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 Entospletinib in Combination With Idelalisib in Adults With Relapsed or Refractory Hematologic Malignancies (NCT01796470), a registered phase 2 study. The primary outcome is Objective Response Rate (ORR).
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT01796470 |
| Phase | Phase 2 |
| Condition | Chronic Lymphocytic Leukemia, Mantle Cell Lymphoma, Diffuse Large B-cell Lymphoma |
| Allocation | Not Stated |
| Design model | Sequential |
| Masking | None (open label) |
| Enrollment | 66 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Gilead Sciences |
| Results posted | Yes |
2. Clinical Question
Population
Adults with relapsed or refractory hematologic malignancies were eligible, including chronic lymphocytic leukemia, mantle cell lymphoma, diffuse large B-cell lymphoma, and indolent non-Hodgkin lymphomas. The registry describes indolent disease categories including follicular lymphoma, lymphoplasmacytoid lymphoma or Waldenström macroglobulinemia, small lymphocytic lymphoma, and marginal zone lymphoma. Enrollment was 66.
Intervention
Participants received entospletinib in combination with idelalisib at one of four dose combinations: 400 mg/100 mg, 600 mg/100 mg, 800 mg/100 mg, or 800 mg/150 mg. After stopping combination treatment and following a washout period, participants could continue entospletinib 400 mg alone.
Comparator
The registry does not describe a like-for-like control comparison. Allocation is not stated, and the study is not a randomized comparison. The listed dose combinations and disease cohorts should not be interpreted as randomized control arms.
Primary question
The primary endpoint was objective response rate, assessed by an Independent Review Committee using revised response criteria and investigator response. It concerned the percentage achieving complete or partial response; for lymphoplasmacytoid lymphoma or Waldenström macroglobulinemia, very good partial response or minor response also counted. The registry reports that the study ended for safety measures and complete data were not collected for any participant, so it does not provide a completed estimate of this endpoint.
3. Trial Design
This was a phase 2, open-label study of entospletinib combined with idelalisib in adults with relapsed or refractory hematologic malignancies. It enrolled 66 participants and included chronic lymphocytic leukemia, mantle cell lymphoma, diffuse large B-cell lymphoma, and indolent non-Hodgkin lymphoma. The registry lists follicular lymphoma and other indolent lymphoma categories among the eligible disease types.
The combination was studied at one of four dose combinations: 400 mg/100 mg, 600 mg/100 mg, 800 mg/100 mg, and 800 mg/150 mg. Following discontinuation of combination treatment and a washout period, participants could continue entospletinib 400 mg monotherapy. The registry describes the study model as sequential, but the sequence of treatment or dose decisions is not reported in the registry record. Allocation is not stated. This was not a randomized comparison, and the registry cautions that the groups are not a like-for-like control comparison.
The study was terminated due to safety measures. Its primary endpoint timeframe was from treatment start to treatment end, up to 18 months. The registry states that complete data were not collected for any participant. Therefore, the planned efficacy question cannot be answered from a completed primary endpoint result in the registry record. The record lists secondary outcomes including treatment-emergent adverse events, treatment-emergent laboratory abnormalities, maximum tolerated dose, progression-free survival, duration of response, and time to response. Results for these outcomes are not reported in the registry record as completed analyses.
The registry record does not report the intended sample-size justification, the detailed dose-sequencing rules, or whether interim analyses were planned. No conclusions about those design features can be drawn from the available record.
4. Participant Flow and Accounting
The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.
Before assignment: 85 participants were screened.
