Pilot Study to Determine Effects of the Btk Inhibitor PCI-32765 on Leukemia Cell Kinetics and Trafficking, Using Heavy Water Labeling in Subjects With CLL and SLL: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Pilot Study to Determine Effects of the Btk Inhibitor PCI-32765 on Leukemia Cell Kinetics and Trafficking, Using Heavy Water Labeling in Subjects With CLL and SLL (NCT01752426), a na phase 1, phase 2 study. The primary outcome is Change in Leukemia Cell Death.

2. Clinical Question

The study asks how PCI-32765, also called ibrutinib, affects leukemia-cell kinetics and trafficking in people with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL). Heavy water is used to label cells so researchers can study cell birth and death rates. The primary question is specifically about change in leukemia-cell death in peripheral blood, while the listed secondary outcome concerns recently born leukemia cells mobilized into the blood.

This is a question about cell kinetics, not a direct question about symptoms, disease control, or survival. The registry’s stated purpose is to learn how the study drug may affect the life cycle of blood-cancer cells. It does not report a numerical answer to that question.

3. Trial Design

The record describes a pilot study with phase 1 and phase 2 designations. It lists a single group, allocation as not applicable, and no masking. The listed enrollment is 30. The study status is completed; the record gives a start date of 2012-12-17 and a primary completion date of 2018-08-09. These dates describe the registry record’s study timeline, not the timing of any individual participant’s measurements.

The group is titled “Heavy Water + PCI-32765.” The registry describes heavy water as 50ml of 70% 2H2O three times a day for the first 5 days, followed by 60 ml daily for a total of 4 weeks in the labeling phase. It states that the first dose was given in clinic and that participants then took individual doses at home. The listed interventions are heavy water and PCI-32765. A PCI-32765 dose and a fuller treatment schedule are not reported in the registry record.

With no separate control group listed, this design does not provide a concurrent comparison with placebo, usual care, or another treatment. The registry therefore describes an observational contrast across measurements in the study group rather than a randomized treatment comparison. The record does not state whether the primary analysis compared measurements with a baseline value, how repeated measurements were combined, or how long each participant contributed data.

The primary outcome is change in leukemia-cell death, expressed as a percentage of cell death and summarized using a median and full range. Its stated timeframe is every three months, up to one year. The secondary outcome concerns the percentage of recently born leukemia cells mobilized into the blood by PCI-32765. Numerical results for these outcomes are 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.

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 Change in Leukemia Cell Death, measured over every three months, up to one year.

The primary endpoint is titled “Change in Leukemia Cell Death.” Its unit is percentage of cell death, and the registry specifies a median with full range as the summary. The description says stable isotopic labeling with deuterated water is used to measure the effects of PCI-32765 on leukemia-cell death in peripheral blood. Measurements are described as occurring every three months, up to one year.

In general, a cell-labeling approach can help estimate cell kinetics by tracking the appearance of a label in cells over time. The intended focus is the life cycle of leukemia cells, rather than only the number of cells present at a single measurement. The registry summary explains that heavy water is used to learn about birth and death rates. This makes the endpoint relevant to the stated biological question about how the drug may affect leukemia-cell turnover.

A median describes the central value of a set of observations, while a full range describes the span from the lowest to the highest observed value. In general, these summaries can convey both a typical observation and the spread of the data, but they do not by themselves describe the precision of an estimated treatment effect. The registry does not report the endpoint’s numerical median, full-range limits, participant-level measurements, or an accompanying confidence interval. It also does not specify in the record how “change” was calculated from measurements over time.

Cell-death kinetics are a biological endpoint, not a direct measure of clinical benefit. The endpoint alone does not establish what happened to symptoms, disease progression, or survival. Those outcomes cannot be inferred from the endpoint description.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry describes a single-group study with no masking and no allocation to a separate comparison group. It identifies the study as phase 1 and phase 2 and gives a pilot-study title. The primary outcome is a repeated biological measurement summarized by a median and full range. Numerical outcome analyses are not reported in the registry record.

What does the median describe?

