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Study was terminated due to safety measures.
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This study will evaluate the efficacy of the combination entospletinib and idelalisib in participants with relapsed or refractory hematologic malignancies. Participants will be enrolled who have one of the following hematological tumor types: chronic lymphocytic leukemia (CLL), mantle cell lymphoma (MCL), diffuse large B-cell lymphoma (DLBCL), or indolent non-Hodgkin lymphomas (iNHL; including follicular lymphoma (FL) and lymphoplasmacytoid lymphoma/Waldenström macroglobulinemia [LPL/WM], small lymphocytic lymphoma [SLL], or marginal zone lymphoma [MZL]).
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Entospletinib + idelalisib | Experimental | Entospletinib plus idelalisib at one of 4 dose combinations (400 mg/100 mg; 600 mg/100 mg; 800 mg/100 mg; 800 mg/150 mg). After discontinuation of entospletinib+idelalisib combination therapy, and following a washout period, participants may continue to receive entospletinib 400 mg monotherapy. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Entospletinib | Drug | Entospletinib tablets administered orally twice daily |
|
| Measure | Description | Time Frame |
|---|---|---|
| Objective Response Rate (ORR) | ORR assessed by the Independent Review Committee (IRC), was based on the International Working Group Revised Response Criteria (Cheson, 2012) and investigator's response, defined as the percentage of participants achieving a complete response (CR) or partial response (PR) (or very good partial response [VGPR] or minor response [MR] for participants with LPL/WM). CR was defined as the complete resolution of all disease-related radiological abnormalities and the disappearance of all signs and symptoms related to the disease. PR was defined as a ≥ 50% reduction in the sum of the products of the longest perpendicular diameters of all index lesions, with no new lesions. VGPR and MR were defined as ≥ 90% and ≥ 25% but < 50% decrease from baseline in serum monoclonal immunoglobulin M (IgM) concentration by serum protein electrophoresis (SPEP) respectively. | Start of treatment to end of treatment (Up to 18 months) |
| Measure | Description | Time Frame |
|---|---|---|
| Percentage of Participants Experiencing Treatment-Emergent Adverse Events | A treatment-emergent Adverse Event (AE) was defined as any AE with an onset date of on or after the study drug start date and no later than 30 days after permanent discontinuation of study drugs or an AE leading to premature discontinuation of study drug. An AE is any untoward medical occurrence in a clinical investigation where participants administered a medicinal product, and which does not necessarily have a causal relationship with this treatment. |
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Key Inclusion Criteria:
Key Exclusion Criteria:
Note: Other protocol defined Inclusion/Exclusion criteria may apply.
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| Name | Affiliation | Role |
|---|---|---|
| Gilead Study Director | Gilead Sciences | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| UC San Diego Moores Cancer Center | La Jolla | California | 92093 | United States | ||
| Pacific Shores Medical Group |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 26968534 | Derived | Barr PM, Saylors GB, Spurgeon SE, Cheson BD, Greenwald DR, O'Brien SM, Liem AK, Mclntyre RE, Joshi A, Abella-Dominicis E, Hawkins MJ, Reddy A, Di Paolo J, Lee H, He J, Hu J, Dreiling LK, Friedberg JW. Phase 2 study of idelalisib and entospletinib: pneumonitis limits combination therapy in relapsed refractory CLL and NHL. Blood. 2016 May 19;127(20):2411-5. doi: 10.1182/blood-2015-12-683516. Epub 2016 Mar 11. |
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85 participants were screened.
Participants were enrolled at study sites in the United States. The first participant was screened on 20 June 2013. The last study visit occurred on 22 December 2016.
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| ID | Title | Description |
|---|---|---|
| FG000 | Entospletinib + Idelalisib CLL | Participants with a documented diagnosis of chronic lymphocytic leukemia (CLL) were included in this arm. Participants were administered 4 dose combinations of entospletinib plus idelalisib tablets orally twice daily under fasted conditions (400 mg/100 mg for 2 weeks, if no dose limiting toxicity (DLT) occurred, increased dose to 600 mg/100 mg for 2 weeks, if no DLT occurred, increased dose to 800 mg/100 mg for 4 weeks, if no DLT occurred, increased dose to 800 mg/150 mg) for up to 6 months. After discontinuation of combination therapy and a washout period of 14-28 days, participants could continue to receive entospletinib 400 mg monotherapy for up to 18 months. |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| Idelalisib | Drug | Idelalisib tablets administered orally twice daily |
|
|
| First dose date up to the last dose date plus 30 days (maximum duration: 19 months) |
| Percentage of Participants Experiencing Treatment-Emergent Laboratory Abnormalities | A treatment-emergent laboratory (Hematology, Serum Chemistry and Urinalysis) abnormality was defined as an abnormality that, compared to baseline, worsens by ≥ 1 grade in the period from the first dose of study drug. Safety as assessed by grading of laboratory values and AEs according to the National Cancer Institutes' Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.03. Grade 0 = none, Grade 1 = mild, Grade 2 = moderate, Grade 3 = severe, Grade 4 = life threatening or disabling. If baseline data are missing, then any graded abnormality (i.e., an abnormality that is Grade ≥ 1 in severity) will be considered treatment-emergent. The percentage of participants in each worst postbaseline grade is reported. | First dose date up to the last dose date plus 30 days (maximum: 18 months) |
| Maximum Tolerated Dose Level | Maximum tolerated dose (MTD) is defined as the highest dose level that was consistently well tolerated without dose limiting toxicity (DLT) for the majority of participants time on treatment (ie,> 50%) as determined by the investigator for each participant. DLTs are defined as Grade 4 hematological toxicities persisting for ≥ 14 days or Grade ≥ 3 toxicities of other types. | First dose (entospelinib + idelalisib) date up to 6 months |
| Progression-free Survival (PFS) | PFS was defined as the interval from the first dose of study drug to the earlier of the first documentation of definitive disease progression or death from any cause. | Start of treatment to end of treatment (Up to 18 months) |
| Duration of Response (DOR) | DOR was defined as the interval from the first-time response (CR or PR [or VGPR or MR for participants with LPL/WM]) is achieved to the earlier of the first documentation of definitive disease progression or death from any cause.CR was defined as the complete resolution of all disease-related radiological abnormalities and the disappearance of all signs and symptoms related to the disease. PR was defined as a ≥ 50% reduction in the sum of the products of the longest perpendicular diameters of all index lesions, with no new lesions. VGPR and MR were defined as ≥ 90% and ≥ 25% but < 50% decrease from baseline in serum monoclonal IgM concentration by SPEP respectively. | Start of treatment to end of treatment (Up to 18 months) |