Overall Study
| Stage | Entospletinib + Idelalisib CLL | Entospletinib + Idelalisib iNHL: FL | Entospletinib + Idelalisib DLBCL | Entospletinib + Idelalisib MCL | Entospletinib + Idelalisib iNHL: Others |
|---|---|---|---|---|---|
| STARTED | 35 | 14 | 6 | 3 | 8 |
| Entospletinib Monotherapy | 4 | 4 | 0 | 0 | 0 |
| COMPLETED | 0 | 0 | 0 | 0 | 0 |
| NOT COMPLETED | 35 | 14 | 6 | 3 | 8 |
Reasons for not completing this period:
| Reason | Entospletinib + Idelalisib CLL | Entospletinib + Idelalisib iNHL: FL | Entospletinib + Idelalisib DLBCL | Entospletinib + Idelalisib MCL | Entospletinib + Idelalisib iNHL: Others |
|---|---|---|---|---|---|
| Adverse Event | 4 | 2 | 2 | 1 | 3 |
| Death | 2 | 0 | 0 | 0 | 1 |
| Initiated New Therapy | 9 | 0 | 0 | 0 | 2 |
| Lost to Follow-up | 0 | 1 | 0 | 0 | 0 |
| Physician Decision | 5 | 4 | 1 | 0 | 1 |
| Progressive Disease | 7 | 7 | 3 | 2 | 0 |
| Protocol Criteria for Withdrawal | 1 | 0 | 0 | 0 | 0 |
| Withdrawal by Subject | 7 | 0 | 0 | 0 | 1 |
Analysis population for the primary outcome, as defined in the registry: The study was terminated due to safety measures. Complete data was not collected for any participant.
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: The Full Analysis Set comprised all participants who received ≥ 1 dose of study drug (entospletinib or idelalisib).
| Characteristic | Unit | Entospletinib + Idelalisib CLL | Entospletinib + Idelalisib iNHL: FL | Entospletinib + Idelalisib DLBCL | Entospletinib + Idelalisib MCL | Entospletinib + Idelalisib iNHL: Others | Total |
|---|---|---|---|---|---|---|---|
| Participants analysed | 35 | 14 | 6 | 3 | 8 | 66 | |
| Age, Continuous | years | 68 (SD 12.9) | 64 (SD 13.4) | 69 (SD 17.4) | 62 (SD 10.8) | 69 (SD 8.9) | 67 (SD 12.7) |
| Sex: Female, Male: Female | Participants | 15 | 6 | 4 | 1 | 5 | 31 |
| Sex: Female, Male: Male | Participants | 20 | 8 | 2 | 2 | 3 | 35 |
| Race/Ethnicity, Customized: Ethnicity – Hispanic or Latino | Participants | 0 | 0 | 0 | 0 | 0 | 0 |
| Race/Ethnicity, Customized: Ethnicity – Not Hispanic or Latino | Participants | 35 | 12 | 6 | 3 | 8 | 64 |
| Race/Ethnicity, Customized: Ethnicity – Not Permitted | Participants | 0 | 2 | 0 | 0 | 0 | 2 |
| Race/Ethnicity, Customized: Race – White/Caucasian | Participants | 27 | 11 | 6 | 3 | 8 | 55 |
| Race/Ethnicity, Customized: Race – Black or African American | Participants | 5 | 1 | 0 | 0 | 0 | 6 |
| Race/Ethnicity, Customized: Race – Native Hawaiian or Other Pacific Islander | Participants | 1 | 0 | 0 | 0 | 0 | 1 |
| Race/Ethnicity, Customized: Race – Asian | Participants | 2 | 0 | 0 | 0 | 0 | 2 |
| Race/Ethnicity, Customized: Race – Other | Participants | 0 | 1 | 0 | 0 | 0 | 1 |
| Race/Ethnicity, Customized: Race – Not Reported | Participants | 0 | 1 | 0 | 0 | 0 | 1 |
| Karnofsky Performance Status: 40 | Participants | 1 | 0 | 0 | 0 | 0 | 1 |
| Karnofsky Performance Status: 50 | Participants | 1 | 0 | 0 | 0 | 0 | 1 |
| Karnofsky Performance Status: 60 | Participants | 2 | 0 | 0 | 1 | 0 | 3 |
| Karnofsky Performance Status: 70 | Participants | 2 | 1 | 1 | 0 | 0 | 4 |
| Karnofsky Performance Status: 80 | Participants | 9 | 7 | 2 | 1 | 5 | 24 |
| Karnofsky Performance Status: 90 | Participants | 14 | 4 | 3 | 1 | 3 | 25 |
| Karnofsky Performance Status: 100 | Participants | 6 | 2 | 0 | 0 | 0 | 8 |
6. Primary Endpoint
The registry lists the primary outcome as Objective Response Rate (ORR), measured over Start of treatment to end of treatment (Up to 18 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 primary endpoint was objective response rate (ORR), the percentage of participants whose disease response met the criteria for complete response or partial response. For participants with lymphoplasmacytoid lymphoma or Waldenström macroglobulinemia, very good partial response or minor response also qualified. The endpoint was assessed by an Independent Review Committee according to the International Working Group Revised Response Criteria and investigator response.
