An Expanded Access, Open-Label Study of Obinutuzumab (GA101) Plus Chlorambucil in Patients With Previously Untreated Chronic Lymphocytic Leukemia: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for An Expanded Access, Open-Label Study of Obinutuzumab (GA101) Plus Chlorambucil in Patients With Previously Untreated Chronic Lymphocytic Leukemia (NCT01868893), a na phase 2 study. The primary outcome is Number of Participants Who Received Obinutuzumab and Chlorambucil in the Study.

2. Clinical Question

3. Trial Design

This was a Phase 2, multicenter, open-label, single-group expanded access study of obinutuzumab plus chlorambucil. Its stated purpose was to provide obinutuzumab to patients with previously untreated CLL in combination with chlorambucil and to evaluate safety and efficacy. The study enrolled 20 participants and is marked completed. The recorded start was 2013-08, and primary completion was 2014-01.

The record describes the intended population as patients with previously untreated, CD20-positive CLL requiring treatment under the IWCLL guidelines, as assessed by the investigator. The intent-to-treat population included all enrolled participants. The registry does not give additional detail about recruitment, exclusions after enrollment, or how many participants completed treatment.

Obinutuzumab was administered intravenously for six 28-day cycles. The record specifies 100 mg on Day 1, 900 mg on Day 2, and 1000 mg on Days 8 and 15 for Cycle 1, followed by 1000 mg on Day 1 of Cycles 2 to 6. Chlorambucil was administered orally, and the listed description begins with a dose of 0.5 mg/kg body weight on Days 1 and 15; the remainder of that schedule is not reported in the registry record.

Because the study had no separate comparator group, its design can describe treatment receipt and outcomes observed among participants, but it cannot make a direct randomized comparison. The registry record does not report a protocol-based sample-size justification, a statistical analysis plan, or interim analyses.

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: Of 20 participants, one patient withdrew from the study due to neutropenia and did not receive any study drug.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Intent-to-Treat population: It included all enrolled participants in the 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.

Population: Safety population which included all enrolled patients who received at least one dose of study drug (obinutuzumab).

6. Primary Endpoint

The registry lists the primary outcome as Number of Participants Who Received Obinutuzumab and Chlorambucil in the Study, measured over Cycles 1 to 6 (28-day cycles).

The primary outcome is the number of participants who received obinutuzumab and chlorambucil during Cycles 1 to 6 (28-day cycles). Its stated population is the intent-to-treat population, defined in the record as all enrolled participants. The endpoint is a participant count, rather than a measure of tumor response, time to an event, or change in a continuous measurement.

In general, a treatment-receipt count can describe whether the study intervention was administered within the defined study period. It may help characterize treatment delivery, but it does not by itself establish how participants responded clinically or whether observed outcomes were caused by treatment. The record’s description identifies the measure as a number of participants; it does not provide a numerical result for this endpoint in the material available for analysis. Enrollment of 20 participants should not be substituted for the endpoint result, because enrollment and receipt of both study drugs are different measures.

The registry also names objective response and several safety outcomes as secondary outcomes. Numerical objective-response findings are not reported in the registry record. Accordingly, the primary count should be read as a treatment-exposure measure, not as an efficacy estimate.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry identifies this as a single-group study with no masking. Those design features matter when interpreting the statistics. A single-group study records outcomes among participants receiving the study regimen, but there is no concurrent study group against which to estimate a between-group difference. Open-label means treatment was not masked in the design. In general, knowledge of treatment can influence reporting, assessment, and clinical decisions; the record does not describe procedures used to address those possibilities.

What a participant count tells us

The primary outcome is a number of participants who received both study drugs during the stated cycles. A count answers a descriptive question: how many participants met that treatment-receipt definition? The record names the intent-to-treat population as all enrolled participants, but the numerical primary-outcome result is not reported in the registry record. Enrollment of 20 is a separate fact and cannot stand in for the number who received both agents.

Counts are often presented with a denominator so readers can understand the population to which they refer. Here, the primary outcome description identifies the intent-to-treat population, while the adverse-event summaries separately report 19 participants at risk. The registry record does not explain the difference between the enrollment count and the adverse-event denominator. It would be inappropriate to assume a reason, or to use one denominator in place of another.

Interpreting adverse-event summaries

The serious adverse-event summary reports 2 participants affected among 19 at risk. The other adverse-event summary reports 18 affected among 19 at risk. These are counts from distinct reported categories. An affected-participant count is not necessarily a count of all events: a participant may have more than one event, and the record does not state whether the same participants appear in multiple categories. The listed serious-event terms each have a reported value of 5.3%. Those percentages are registry entries; no further calculation is needed to interpret them as posted.