| Time to Response (TTR) | TTR was defined as the interval from the first dose of entospletinib/idelalisib to the time response (CR or PR [or VGPR or MR for participants with LPL/WM]) is first achieved. CR was defined as the complete resolution of all disease-related radiological abnormalities and the disappearance of all signs and symptoms related to the disease. PR was defined as a ≥ 50% reduction in the sum of the products of the longest perpendicular diameters of all index lesions, with no new lesions. VGPR and MR were defined as ≥ 90% and ≥ 25% but < 50% decrease from baseline in serum monoclonal IgM concentration by SPEP respectively. | Start of treatment to end of treatment (Up to 18 months) |
| Long Beach |
| California |
| 90813 |
| United States |
| Ventura County Hematology Oncology Specialists | Oxnard | California | 93030 | United States |
| Cancer Center of Santa Barbara | Santa Barbara | California | 93105 | United States |
| Georgetown University Medical Center | Washington D.C. | District of Columbia | 20007 | United States |
| Collaborative Research Group LLC | Boynton Beach | Florida | 33435 | United States |
| Weill Cornell Medical College | New York | New York | 10021 | United States |
| University of Rochester, James P. Wilmot Cancer Center | Rochester | New York | 14642 | United States |
| Signal Point Clinical Research Center, LLC | Middletown | Ohio | 45042 | United States |
| Oregon Health and Science University | Portland | Oregon | 97239 | United States |
| Charleston Hematology Oncology | Charleston | South Carolina | 29414 | United States |
| MD Anderson Cancer Center | Houston | Texas | 77030 | United States |
| Northwest Medical Specialties | Tacoma | Washington | 98405 | United States |
| FG001 | Entospletinib + Idelalisib iNHL: FL | Participants with a documented diagnosis of indolent non-Hodgkin lymphoma (iNHL) with follicular lymphoma (FL) were included in this arm. Participants were administered 4 dose combinations of entospletinib plus idelalisib tablets orally twice daily under fasted conditions (400 mg/100 mg for 2 weeks, if no dose limiting toxicity (DLT) occurred, increased dose to 600 mg/100 mg for 2 weeks, if no DLT occurred, increased dose to 800 mg/100 mg for 4 weeks, if no DLT occurred increased dose to 800 mg/150 mg) for up to 6 months. After discontinuation of combination therapy and a washout period of 14-28 days, participants could continue to receive entospletinib 400 mg monotherapy for up to 18 months. |
| FG002 | Entospletinib + Idelalisib DLBCL | Participants with a documented diagnosis of diffuse large B-cell lymphoma (DLBCL) were included in this arm. Participants were administered 4 dose combinations of entospletinib plus idelalisib tablets orally twice daily under fasted conditions (400 mg/100 mg for 2 weeks, if no dose limiting toxicity (DLT) occurred ,increased dose to 600 mg/100 mg for 2 weeks, if no DLT occurred, increased dose to 800 mg/100 mg for 4 weeks, if no DLT occurred, increased dose to 800 mg/150 mg) for up to 6 months. After discontinuation of combination therapy and a washout period of 14-28 days, participants could continue to receive entospletinib 400 mg monotherapy for up to 18 months. |
| FG003 | Entospletinib + Idelalisib MCL | Participants with a documented diagnosis of mantle cell lymphoma (MCL) were included in this arm. Participants were administered 4 dose combinations of entospletinib plus idelalisib tablets orally twice daily under fasted conditions (400 mg/100 mg for 2 weeks, if no dose limiting toxicity (DLT) occurred, increased dose to 600 mg/100 mg for 2 weeks, if no DLT occurred, increased dose to 800 mg/100 mg for 4 weeks, if no DLT occurred, increased dose to 800 mg/150 mg) for up to 6 months. After discontinuation of combination therapy and a washout period of 14-28 days, participants could continue to receive entospletinib 400 mg monotherapy for up to 18 months. |
| FG004 | Entospletinib + Idelalisib iNHL: Others | Participants with a documented diagnosis of iNHL with other subtypes lymphoplasmacytic lymphoma (LPL)/Waldenstrom macroglobulinemia (WM), small lymphocytic lymphoma (SLL), and marginal zone lymphoma (MZL) were included in this arm. Participants were administered 4 dose combinations of entospletinib plus idelalisib tablets orally twice daily under fasted conditions (400 mg/100 mg for 2 weeks, if no dose limiting toxicity (DLT) increased to 600 mg/100 mg for 2 weeks, if no DLT increased to 800 mg/100 mg for 4 weeks, if no DLT increased to 800 mg/150 mg) for up to 6 months. After discontinuation of combination therapy and a washout period of 14-28 days, participants could continue to receive entospletinib 400 mg monotherapy for up to 18 months. |
| Entospletinib Monotherapy | Participants who received monotherapy when combination therapy was discontinued. |
|
| COMPLETED |
|
| NOT COMPLETED |
|
|
The Full Analysis Set comprised all participants who received ≥ 1 dose of study drug (entospletinib or idelalisib).
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| ID | Title | Description |
|---|---|---|
| BG000 | Entospletinib + Idelalisib CLL | Participants with a documented diagnosis of chronic lymphocytic leukemia (CLL) were included in this arm. Participants were administered 4 dose combinations of entospletinib plus idelalisib tablets orally twice daily under fasted conditions (400 mg/100 mg for 2 weeks, if no dose limiting toxicity (DLT) occurred, increased dose to 600 mg/100 mg for 2 weeks, if no DLT occurred, increased dose to 800 mg/100 mg for 4 weeks, if no DLT occurred, increased dose to 800 mg/150 mg) for up to 6 months. After discontinuation of combination therapy and a washout period of 14-28 days, participants could continue to receive entospletinib 400 mg monotherapy for up to 18 months. |
| BG001 | Entospletinib + Idelalisib iNHL: FL | Participants with a documented diagnosis of indolent non-Hodgkin lymphoma (iNHL) with follicular lymphoma (FL) were included in this arm. Participants were administered 4 dose combinations of entospletinib plus idelalisib tablets orally twice daily under fasted conditions (400 mg/100 mg for 2 weeks, if no dose limiting toxicity (DLT) occurred, increased dose to 600 mg/100 mg for 2 weeks, if no DLT occurred, increased dose to 800 mg/100 mg for 4 weeks, if no DLT occurred increased dose to 800 mg/150 mg) for up to 6 months. After discontinuation of combination therapy and a washout period of 14-28 days, participants could continue to receive entospletinib 400 mg monotherapy for up to 18 months |
| BG002 | Entospletinib + Idelalisib DLBCL | Participants with a documented diagnosis of diffuse large B-cell lymphoma (DLBCL) were included in this arm. Participants were administered 4 dose combinations of entospletinib plus idelalisib tablets orally twice daily under fasted conditions (400 mg/100 mg for 2 weeks, if no dose limiting toxicity (DLT) occurred ,increased dose to 600 mg/100 mg for 2 weeks, if no DLT occurred, increased dose to 800 mg/100 mg for 4 weeks, if no DLT occurred, increased dose to 800 mg/150 mg) for up to 6 months. After discontinuation of combination therapy and a washout period of 14-28 days, participants could continue to receive entospletinib 400 mg monotherapy for up to 18 months. |
| BG003 | Entospletinib + Idelalisib MCL | Participants with a documented diagnosis of mantle cell lymphoma (MCL) were included in this arm. Participants were administered 4 dose combinations of entospletinib plus idelalisib tablets orally twice daily under fasted conditions (400 mg/100 mg for 2 weeks, if no dose limiting toxicity (DLT) occurred, increased dose to 600 mg/100 mg for 2 weeks, if no DLT occurred, increased dose to 800 mg/100 mg for 4 weeks, if no DLT occurred, increased dose to 800 mg/150 mg) for up to 6 months. After discontinuation of combination therapy and a washout period of 14-28 days, participants could continue to receive entospletinib 400 mg monotherapy for up to 18 months. |