In general, response rate is used to describe how often a defined response category is observed during a study. Complete response and partial response represent distinct levels of response under the stated criteria; the registry defines complete response by resolution of disease-related radiological abnormalities and disappearance of disease-related signs and symptoms. Partial response uses a specified reduction in the combined measurements of index lesions, with no new lesions. For the specified lymphoplasmacytoid lymphoma or Waldenström macroglobulinemia subgroup, response categories were based on changes in serum monoclonal immunoglobulin M concentration.
The endpoint timeframe ran from treatment start to treatment end, up to 18 months. The registry states that the trial was terminated due to safety measures and complete data were not collected for any participant. As a result, no completed ORR estimate is reported in the registry record. The endpoint definition explains what the study intended to measure, but does not itself establish the response experienced by participants.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The central interpretive limitation is that the registry record does not report a completed primary efficacy result. It defines objective response rate and its response categories, but also states that the study was terminated due to safety measures and complete data were not collected for any participant. An endpoint definition is not an outcome estimate. Without a reported numerator, denominator, or analysis, the registry record does not establish the frequency of response.
The record lists enrollment of 66 and describes disease-specific groups in the safety information. Those details do not supply a complete efficacy analysis, and they do not show how many participants had evaluable response assessments. The number enrolled should not be treated as the denominator for an endpoint when complete data were not collected. The registry does not report how many participants had a post-baseline assessment, how missing assessments were handled, or whether any participants were included in an efficacy analysis.
There is also no randomized control comparison. The study is open-label, allocation is not stated, and the registry explicitly cautions that the groups are not a like-for-like control comparison. Consequently, the record cannot support a comparative estimate of treatment effect against a control group. The listed dose combinations and disease cohorts do not remedy this limitation: comparisons across dose or disease groups would not be randomized comparisons on the information recorded.
The posted safety figures describe counts of participants affected by serious events and other events in disease-specific groups, along with reported deaths and a list of serious-event terms. These figures provide safety information as recorded, but they do not by themselves establish that the study drugs caused an event or death. The registry information presented does not specify event timing, individual clinical circumstances, or a causal assessment. Such interpretation should not be inferred from counts alone.
In general, an estimate is more informative when its denominator, analysis population, and uncertainty are clear. A confidence interval, when reported, describes a range of values compatible with the data and analysis under its assumptions; it does not turn incomplete outcome collection into complete follow-up. No confidence interval or completed ORR estimate is reported in the registry record.
Planning illustrations based on an observed effect are not observed power and are not trial results. The registry gives assumptions for such illustrations, including a two-sided significance level of 0.05, equal allocation between two arms, a normal approximation, and effects expressed as fractions of an observed effect. The actual illustration values are not reported in the registry record. Because no completed primary result is available, those planning concepts should not be read as evidence of efficacy or as a substitute for the missing endpoint analysis.
9. Statistical Methods Explained
What the registry says about the design. The study is described as phase 2, open-label, and sequential. Open-label means that the study was not masked. In general, masking can reduce the influence of knowledge about treatment on some assessments or decisions; in an open-label study, such knowledge is not concealed. The registry does not provide enough detail to describe how the sequential model operated, so no specific sequence of dose assignment or treatment decisions should be assumed.
