Duvelisib and Venetoclax in Relapsed or Refractory CLL or SLL or RS: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Duvelisib and Venetoclax in Relapsed or Refractory CLL or SLL or RS (NCT03534323), a non-randomized phase 1, phase 2 study. The primary outcome is Complete Response Rate (CRR).

2. Clinical Question

The study asks whether complete responses occur among participants with relapsed or refractory chronic lymphocytic leukemia (CLL), small lymphocytic lymphoma (SLL), or Richter’s syndrome who receive duvelisib with venetoclax. It was a Phase I/II study with a non-randomized, single-group model. The registry describes several dose levels in Phase I and a Phase II regimen; it does not describe a concurrent control group.

The title names complete response rate as the primary endpoint. The endpoint description says response was defined as the proportion achieving complete response using IWCLL 2008 criteria for CLL and Lugano 2014 criteria for Richter’s syndrome. The record does not provide outcome values by disease group or dose level. It also does not report a result that would allow the response estimate to be judged for precision.

3. Trial Design

This is a completed Phase I/II study sponsored by Dana-Farber Cancer Institute. The registry lists a start date of 2018-07-12, primary completion on 2024-12-01, and enrollment of 55. The allocation is non-randomized, masking is none, and the model is single-group. These design features mean the registry does not describe a randomized comparison with a control treatment.

Phase I included three dose levels. Level 1 paired venetoclax 100 mg daily with duvelisib 25 mg twice daily; the description says duvelisib was given alone for the first seven days, with venetoclax added on day 8. Level 2 paired venetoclax 200 mg daily with duvelisib 25 mg twice daily. Level 3 paired venetoclax 400 mg daily with duvelisib 25 mg twice daily. The Phase II regimen also lists venetoclax 400 mg daily with duvelisib 25 mg twice daily.

The Phase I descriptions state that participants were to be admitted for administration of the initial venetoclax dose at dose escalation; the wording for Level 1 is incomplete. The registry does not report the eventual recommended Phase II dose or the maximum tolerated dose as a result. Although the Phase II regimen is specified, the reported record does not establish that this regimen was the maximum tolerated dose.

The primary response assessments were scheduled at the end of cycles 3, 6 and 13, with 28 days per cycle. The registry describes Phase I as a safety-driven 3+3 design with very small cohorts, not powered for efficacy comparisons by dose level. It says the study was statistically designed to evaluate complete response at the recommended Phase II dose. The remainder of the sentence describing the intended population for that evaluation is incomplete, so the exact planned analysis population is not fully reported.

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

Analysis population for the primary outcome, as defined in the registry: CR is not reported by dose level because Phase I is a safety-driven 3+3 design with very small cohorts that are not powered for efficacy comparisons. The trial is statistically designed to evaluate CR at the recommended Phase II dose, so combining patients treated at the MTD provides the clinically interpretable estimate while avoiding unreliable, underpowered subgroup comparisons.

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 Complete Response Rate (CRR), measured over Response assessment on the end of cycle 3, 6 and 13. With 28 days per cycle..

The primary endpoint is titled Complete Response Rate (CRR), expressed as the proportion of participants. Its stated timeframe is response assessment at the end of cycles 3, 6 and 13, with 28 days per cycle. The description says the overall response rate was defined as the proportion achieving complete response, assessed using IWCLL 2008 criteria for CLL and Lugano 2014 criteria for Richter’s syndrome. The wording therefore uses an overall-response label while defining the measure as complete response; the registry does not explain this naming difference.

A proportion conveys how frequently the specified outcome was observed in the assessed population. A confidence interval describes uncertainty around an estimate: in general, a wider interval indicates less precision, while a narrower interval indicates greater precision. The registry lists a 95% confidence interval as the dispersion measure, but does not report the endpoint estimate, its interval limits, the number assessed at each time, or the response results by disease type.