| BG004 | Entospletinib + Idelalisib iNHL: Others | Participants with a documented diagnosis of iNHL with other subtypes lymphoplasmacytic lymphoma (LPL)/Waldenstrom macroglobulinemia (WM), small lymphocytic lymphoma (SLL) and marginal zone lymphoma (MZL) were included in this arm. Participants were administered 4 dose combinations of entospletinib plus idelalisib tablets orally twice daily under fasted conditions (400 mg/100 mg for 2 weeks, if no dose limiting toxicity (DLT) increased to 600 mg/100 mg for 2 weeks, if no DLT increased to 800 mg/100 mg for 4 weeks, if no DLT increased to 800 mg/150 mg) for up to 6 months. After discontinuation of combination therapy and a washout period of 14-28 days, participants could continue to receive entospletinib 400 mg monotherapy for up to 18 months. |
| BG005 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean | Standard Deviation | years |
| |||||||||||||||
| Sex: Female, Male | Count of Participants | Participants | No |
| |||||||||||||||
| Race/Ethnicity, Customized | Not Permitted Category used, as local regulators did not allow collection of race or ethnicity information. | Count of Participants | Participants | No |
| ||||||||||||||
| Race/Ethnicity, Customized | Count of Participants | Participants | No |
| |||||||||||||||
| Karnofsky Performance Status | Karnofsky Performance Status will be assessed on a scale of 0-100 where 0 indicates death and 100 indicates normal activity. | Count of Participants | Participants | No |
|
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Objective Response Rate (ORR) | ORR assessed by the Independent Review Committee (IRC), was based on the International Working Group Revised Response Criteria (Cheson, 2012) and investigator's response, defined as the percentage of participants achieving a complete response (CR) or partial response (PR) (or very good partial response [VGPR] or minor response [MR] for participants with LPL/WM). CR was defined as the complete resolution of all disease-related radiological abnormalities and the disappearance of all signs and symptoms related to the disease. PR was defined as a ≥ 50% reduction in the sum of the products of the longest perpendicular diameters of all index lesions, with no new lesions. VGPR and MR were defined as ≥ 90% and ≥ 25% but < 50% decrease from baseline in serum monoclonal immunoglobulin M (IgM) concentration by serum protein electrophoresis (SPEP) respectively. | The study was terminated due to safety measures. Complete data was not collected for any participant. | Posted | Start of treatment to end of treatment (Up to 18 months) |
|
| |||||||||||||||||||||||||||||||
| Secondary | Percentage of Participants Experiencing Treatment-Emergent Adverse Events | A treatment-emergent Adverse Event (AE) was defined as any AE with an onset date of on or after the study drug start date and no later than 30 days after permanent discontinuation of study drugs or an AE leading to premature discontinuation of study drug. An AE is any untoward medical occurrence in a clinical investigation where participants administered a medicinal product, and which does not necessarily have a causal relationship with this treatment. | The Safety Analysis Set comprised all participants who received ≥ 1 dose of study drug (entospletinib or idelalisib). | Posted | Number | percentage of participants | First dose date up to the last dose date plus 30 days (maximum duration: 19 months) |
| ||||||||||||||||||||||||||||||
| Secondary | Percentage of Participants Experiencing Treatment-Emergent Laboratory Abnormalities | A treatment-emergent laboratory (Hematology, Serum Chemistry and Urinalysis) abnormality was defined as an abnormality that, compared to baseline, worsens by ≥ 1 grade in the period from the first dose of study drug. Safety as assessed by grading of laboratory values and AEs according to the National Cancer Institutes' Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.03. Grade 0 = none, Grade 1 = mild, Grade 2 = moderate, Grade 3 = severe, Grade 4 = life threatening or disabling. If baseline data are missing, then any graded abnormality (i.e., an abnormality that is Grade ≥ 1 in severity) will be considered treatment-emergent. The percentage of participants in each worst postbaseline grade is reported. | Participants in the Safety Analysis Set were analyzed. | Posted | Number | percentage of participants | First dose date up to the last dose date plus 30 days (maximum: 18 months) |
| ||||||||||||||||||||||||||||||
| Secondary | Maximum Tolerated Dose Level | Maximum tolerated dose (MTD) is defined as the highest dose level that was consistently well tolerated without dose limiting toxicity (DLT) for the majority of participants time on treatment (ie,> 50%) as determined by the investigator for each participant. DLTs are defined as Grade 4 hematological toxicities persisting for ≥ 14 days or Grade ≥ 3 toxicities of other types. | The study was terminated due to safety measures. Complete data was not collected for any participant. | Posted | First dose (entospelinib + idelalisib) date up to 6 months |
| ||||||||||||||||||||||||||||||||
| Secondary | Progression-free Survival (PFS) | PFS was defined as the interval from the first dose of study drug to the earlier of the first documentation of definitive disease progression or death from any cause. | The study was terminated due to safety measures. Complete data was not collected for any participant. | Posted | Start of treatment to end of treatment (Up to 18 months) |
| ||||||||||||||||||||||||||||||||
| Secondary | Duration of Response (DOR) | DOR was defined as the interval from the first-time response (CR or PR [or VGPR or MR for participants with LPL/WM]) is achieved to the earlier of the first documentation of definitive disease progression or death from any cause.CR was defined as the complete resolution of all disease-related radiological abnormalities and the disappearance of all signs and symptoms related to the disease. PR was defined as a ≥ 50% reduction in the sum of the products of the longest perpendicular diameters of all index lesions, with no new lesions. VGPR and MR were defined as ≥ 90% and ≥ 25% but < 50% decrease from baseline in serum monoclonal IgM concentration by SPEP respectively. | The study was terminated due to safety measures. Complete data was not collected for any participant. | Posted | Start of treatment to end of treatment (Up to 18 months) |
| ||||||||||||||||||||||||||||||||
| Secondary | Time to Response (TTR) | TTR was defined as the interval from the first dose of entospletinib/idelalisib to the time response (CR or PR [or VGPR or MR for participants with LPL/WM]) is first achieved. CR was defined as the complete resolution of all disease-related radiological abnormalities and the disappearance of all signs and symptoms related to the disease. PR was defined as a ≥ 50% reduction in the sum of the products of the longest perpendicular diameters of all index lesions, with no new lesions. VGPR and MR were defined as ≥ 90% and ≥ 25% but < 50% decrease from baseline in serum monoclonal IgM concentration by SPEP respectively. | The study was terminated due to safety measures. Complete data was not collected for any participant. | Posted | Start of treatment to end of treatment (Up to 18 months) |
|
First dose date up to the last dose date plus 30 days (maximum duration: 19 months); All-Cause Mortality: Baseline to Last Follow-Up Visit (Up to 3.6 years)
The Safety Analysis Set comprised all participants who received ≥ 1 dose of study drug (entospletinib or idelalisib).
