A Study Evaluating the Efficacy of Obinutuzumab and Bendamustine Treatment in Participants With Refractory or Relapsed Chronic Lymphocytic Leukemia: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Study Evaluating the Efficacy of Obinutuzumab and Bendamustine Treatment in Participants With Refractory or Relapsed Chronic Lymphocytic Leukemia (NCT02071225), a na phase 2 study. The primary outcome is Overall Response Rate (ORR) as Assessed by the Investigator Using the International Workshop on Chronic Lymphocytic Leukemia (IWCLL) 2008 Criteria.

2. Clinical Question

3. Trial Design

This was a Phase II, single-group trial of obinutuzumab plus bendamustine in participants with refractory or relapsed CLL. The registry record lists Hoffmann-La Roche as the sponsor, enrollment of 72, and study status as COMPLETED. The recorded start date is 2014-04-09, and the primary completion date is 2018-11-19. The record does not give a separate date for study completion.

All participants were assigned to the combination treatment group; the design is recorded as SINGLE GROUP. Allocation is NA, and masking is NONE. These details mean the trial was not structured as a randomized comparison between treatment groups. Outcomes can describe what was recorded among participants receiving the regimen, but this design alone cannot separate treatment-associated changes from changes that might have occurred for other reasons or from differences in the participants' course over time.

The regimen consisted of obinutuzumab and bendamustine, administered intravenously in cycles lasting 28 days, for a maximum of six cycles. The expected treatment duration was 6 months, with follow-up planned for 2 years. The primary endpoint timeframe was 2-3 months after the last dose, up to approximately 9 months. The registry also lists secondary outcomes including investigator-assessed best response, progression-free survival, overall survival, event-free survival, disease-free survival, duration of response, time to re-treatment or new anti-leukemia therapy, and minimal residual disease negativity.

The registry record does not report the rationale for the planned enrollment, detailed eligibility criteria, protocol deviations, or a statistical analysis plan. It also does not report how many enrolled participants received both treatments or contributed to the efficacy population. Although the record indicates that the study is completed, the primary response result is not reported in the registry record.

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: Participants enrolled in the study had documented CD20-positive B-cell type relapsed or refractory chronic lymphocytic leukemia (CLL).

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Efficacy population included all participants, who received at least one dose of both treatments (bendamustine and obinutuzumab).

5. Baseline Characteristics

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

Population: Intent-to-treat (ITT) population included all participants, who received at least one dose of any treatment.

6. Primary Endpoint

The registry lists the primary outcome as Overall Response Rate (ORR) as Assessed by the Investigator Using the International Workshop on Chronic Lymphocytic Leukemia (IWCLL) 2008 Criteria, measured over 2-3 months after last dose of the study treatment (up to approximately 9 months).

The primary endpoint was investigator-assessed overall response rate (ORR), expressed as the percentage of participants who achieved complete response (CR), incomplete CR (CRi), or partial response (PR), according to the International Workshop on Chronic Lymphocytic Leukemia 2008 criteria. The registry defines CR using lymphocyte count, lymphadenopathy, liver and spleen findings, disease or constitutional symptoms, blood counts, and bone marrow status. CRi is defined as CR with persistent cytopenia. PR requires specified reductions in lymphocyte count and disease findings, along with specified blood-count criteria.

ORR is a binary-response summary: each participant is classified as having achieved one of the listed response categories or not, and the endpoint summarizes the proportion meeting that definition. General statistical context: a response proportion offers a direct description of how frequently a prespecified response was recorded in the assessed population. It does not, by itself, describe how long a response lasts or establish what would have happened to the same participants under a different treatment. The registry lists duration of response and time-to-event outcomes separately among the secondary outcomes.

The response assessment was scheduled for 2-3 months after the last dose, up to approximately 9 months. The efficacy population included all participants who received at least one dose of both treatments. The record specifies a 95% confidence interval as the dispersion measure, but neither the ORR estimate nor its interval is reported in the registry record. Therefore, the magnitude and precision of the primary endpoint cannot be assessed from this registry entry.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry identifies the primary outcome as a percentage of participants and names a 95% confidence interval as its dispersion measure. It defines the response categories and the efficacy population, but the actual estimate, interval limits, and analysis details are not reported in the registry record. The methods below explain how such statistics are generally interpreted; they do not establish which unreported procedures were used in this trial.