In general, the median is the middle value after observations are ordered. It can be useful when measurements are skewed or include extreme values, because the median is less affected by those extremes than the arithmetic mean. It describes the center of the observed values, not the uncertainty around a treatment effect. A median difference between measurements would need a clearly defined comparison and a method for estimating uncertainty before it could support an inferential conclusion. The registry does not report the numerical median or a method for comparing medians over time.

What does the full range add?

In general, the full range gives the lowest and highest observations, so it conveys the observed span. It does not show how many observations lie near the center, whether the distribution has clusters, or how stable the estimated center may be. A range can be wide because of a few extreme values. It is therefore useful context for the data but is not a substitute for a confidence interval or a complete description of the distribution. Numerical range limits are not reported in the registry record.

Why use heavy-water labeling?

The registry says heavy water is used to label cells and learn about their birth and death rates. In general, stable-isotope labeling can provide information about biological turnover by tracking incorporation of a label over time. The endpoint description specifies leukemia-cell death in peripheral blood, while the secondary outcome concerns recently born leukemia cells mobilized into blood. These are related to cell kinetics but represent different biological quantities. The registry does not describe the detailed calculation used to turn labeling observations into the reported percentage of cell death.

How should repeated measurements be understood?

The stated measurement timeframe is every three months, up to one year. In general, repeated measurements from the same person are correlated: observations from one person are not necessarily independent of one another. An analysis of longitudinal data may need to account for this dependence, define how time is represented, and specify how incomplete follow-up is handled. The registry does not report the statistical model, the planned contrast across time, or whether the analysis used all measurements or a particular time point.

Measurements may also vary because of biological fluctuation, laboratory procedures, or differences in the timing of collection. In general, repeated observations can help describe a pattern over time, but interpretation depends on the measurement process and analysis choices. The registry’s outcome description gives the measurement concept and schedule but does not report technical performance, a measurement-error assessment, or the specific analysis procedures.

What can a single-group design estimate?

In general, a single-group study can describe outcomes among participants who receive the study regimen. If measurements are available at multiple times, it may also describe within-group change. Without a separate comparator group, however, it does not directly estimate how outcomes would have differed under an alternative treatment or no treatment. A before-and-after pattern cannot alone distinguish an intervention effect from other time-related influences. The registry identifies no randomized comparison and does not report a control group.

The record labels allocation as not applicable and masking as none. These design features should not be read as evidence that a particular bias occurred; they identify the design’s structure. In general, an unmasked study may be more vulnerable to measurement or assessment influences when outcomes involve judgment. The registry does not explain whether outcome measurement or laboratory assessment was blinded to treatment timing.

What would uncertainty measures contribute?

In general, a confidence interval describes a range of effect values compatible with the data and analysis under the method’s assumptions. It can communicate precision as well as the direction and magnitude of an estimate. A p-value addresses a different question about compatibility with a specified null model; it does not measure the size or clinical importance of an effect. Neither a confidence interval nor a p-value for the primary endpoint is reported in the registry record. No inferential result can therefore be interpreted from the endpoint definition alone.

The record lists enrollment of 30, but the number contributing to the primary outcome at each time is not reported in the registry record. Enrollment does not itself reveal how many observations were available for analysis or how much information those observations contain. The record also does not describe a sample-size justification, interim analyses, or a statistical analysis plan. Any planning illustration should be understood as a planning aid rather than as observed evidence or observed power; numerical planning results are not reported in the registry record.

Finally, the registry lists a secondary cell-mobilization outcome as well as the primary cell-death outcome. In general, examining multiple outcomes can raise multiplicity questions because the chance of at least one apparently notable result may depend on how many statistical comparisons are made and how they are selected. The record does not report which comparisons were tested, how they were prioritized, or whether multiplicity was addressed. Since numerical analyses are not listed, there are no reported estimates to assess for multiplicity-adjusted or unadjusted interpretation.

10. Multiplicity, Missing Data and Analysis Populations

The registry identifies a primary outcome of change in leukemia-cell death and a secondary outcome concerning recently born leukemia cells mobilized into blood. It lists two outcome measures, but no analysis records are listed. Numerical estimates and tests for either outcome are not reported in the registry record.