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Entospletinib + Idelalisib CLL | Participants with a documented diagnosis of chronic lymphocytic leukemia (CLL) were included in this arm. Participants were administered 4 dose combinations of entospletinib plus idelalisib tablets orally twice daily under fasted conditions (400 mg/100 mg for 2 weeks, if no dose limiting toxicity (DLT) occurred, increased dose to 600 mg/100 mg for 2 weeks, if no DLT occurred, increased dose to 800 mg/100 mg for 4 weeks, if no DLT occurred, increased dose to 800 mg/150 mg) for up to 6 months. After discontinuation of combination therapy and a washout period of 14-28 days, participants could continue to receive entospletinib 400 mg monotherapy for up to 18 months. | 3 | 35 | 24 | 35 | 34 | 35 |
| EG001 | Entospletinib + Idelalisib iNHL: FL | Participants with a documented diagnosis of indolent non-Hodgkin lymphoma (iNHL) with follicular lymphoma (FL) were included in this arm. Participants were administered 4 dose combinations of entospletinib plus idelalisib tablets orally twice daily under fasted conditions (400 mg/100 mg for 2 weeks, if no dose limiting toxicity (DLT) occurred, increased dose to 600 mg/100 mg for 2 weeks, if no DLT occurred, increased dose to 800 mg/100 mg for 4 weeks, if no DLT occurred increased dose to 800 mg/150 mg) for up to 6 months. After discontinuation of combination therapy and a washout period of 14-28 days, participants could continue to receive entospletinib 400 mg monotherapy for up to 18 months. | 1 | 14 | 2 | 14 | 14 | 14 |
| EG002 | Entospletinib + Idelalisib DLBCL | Participants with a documented diagnosis of diffuse large B-cell lymphoma (DLBCL) were included in this arm. Participants were administered 4 dose combinations of entospletinib plus idelalisib tablets orally twice daily under fasted conditions (400 mg/100 mg for 2 weeks, if no dose limiting toxicity (DLT) occurred ,increased dose to 600 mg/100 mg for 2 weeks, if no DLT occurred, increased dose to 800 mg/100 mg for 4 weeks, if no DLT occurred, increased dose to 800 mg/150 mg) for up to 6 months. After discontinuation of combination therapy and a washout period of 14-28 days, participants could continue to receive entospletinib 400 mg monotherapy for up to 18 months. | 2 | 6 | 4 | 6 | 6 | 6 |
| EG003 | Entospletinib + Idelalisib MCL | Participants with a documented diagnosis of mantle cell lymphoma (MCL) were included in this arm. Participants were administered 4 dose combinations of entospletinib plus idelalisib tablets orally twice daily under fasted conditions (400 mg/100 mg for 2 weeks, if no dose limiting toxicity (DLT) occurred, increased dose to 600 mg/100 mg for 2 weeks, if no DLT occurred, increased dose to 800 mg/100 mg for 4 weeks, if no DLT occurred, increased dose to 800 mg/150 mg) for up to 6 months. After discontinuation of combination therapy and a washout period of 14-28 days, participants could continue to receive entospletinib 400 mg monotherapy for up to 18 months. | 2 | 3 | 2 | 3 | 3 | 3 |
| EG004 | Entospletinib + Idelalisib iNHL: Others | Participants with a documented diagnosis of iNHL with other subtypes lymphoplasmacytic lymphoma (LPL)/Waldenstrom macroglobulinemia (WM), small lymphocytic lymphoma (SLL), and marginal zone lymphoma (MZL) were included in this arm. Participants were administered 4 dose combinations of entospletinib plus idelalisib tablets orally twice daily under fasted conditions (400 mg/100 mg for 2 weeks, if no dose limiting toxicity (DLT) increased to 600 mg/100 mg for 2 weeks, if no DLT increased to 800 mg/100 mg for 4 weeks, if no DLT increased to 800 mg/150 mg) for up to 6 months. After discontinuation of combination therapy and a washout period of 14-28 days, participants could continue to receive entospletinib 400 mg monotherapy for up to 18 months. | 2 | 8 | 5 | 8 | 8 | 8 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Febrile neutropenia | Blood and lymphatic system disorders | MedDRA (17.1) | Systematic Assessment |
| |
| Abdominal pain | Gastrointestinal disorders | MedDRA (17.1) | Systematic Assessment |
| |
| Abdominal pain upper | Gastrointestinal disorders | MedDRA (17.1) | Systematic Assessment |
| |
| Diarrhoea | Gastrointestinal disorders | MedDRA (17.1) | Systematic Assessment |
| |
| Drug interaction | General disorders | MedDRA (17.1) | Systematic Assessment |
| |
| Pyrexia | General disorders | MedDRA (17.1) | Systematic Assessment |
| |
| Bacteraemia | Infections and infestations | MedDRA (17.1) | Systematic Assessment |
| |
| Bronchopulmonary aspergillosis | Infections and infestations | MedDRA (17.1) | Systematic Assessment |
| |
| Fungal infection | Infections and infestations | MedDRA (17.1) | Systematic Assessment |
| |
| Lung infection | Infections and infestations | MedDRA (17.1) | Systematic Assessment |
| |
| Pneumonia | Infections and infestations | MedDRA (17.1) | Systematic Assessment |
| |
| Sepsis | Infections and infestations | MedDRA (17.1) | Systematic Assessment |
| |
| Alanine aminotransferase increased | Investigations | MedDRA (17.1) | Systematic Assessment |
| |
| Aspartate aminotransferase increased | Investigations | MedDRA (17.1) | Systematic Assessment |
| |
| Blood bilirubin increased | Investigations | MedDRA (17.1) | Systematic Assessment |
| |
| International normalised ratio increased | Investigations | MedDRA (17.1) | Systematic Assessment |
| |
| Lymphocyte count increased | Investigations | MedDRA (17.1) | Systematic Assessment |
| |
| Altered state of consciousness | Nervous system disorders | MedDRA (17.1) | Systematic Assessment |
| |
| Cerebrovascular accident | Nervous system disorders | MedDRA (17.1) | Systematic Assessment |
| |
| Confusional state | Psychiatric disorders | MedDRA (17.1) | Systematic Assessment |
| |
| Hydronephrosis | Renal and urinary disorders | MedDRA (17.1) | Systematic Assessment |
| |
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA (17.1) | Systematic Assessment |
| |
| Hypoxia | Respiratory, thoracic and mediastinal disorders | MedDRA (17.1) | Systematic Assessment |
| |
| Pneumonitis | Respiratory, thoracic and mediastinal disorders | MedDRA (17.1) | Systematic Assessment |
| |
| Pulmonary embolism | Respiratory, thoracic and mediastinal disorders | MedDRA (17.1) | Systematic Assessment |
| |
| Respiratory failure | Respiratory, thoracic and mediastinal disorders | MedDRA (17.1) | Systematic Assessment |
| |
| Erythema multiforme | Skin and subcutaneous tissue disorders | MedDRA (17.1) | Systematic Assessment |
| |
| Deep vein thrombosis | Vascular disorders | MedDRA (17.1) | Systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anaemia | Blood and lymphatic system disorders | MedDRA (17.1) | Systematic Assessment |
| |
| Increased tendency to bruise | Blood and lymphatic system disorders | MedDRA (17.1) | Systematic Assessment |
| |
| Leukopenia | Blood and lymphatic system disorders | MedDRA (17.1) | Systematic Assessment |
| |
| Lymphadenopathy | Blood and lymphatic system disorders | MedDRA (17.1) | Systematic Assessment |
| |
| Lymphopenia | Blood and lymphatic system disorders | MedDRA (17.1) | Systematic Assessment |
| |
| Neutropenia | Blood and lymphatic system disorders | MedDRA (17.1) | Systematic Assessment |
| |
| Pancytopenia | Blood and lymphatic system disorders | MedDRA (17.1) | Systematic Assessment |
| |
| Thrombocytopenia | Blood and lymphatic system disorders | MedDRA (17.1) | Systematic Assessment |
| |
| Atrial fibrillation | Cardiac disorders | MedDRA (17.1) | Systematic Assessment |
| |
| Palpitations | Cardiac disorders | MedDRA (17.1) | Systematic Assessment |
| |
| Supraventricular tachycardia | Cardiac disorders | MedDRA (17.1) | Systematic Assessment |
