This page provides an independent statistical analysis and educational interpretation of publicly reported results. ClinicalTrials.gov provides the official trial registry record. Numerical trial results on this page are restricted to the results posted in the ClinicalTrials.gov record; calculations added by Clinical Biostats are labelled as such.
1. Trial at a Glance
This page covers the registry results for Study to Assess the Efficacy and Safety of Ublituximab and Umbralisib in Participants With Chronic Lymphocytic Leukemia (CLL) Currently Treated With Ibrutinib, Acalabrutinib or Venetoclax (NCT04016805), a non-randomized phase 2 study. The primary outcome is Rate of Undetected Minimal Residual Disease (U-MRD).
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT04016805 |
| Phase | Phase 2 |
| Condition | Chronic Lymphocytic Leukemia |
| Allocation | Non-Randomized |
| Design model | Parallel |
| Masking | None (open label) |
| Enrollment | 41 |
| Arms in the primary outcome | n/a |
| Lead sponsor | TG Therapeutics, Inc. |
| Results posted | Yes |
2. Clinical Question
Population
Participants had chronic lymphocytic leukemia and were currently receiving ibrutinib, acalabrutinib or venetoclax. The registry record does not report detailed eligibility criteria, such as disease characteristics or prior treatment requirements, so the intended population cannot be described more narrowly from this record.
Intervention
The study assessed adding ublituximab and umbralisib to the participant's ongoing treatment. The listed combinations were ublituximab, umbralisib and ibrutinib; ublituximab, umbralisib and venetoclax; and ublituximab, umbralisib and acalabrutinib.
Comparator
No randomized control group is described. The record identifies a non-randomized, parallel design and lists three treatment combinations. It does not establish a like-for-like control comparison among them.
Primary question
The planned primary question was whether participants achieved undetectable minimal residual disease in peripheral blood, confirmed by a central laboratory, during a timeframe of up to approximately 23 months. The registry states that this outcome was not collected or analyzed as planned after termination.
In statistical terms, this is a question about the proportion of participants meeting a laboratory-defined response criterion, rather than a comparison of time until an event. A usable answer would require outcome observations and a clearly specified analysis population for each treatment combination. The registry does not report those observations or an analysis of the primary outcome, so the planned question cannot be answered from the posted results.
The record also lists overall response rate and treatment-emergent adverse events as secondary outcomes. Their presence identifies additional intended areas of assessment, but does not itself establish that results were collected or analyzed. The registry does not report numerical results for those outcomes in the information available for this trial.
3. Trial Design
This was a Phase 2, non-randomized, non-masked, parallel study. The registry reports an enrollment of 41 and describes the study as evaluating the addition of ublituximab and umbralisib for people with chronic lymphocytic leukemia who were already being treated with ibrutinib, acalabrutinib or venetoclax. The study start date is 2019-08-05, and the primary completion date is 2022-05-22. Its status is terminated.
The record's brief summary calls the study a two-cohort trial, while its arm descriptions list three combinations: ublituximab plus umbralisib with ibrutinib, with venetoclax, or with acalabrutinib. The registry record does not explain this difference. It is therefore safest to describe the listed treatment combinations without assuming how participants were allocated between them or how the cohorts were defined.
In the ibrutinib and venetoclax combinations, ublituximab is described as a 900 mg intravenous infusion once every cycle through cycle 6, then every three cycles up to 24 cycles. Umbralisib is described as an 800 mg oral tablet daily through cycles 1–24. Ibrutinib and venetoclax are described as daily oral tablets. In the acalabrutinib combination, the listed oral capsule is taken every 12 hours. The record defines a cycle as 28 days.
Because allocation was non-randomized and masking was absent, the design does not support interpreting differences between treatment combinations as if they came from randomized, blinded assignment. The registry record does not report the allocation process, a control group receiving only the pre-existing treatment, or a statistical plan for adjusting comparisons. Those details 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
| Stage | Ublituximab + Umbralisib + Ibrutinib | Ublituximab + Umbralisib + Venetoclax | Ublituximab + Umbralisib + Acalabrutinib |
|---|---|---|---|
| STARTED | 30 | 6 | 5 |
| COMPLETED | 0 | 0 | 0 |
| NOT COMPLETED | 30 | 6 | 5 |
Reasons for not completing this period:
| Reason | Ublituximab + Umbralisib + Ibrutinib | Ublituximab + Umbralisib + Venetoclax | Ublituximab + Umbralisib + Acalabrutinib |
|---|---|---|---|
| Sponsor's Discretion | 30 | 6 | 5 |
Analysis population for the primary outcome, as defined in the registry: Data for this outcome measure was not collected or analyzed as planned as the study was terminated due to sponsor's business decision.