What does a response percentage represent?

General statistical context: a response percentage is formed by classifying participants according to a prespecified response definition and summarizing the share who meet it. In this trial, the definition combines CR, CRi, and PR under the IWCLL 2008 criteria. The registry says the efficacy population included participants who received at least one dose of both treatments. It does not report the number of participants in that population, the number meeting the response definition, or how participants with unavailable assessments were handled. Those missing details prevent reconstruction or independent checking of the endpoint from the registry entry.

The endpoint also depends on clinical assessments and their criteria. The record describes CR, CRi, and PR, including blood-count and disease-finding requirements. General statistical context: applying a response definition consistently is important because endpoint classification determines which participants count as responders. The registry does not describe assessor training, review procedures, or independent confirmation of investigator assessments, so those features are not reported in the registry record.

How should the confidence interval be read?

General statistical context: a confidence interval expresses uncertainty around an estimated quantity under a specified statistical procedure and its assumptions. A 95% confidence interval is not a statement that a particular participant has a 95% chance of responding, nor does it remove uncertainty about selection, measurement, or study design. The interval's width is useful for judging precision, but the interval endpoints are not reported in the registry record. Thus, the stated confidence level alone does not show how precise the estimated response rate was.

The registry does not identify the calculation method for the primary endpoint interval. Methods for a proportion can differ in their behavior, especially when the sample is limited or the observed proportion is near a boundary. General statistical context: the chosen method and the underlying numerator and denominator are necessary to reproduce or assess an interval. Since the registry entry omits the estimate, interval limits, and method, no particular calculation should be attributed to this trial.

What does a single-group design allow?

General statistical context: a single-group study can describe outcomes among participants who received a regimen, but it does not supply a randomized concurrent estimate of what would have happened under a different condition. Randomization helps balance measured and unmeasured characteristics between comparison groups on average; it is not present in this design. The registry records allocation as NA, masking as NONE, and the model as SINGLE GROUP. Accordingly, no treatment contrast or comparative effect estimate can be derived from the design details in this record.

The record does not report whether an interim analysis was planned or conducted, whether the endpoint was adjusted for baseline characteristics, or what inferential procedures were used beyond naming the confidence interval. The analysis plan is not reported in the registry record. It would be inappropriate to infer a testing strategy, a stopping rule, or a model from the trial phase or endpoint description.

What are the planning illustrations?

The record includes assumptions for a sample-size planning illustration based on an observed effect: two-sided significance level 0.05, equal allocation between two arms, and a normal approximation, with the effect to detect described as a stated fraction of the observed effect. For time-to-event outcomes, the illustration uses a total number of events; for other outcomes, it expresses participants per arm. These are planning assumptions, not the trial's stated design rationale and not observed power. The registry does not report a protocol sample-size justification or the numerical planning results in the registry record for this analysis.

General statistical context: a planning calculation asks what amount of information might be needed under chosen assumptions to detect a specified effect. It is conditional on those assumptions and does not measure how likely the completed trial was to detect an effect after the data have been observed. In particular, a sample-size illustration based on an observed effect must not be presented as observed power. The study itself is recorded as a single group, whereas the illustration assumptions describe two-arm planning; it is not a randomized comparison in this trial.

Why can variability matter?

General statistical context: for count or rate outcomes, over-dispersion means that the observed variability exceeds what a simpler model assumes. If a model ignores over-dispersion, uncertainty can be understated and inference can be too optimistic. The registry entry does not state that a count model was used for the primary binary response outcome, and it does not report a model or over-dispersion assessment for secondary outcomes. This general issue should not be mistaken for a documented feature of the trial's analysis.

In sum, the record contains endpoint definitions and a confidence level but not the primary estimate, interval, or detailed statistical procedures. The statistical meaning of an observed ORR would depend on its population, missing-data handling, assessment process, and uncertainty estimate. Those details are not reported in the registry record, so interpretation should remain limited to the design and outcome definitions that are documented.