| |
| Tachycardia | Cardiac disorders | MedDRA (17.1) | Systematic Assessment |
| |
| Ear pain | Ear and labyrinth disorders | MedDRA (17.1) | Systematic Assessment |
| |
| Abdominal pain | Gastrointestinal disorders | MedDRA (17.1) | Systematic Assessment |
| |
| Abdominal pain upper | Gastrointestinal disorders | MedDRA (17.1) | Systematic Assessment |
| |
| Abdominal tenderness | Gastrointestinal disorders | MedDRA (17.1) | Systematic Assessment |
| |
| Chapped lips | Gastrointestinal disorders | MedDRA (17.1) | Systematic Assessment |
| |
| Constipation | Gastrointestinal disorders | MedDRA (17.1) | Systematic Assessment |
| |
| Diarrhoea | Gastrointestinal disorders | MedDRA (17.1) | Systematic Assessment |
| |
| Dyschezia | Gastrointestinal disorders | MedDRA (17.1) | Systematic Assessment |
| |
| Dyspepsia | Gastrointestinal disorders | MedDRA (17.1) | Systematic Assessment |
| |
| Dysphagia | Gastrointestinal disorders | MedDRA (17.1) | Systematic Assessment |
| |
| Faeces soft | Gastrointestinal disorders | MedDRA (17.1) | Systematic Assessment |
| |
| Flatulence | Gastrointestinal disorders | MedDRA (17.1) | Systematic Assessment |
| |
| Gastritis | Gastrointestinal disorders | MedDRA (17.1) | Systematic Assessment |
| |
| Gastrooesophageal reflux disease | Gastrointestinal disorders | MedDRA (17.1) | Systematic Assessment |
| |
| Gingival pain | Gastrointestinal disorders | MedDRA (17.1) | Systematic Assessment |
| |
| Mouth ulceration | Gastrointestinal disorders | MedDRA (17.1) | Systematic Assessment |
| |
| Nausea | Gastrointestinal disorders | MedDRA (17.1) | Systematic Assessment |
| |
| Oral discomfort | Gastrointestinal disorders | MedDRA (17.1) | Systematic Assessment |
| |
| Stomatitis | Gastrointestinal disorders | MedDRA (17.1) | Systematic Assessment |
| |
| Vomiting | Gastrointestinal disorders | MedDRA (17.1) | Systematic Assessment |
| |
| Asthenia | General disorders | MedDRA (17.1) | Systematic Assessment |
| |
| Catheter site pain | General disorders | MedDRA (17.1) | Systematic Assessment |
| |
| Chest discomfort | General disorders | MedDRA (17.1) | Systematic Assessment |
| |
| Chest pain | General disorders | MedDRA (17.1) | Systematic Assessment |
| |
| Chills | General disorders | MedDRA (17.1) | Systematic Assessment |
| |
| Discomfort | General disorders | MedDRA (17.1) | Systematic Assessment |
| |
| Fatigue | General disorders | MedDRA (17.1) | Systematic Assessment |
| |
| Malaise | General disorders | MedDRA (17.1) | Systematic Assessment |
| |
| Mucosal inflammation | General disorders | MedDRA (17.1) | Systematic Assessment |
| |
| Oedema peripheral | General disorders | MedDRA (17.1) | Systematic Assessment |
| |
| Pain | General disorders | MedDRA (17.1) | Systematic Assessment |
| |
| Peripheral swelling | General disorders | MedDRA (17.1) | Systematic Assessment |
| |
| Pyrexia | General disorders | MedDRA (17.1) | Systematic Assessment |
| |
| Cholelithiasis | Hepatobiliary disorders | MedDRA (17.1) | Systematic Assessment |
| |
| Hyperbilirubinaemia | Hepatobiliary disorders | MedDRA (17.1) | Systematic Assessment |
| |
| Jaundice | Hepatobiliary disorders | MedDRA (17.1) | Systematic Assessment |
| |
| Hypogammaglobulinaemia | Immune system disorders | MedDRA (17.1) | Systematic Assessment |
| |
| Cellulitis | Infections and infestations | MedDRA (17.1) | Systematic Assessment |
| |
| Conjunctivitis | Infections and infestations | MedDRA (17.1) | Systematic Assessment |
| |
| Herpes zoster | Infections and infestations | MedDRA (17.1) | Systematic Assessment |
| |
| Localised infection | Infections and infestations | MedDRA (17.1) | Systematic Assessment |
| |
| Mucosal infection | Infections and infestations | MedDRA (17.1) | Systematic Assessment |
| |
| Nasopharyngitis | Infections and infestations | MedDRA (17.1) | Systematic Assessment |
| |
| Oesophageal candidiasis | Infections and infestations | MedDRA (17.1) | Systematic Assessment |
| |
| Oral candidiasis | Infections and infestations | MedDRA (17.1) | Systematic Assessment |
| |
| Pharyngitis streptococcal | Infections and infestations | MedDRA (17.1) | Systematic Assessment |
| |
| Pyelonephritis | Infections and infestations | MedDRA (17.1) | Systematic Assessment |
| |
| Respiratory tract infection | Infections and infestations | MedDRA (17.1) | Systematic Assessment |
| |
| Sinusitis | Infections and infestations | MedDRA (17.1) | Systematic Assessment |
| |
| Upper respiratory tract infection | Infections and infestations | MedDRA (17.1) | Systematic Assessment |
| |
| Contusion | Injury, poisoning and procedural complications | MedDRA (17.1) | Systematic Assessment |
| |
| Periorbital haematoma | Injury, poisoning and procedural complications | MedDRA (17.1) | Systematic Assessment |
| |
| Alanine aminotransferase increased | Investigations | MedDRA (17.1) | Systematic Assessment |
| |
| Aspartate aminotransferase increased | Investigations | MedDRA (17.1) | Systematic Assessment |
| |
| Blood alkaline phosphatase increased | Investigations | MedDRA (17.1) | Systematic Assessment |
| |
| Blood bilirubin increased | Investigations | MedDRA (17.1) | Systematic Assessment |
| |
| Blood creatinine increased | Investigations | MedDRA (17.1) | Systematic Assessment |
| |
| Blood glucose increased | Investigations | MedDRA (17.1) | Systematic Assessment |
| |
| International normalised ratio abnormal | Investigations | MedDRA (17.1) | Systematic Assessment |
| |
| Neutrophil count decreased | Investigations | MedDRA (17.1) | Systematic Assessment |
| |
| Urine output decreased | Investigations | MedDRA (17.1) | Systematic Assessment |
| |
| Weight decreased | Investigations | MedDRA (17.1) | Systematic Assessment |
| |
| White blood cell count decreased | Investigations | MedDRA (17.1) | Systematic Assessment |
| |
| Decreased appetite | Metabolism and nutrition disorders | MedDRA (17.1) | Systematic Assessment |
| |
| Hyperuricaemia | Metabolism and nutrition disorders | MedDRA (17.1) | Systematic Assessment |
| |
| Hypoalbuminaemia | Metabolism and nutrition disorders | MedDRA (17.1) | Systematic Assessment |
| |
| Hypocalcaemia | Metabolism and nutrition disorders | MedDRA (17.1) | Systematic Assessment |
| |
| Hypokalaemia | Metabolism and nutrition disorders | MedDRA (17.1) | Systematic Assessment |
| |
| Hypomagnesaemia | Metabolism and nutrition disorders | MedDRA (17.1) | Systematic Assessment |
| |
| Hyponatraemia | Metabolism and nutrition disorders | MedDRA (17.1) | Systematic Assessment |
| |
| Hypophosphataemia | Metabolism and nutrition disorders | MedDRA (17.1) | Systematic Assessment |
| |
| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA (17.1) | Systematic Assessment |
| |
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA (17.1) | Systematic Assessment |
| |
| Joint swelling | Musculoskeletal and connective tissue disorders | MedDRA (17.1) | Systematic Assessment |
| |
| Muscle spasms | Musculoskeletal and connective tissue disorders | MedDRA (17.1) | Systematic Assessment |
| |
| Muscular weakness | Musculoskeletal and connective tissue disorders | MedDRA (17.1) | Systematic Assessment |
| |
| Musculoskeletal discomfort | Musculoskeletal and connective tissue disorders | MedDRA (17.1) | Systematic Assessment |
| |
| Myalgia | Musculoskeletal and connective tissue disorders | MedDRA (17.1) | Systematic Assessment |
| |
| Neck pain | Musculoskeletal and connective tissue disorders | MedDRA (17.1) | Systematic Assessment |
| |
| Osteopenia | Musculoskeletal and connective tissue disorders | MedDRA (17.1) | Systematic Assessment |
| |
| Pain in extremity | Musculoskeletal and connective tissue disorders | MedDRA (17.1) | Systematic Assessment |