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.
| Characteristic | Unit | Ublituximab + Umbralisib + Ibrutinib | Ublituximab + Umbralisib + Venetoclax | Ublituximab + Umbralisib + Acalabrutinib | Total |
|---|---|---|---|---|---|
| Participants analysed | 30 | 6 | 5 | 41 | |
| Age, Continuous | years | 63 (48 to 81) | 54.5 (41 to 67) | 71 (57 to 77) | 63 (41 to 77) |
| Sex: Female, Male: Female | Participants | 7 | 1 | 0 | 8 |
| Sex: Female, Male: Male | Participants | 23 | 5 | 5 | 33 |
| Race and Ethnicity Not Collected | Participants | — | — | — | 0 |
6. Primary Endpoint
The registry lists the primary outcome as Rate of Undetected Minimal Residual Disease (U-MRD), measured over Up to approximately 23 months.
| Element | Registry entry |
|---|---|
| Result type | N/A |
| Measure of spread | not applicable |
| Unit | not stated |
| Endpoint classification | not reduced to a single comparison |
The planned primary endpoint was the rate of undetected minimal residual disease, or U-MRD. The registry defines this as the proportion of participants with undetectable MRD in peripheral blood, confirmed by a central laboratory. The planned timeframe was up to approximately 23 months.
In general, MRD assessment looks for evidence of disease at a level below what may be captured by broader clinical measures. A peripheral-blood result provides a laboratory-based way to classify whether MRD was detectable under the study's assay and confirmation procedures. The endpoint is expressed as a proportion because each participant is classified according to whether the specified finding is present or absent. This general description does not establish the assay's sensitivity, testing schedule, or any threshold beyond the registry's description; those details are not reported in the registry record.
A proportion can be informative about how often a defined response criterion is observed in the assessed study population. Its interpretation depends on the people included in the denominator, the timing and completeness of testing, and the laboratory definition. Here, the registry explicitly states that the primary outcome was not collected or analyzed as planned because the study was terminated due to the sponsor's business decision. Consequently, no primary endpoint rate or precision estimate is reported in the registry record, and the endpoint cannot be interpreted as an observed response result.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The central statistical fact is that the primary outcome has no reported analysis. The registry describes U-MRD as a planned outcome, defines the laboratory criterion, and gives a timeframe of up to approximately 23 months. It also states that data for this outcome were not collected or analyzed as planned because the study was terminated due to the sponsor's business decision. The record therefore does not provide a rate, a denominator for an analyzed population, or an estimate of uncertainty for U-MRD.
The reported enrollment of 41 is not a substitute for the missing outcome data. Enrollment describes the study's recorded size, but it does not show how many participants had evaluable peripheral-blood testing, how participants were distributed across the listed combinations, or whether any met the U-MRD definition. Those details are not reported in the registry record. Without them, a reader cannot estimate the outcome proportion or assess its precision.
The design also limits what comparisons could mean. Allocation was non-randomized, masking was absent, and the record lists three combinations rather than a randomized control group. Participants on different background treatments may differ in ways related to their treatment history or clinical characteristics; this is a general concern with non-randomized comparisons, not a claim about differences observed in this study. The registry does not report enough information to determine whether such factors were measured or addressed analytically. No like-for-like causal comparison is established by the record.
The registry lists overall response rate and treatment-emergent adverse events as secondary outcomes, but it does not provide numerical results or analyses for them in the registry entries. It also reports zero in the at-risk and affected fields for each of the three adverse-event groups. With zero participants recorded as at risk in those fields, these entries do not provide an interpretable incidence estimate and should not be read as evidence that no adverse events occurred.
In general, estimates from clinical studies are more informative when accompanied by uncertainty measures, such as confidence intervals, which indicate the range of values reasonably compatible with the observed data under a specified analysis. No such outcome estimate or interval is reported. The absence of a result means the planned efficacy question is unresolved in this registry record; it is not evidence for or against a particular treatment effect.
9. Statistical Methods Explained
The registry identifies a planned binary laboratory outcome: whether MRD was undetectable in peripheral blood, confirmed by a central laboratory. The intended summary, a rate or proportion, is generally calculated by dividing the number of participants meeting a defined criterion by the number of participants assessed under a stated analysis rule. That is a general explanation of a proportion, not a calculation for this study. The registry states that the primary outcome was not collected or analyzed as planned, and it does not report an observed numerator or an analyzed denominator.
What does a proportion describe?
In general, a proportion describes the share of an analysis population that meets a specified condition. It is only interpretable alongside the definition of that population and the handling of participants whose outcome is unavailable. For a laboratory response outcome, the timing of measurement, the assay definition, and the rules for classifying missing or unevaluable tests can all affect the reported rate. The registry gives the broad outcome definition and timeframe, but the detailed testing schedule and missing-result rules are not reported in the registry record.