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("Obinutuzumab + Bendamustine")
n      <- c(70)
events <- c(55)
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  Obinutuzumab + Bendamustine  70  55  78.6  67.1  87.5  67.6  86.6  67.6  86.5

11. Multiplicity, Missing Data and Analysis Populations

The registry lists 15 outcome measures, including the primary ORR and secondary response and time-to-event outcomes. It records zero analyses. The registry record does not report a multiplicity strategy, such as a hierarchy of hypotheses, adjustment method, or designation of which secondary outcomes were confirmatory. When many outcomes are examined, general statistical context is that the chance of at least one apparently notable result can increase if each is assessed separately. Whether that issue arose in analyses of this trial cannot be determined from the registry entry.

The primary endpoint is defined, but its observed estimate and 95% confidence interval are not reported in the registry record. Results for the listed secondary outcomes are also not included in the registry record. The registry does not report outcome-specific analysis populations, statistical models, or the handling of repeated assessments. No p-values or hypothesis-testing results are reported in the registry record.

The efficacy population was defined as participants who received at least one dose of both treatments. The number meeting that criterion is not reported in the registry record. The entry does not explain how missing response assessments, withdrawals, incomplete treatment, or other unavailable outcome data were handled. It also does not state whether an intention-to-treat population was defined or whether participants were excluded from analyses for any reason. These omissions affect the ability to understand which participants contributed to an endpoint and how missing observations might influence an estimate.

For survival outcomes, the record lists several time-to-event measures but does not describe censoring rules, follow-up completeness, or the analysis population. Those methods are not reported in the registry record. The recorded follow-up expectation of 2 years does not establish how much follow-up was actually observed for each participant. As a result, neither multiplicity control nor missing-data handling can be evaluated from the registry information.

12. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Deaths

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: neutropenia (12.5%), febrile neutropenia (11.1%), pyrexia (11.1%), pneumonia (11.1%), respiratory tract infection (8.3%).

The registry reports one treatment group with 72 participants at risk for the adverse-event summaries. Serious adverse events affected 37 participants, and other adverse events affected 67 participants. The record also reports 25 deaths. It does not provide a timeframe for these counts, identify whether deaths were attributed to treatment, or explain how adverse events were coded or collected. These counts should therefore be read as descriptive registry figures, not as causal findings.

The listed serious adverse event terms include neutropenia at 12.5%, and febrile neutropenia, pyrexia, and pneumonia at 11.1% each. Respiratory tract infection is listed at 8.3%, and septic shock at 4.2%. The registry entry does not report the number of participants contributing to each term's percentage, whether participants could contribute to more than one term, or the event grades and timing. The terms may overlap within participants, so their percentages should not be added together.

General statistical context: safety counts are easier to compare when exposure time, event definitions, severity, and attribution are reported consistently. A single-group count without a comparator cannot indicate whether an event was more or less frequent than under another treatment. The registry record also does not give exposure-adjusted rates or a detailed accounting of treatment discontinuation due to adverse events. These limitations prevent a comparative interpretation of the safety figures.

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

The registry describes a Phase II study of obinutuzumab plus bendamustine in participants with refractory or relapsed CLL. Its design is single-group, with enrollment of 72 and no randomized comparator. It specifies investigator-assessed ORR as the primary endpoint, defined using IWCLL 2008 response categories and assessed 2-3 months after the last dose, up to approximately 9 months. These registry entries describe the research question and the planned outcome framework.

The primary result itself is not reported in the registry record. There is no ORR estimate or confidence interval to assess, and the record does not give the efficacy-population size or number of responders. Consequently, the registry entry does not establish the observed response frequency or its precision. Absence of a posted result is not equivalent to a finding of no response, and it is not a basis for claiming that the regimen did or did not have an effect.

Even if a response proportion were available, the single-group design would constrain its interpretation. An observed proportion can describe outcomes among assessed participants, but without a concurrent randomized comparator it cannot provide a like-for-like estimate of the difference between treatment strategies. Differences in participant characteristics, disease course, assessment, and follow-up could matter. The registry record does not report an external comparison or a method for adjusting for such differences.

The listed serious adverse event and other adverse event counts offer descriptive safety information, as do the reported deaths and serious-event terms. The entry does not provide the timing, attribution, exposure-adjusted rates, or comparison data needed to make a causal or comparative safety assessment. General statistical context: descriptive counts can identify what was recorded but do not, on their own, establish why an event occurred.