In general, multiplicity arises when investigators make multiple statistical comparisons or assess multiple outcomes. Without a prespecified analysis plan, it can be difficult to distinguish primary confirmatory comparisons from exploratory ones or to know whether any adjustment was intended. The registry record does not report a multiplicity strategy, a hierarchy of comparisons, or how repeated measurements were included in the testing plan. It would not be appropriate to assume that an adjustment was or was not performed beyond what the record states.

Missing-data handling is also not reported in the registry record. The stated measurement schedule extends every three months, up to one year, but the record does not say how many measurements were collected, whether participants missed visits, why any data were unavailable, or how incomplete follow-up was handled. In general, results from repeated-measure studies can depend on assumptions about why data are missing and on the method used to address missing observations. Those assumptions cannot be evaluated without the analysis description and data summaries.

The analysis population is not reported in the registry record. The record does not specify whether outcome analyses included all enrolled participants, only those with labeling measurements, or another defined group. It also does not describe exclusions or the handling of participants who did not complete the measurement schedule. The listed enrollment of 30 should not be treated as the denominator for every outcome or time point without that information.

The statistical analysis plan, sample-size justification, and interim-analysis procedures are not reported in the registry record. Accordingly, the available information does not establish how analyses were planned, whether any were changed, or how incomplete data and multiple outcomes were addressed.

11. 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: atrial fibrillation (16.7%), pleural effusions (10.0%), neoplasms benign, malignant and unspecified (6.7%), gastric hemorrhage (3.3%), hematoma (3.3%).

The registry lists one group, “Heavy Water + PCI-32765,” with 30 participants at risk for serious adverse events and 16 affected. It also lists 30 at risk for other adverse events and 30 affected, with 3 deaths recorded. These are registry counts; they do not, on their own, establish the cause of an event or whether it was related to either intervention.

The listed serious adverse-event terms and percentages are atrial fibrillation, 16.7%; pleural effusions, 10.0%; neoplasms benign, malignant and unspecified, 6.7%; gastric hemorrhage, 3.3%; hematoma, 3.3%; and lung infection, 3.3%. The registry’s listing gives terms and percentages but does not provide additional details about timing, severity within each term, duration, recurrence, or attribution. These percentages should be read as the registry reports them, not as evidence of causation.

In general, adverse-event summaries depend on how events are defined, collected, coded, and attributed. The registry record does not describe those procedures in detail. The group-level counts also do not show how events were distributed over time or whether one participant experienced more than one event. The figures are descriptive safety information and should be interpreted alongside the study’s single-group design and the absence of a listed comparator.

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

The record describes a pilot investigation of leukemia-cell kinetics during treatment with PCI-32765 (ibrutinib) and heavy-water labeling. It establishes that the primary biological question concerns change in leukemia-cell death in peripheral blood and that the secondary outcome concerns mobilization of recently born leukemia cells into blood. It does not report numerical results for either outcome.

That absence matters. Without an observed estimate, the record cannot show whether the primary endpoint increased, decreased, or remained similar over time. Without a confidence interval or other uncertainty measure, the precision of any estimated change cannot be assessed. The outcome definitions and measurement schedule describe what the study intended to examine, not what the results were.

The single-group design also limits what a reported within-group pattern could establish. In general, a change over time among treated participants does not by itself identify the effect of treatment relative to an alternative. There is no separate comparator group listed in the record, and no randomized comparison is described. The record therefore does not provide a basis for attributing a change specifically to PCI-32765.

Cell kinetics are not interchangeable with clinical outcomes. Evidence about cell birth, death, or movement into blood would not on its own establish changes in symptoms, disease progression, quality of life, or survival. The registry does not report results for those clinical outcomes. Nor does the endpoint description establish whether the observed biological measurements, if any, were clinically meaningful.

The safety information is descriptive and comes from the single listed group. It includes counts for participants affected by serious and other adverse events and a list of serious-event terms with percentages. These figures do not establish that the study interventions caused the events, and the record provides no comparison group for evaluating relative safety.

The appropriate conclusion is limited: the registry records a completed pilot study with a biological labeling aim, a specified primary endpoint, and safety summaries. Its outcome values and statistical analyses are not reported in the registry record. No conclusion about the size, certainty, cause, or clinical importance of an effect can be drawn from the information recorded.