Complete response is used as a defined clinical response category rather than as a direct measure of survival or duration of response. Its interpretation depends on the response criteria and assessment schedule. The registry record does not report additional detail about how assessments were adjudicated, how responses across the listed assessment times were combined, or whether missing assessments affected endpoint classification.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The methods information in the registry is limited. It identifies the study as Phase I/II, non-randomized, unmasked, and single-group, and describes a safety-driven 3+3 design for Phase I. It identifies the primary endpoint and the confidence interval type, but does not give a full statistical analysis plan. The distinctions below explain what those listed methods generally mean and what cannot be inferred from the record.

What does a single-group design tell us?

In general, a single-group study describes outcomes among participants receiving the study regimen without a concurrent randomized control group. An observed response proportion can summarize the experience of the participants included in that analysis. It cannot, on its own, separate the effect of treatment from other explanations for the observed outcome. Non-random allocation also means that differences between dose-level groups can reflect how participants entered or progressed through the study, rather than a treatment effect. The registry does not report a randomized comparison or a causal comparison plan.

How should the Phase I design be understood?

The record calls Phase I a safety-driven 3+3 design and says the cohorts were very small and not powered for efficacy comparisons. In general, a 3+3 dose-escalation approach evaluates dose levels in small cohorts to inform safety and dose selection. It is not designed to provide precise comparisons of response rates across dose levels. The record does not report the dose-escalation decision rules, dose-limiting toxicity definition, or the final maximum tolerated or recommended Phase II dose. Those details are not reported in the registry record.

What does the confidence interval represent?

The endpoint lists a 95% confidence interval. In general, a confidence interval gives a range of values compatible with the observed data under the statistical procedure used. It communicates precision as well as the point estimate; it is not a guarantee that the true value lies in the interval. The registry does not report the point estimate or interval limits, nor does it identify the method used to calculate the interval. Without those details, the precision of the primary response estimate cannot be assessed.

What can be inferred from the planning assumptions?

The record describes a planning illustration based on the observed effect, with a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation; the target effect is described as a stated fraction of the observed effect. For time-to-event outcomes, the stated convention is a total number of events using Schoenfeld; for other outcomes, the convention is participants per arm. These are planning assumptions, not a description of the trial’s own design. The study itself is listed as single-group and non-randomized. The record does not report the calculated planning values in the information available for this analysis, and such illustrations are not observed power.

In general, a sample-size illustration asks how many participants or events might be required under specified assumptions. It depends on the anticipated effect and other design choices. It does not establish that the completed study had that size, nor does it show the probability that a particular result is true. The registry does not report the study’s own sample-size justification, so the planning illustration should not be attributed to the trial protocol.

Why can outcome definitions affect interpretation?

The primary endpoint is titled Complete Response Rate, while its description calls the measure overall response rate and defines it as the proportion achieving complete response. The listed criteria are IWCLL 2008 for CLL and Lugano 2014 for Richter’s syndrome. In general, outcome criteria determine which observations qualify as an event and help make response classifications consistent. However, the registry does not report how the different disease criteria were applied in a combined analysis, how results were pooled across diagnoses, or whether response assessment was independently reviewed.

The time points are described as the ends of cycles 3, 6 and 13, with 28 days per cycle. A response measured at a scheduled assessment is a status at that time, whereas a response accumulated over a period can use a different definition. The registry does not specify whether the primary estimate used the best response across assessments, a particular assessment, or another rule. That distinction matters, but the analysis rule is not reported in the registry record.

Finally, the record lists no analyses and gives no reported primary endpoint result. It does not describe an inferential model, adjustment variables, hypothesis-testing procedure, or confidence-interval calculation method. General explanations of these methods cannot fill in a plan that is not reported. Interpretation should therefore remain limited to the design and endpoint definitions actually documented.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists the primary complete response endpoint and secondary outcomes of 12-month Progression-Free Survival (PFS) Rate, 1-year Overall Survival (OS), and 1-year MRD Negativity Rate. It also lists five outcome measures, but does not provide outcome estimates in the record. The registry does not report how many hypotheses were formally tested, whether testing was ordered hierarchically, or whether any adjustment for multiple outcomes or assessment times was planned. A multiplicity strategy is therefore not reported in the registry record.