Why a control comparison matters. In general, a randomized control comparison assigns participants to groups by chance, which can help make groups comparable in expectation and support a causal comparison. This study is not a randomized comparison, and allocation is not stated. The registry specifically cautions that the groups are not a like-for-like control comparison. Thus, differences across disease cohorts or listed dose combinations cannot automatically be attributed to dose or treatment. The record does not state a comparative statistical plan.
How response rate is defined. ORR is a proportion: in general, it is the number of participants meeting the response definition divided by the relevant analysis population. The registry specifies the response categories and assessment approach, but complete data were not collected for any participant. It does not report an analysis population or completed response count. Therefore, the definition can be explained, but the response proportion cannot be reconstructed from this record.
What uncertainty measures would contribute. In general, a confidence interval conveys the precision of an estimate by giving a range of values compatible with the observed data under the method’s assumptions. A narrower interval usually indicates greater precision, while a wider interval indicates more uncertainty. An interval does not remove bias from missing observations or turn an uncontrolled comparison into a randomized one. No ORR confidence interval is reported in the registry record, and the record does not contain a completed ORR estimate around which to interpret one.
What significance testing can and cannot say. In general, a p-value measures how incompatible the observed data are with a specified null model, assuming that model and the analysis assumptions hold. It is not the probability that a treatment works, and it does not measure clinical importance. The registry record contains no reported analysis records for the primary endpoint and no p-value for ORR. The statistical analysis plan, including any planned tests or adjustment procedures, is not reported in the registry record.
Why missingness matters. General statistical practice distinguishes between participants enrolled, participants with an outcome assessment, and participants included in a particular analysis. Those counts can differ. If outcome data are incomplete, an estimate based only on observed assessments may be affected if the missingness is related to participant status or outcome. Alternative approaches to missing data rely on assumptions; they do not recover information that was never collected without qualification. Here, the registry states that complete data were not collected for any participant, but does not report the extent or pattern of missingness, the reasons by participant, or a missing-data method.
Safety counts are descriptive. General safety reporting often describes how many participants experienced an event, with separate summaries for serious events and other events. These counts are useful for describing what was recorded, but interpretation depends on definitions, observation time, event coding, and whether events were judged related to treatment. The record gives disease-group counts at risk and affected, deaths, and frequently reported serious-event terms. It does not provide a causal interpretation or detailed event-level analysis in the information.
Over-dispersion in general. For count outcomes, a simple statistical model may assume that variation follows a specified distribution. Over-dispersion means the observed variability is greater than that model allows. If ignored, standard errors can be too small and intervals or tests may appear more precise than warranted. This is a general concept; the registry record does not report a count-outcome model or indicate whether over-dispersion was assessed.
Planning illustrations. The stated planning assumptions use a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. They describe illustration calculations based on fractions of an observed effect; time-to-event illustrations are described as total event counts, while other illustrations are participants per arm for 80% or 90% power. These are planning quantities, not observed power. The numerical planning illustrations and the observed effect used for them are not reported in the registry record. They should not be interpreted as an analysis of this trial’s incomplete outcomes.
10. Multiplicity, Missing Data and Analysis Populations
Multiplicity arises when a study tests or estimates several outcomes, subgroups, doses, or time points. In general, as the number of statistical tests grows, the chance of at least one apparently unusual result can increase if each test is interpreted separately. Researchers may prespecify a primary endpoint, use an adjustment method, or treat secondary analyses as exploratory. Which approach is appropriate depends on the design and analysis plan.
The registry identifies ORR as the primary endpoint and lists secondary outcomes: treatment-emergent adverse events, treatment-emergent laboratory abnormalities, maximum tolerated dose, progression-free survival, duration of response, and time to response. It does not report a multiplicity strategy or a statistical analysis plan. The record also does not report completed analyses for these outcomes. The reader therefore cannot determine whether statistical testing was planned, how endpoints were prioritized analytically, or whether any adjustment for multiple comparisons was intended.