For an estimated proportion, a confidence interval can communicate statistical precision. In general, a narrow interval indicates less sampling uncertainty than a wide interval, while neither interval width nor the estimate alone addresses possible bias in how participants entered the study or were assessed. Because no U-MRD estimate is reported, there is no study-specific confidence interval to interpret. It is not possible to characterize precision from the planned endpoint definition alone.
What can the design support?
A non-randomized design does not assign participants by chance to treatment groups. In general, this can leave treatment groups different in prognostic characteristics, including characteristics related to prior care or disease status. Such differences may complicate comparisons even if observed outcomes are available. Randomization is one method of balancing known and unknown factors on average; it is not part of the design described in this record.
The record states that the study was parallel and non-masked. A parallel design means participants are assigned to a treatment group and followed in that group rather than crossing between treatment combinations, as a general design concept. Non-masking means treatment assignment was not concealed from participants or study personnel as described by the record. These design features do not by themselves establish that results are biased, but they matter when interpreting a comparison. The record does not report a randomized comparator or analysis method intended to address confounding.
What does the registry report about analysis?
The registry lists three outcome measures, including U-MRD, overall response rate, and treatment-emergent adverse events. It reports no analyses for the study. In statistical reporting, an analysis plan commonly specifies the target population, outcome definition, handling of missing values, comparison method, and any adjustment for multiple outcomes or groups. The plan is not reported in the registry record, so these choices cannot be assessed.
The registry identifies the primary outcome as not collected or analyzed as planned. This differs from a completed analysis with an estimate that is imprecise or statistically inconclusive. There is no posted primary estimate to classify as positive, negative, or inconclusive. Likewise, no re-calculation from posted summary statistics is possible because no relevant outcome summary statistics are reported.
In general, a statistical test evaluates data under a model and a specified null hypothesis; a p-value, when reported, describes how compatible the data are with that hypothesis under the model. It does not measure the probability that a treatment works or the size or importance of an effect. No primary analysis or p-value is reported for this trial. The registry also does not report whether any interim analyses were planned or conducted.
Why does missing outcome information matter?
When an outcome is not available for analysis, its absence should not be silently treated as either a response or a nonresponse. In general, missingness can alter an estimated rate if the participants with observed outcomes differ from those without them. Appropriate handling depends on the study question and the reasons outcome data are missing. Here, the record says the primary endpoint was not collected or analyzed as planned, but it does not describe participant-level availability, missing-data assumptions, or imputation methods. No missing-data adjustment can be evaluated.
These limitations are distinct from ordinary sampling uncertainty. A confidence interval can describe uncertainty under an analysis, but it cannot correct an endpoint that was not analyzed or resolve unmeasured differences created by non-randomized allocation. For this record, the main methodological conclusion is therefore about the limits of interpretation: the endpoint was planned, but the registry provides no analysis with which to estimate it.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists U-MRD as the primary outcome and identifies overall response rate and treatment-emergent adverse events as secondary outcomes. Considering several outcomes raises a general multiplicity issue: the more questions assessed, the more opportunities there may be for a chance finding if each is tested separately. Statistical plans can address this by specifying which outcomes are primary, how tests are ordered, or whether error rates are adjusted. The record's identification of a primary outcome distinguishes its stated role, but the detailed plan for multiple testing is not reported in the registry record.
No analyses are reported. As a result, there are no posted estimates or tests to evaluate for multiplicity, and no evidence in the record that a particular adjustment was or was not applied. Whether interim analyses were planned or performed is also not reported in the registry record. It would be inappropriate to infer either an interim monitoring plan or its absence from the endpoint results.
Missing outcome information is especially consequential because the registry says the primary measure was not collected or analyzed as planned. The record does not describe which participants had endpoint assessments, why any individual result might be unavailable, or how an incomplete assessment would have been handled. In general, missing-data methods rely on assumptions about the relationship between observed and unobserved outcomes. Without a reported analysis population or missing-data strategy, those assumptions cannot be examined.
The registry does not specify analysis populations, such as whether analyses were intended to include all enrolled participants or only those with evaluable testing. It also does not report the statistical analysis plan or sample-size justification. The enrollment of 41 alone does not reveal the intended power for the primary outcome, nor can it substitute for a completed analysis. These gaps limit assessment of both the planned inferential approach and the reliability of any treatment comparison.
11. What the Result Does, and Does Not, Mean
The record establishes that a Phase 2 study was planned to assess ublituximab and umbralisib added to ongoing treatment in participants with chronic lymphocytic leukemia. It specifies a central-laboratory definition for the primary U-MRD outcome and lists overall response rate and treatment-emergent adverse events as secondary outcomes. It also records an enrollment of 41 and a terminated status.
The record does not establish what proportion of participants achieved U-MRD, whether outcomes differed among the listed treatment combinations, or how precisely any effect was estimated. The primary outcome was not collected or analyzed as planned, and no secondary outcome estimates or analyses are reported in the registry record. No conclusion about efficacy can be drawn from the absence of these results.
