none. The record therefore does not offer a randomized control comparison. The diverse condition list also means that results, if reported, might reflect different diagnoses and clinical circumstances; subgroup results and baseline characteristics are not reported in the registry record.

How should a count endpoint be read?

A count reports how many participants meet a defined outcome. For interpretation, the count needs a clear denominator and a stated analysis population, along with rules for participants whose outcome cannot be assessed. The record gives enrollment and adverse-event risk-set counts, but does not report the primary endpoint count or the endpoint’s analysis population. The reason that adverse-event denominators differ from recorded enrollment is not reported in the registry record.

A confidence interval, in general, describes the statistical uncertainty around an estimate under the assumptions of the method used. It is not a guarantee that the true value lies in the interval, and its width depends in part on the amount of information and the variability in the data. No primary endpoint estimate or confidence interval is reported in the registry record, so its precision cannot be evaluated from the available information.

What does the safety rule contribute?

The protocol stopping rule is a decision criterion, not an outcome estimate. It says the study would be suspended if sufficient evidence indicated that the true grade 4-5 non-hematologic toxicity rate exceeded 10%. In general, a stopping rule describes a prespecified response to accumulating safety evidence; whether it was invoked must be established from study conduct or results. That information is not reported in the registry record.

Safety summaries also need clear event definitions and distinctions between participants with events and event episodes. A count of affected participants is not necessarily a count of all event occurrences. The registry fields identify participants at risk and affected within the serious and other categories, but the meaning and scope of “other” are not further reported in the record. The reported serious-event count should therefore be read as a summary category, not as a complete characterization of all treatment-related harms.

How do planning calculations differ from observed results?

In general, sample-size calculations are planning illustrations based on assumptions about the outcome, effect to detect, allocation, significance level, and statistical method. They describe the size of a hypothetical future study under those assumptions. They are not results from the enrolled study and are not observed power. The planning assumptions associated with the calculations describe a two-sided significance level of 0.05, equal allocation between two arms, a normal approximation, and effects expressed as fractions of an observed effect. Those assumptions do not turn this single-group study into a two-arm comparison.

No numerical planning results or observed effect estimates are reported in the registry record. Consequently, no planning sample size can be interpreted as a result of this trial. The sponsor’s analysis is not reported in the registry record, and there are no reported recalculated estimates to compare with it.

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("Treatment")
n      <- c(51)
events <- c(51)
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  Treatment  51  51  100.0  93.0  100.0  93.0  100.0  93.2  100.0

11. Multiplicity, Missing Data and Analysis Populations

The record lists several secondary outcome areas in addition to the primary endpoint: overall and complete response rates, hematologic and non-hematologic adverse events, and peripheral blood stem cell collection. Looking at multiple outcomes can raise multiplicity concerns in general, because the chance of at least one apparently notable result can increase when many hypotheses are examined. Whether and how that issue was addressed depends on the statistical plan.

The statistical plan, including any multiplicity adjustment or hierarchy among outcomes, is not reported in the registry record. The record lists four outcome measures, but it does not provide numerical results for the primary endpoint or secondary outcomes. It reports no analyses. It is therefore not possible to assess which analyses were planned, whether all planned analyses were reported, or how multiple comparisons were handled.

Missing-data methods and analysis populations are also not reported in the registry record. The enrollment figure and adverse-event risk sets do not establish how participants were handled for the primary endpoint or other outcomes. In general, missing outcomes can affect an estimate when the people without measurements differ systematically from those with measurements. A sound interpretation requires knowing the amount and pattern of missingness, the analysis population, and the assumptions or methods used to address it. Those details are unavailable.

The record does not report interim analyses or a statistical analysis plan. Their existence or absence should not be inferred from the safety stopping rule alone: a stopping rule describes a safety criterion, while interim analyses and their methods require separate documentation.

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 non-serious adverse event terms

The registry’s adverse-event summary records 51 participants at risk and 0 affected in the serious category. In the category labelled “other,” it records 51 at risk and 45 affected. These are participant counts as categorized in the registry record; the registry entries do not define “other” in enough detail to equate it with a specific severity or causality classification. The record does not list serious adverse-event terms.

These figures should not be read as a complete account of event frequency or clinical severity. A participant count does not necessarily equal the number of event episodes, and the record does not supply event-level descriptions, timing, duration, or attribution. The primary endpoint’s safety suspension rule concerns grade 4-5 non-hematologic toxicity and a threshold of 10%, but the summary counts do not state whether that rule was triggered or provide the corresponding rate.

Deaths are recorded as null. Null does not establish that there were no deaths; the death count is not reported in the registry record. The record also does not explain why the adverse-event risk sets differ from enrollment. These limitations prevent a fuller interpretation of the safety summary.