Missing data are a separate concern. The record states that complete data were not collected for any participant, but does not report how many participants had each outcome assessed, the timing or reasons for incomplete collection, or the method used to address missing observations. In general, missingness can reduce precision and may bias an estimate if the likelihood of missing data is related to the outcome. A complete-case analysis, imputation, or another approach would each require information and assumptions that are not reported.
The analysis populations are also not reported in the registry record. It is not stated which participants were intended for the efficacy analysis, whether safety summaries included all exposed participants, or how participants who stopped treatment were to be handled for each endpoint. Without those definitions and completed outcome collection, neither the effective denominator nor the consequences of missingness can be assessed. The registry’s enrollment count should not be substituted for an endpoint-specific analysis population.
11. Safety Results
The registry reports serious adverse events as affected participants divided by participants at risk.
| Arm | Participants with serious adverse events | Participants at risk | Percentage |
|---|---|---|---|
| Entospletinib + Idelalisib CLL | 24 | 35 | 68.6% |
| Entospletinib + Idelalisib iNHL: FL | 2 | 14 | 14.3% |
| Entospletinib + Idelalisib DLBCL | 4 | 6 | 66.7% |
| Entospletinib + Idelalisib MCL | 2 | 3 | 66.7% |
| Entospletinib + Idelalisib iNHL: Others | 5 | 8 | 62.5% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Entospletinib + Idelalisib CLL | 3 of 35 |
| Entospletinib + Idelalisib iNHL: FL | 1 of 14 |
| Entospletinib + Idelalisib DLBCL | 2 of 6 |
| Entospletinib + Idelalisib MCL | 2 of 3 |
| Entospletinib + Idelalisib iNHL: Others | 2 of 8 |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 5% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Entospletinib + Idelalisib CLL | 34 of 35 |
| Entospletinib + Idelalisib iNHL: FL | 14 of 14 |
| Entospletinib + Idelalisib DLBCL | 6 of 6 |
| Entospletinib + Idelalisib MCL | 3 of 3 |
| Entospletinib + Idelalisib iNHL: Others | 8 of 8 |
Most frequent serious adverse event terms
| Event term | Organ system | Entospletinib + Idelalisib CLL | Entospletinib + Idelalisib iNHL: FL | Entospletinib + Idelalisib DLBCL | Entospletinib + Idelalisib MCL | Entospletinib + Idelalisib iNHL: Others |
|---|---|---|---|---|---|---|
| Pneumonitis | Respiratory, thoracic and mediastinal disorders | 8 of 35 | 0 of 14 | 2 of 6 | 0 of 3 | 1 of 8 |
| Pneumonia | Infections and infestations | 5 of 35 | 0 of 14 | 0 of 6 | 0 of 3 | 0 of 8 |
| Febrile neutropenia | Blood and lymphatic system disorders | 2 of 35 | 0 of 14 | 0 of 6 | 0 of 3 | 2 of 8 |
| Lung infection | Infections and infestations | 1 of 35 | 1 of 14 | 0 of 6 | 1 of 3 | 1 of 8 |
| Sepsis | Infections and infestations | 1 of 35 | 0 of 14 | 0 of 6 | 0 of 3 | 2 of 8 |
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | 1 of 35 | 0 of 14 | 0 of 6 | 1 of 3 | 0 of 8 |
| Hypoxia | Respiratory, thoracic and mediastinal disorders | 1 of 35 | 0 of 14 | 1 of 6 | 0 of 3 | 0 of 8 |
| Abdominal pain | Gastrointestinal disorders | 0 of 35 | 1 of 14 | 0 of 6 | 0 of 3 | 0 of 8 |
| Abdominal pain upper | Gastrointestinal disorders | 1 of 35 | 0 of 14 | 0 of 6 | 0 of 3 | 0 of 8 |
| Diarrhoea | Gastrointestinal disorders | 1 of 35 | 0 of 14 | 0 of 6 | 0 of 3 | 0 of 8 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Entospletinib + Idelalisib CLL | Entospletinib + Idelalisib iNHL: FL | Entospletinib + Idelalisib DLBCL | Entospletinib + Idelalisib MCL | Entospletinib + Idelalisib iNHL: Others |
|---|---|---|---|---|---|---|
| Fatigue | General disorders | 15 of 35 | 6 of 14 | 4 of 6 | 0 of 3 | 3 of 8 |
| Nausea | Gastrointestinal disorders | 14 of 35 | 7 of 14 | 4 of 6 | 1 of 3 | 1 of 8 |