In general, a study's planned question, its observed data, and the interpretation of those data are separate things. A clearly defined endpoint can describe what investigators intended to measure, but it is not an outcome finding. Likewise, enrollment does not establish that participants completed endpoint testing or that any specific response occurred. For this study, the registry's statement about non-collection and non-analysis governs interpretation of the primary endpoint.
The non-randomized design also means that the three listed combinations should not be treated as randomized alternatives. Even if outcome estimates were available, differences could reflect the participant groups or their background treatments as well as the added drugs. The registry does not report a randomized comparison or enough analytic detail to resolve that issue.
The termination reason recorded is a sponsor business decision. The record does not state that termination followed an efficacy finding, a safety finding, or a statistical stopping rule. Therefore, the status alone should not be interpreted as evidence about benefit or harm. The appropriate reading is limited: the trial question was specified, but the posted record does not supply results that answer it.
12. Why This Trial Matters Statistically
This trial matters statistically because its primary question is recognizable and clinically oriented, but the registry record does not provide the outcome data needed to quantify it. The endpoint was defined as a proportion meeting a central-laboratory MRD criterion in peripheral blood. That definition makes clear what the planned measurement was intended to capture, while the termination and lack of analysis leave the rate unknown.
The design also illustrates why a treatment comparison requires more than listing treatment groups. Participants were not randomized, the study was not masked, and the listed combinations retain different ongoing therapies. In general, this structure can make cross-group comparisons difficult to interpret because assignment and background treatment may be associated with participant characteristics. The registry record does not describe a comparison method or adjustment strategy that would support a causal interpretation.
Another important distinction is between a missing result and a null result. A null result would require observed data analyzed under a stated method; this record instead states that the primary endpoint was not collected or analyzed as planned. Treating the two situations as equivalent would misrepresent the evidence. Likewise, the enrollment figure cannot replace outcome-specific denominators or uncertainty estimates.
The record lists additional response and safety outcomes, but no numerical analyses are reported for them. This underscores the value of complete outcome reporting: readers need estimates, denominators, and methods to understand both the magnitude and precision of findings. Without those elements, the statistical contribution of the registry is primarily to document the study question, design, and incomplete outcome record rather than to establish an efficacy or safety result.
13. 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 is that the planned primary outcome was not collected or analyzed as planned. The registry attributes this to termination due to the sponsor's business decision, but does not report a primary outcome estimate, denominator, or uncertainty measure. The reason recorded for termination should not be taken as an efficacy or safety conclusion.
Important design details are also unavailable. Although the study is described as non-randomized, non-masked and parallel, the registry record does not explain how participants entered each listed combination, whether a control group was planned, or how the described two cohorts relate to the three combinations. Detailed eligibility criteria and an analysis plan are not reported in the registry record.
The record does not report the endpoint assessment schedule, assay characteristics, analysis populations, or rules for incomplete and missing assessments. These details would be needed to judge the operational meaning of the U-MRD endpoint and how a rate would have been constructed. The reason for missing endpoint data at the participant level is also not described.
Although secondary outcomes are listed, numerical results and analyses are not reported. The adverse-event fields contain zero entries for participants at risk and participants affected in each listed group; these fields therefore do not provide interpretable event rates. They should not be read as demonstrating an absence of adverse events.
Finally, the registry identifies an enrollment of 41 but does not report how this enrollment relates to the separate treatment combinations or to any endpoint-evaluable population. A sample-size justification and plans for interim analysis or multiplicity handling are not reported in the registry record. These limitations prevent a quantitative assessment of treatment effects and their precision.
14. Related Tutorials
15. Related Statistical Calculators
16. Sources
- ClinicalTrials.gov: Study to Assess the Efficacy and Safety of Ublituximab and Umbralisib in Participants With Chronic Lymphocytic Leukemia (CLL) Currently Treated With Ibrutinib, Acalabrutinib or Venetoclax — NCT04016805.
- Registry record last updated 2023-07-24; status last verified 2023-07.
- Results first posted 2023-07-24.
- 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.
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17. Record Summary
This registry record describes a Phase 2, non-randomized, non-masked, parallel study in chronic lymphocytic leukemia. It assessed adding ublituximab and umbralisib to ongoing ibrutinib, venetoclax or acalabrutinib treatment. The record reports enrollment of 41, a study start date of 2019-08-05, a primary completion date of 2022-05-22, and terminated status.
The planned primary outcome was the proportion with undetectable MRD in peripheral blood confirmed by a central laboratory, assessed over up to approximately 23 months. The registry states that this outcome was not collected or analyzed as planned because of a sponsor business decision. Overall response rate and treatment-emergent adverse events are listed as secondary outcomes, but numerical analyses are not reported. The record does not establish a treatment effect or a safety estimate.