13. Why This Trial Matters Statistically

This study is statistically notable for asking a mechanistic question that differs from a conventional comparison of clinical outcomes. Heavy-water labeling is intended to support measurement of leukemia-cell birth and death rates, and the primary endpoint focuses on cell death in peripheral blood. Such a question concerns the dynamics behind the number of cells observed, rather than only a snapshot of cell counts.

That distinction makes the measurement and analysis especially important. In general, a kinetic endpoint depends on how labeling observations are collected and translated into an estimate of cell turnover. Repeated measurements can describe how a biological process changes over time, but they also require clear definitions of the time contrast and appropriate treatment of within-person dependence. The registry record identifies the measurement schedule and summary statistic, but it does not report the analysis method or numerical outcome values.

The design illustrates a common trade-off in early or pilot research. A single-group study can focus on whether a biological measurement is feasible to collect and describe what happens within the enrolled group. It does not offer the direct treatment contrast that a randomized control group can provide. This limits causal interpretation, even when a biological endpoint is scientifically informative.

The record also provides a useful reminder that an endpoint’s biological relevance and its clinical meaning are separate questions. Cell death and mobilization may illuminate aspects of disease biology, but the registry does not report whether those measurements corresponded to a clinical outcome. Nor does it present numerical results that would allow readers to assess the size or precision of the biological signal.

Finally, registry completeness affects statistical interpretation. The study is marked completed and its outcomes are named, yet numerical results and analyses are not listed. Without those details, readers cannot evaluate variability, missingness, multiplicity, or the precision of any estimated effect. The distinction between a carefully framed research question and a reported statistical result is central to reading this record.

14. 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 principal limitation for interpreting this record is that numerical outcome results are not reported in the registry record. The primary endpoint is defined, but its median and full range are absent. The secondary outcome is named, but its numerical results are also absent. No effect estimate, confidence interval, or p-value is reported, so the size and precision of any observed pattern cannot be assessed.

The single-group design provides no listed concurrent control. This precludes a direct randomized comparison and limits causal interpretation of any change over time. The record does not describe a baseline comparison, the specific contrast used for the primary endpoint, or a model for repeated measurements.

Although enrollment is listed as 30, the number contributing measurements at each time point is not reported in the registry record. Follow-up completeness, missing-data reasons, and methods for handling missing observations are also not reported. The analysis population is unspecified, so enrollment should not be assumed to equal the number analyzed for every endpoint.

The registry does not report the statistical analysis plan, sample-size justification, interim analyses, or multiplicity procedures. It also does not provide details about the calculation of the cell-death measure, measurement precision, or whether outcome assessment was masked. These omissions limit assessment of the planned statistical methods and potential sources of measurement uncertainty.

Finally, the primary endpoint is biological rather than a direct clinical outcome, and the record does not report clinical-outcome results. The safety information is descriptive, with no comparator group to contextualize event frequencies. These design and reporting limits mean the record supports description of the study’s aim and structure, but not a conclusion about efficacy, causality, or clinical benefit.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Pilot Study to Determine Effects of the Btk Inhibitor PCI-32765 on Leukemia Cell Kinetics and Trafficking, Using Heavy Water Labeling in Subjects With CLL and SLL — NCT01752426.
• Registry record last updated 2020-02-24; status last verified 2020-02.
• Results first posted 2020-02-24.
• 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.

18. Record Summary

This completed pilot study is listed as phase 1 and phase 2, with a single group and enrollment of 30. It examined PCI-32765 (ibrutinib) alongside heavy-water labeling in participants with CLL or SLL. The primary endpoint was change in leukemia-cell death in peripheral blood, summarized by a median and full range and measured every three months, up to one year. The secondary outcome concerned recently born leukemia cells mobilized into blood.

The registry reports serious and other adverse-event counts and lists serious-event terms with percentages. It does not report numerical results for either efficacy-related outcome, statistical analyses, missing-data methods, or an analysis population. The record therefore describes the study’s biological aim and design but does not establish the magnitude, precision, or cause of an outcome change.