| |
| Dizziness | Nervous system disorders | MedDRA (17.1) | Systematic Assessment |
| |
| Dysgeusia | Nervous system disorders | MedDRA (17.1) | Systematic Assessment |
| |
| Headache | Nervous system disorders | MedDRA (17.1) | Systematic Assessment |
| |
| Hypoaesthesia | Nervous system disorders | MedDRA (17.1) | Systematic Assessment |
| |
| Neuropathy peripheral | Nervous system disorders | MedDRA (17.1) | Systematic Assessment |
| |
| Paraesthesia | Nervous system disorders | MedDRA (17.1) | Systematic Assessment |
| |
| Peripheral sensory neuropathy | Nervous system disorders | MedDRA (17.1) | Systematic Assessment |
| |
| Presyncope | Nervous system disorders | MedDRA (17.1) | Systematic Assessment |
| |
| Syncope | Nervous system disorders | MedDRA (17.1) | Systematic Assessment |
| |
| Anxiety | Psychiatric disorders | MedDRA (17.1) | Systematic Assessment |
| |
| Confusional state | Psychiatric disorders | MedDRA (17.1) | Systematic Assessment |
| |
| Depression | Psychiatric disorders | MedDRA (17.1) | Systematic Assessment |
| |
| Insomnia | Psychiatric disorders | MedDRA (17.1) | Systematic Assessment |
| |
| Restlessness | Psychiatric disorders | MedDRA (17.1) | Systematic Assessment |
| |
| Suicidal ideation | Psychiatric disorders | MedDRA (17.1) | Systematic Assessment |
| |
| Chromaturia | Renal and urinary disorders | MedDRA (17.1) | Systematic Assessment |
| |
| Haematuria | Renal and urinary disorders | MedDRA (17.1) | Systematic Assessment |
| |
| Nephrolithiasis | Renal and urinary disorders | MedDRA (17.1) | Systematic Assessment |
| |
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA (17.1) | Systematic Assessment |
| |
| Dysphonia | Respiratory, thoracic and mediastinal disorders | MedDRA (17.1) | Systematic Assessment |
| |
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA (17.1) | Systematic Assessment |
| |
| Epistaxis | Respiratory, thoracic and mediastinal disorders | MedDRA (17.1) | Systematic Assessment |
| |
| Lung infiltration | Respiratory, thoracic and mediastinal disorders | MedDRA (17.1) | Systematic Assessment |
| |
| Nasal congestion | Respiratory, thoracic and mediastinal disorders | MedDRA (17.1) | Systematic Assessment |
| |
| Oropharyngeal pain | Respiratory, thoracic and mediastinal disorders | MedDRA (17.1) | Systematic Assessment |
| |
| Pleural effusion | Respiratory, thoracic and mediastinal disorders | MedDRA (17.1) | Systematic Assessment |
| |
| Productive cough | Respiratory, thoracic and mediastinal disorders | MedDRA (17.1) | Systematic Assessment |
| |
| Rhinitis allergic | Respiratory, thoracic and mediastinal disorders | MedDRA (17.1) | Systematic Assessment |
| |
| Sinus congestion | Respiratory, thoracic and mediastinal disorders | MedDRA (17.1) | Systematic Assessment |
| |
| Sneezing | Respiratory, thoracic and mediastinal disorders | MedDRA (17.1) | Systematic Assessment |
| |
| Throat irritation | Respiratory, thoracic and mediastinal disorders | MedDRA (17.1) | Systematic Assessment |
| |
| Throat tightness | Respiratory, thoracic and mediastinal disorders | MedDRA (17.1) | Systematic Assessment |
| |
| Upper respiratory tract congestion | Respiratory, thoracic and mediastinal disorders | MedDRA (17.1) | Systematic Assessment |
| |
| Drug eruption | Skin and subcutaneous tissue disorders | MedDRA (17.1) | Systematic Assessment |
| |
| Dry skin | Skin and subcutaneous tissue disorders | MedDRA (17.1) | Systematic Assessment |
| |
| Eczema | Skin and subcutaneous tissue disorders | MedDRA (17.1) | Systematic Assessment |
| |
| Erythema | Skin and subcutaneous tissue disorders | MedDRA (17.1) | Systematic Assessment |
| |
| Hyperhidrosis | Skin and subcutaneous tissue disorders | MedDRA (17.1) | Systematic Assessment |
| |
| Night sweats | Skin and subcutaneous tissue disorders | MedDRA (17.1) | Systematic Assessment |
| |
| Pruritus | Skin and subcutaneous tissue disorders | MedDRA (17.1) | Systematic Assessment |
| |
| Rash | Skin and subcutaneous tissue disorders | MedDRA (17.1) | Systematic Assessment |
| |
| Rash generalised | Skin and subcutaneous tissue disorders | MedDRA (17.1) | Systematic Assessment |
| |
| Rash maculo-papular | Skin and subcutaneous tissue disorders | MedDRA (17.1) | Systematic Assessment |
| |
| Rash pruritic | Skin and subcutaneous tissue disorders | MedDRA (17.1) | Systematic Assessment |
| |
| Flushing | Vascular disorders | MedDRA (17.1) | Systematic Assessment |
| |
| Hypertension | Vascular disorders | MedDRA (17.1) | Systematic Assessment |
| |
| Hypotension | Vascular disorders | MedDRA (17.1) | Systematic Assessment |
| |
| Thrombophlebitis superficial | Vascular disorders | MedDRA (17.1) | Systematic Assessment |
|
As a result of the early termination of the trial for safety, the efficacy endpoints were not evaluable due to insufficient treatment exposure.
After conclusion of the study and without prior written approval from Gilead, investigators in this study may communicate, orally present, or publish in scientific journals or other media only after the following conditions have been met:
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Gilead Clinical Study Information Center | Gilead Sciences | 1-833-445-3230 (GILEAD-0) | GileadClinicalTrials@gilead.com |
| ID | Term |
|---|---|
| D015451 | Leukemia, Lymphocytic, Chronic, B-Cell |
| D020522 | Lymphoma, Mantle-Cell |
| D016403 | Lymphoma, Large B-Cell, Diffuse |
| D007938 | Leukemia |
| D008223 | Lymphoma |
| D008258 | Waldenstrom Macroglobulinemia |
| ID | Term |
|---|---|
| D015448 | Leukemia, B-Cell |
| D007945 | Leukemia, Lymphoid |
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
| D006402 | Hematologic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
| D008232 | Lymphoproliferative Disorders |
| D008206 | Lymphatic Diseases |
| D007160 | Immunoproliferative Disorders |
| D007154 | Immune System Diseases |
| D002908 | Chronic Disease |
| D020969 | Disease Attributes |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D008228 | Lymphoma, Non-Hodgkin |
| D016393 | Lymphoma, B-Cell |
| D054219 | Neoplasms, Plasma Cell |
| D020141 | Hemostatic Disorders |
| D014652 | Vascular Diseases |
| D002318 | Cardiovascular Diseases |
| D010265 | Paraproteinemias |
| D001796 | Blood Protein Disorders |
| D006474 | Hemorrhagic Disorders |
Not provided
Not provided
| ID | Term |
|---|---|
| C000589391 | 6-(1H-indazol-6-yl)-N-(4-morpholinophenyl)imidazo(1,2-a)pyrazin-8-amine |
| C552946 | idelalisib |
Not provided
Not provided
Not provided
| Male |
|
| Not Hispanic or Latino |
|
| Not Permitted |
|
| Black or African American |
|
| Native Hawaiian or Other Pacific Islander |
|
| Asian |
|
| Other |
|
| Not Reported |
|
| 50 |
|
| 60 |
|
| 70 |
|
| 80 |
|
| 90 |
|
| 100 |
|
Participants with a documented diagnosis of indolent non-Hodgkin lymphoma (iNHL) with follicular lymphoma (FL) were included in this arm. Participants were administered 4 dose combinations of entospletinib plus idelalisib tablets orally twice daily under fasted conditions (400 mg/100 mg for 2 weeks, if no dose limiting toxicity (DLT) occurred, increased dose to 600 mg/100 mg for 2 weeks, if no DLT occurred, increased dose to 800 mg/100 mg for 4 weeks, if no DLT occurred increased dose to 800 mg/150 mg) for up to 6 months. After discontinuation of combination therapy and a washout period of 14-28 days, participants could continue to receive entospletinib 400 mg monotherapy for up to 18 months. |