Missing-data handling is also not reported. The record does not state how participants without an evaluable response assessment were treated, how incomplete follow-up affected survival outcomes, or whether any imputation method was planned. It does not provide counts of participants assessed for the primary endpoint at the scheduled assessment times. Enrollment of 55 is reported, but that figure alone does not establish how many participants contributed to each endpoint analysis.

The analysis populations are not fully described. The primary endpoint population text says Phase I response is not reported by dose level because the cohorts are small and safety-driven, and that the study was designed to evaluate complete response at the recommended Phase II dose. It also mentions combining participants treated at the maximum tolerated dose, but the sentence ends before the rationale is complete. The registry does not report whether the primary analysis included all treated participants, only participants at a specified dose, or another population. It does not report a per-protocol or intention-to-treat definition.

These omissions prevent assessment of whether missing observations, repeated assessments, or multiple outcomes affected the reported inference. The record lists zero analyses, and no statistical analysis details or endpoint results are reported.

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 0% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: neutrophil count decreased (100.0%), lymphocyte count increased (100.0%), lymphocyte count decreased (66.7%), anemia (33.3%), febrile neutropenia (33.3%).

The serious adverse-event entries are organized by the listed dose groups. For Phase 1 Level 1, the registry lists 3 participants at risk and 3 with serious adverse events; the corresponding counts for other adverse events are 3 at risk and 3 affected, with 0 deaths. For Phase 1 Level 2, the counts are 3 at risk and 3 with serious adverse events, 3 at risk and 3 with other adverse events, and 1 death. For Phase 1 Level 3, the counts are 6 at risk and 6 with serious adverse events, 6 at risk and 6 with other adverse events, and 1 death. For Phase 2, the counts are 32 at risk and 28 with serious adverse events, 32 at risk and 31 with other adverse events, and 3 deaths.

These are group-level counts in the registry record. They should not be read as counts of individual episodes, and they do not establish when events occurred or how long participants were followed. The record does not report event severity grading, attribution to study drugs, event timing, or causes of death. It also does not describe a statistical comparison of safety between dose groups.

The registry lists neutrophil count decreased and lymphocyte count increased at 100.0%, lymphocyte count decreased at 66.7%, and anemia, febrile neutropenia, and diarrhea at 33.3% among the top serious-event terms. The denominator and calculation details for these percentages are not reported in the registry record, so they should be interpreted as registry-listed percentages rather than as fully characterized risks.

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

The record documents a study of duvelisib with venetoclax in relapsed or refractory CLL or SLL, or Richter’s syndrome, and describes its Phase I and Phase II regimens. It identifies complete response rate as the primary endpoint and specifies response-assessment times and criteria. It also reports selected safety counts by dose group. These registry entries describe the intended question and some reported study information.

The record does not report the primary endpoint estimate or its 95% confidence interval. It therefore does not show how many participants achieved complete response, how precise an estimate would be, or how response varied across disease groups. No efficacy result can be inferred from the trial’s completion status, enrollment, treatment descriptions, or safety counts. The absence of a posted estimate is not a finding of no response.

The study’s non-randomized, single-group design does not provide a concurrent control comparison. Even if a response result were available, a response proportion alone would describe outcomes in the analyzed study population; it would not establish the contribution of each drug or quantify an advantage over another treatment. The registry itself says that Phase I cohorts were small and not powered for efficacy comparisons by dose level. The dose-level groups should not be treated as if they were randomized arms.

Safety counts also need a limited interpretation. They document participants listed as affected in each group and deaths recorded in the registry, but the information does not identify event attribution, timing, or causes of death. The listed serious-event term percentages have no reported denominator in the record. They cannot, by themselves, characterize comparative risk or establish a causal relationship.