The record also lists multiple secondary outcomes, while the analysis count is zero and detailed statistical procedures are not reported. Thus, it does not allow evaluation of multiplicity, missing-data handling, or the analysis methods for the listed outcomes. The appropriate reading is limited to the documented design, treatment schedule, endpoint definition, and posted safety counts; clinical conclusions about comparative benefit or harm are not supported by the registry entry alone.

14. Why This Trial Matters Statistically

This trial is statistically notable as a completed Phase II study with a clearly named response endpoint but without a reported primary endpoint estimate in the registry record. That distinction matters: knowing the endpoint definition is not the same as knowing the result. Without the response proportion and its 95% confidence interval, readers cannot judge either the estimated frequency of response or its precision from this record.

The design is also important. The study used a single treatment group, with allocation recorded as NA and masking as NONE. Such a design can describe outcomes among treated participants, but it does not provide a randomized comparison. This limits the kinds of statistical claims that could be supported even if the response result were posted. A response proportion in one group is not a direct estimate of the difference between that regimen and another treatment.

The record specifies an efficacy population based on receipt of at least one dose of both treatments. However, it does not report the size of that population or how missing assessments were handled. These details are central to interpreting a response percentage because they determine whose outcomes enter the summary and how unavailable outcomes are treated. The record also lists 15 outcome measures but zero analyses, with no reported multiplicity plan.

Finally, the safety counts demonstrate why statistical interpretation requires more than event totals. The registry reports serious and other adverse events and deaths, but does not describe exposure-adjusted rates, attribution, or a control group. These limitations do not make the recorded counts uninformative; they define what the counts can and cannot establish. Overall, the record illustrates the difference between a trial's design and endpoint definitions and the statistical results needed to evaluate an endpoint quantitatively.

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 most important trial-specific limitation for interpreting efficacy is that the registry record does not report the primary ORR estimate or its 95% confidence interval. The response definition and assessment timeframe are described, but the number of responders and the size of the efficacy population are not. Therefore, neither the observed response frequency nor its uncertainty can be assessed from this entry.

The study is recorded as a single-group trial, with allocation NA and masking NONE. It has no like-for-like concurrent control group, so it cannot provide a randomized comparison of treatment outcomes. The registry does not report an external comparator or adjusted comparison. Any description of outcomes in the treatment group would therefore need to remain descriptive rather than comparative.

The efficacy population included participants who received at least one dose of both treatments, but the record does not state how many participants met this criterion. It does not report the handling of missing assessments, withdrawals, incomplete treatment, or exclusions from endpoint analyses. The registry also does not explain how investigator assessments were reviewed, whether response assessments were independently confirmed, or whether protocol deviations affected analysis.

Although 15 outcome measures are listed, the registry records zero analyses and does not describe a multiplicity plan. Detailed analysis methods, including the method for calculating the confidence interval, are not reported in the registry record. For secondary time-to-event outcomes, censoring methods and follow-up completeness are also not described. The planned 2 years of follow-up does not specify the follow-up actually available for each participant.

Safety reporting is limited by the absence of event timing, severity details, treatment attribution, and exposure-adjusted rates. The recorded deaths have no reported cause or relationship to treatment in the registry record described. These omissions constrain interpretation of both efficacy and safety and should be distinguished from evidence that an outcome was absent.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: A Study Evaluating the Efficacy of Obinutuzumab and Bendamustine Treatment in Participants With Refractory or Relapsed Chronic Lymphocytic Leukemia — NCT02071225.
• Registry record last updated 2020-02-07; status last verified 2020-02.
• Results first posted 2019-11-26.
• 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

NCT02071225 is a completed Phase II, single-group study sponsored by Hoffmann-La Roche. It enrolled 72 participants with refractory or relapsed CLL and evaluated obinutuzumab plus bendamustine. The recorded start date is 2014-04-09, and the primary completion date is 2018-11-19. Treatment was planned for up to six 28-day cycles, with expected treatment lasting 6 months and follow-up lasting 2 years.

The primary endpoint was investigator-assessed ORR by IWCLL 2008 criteria, measured 2-3 months after the last dose, up to approximately 9 months. The registry record specifies a 95% confidence interval but does not report the ORR estimate or interval. It lists 15 outcome measures and zero analyses. Safety summaries report 37 participants affected by serious adverse events, 67 by other adverse events, and 25 deaths in the treatment group; timing and attribution are not reported in the registry record.