| OG002 | Entospletinib + Idelalisib DLBCL | Participants with a documented diagnosis of diffuse large B-cell lymphoma (DLBCL) were included in this arm. Participants were administered 4 dose combinations of entospletinib plus idelalisib tablets orally twice daily under fasted conditions (400 mg/100 mg for 2 weeks, if no dose limiting toxicity (DLT) occurred ,increased dose to 600 mg/100 mg for 2 weeks, if no DLT occurred, increased dose to 800 mg/100 mg for 4 weeks, if no DLT occurred, increased dose to 800 mg/150 mg) for up to 6 months. After discontinuation of combination therapy and a washout period of 14-28 days, participants could continue to receive entospletinib 400 mg monotherapy for up to 18 months. |
| OG003 | Entospletinib + Idelalisib MCL | Participants with a documented diagnosis of mantle cell lymphoma (MCL) were included in this arm. Participants were administered 4 dose combinations of entospletinib plus idelalisib tablets orally twice daily under fasted conditions (400 mg/100 mg for 2 weeks, if no dose limiting toxicity (DLT) occurred, increased dose to 600 mg/100 mg for 2 weeks, if no DLT occurred, increased dose to 800 mg/100 mg for 4 weeks, if no DLT occurred, increased dose to 800 mg/150 mg) for up to 6 months. After discontinuation of combination therapy and a washout period of 14-28 days, participants could continue to receive entospletinib 400 mg monotherapy for up to 18 months. |
| OG004 | Entospletinib + Idelalisib iNHL: Others | Participants with a documented diagnosis of iNHL with other subtypes lymphoplasmacytic lymphoma (LPL)/Waldenstrom macroglobulinemia (WM), small lymphocytic lymphoma (SLL) and marginal zone lymphoma (MZL) were included in this arm. Participants were administered 4 dose combinations of entospletinib plus idelalisib tablets orally twice daily under fasted conditions (400 mg/100 mg for 2 weeks, if no dose limiting toxicity (DLT) increased to 600 mg/100 mg for 2 weeks, if no DLT increased to 800 mg/100 mg for 4 weeks, if no DLT increased to 800 mg/150 mg) for up to 6 months. After discontinuation of combination therapy and a washout period of 14-28 days, participants could continue to receive entospletinib 400 mg monotherapy for up to 18 months. |
|
|
| OG001 | Entospletinib + Idelalisib iNHL: FL | Participants with a documented diagnosis of indolent non-Hodgkin lymphoma (iNHL) with follicular lymphoma (FL) were included in this arm. Participants were administered 4 dose combinations of entospletinib plus idelalisib tablets orally twice daily under fasted conditions (400 mg/100 mg for 2 weeks, if no dose limiting toxicity (DLT) occurred, increased dose to 600 mg/100 mg for 2 weeks, if no DLT occurred, increased dose to 800 mg/100 mg for 4 weeks, if no DLT occurred increased dose to 800 mg/150 mg) for up to 6 months. After discontinuation of combination therapy and a washout period of 14-28 days, participants could continue to receive entospletinib 400 mg monotherapy for up to 18 months. |
| OG002 | Entospletinib + Idelalisib DLBCL | Participants with a documented diagnosis of diffuse large B-cell lymphoma (DLBCL) were included in this arm. Participants were administered 4 dose combinations of entospletinib plus idelalisib tablets orally twice daily under fasted conditions (400 mg/100 mg for 2 weeks, if no dose limiting toxicity (DLT) occurred ,increased dose to 600 mg/100 mg for 2 weeks, if no DLT occurred, increased dose to 800 mg/100 mg for 4 weeks, if no DLT occurred, increased dose to 800 mg/150 mg) for up to 6 months. After discontinuation of combination therapy and a washout period of 14-28 days, participants could continue to receive entospletinib 400 mg monotherapy for up to 18 months. |
| OG003 | Entospletinib + Idelalisib MCL | Participants with a documented diagnosis of mantle cell lymphoma (MCL) were included in this arm. Participants were administered 4 dose combinations of entospletinib plus idelalisib tablets orally twice daily under fasted conditions (400 mg/100 mg for 2 weeks, if no dose limiting toxicity (DLT) occurred, increased dose to 600 mg/100 mg for 2 weeks, if no DLT occurred, increased dose to 800 mg/100 mg for 4 weeks, if no DLT occurred, increased dose to 800 mg/150 mg) for up to 6 months. After discontinuation of combination therapy and a washout period of 14-28 days, participants could continue to receive entospletinib 400 mg monotherapy for up to 18 months. |
| OG004 | Entospletinib + Idelalisib iNHL: Others | Participants with a documented diagnosis of iNHL with other subtypes lymphoplasmacytic lymphoma (LPL)/ Waldenstrom macroglobulinemia (WM), small lymphocytic lymphoma (SLL), and marginal zone lymphoma (MZL) were included in this arm. Participants were administered 4 dose combinations of entospletinib plus idelalisib tablets orally twice daily under fasted conditions (400 mg/100 mg for 2 weeks, if no dose limiting toxicity (DLT) increased to 600 mg/100 mg for 2 weeks, if no DLT increased to 800 mg/100 mg for 4 weeks, if no DLT increased to 800 mg/150 mg) for up to 6 months. After discontinuation of combination therapy and a washout period of 14-28 days, participants could continue to receive entospletinib 400 mg monotherapy for up to 18 months. |
|
|
| OG002 | Entospletinib + Idelalisib DLBCL | Participants with a documented diagnosis of diffuse large B-cell lymphoma (DLBCL) were included in this arm. Participants were administered 4 dose combinations of entospletinib plus idelalisib tablets orally twice daily under fasted conditions (400 mg/100 mg for 2 weeks, if no dose limiting toxicity (DLT) occurred ,increased dose to 600 mg/100 mg for 2 weeks, if no DLT occurred, increased dose to 800 mg/100 mg for 4 weeks, if no DLT occurred, increased dose to 800 mg/150 mg) for up to 6 months. After discontinuation of combination therapy and a washout period of 14-28 days, participants could continue to receive entospletinib 400 mg monotherapy for up to 18 months. |
| OG003 | Entospletinib + Idelalisib MCL | Participants with a documented diagnosis of mantle cell lymphoma (MCL) were included in this arm. Participants were administered 4 dose combinations of entospletinib plus idelalisib tablets orally twice daily under fasted conditions (400 mg/100 mg for 2 weeks, if no dose limiting toxicity (DLT) occurred, increased dose to 600 mg/100 mg for 2 weeks, if no DLT occurred, increased dose to 800 mg/100 mg for 4 weeks, if no DLT occurred, increased dose to 800 mg/150 mg) for up to 6 months. After discontinuation of combination therapy and a washout period of 14-28 days, participants could continue to receive entospletinib 400 mg monotherapy for up to 18 months. |
| OG004 | Entospletinib + Idelalisib iNHL: Others | Participants with a documented diagnosis of iNHL with other subtypes lymphoplasmacytic lymphoma (LPL)/Waldenstrom macroglobulinemia (WM), small lymphocytic lymphoma (SLL) and marginal zone lymphoma (MZL) were included in this arm. Participants were administered 4 dose combinations of entospletinib plus idelalisib tablets orally twice daily under fasted conditions (400 mg/100 mg for 2 weeks, if no dose limiting toxicity (DLT) increased to 600 mg/100 mg for 2 weeks, if no DLT increased to 800 mg/100 mg for 4 weeks, if no DLT increased to 800 mg/150 mg) for up to 6 months. After discontinuation of combination therapy and a washout period of 14-28 days, participants could continue to receive entospletinib 400 mg monotherapy for up to 18 months. |
|
| OG002 | Entospletinib + Idelalisib DLBCL | Participants with a documented diagnosis of diffuse large B-cell lymphoma (DLBCL) were included in this arm. Participants were administered 4 dose combinations of entospletinib plus idelalisib tablets orally twice daily under fasted conditions (400 mg/100 mg for 2 weeks, if no dose limiting toxicity (DLT) occurred ,increased dose to 600 mg/100 mg for 2 weeks, if no DLT occurred, increased dose to 800 mg/100 mg for 4 weeks, if no DLT occurred, increased dose to 800 mg/150 mg) for up to 6 months. After discontinuation of combination therapy and a washout period of 14-28 days, participants could continue to receive entospletinib 400 mg monotherapy for up to 18 months. |