Accordingly, the registry supports a design-level and reporting-level account, not a conclusion about efficacy. Key outcome values, analysis populations, missing-data rules, and statistical methods are not reported in the registry record. Interpretation should distinguish those omissions from the results themselves.

13. Why This Trial Matters Statistically

This trial raises several statistical issues that are especially important in early-phase combination studies. Phase I dose escalation has a safety focus, and the registry explicitly cautions that its small cohorts were not powered for efficacy comparisons. That distinction helps prevent response counts from being overinterpreted as evidence that one dose level performs better than another.

The transition from Phase I to Phase II also makes the analysis population important. The registry says that the study was designed to evaluate complete response at the recommended Phase II dose and refers to participants treated at the maximum tolerated dose, but the population statement is incomplete. Without a clear description of who contributes to the primary estimate, it is difficult to know precisely what population a response rate would describe.

The endpoint wording deserves attention as well. The title says Complete Response Rate, while the description calls the measure overall response rate and defines it as the proportion achieving complete response. For CLL and Richter’s syndrome, the registry names different response criteria. Clear reporting of how those criteria are applied and combined would be necessary to interpret a shared endpoint across the study population.

Finally, the registry record gives no primary response estimate, confidence interval, or analysis details. This means neither the size nor the precision of the efficacy result can be assessed. A completed study can still have incomplete result reporting in the registry. Separating what the record documents from what it leaves unreported is essential: the design and safety entries can be described, but they cannot replace the missing endpoint analysis.

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 most consequential limitation of the registry record is the absence of a reported primary endpoint estimate and confidence interval. Without these, the response outcome cannot be quantified or assessed for precision. The record also does not provide counts assessed at each response time or results by disease type. The primary endpoint description combines terminology that is not fully reconciled: it is titled complete response rate but calls the measure overall response rate while defining it as the proportion achieving complete response.

The design is non-randomized and single-group, so there is no concurrent control arm described. Phase I dose groups are small, safety-driven cohorts, and the registry says they are not powered for efficacy comparisons. This limits comparisons across dose levels. The exact primary analysis population is also unclear because the registry’s population statement is incomplete, and it does not report whether Phase I participants were included in the primary analysis.

Other statistical details are not reported in the registry record, including the analysis plan, confidence-interval method, multiplicity handling, missing-data rules, analysis-population definitions, and sample-size justification. The record lists secondary outcomes but supplies no result estimates for them in the information described. It does not explain how response criteria were harmonized across CLL and Richter’s syndrome.

Safety information is also limited. The registry lists affected participants, deaths, and selected serious-event terms, but does not report event timing, attribution, severity grading, follow-up duration, causes of death, or percentage denominators for the selected terms. These omissions restrict interpretation of both efficacy and safety reporting.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Duvelisib and Venetoclax in Relapsed or Refractory CLL or SLL or RS — NCT03534323.
• Registry record last updated 2026-10-28; status last verified 2026-10.
• Results first posted 2026-03-23.
• 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

NCT03534323 is a completed Phase I/II study sponsored by Dana-Farber Cancer Institute. The registry lists enrollment of 55, a start date of 2018-07-12, and primary completion on 2024-12-01. The study is non-randomized, unmasked, and single-group.

It evaluated duvelisib with venetoclax in participants with relapsed or refractory CLL or SLL, or Richter’s syndrome. Phase I lists venetoclax dose levels of 100 mg, 200 mg, and 400 mg daily with duvelisib 25 mg twice daily; Phase II lists 400 mg daily venetoclax with 25 mg twice-daily duvelisib. The primary endpoint is titled Complete Response Rate, with assessments at the end of cycles 3, 6 and 13, each 28 days long.

The registry lists serious adverse-event counts and deaths by dose group, but does not report the primary endpoint result, its confidence interval, or a full analysis plan. The primary response estimate and its precision are therefore not available in the registry record.