In general, adverse-event summaries describe events observed in a defined study population. They do not, by themselves, determine whether an event was caused by a treatment. Causal interpretation depends on study design and additional clinical and statistical information. A comparator can help estimate how event occurrence differs between groups, but this study has no separate comparator. The registry record also does not report event timing, participant-level overlap, or a complete account of how events were assessed.

Uncertainty and statistical tests

In general, a confidence interval gives a range of values compatible with an estimate under the statistical method used. Its width conveys precision: wider intervals indicate greater uncertainty, while narrower intervals indicate greater precision. A confidence interval does not remove limitations in design, and it cannot establish causation in a single-group study. No confidence interval for the primary outcome or objective response is reported in the registry record.

In general, a p-value describes how compatible observed data are with a specified statistical model and null hypothesis. It is not a measure of the size or clinical importance of an effect, and it does not give the probability that a treatment works. The registry record lists no analyses for the outcomes described in the registry record, and no p-value or inferential result is reported for the primary outcome. The statistical plan, including any prespecified testing approach, is not reported in the registry record.

Planning illustrations are not trial results

The sample-size assumptions describe planning illustrations using a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. They describe an effect to detect as a stated fraction of the observed effect. These are assumptions for planning illustrations, not the design of this single-group study. The registry record identifies no randomized two-arm allocation, and no numerical sample-size illustration is reported in the record. Such planning values are not observed power and do not change what the study actually measured.

In general, a planning calculation asks how much information a future study might need under chosen assumptions. Its answer depends on those assumptions and does not show that the current study had a particular probability of finding an effect. The record does not report the protocol’s sample-size justification or enough numerical outcome information to reproduce a planning calculation. No such calculation should be treated as an observed result.

Over-dispersion is a general issue when variation in count outcomes exceeds what a chosen statistical model assumes. If a model does not account for that extra variation, uncertainty can be understated. The registry record does not identify a model for count outcomes or report a dispersion assessment, so no claim about whether over-dispersion affected this study can be made.

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", "Chlorambucil")
n      <- c(20, 20)
events <- c(19, 19)
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  20  19  95.0  75.1  99.9  76.4  99.1  76.2  98.8
ARM  Chlorambucil  20  19  95.0  75.1  99.9  76.4  99.1  76.2  98.8

11. Multiplicity, Missing Data and Analysis Populations

The registry lists a primary outcome measuring the number of participants who received obinutuzumab and chlorambucil, along with secondary outcomes covering adverse events and objective response. When a study examines several outcomes, general statistical practice may include a plan for how to interpret multiple tests or estimates, because examining many outcomes can increase the chance of apparently notable results arising by chance. The registry record does not report a multiplicity strategy, a hierarchy of secondary outcomes, or an analysis plan. No statistical analyses are listed in the record.

The record defines the intent-to-treat population as all enrolled participants. That definition identifies who is included in the stated population, but it does not specify how missing outcome observations were handled. Missing-data methods, reasons for missingness, and the amount of missing outcome data are not reported in the registry record. The record also does not describe whether participants who discontinued treatment remained in each outcome analysis.

These omissions limit how far the outcome summaries can be interpreted. In general, missingness can affect estimates when participants with unobserved outcomes differ from those with observed outcomes. A stated analysis population alone does not resolve that issue. Similarly, the presence of several named outcomes does not reveal whether statistical tests were conducted or how results were selected for reporting.

The registry record does not report interim analyses, any adjustment for multiple comparisons, or a prespecified approach to missing observations. Those details should be treated as unreported, not assumed to have been absent from the underlying conduct of the study.

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: anaemia (5.3%), esophageal hemorrhage (5.3%), eesophageal ulcers (5.3%), infusion related reaction (5.3%).

The serious adverse-event summary for Obinutuzumab + Chlorambucil lists 19 participants at risk and 2 affected. The other adverse-event summary lists 19 at risk and 18 affected. These are participant counts in the categories recorded, not a comparison between treatment groups: the study had no separate comparator group. The record lists Anaemia, Esophageal hemorrhage, Eesophageal ulcers, and Infusion Related Reaction among serious-event terms, each with a reported value of 5.3%.

These summaries should be read as descriptive registry results. They do not show whether affected participants experienced more than one event, whether events overlapped across categories, or when events occurred. The registry record does not provide those details. It also does not report deaths; that absence does not establish that there were none. A count of participants with an event is distinct from a count of events, and neither count alone establishes that the study drugs caused an event.

The registry lists adverse events, serious adverse events, events of Grade 3 and above severity, events of special interest, events leading to obinutuzumab discontinuation or dose delays, and death as safety outcomes. Numerical results for all of these outcomes are not reported in the registry record. The available figures therefore describe only the reported categories and should not be treated as a complete safety profile.

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

This study contributes a registry record of an open-label, single-group expanded access experience with obinutuzumab plus chlorambucil in previously untreated CLL. It identifies the enrolled population, treatment regimen, primary treatment-receipt outcome, and several intended safety and response outcomes. The record reports 20 enrolled participants and adverse-event counts for participants at risk and affected. Those details describe the study and its posted results, but they do not establish a comparative treatment effect.