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

The record establishes that this was a completed phase II, single-group study of a four-drug regimen in previously treated lymphoid malignancies. It specifies a primary safety-related treatment-delivery endpoint and a stopping rule for grade 4-5 non-hematologic toxicity. It also records adverse-event summary counts. These details describe the study’s design and the outcomes it intended to assess.

The record does not report the primary endpoint result, response rates, stem cell collection results, or a numerical estimate of the regimen’s effect. The adverse-event summary cannot replace those missing outcomes, and its categories are not fully defined in the available information. Accordingly, the registry record does not show whether the primary delivery criterion was met, what response was observed, or how precisely any treatment effect was estimated.

In general, observing outcomes in a single treatment group cannot distinguish the effect of treatment from other explanations for those outcomes. A comparison group can help address that question, depending on its design and analysis. This study has no separate comparator group in the record. It therefore cannot establish how outcomes would compare with another treatment or with no treatment.

The information also does not establish that treatment works or does not work. Missing results are not evidence of no effect, just as enrollment and treatment administration alone are not evidence of benefit. The appropriate reading is limited to the design, endpoint definitions, and safety counts actually reported, while recognizing that major outcome and analysis details are not reported in the registry record.

14. Why This Trial Matters Statistically

This study illustrates why a clinical trial’s design and endpoint definition matter as much as its treatment list. Its primary endpoint is not a conventional comparative efficacy contrast: it counts participants who received therapy without incurring protocol suspension rules. The safety stopping threshold provides context for that endpoint, but the record does not report the endpoint result or whether the rule was triggered.

The single-group design is another important statistical feature. It can describe outcomes among treated participants, but it does not create a direct estimate of how outcomes differ from those under another treatment. This distinction is especially important when interpreting response outcomes, which are listed but lack numerical results in the registry record.

The record also illustrates the importance of denominators and outcome definitions. Enrollment is recorded as 55, while the adverse-event summary lists risk sets of 51. The reason is not reported in the registry record. The categories include a serious-event count and an “other” category, but the latter is not fully defined in the available information. Transparent reporting of analysis populations, event definitions, and missing data would help readers judge the estimates.

Finally, a protocol stopping threshold and a statistical analysis plan answer different questions. The threshold describes a safety decision criterion; it does not reveal how the endpoint was analyzed, how uncertainty was quantified, or how secondary outcomes were handled. Those methods are not reported in the registry record. The case underscores the limits of interpreting a trial from design descriptions and partial result summaries alone.

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 central limitation for statistical interpretation is that the primary endpoint result is not reported in the registry record. Although the endpoint and its assessment timeframe are defined, the count of participants meeting it and any measure of uncertainty are unavailable. Numerical results for the listed response and stem cell collection outcomes are also not reported.

The design is single-group, with no separate comparator. It cannot provide a direct randomized comparison or distinguish treatment effects from other influences on outcomes. The broad list of lymphoid malignancies further limits how specifically any overall result could be interpreted without diagnostic subgroup counts and baseline characteristics, which are not reported in the registry record.

The safety summary is incomplete for detailed interpretation. The serious-event category records 0 affected among 51 at risk, while the “other” category records 45 affected among 51 at risk. The meaning of “other,” event-level details, and the reason for the difference between enrollment and risk-set counts are not reported. Deaths are null, not a reported zero count.

The record does not report the statistical analysis plan, analysis populations, missing-data methods, multiplicity handling, or interim analyses. It also does not report whether the safety stopping rule was triggered. These omissions make it difficult to assess the planned analyses, the completeness of outcome reporting, and the precision of any treatment-related estimates. The registry entries support a description of the study structure and selected safety counts, not a full evaluation of its clinical outcomes.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Gemcitabine Hydrochloride, Carboplatin, Dexamethasone, and Rituximab in Treating Patients With Previously Treated Lymphoid Malignancies — NCT00072514.
• Registry record last updated 2017-06-29; status last verified 2017-05.
• Results first posted 2017-06-29.
• 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 record describes a completed phase II, single-group study sponsored by Fred Hutchinson Cancer Center, with recorded enrollment of 55. It evaluates gemcitabine hydrochloride, carboplatin, dexamethasone, and rituximab in previously treated lymphoid malignancies. The primary endpoint counts participants who received the investigational therapy without incurring protocol suspension rules, assessed at 3-4 weeks after treatment completion.

The protocol description includes a safety stopping rule tied to grade 4-5 non-hematologic toxicity. The record lists response, adverse events, and peripheral blood stem cell collection among secondary outcomes. It reports adverse-event summary counts, but the primary endpoint result and numerical secondary outcome results are not reported in the registry record. The analysis plan, analysis populations, and missing-data methods are also not reported.