| OG003 | Entospletinib + Idelalisib MCL | Participants with a documented diagnosis of mantle cell lymphoma (MCL) were included in this arm. Participants were administered 4 dose combinations of entospletinib plus idelalisib tablets orally twice daily under fasted conditions (400 mg/100 mg for 2 weeks, if no dose limiting toxicity (DLT) occurred, increased dose to 600 mg/100 mg for 2 weeks, if no DLT occurred, increased dose to 800 mg/100 mg for 4 weeks, if no DLT occurred, increased dose to 800 mg/150 mg) for up to 6 months. After discontinuation of combination therapy and a washout period of 14-28 days, participants could continue to receive entospletinib 400 mg monotherapy for up to 18 months. |
| OG004 | Entospletinib + Idelalisib iNHL: Others | Participants with a documented diagnosis of iNHL with other subtypes lymphoplasmacytic lymphoma (LPL)/Waldenstrom macroglobulinemia (WM), small lymphocytic lymphoma (SLL) and marginal zone lymphoma (MZL) were included in this arm. Participants were administered 4 dose combinations of entospletinib plus idelalisib tablets orally twice daily under fasted conditions (400 mg/100 mg for 2 weeks, if no dose limiting toxicity (DLT) increased to 600 mg/100 mg for 2 weeks, if no DLT increased to 800 mg/100 mg for 4 weeks, if no DLT increased to 800 mg/150 mg) for up to 6 months. After discontinuation of combination therapy and a washout period of 14-28 days, participants could continue to receive entospletinib 400 mg monotherapy for up to 18 months. |
|
| Entospletinib + Idelalisib iNHL: FL |
Participants with a documented diagnosis of indolent non-Hodgkin lymphoma (iNHL) with follicular lymphoma (FL) were included in this arm. Participants were administered 4 dose combinations of entospletinib plus idelalisib tablets orally twice daily under fasted conditions (400 mg/100 mg for 2 weeks, if no dose limiting toxicity (DLT) occurred, increased dose to 600 mg/100 mg for 2 weeks, if no DLT occurred, increased dose to 800 mg/100 mg for 4 weeks, if no DLT occurred increased dose to 800 mg/150 mg) for up to 6 months. After discontinuation of combination therapy and a washout period of 14-28 days, participants could continue to receive entospletinib 400 mg monotherapy for up to 18 months. |
| OG002 | Entospletinib + Idelalisib DLBCL | Participants with a documented diagnosis of diffuse large B-cell lymphoma (DLBCL) were included in this arm. Participants were administered 4 dose combinations of entospletinib plus idelalisib tablets orally twice daily under fasted conditions (400 mg/100 mg for 2 weeks, if no dose limiting toxicity (DLT) occurred ,increased dose to 600 mg/100 mg for 2 weeks, if no DLT occurred, increased dose to 800 mg/100 mg for 4 weeks, if no DLT occurred, increased dose to 800 mg/150 mg) for up to 6 months. After discontinuation of combination therapy and a washout period of 14-28 days, participants could continue to receive entospletinib 400 mg monotherapy for up to 18 months. |
| OG003 | Entospletinib + Idelalisib MCL | Participants with a documented diagnosis of mantle cell lymphoma (MCL) were included in this arm. Participants were administered 4 dose combinations of entospletinib plus idelalisib tablets orally twice daily under fasted conditions (400 mg/100 mg for 2 weeks, if no dose limiting toxicity (DLT) occurred, increased dose to 600 mg/100 mg for 2 weeks, if no DLT occurred, increased dose to 800 mg/100 mg for 4 weeks, if no DLT occurred, increased dose to 800 mg/150 mg) for up to 6 months. After discontinuation of combination therapy and a washout period of 14-28 days, participants could continue to receive entospletinib 400 mg monotherapy for up to 18 months. |
| OG004 | Entospletinib + Idelalisib iNHL: Others | Participants with a documented diagnosis of iNHL with other subtypes lymphoplasmacytic lymphoma (LPL)/Waldenstrom macroglobulinemia (WM), small lymphocytic lymphoma (SLL) and marginal zone lymphoma (MZL) were included in this arm. Participants were administered 4 dose combinations of entospletinib plus idelalisib tablets orally twice daily under fasted conditions (400 mg/100 mg for 2 weeks, if no dose limiting toxicity (DLT) increased to 600 mg/100 mg for 2 weeks, if no DLT increased to 800 mg/100 mg for 4 weeks, if no DLT increased to 800 mg/150 mg) for up to 6 months. After discontinuation of combination therapy and a washout period of 14-28 days, participants could continue to receive entospletinib 400 mg monotherapy for up to 18 months. |
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Participants with a documented diagnosis of indolent non-Hodgkin lymphoma (iNHL) with follicular lymphoma (FL) were included in this arm. Participants were administered 4 dose combinations of entospletinib plus idelalisib tablets orally twice daily under fasted conditions (400 mg/100 mg for 2 weeks, if no dose limiting toxicity (DLT) occurred, increased dose to 600 mg/100 mg for 2 weeks, if no DLT occurred, increased dose to 800 mg/100 mg for 4 weeks, if no DLT occurred increased dose to 800 mg/150 mg) for up to 6 months. After discontinuation of combination therapy and a washout period of 14-28 days, participants could continue to receive entospletinib 400 mg monotherapy for up to 18 months. |
| OG002 | Entospletinib + Idelalisib DLBCL | Participants with a documented diagnosis of diffuse large B-cell lymphoma (DLBCL) were included in this arm. Participants were administered 4 dose combinations of entospletinib plus idelalisib tablets orally twice daily under fasted conditions (400 mg/100 mg for 2 weeks, if no dose limiting toxicity (DLT) occurred ,increased dose to 600 mg/100 mg for 2 weeks, if no DLT occurred, increased dose to 800 mg/100 mg for 4 weeks, if no DLT occurred, increased dose to 800 mg/150 mg) for up to 6 months. After discontinuation of combination therapy and a washout period of 14-28 days, participants could continue to receive entospletinib 400 mg monotherapy for up to 18 months. |
| OG003 | Entospletinib + Idelalisib MCL | Participants with a documented diagnosis of mantle cell lymphoma (MCL) were included in this arm. Participants were administered 4 dose combinations of entospletinib plus idelalisib tablets orally twice daily under fasted conditions (400 mg/100 mg for 2 weeks, if no dose limiting toxicity (DLT) occurred, increased dose to 600 mg/100 mg for 2 weeks, if no DLT occurred, increased dose to 800 mg/100 mg for 4 weeks, if no DLT occurred, increased dose to 800 mg/150 mg) for up to 6 months. After discontinuation of combination therapy and a washout period of 14-28 days, participants could continue to receive entospletinib 400 mg monotherapy for up to 18 months. |
| OG004 | Entospletinib + Idelalisib iNHL: Others | Participants with a documented diagnosis of iNHL with other subtypes lymphoplasmacytic lymphoma (LPL)/Waldenstrom macroglobulinemia (WM), small lymphocytic lymphoma (SLL) and marginal zone lymphoma (MZL) were included in this arm. Participants were administered 4 dose combinations of entospletinib plus idelalisib tablets orally twice daily under fasted conditions (400 mg/100 mg for 2 weeks, if no dose limiting toxicity (DLT) increased to 600 mg/100 mg for 2 weeks, if no DLT increased to 800 mg/100 mg for 4 weeks, if no DLT increased to 800 mg/150 mg) for up to 6 months. After discontinuation of combination therapy and a washout period of 14-28 days, participants could continue to receive entospletinib 400 mg monotherapy for up to 18 months. |
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