| Pyrexia | General disorders | 10 of 35 | 5 of 14 | 5 of 6 | 1 of 3 | 1 of 8 |
| Diarrhoea | Gastrointestinal disorders | 14 of 35 | 2 of 14 | 2 of 6 | 0 of 3 | 1 of 8 |
| Headache | Nervous system disorders | 9 of 35 | 4 of 14 | 1 of 6 | 2 of 3 | 1 of 8 |
| Cough | Respiratory, thoracic and mediastinal disorders | 10 of 35 | 2 of 14 | 1 of 6 | 1 of 3 | 2 of 8 |
| Constipation | Gastrointestinal disorders | 11 of 35 | 2 of 14 | 2 of 6 | 0 of 3 | 0 of 8 |
| Alanine aminotransferase increased | Investigations | 6 of 35 | 4 of 14 | 1 of 6 | 1 of 3 | 2 of 8 |
| Aspartate aminotransferase increased | Investigations | 7 of 35 | 4 of 14 | 1 of 6 | 0 of 3 | 2 of 8 |
| Gastrooesophageal reflux disease | Gastrointestinal disorders | 8 of 35 | 0 of 14 | 2 of 6 | 1 of 3 | 2 of 8 |
Serious events with the highest arm-level rate: lung infection (33.3%), dyspnoea (33.3%), pneumonitis (33.3%), febrile neutropenia (25.0%), sepsis (25.0%).
The registry reports serious-event and other-event counts for disease-specific groups receiving entospletinib plus idelalisib. For each group, it gives the number at risk and the number affected, and it separately lists deaths. These are descriptive counts, not a comparison with an untreated or randomized control group. The groups are not a like-for-like control comparison, and the registry does not state that allocation was randomized.
The reported serious-event terms and frequencies include lung infection, dyspnoea, and pneumonitis at 33.3% each; febrile neutropenia and sepsis at 25.0% each; and hydronephrosis at 16.7%. These are the frequencies recorded for the listed terms. The registry record does not provide enough detail to infer the timing, duration, severity distribution, or treatment attribution for each term from the percentages alone. The terms should not be interpreted as proof that the study drugs caused the events.
Deaths are reported by group, but the information does not establish their causes or relationship to treatment. The study was terminated due to safety measures, a relevant context for reading the safety record; it does not, by itself, explain the cause of each event or death. The registry does not report a complete safety analysis or detailed event-level narratives.
12. What the Result Does, and Does Not, Mean
The registry record establishes that a phase 2, open-label study of entospletinib plus idelalisib enrolled 66 adults with relapsed or refractory hematologic malignancies and was terminated due to safety measures. It also records disease-group safety counts and a list of serious-event terms and frequencies. These are the main descriptive details available for interpretation.
The record does not establish the study’s primary efficacy result. ORR was defined in advance as a response measure with specified disease criteria, but complete data were not collected for any participant. No completed ORR estimate or analysis is reported. Consequently, the record does not show how often participants responded, how precise an estimate might have been, or how response compared with an alternative treatment.
The information also does not show that one dose combination was superior to another. The study was not a randomized comparison, allocation is not stated, and the registry warns that groups are not like-for-like controls. Any apparent differences among the listed groups would need to be interpreted in light of disease mix, incomplete data, and the absence of a stated randomized allocation process.
Safety counts describe events recorded among participants in the listed groups. They do not by themselves establish causation, and the registry does not provide detailed case information or a causal assessment for each event. The termination for safety measures is important context, but the record does not explain the specific decision process or identify a definitive cause for each safety event.