The primary outcome is a count of participants who received both agents during Cycles 1 to 6 (28-day cycles). Its numerical result is not reported in the registry record. Objective response is named as a secondary outcome, but its numerical result is also not reported. The adverse-event counts are descriptive and come from a group without a separate comparator. They cannot show whether event occurrence was more or less frequent than it would have been under another treatment.

In general, causal interpretation requires care because outcomes in a single group can reflect the treatment, the underlying condition, participant characteristics, clinical care, or other influences. An open-label design can also affect assessment and reporting. The record does not provide a comparative estimate that separates these possible influences. Nor does it report enough information to assess missing outcomes, the statistical analysis plan, or precision for the primary endpoint.

The findings should therefore be understood as registry-reported observations, not as a definitive estimate of comparative benefit or harm. The named outcomes indicate what the study sought to assess; they do not substitute for numerical results. Likewise, the absence of a reported result does not establish that the outcome did not occur. The record’s limits concern what can be concluded from the posted information, rather than proving that an unreported outcome was absent.

14. Why This Trial Matters Statistically

Statistically, this study is a useful example of how design determines the questions that outcome data can answer. Its single-group structure allows descriptive reporting of treatment receipt and observed events among enrolled participants. It does not provide a concurrent comparator for estimating a difference between treatment strategies. That distinction remains important even when a registry lists both safety and response outcomes.

The primary outcome is a participant count, which is straightforward in concept but still depends on a clear definition of who qualifies as having received both drugs and how missing information is handled. The record defines the intent-to-treat population as all enrolled participants, but it does not report the numerical primary-outcome result or missing-data procedures. Enrollment is reported as 20; it should not be substituted for the treatment-receipt count.

The adverse-event summaries also illustrate why denominators and outcome definitions matter. The serious-event and other-event categories each list 19 participants at risk, with 2 and 18 affected, respectively. These figures describe different categories and cannot be turned into a comparative risk estimate when no comparison group is present. The registry record does not explain why the adverse-event denominator differs from enrollment.

More broadly, the record distinguishes named outcomes from reported analyses. It lists objective response and several safety outcomes, but numerical results are not available for all of them in the information. Statistical interpretation depends not only on the study question but also on complete outcome reporting, analysis methods, and uncertainty estimates. The record does not report the analysis plan or confidence intervals for the primary outcome. Recognizing those gaps helps keep descriptive evidence separate from comparative inference.

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 design is open-label and single-group, with allocation listed as NA and masking as none. There is no separate comparator, so the record cannot provide a direct between-group estimate. The expanded access purpose was to provide obinutuzumab with chlorambucil and evaluate safety and efficacy; the registry record does not describe a randomized comparison.

The enrollment was 20, and the primary outcome is defined as the number who received both study drugs during Cycles 1 to 6 (28-day cycles). However, the numerical primary-outcome result is not reported in the registry record. The adverse-event summaries list 19 participants at risk, and the record does not explain how that denominator relates to enrollment. The number who completed treatment is not reported in the registry record.

Objective response is listed as a secondary outcome, but its numerical result is not reported in the registry record. Numerical findings for all named safety outcomes are likewise not reported in the information available for this analysis. Deaths are not reported; this should not be interpreted as a zero count. The available adverse-event summaries do not describe timing, recurrence, overlap among participants, or causal assessment.

The registry record does not report a statistical analysis plan, missing-data procedures, multiplicity handling, interim analyses, or a protocol-based sample-size justification. The chlorambucil dosing description is incomplete in the record. Together, these limits constrain interpretation of both outcome completeness and precision. They do not establish that unreported procedures or outcomes were absent; they indicate that they are not reported in the registry record.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: An Expanded Access, Open-Label Study of Obinutuzumab (GA101) Plus Chlorambucil in Patients With Previously Untreated Chronic Lymphocytic Leukemia — NCT01868893.
• Registry record last updated 2017-04-17; status last verified 2017-03.
• Results first posted 2016-11-07.
• 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

NCT01868893 is a completed Phase 2, multicenter, open-label, single-group expanded access study of obinutuzumab plus chlorambucil in previously untreated CLL. The study enrolled 20 participants. Its recorded start was 2013-08, and primary completion was 2014-01. The primary outcome is the number of participants who received both study drugs during Cycles 1 to 6 (28-day cycles), with an intent-to-treat population defined as all enrolled participants.

The serious adverse-event summary lists 2 participants affected among 19 at risk; the other adverse-event summary lists 18 affected among 19 at risk. Objective response and additional safety outcomes are named, but numerical results for several outcomes are not reported in the registry record. The single-group design supports descriptive interpretation, not a direct comparison with another treatment.