In general, an incomplete study can still leave useful descriptive information, but it cannot answer every planned question. The posted record supports a description of the design, intended endpoint, termination, and reported safety counts. It does not support a completed estimate of efficacy, a comparative treatment effect, or a conclusion about the certainty of an effect.
13. Why This Trial Matters Statistically
This trial illustrates the distinction between a clearly defined endpoint and an estimable endpoint. ORR has specified response categories, assessment criteria, and a timeframe. Yet a precise definition alone does not produce an estimate: the registry states that complete data were not collected for any participant and reports no completed primary endpoint analysis. In clinical statistics, outcome collection and analysis-population definitions are essential parts of the evidence, not administrative details.
The record also demonstrates why trial structure matters when interpreting differences. The study was open-label, allocation is not stated, and it was not a randomized comparison. The registry explicitly cautions that the groups do not represent a like-for-like control comparison. A numerical contrast across cohorts or dose combinations, even if available, would not have the same interpretation as a prespecified randomized treatment comparison.
Safety information requires similarly careful reading. Counts of participants affected, deaths, and serious-event terms can describe what was recorded, but attribution and context require more than a count. The termination due to safety measures is part of the trial’s history, while the registry does not report the detailed event-level evidence needed to connect each event or death to treatment.
Finally, planning calculations and observed findings answer different questions. Planning illustrations describe hypothetical sample-size requirements under stated assumptions; they are not observed power or evidence that an endpoint effect was demonstrated. When a trial ends before complete outcome collection, such illustrations cannot fill the gap left by missing results. This record is therefore useful for teaching how design, missing outcomes, and the limits of descriptive safety data shape what can be concluded from a clinical trial registry.
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 study’s termination and incomplete outcome collection are the most direct limitations for interpreting its intended efficacy endpoint. The registry states that termination was due to safety measures and that complete data were not collected for any participant. It does not report a completed ORR analysis, an analysis population, or the number of participants with evaluable response assessments. The primary efficacy question therefore remains unanswered in the registry record.
The open-label design means treatment was not masked. In general, awareness of treatment can influence assessment or reporting, although the registry does not document whether such influence occurred in this study. The primary response endpoint included Independent Review Committee assessment and investigator response, but the record does not report how those assessments aligned or provide completed results from either source.
There was no randomized control comparison, and allocation is not stated. The disease groups included different malignancies and the treatment regimen included several dose combinations, so they should not be treated as interchangeable comparator groups. The registry does not report a controlled estimate of treatment effect or enough information to infer a causal contrast.
Important analytical details are not reported in the registry record, including the sample-size justification, statistical analysis plan, multiplicity strategy, missing-data approach, and endpoint-specific analysis populations. The registry also does not give a detailed explanation of the termination decision or event-level causal assessments for the safety information. These omissions limit both efficacy interpretation and the degree of detail available for understanding the safety counts.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Entospletinib in Combination With Idelalisib in Adults With Relapsed or Refractory Hematologic Malignancies — NCT01796470.
- Registry record last updated 2020-06-02; status last verified 2020-05.
- Results first posted 2020-06-02.
- 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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18. Record Summary
This phase 2, open-label, sequential study evaluated entospletinib with idelalisib in adults with relapsed or refractory hematologic malignancies. Enrollment was 66. The combination was studied at four dose combinations, with possible entospletinib monotherapy after combination treatment ended and a washout period. The primary endpoint was ORR, assessed using defined response criteria and investigator response.
The study was terminated due to safety measures. The registry states that complete data were not collected for any participant, and it does not report a completed primary endpoint analysis. Safety information includes disease-group counts of participants affected by serious and other events, deaths, and selected serious-event terms. The study was not a randomized comparison, allocation is not stated, and the registry cautions against treating groups as like-for-like controls. The record supports descriptive interpretation, not a completed efficacy estimate or comparative treatment conclusion.