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| ID | Type | Description | Link |
|---|---|---|---|
| 2016-002768-15 | EudraCT Number | ||
| CLLRUmbrella2 | Other Identifier | German CLL Study Group |
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| Name | Class |
|---|---|
| German CLL Study Group | OTHER |
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The primary objective of this study is to determine the preliminary efficacy of the combination of tirabrutinib (formerly GS-4059) and entospletinib with obinutuzumab in adults with relapsed or refractory chronic lymphocytic leukemia (CLL).
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Tirabrutinib + Entospletinib | Experimental | Participants will receive tirabrutinib 80 mg (4 x 20 mg tablets/2 x 40 mg tablets/1 x 80 mg tablet) + entospletinib 400 mg (2 x 200 mg tablets) for up to 104 weeks. |
|
| Tirabrutinib + Entospletinib + Obinutuzumab | Experimental | Participants will receive tirabrutinib 80 mg (4 x 20 mg tablets/ 2 x 40 mg tablets/ 1 x 80 mg tablet) + entospletinib 400 mg (2 x 200 mg tablets) for up to 104 weeks + obinutuzumab 100 mg on Day 1, 900 mg on Day 1 or 2, and 1000 mg subsequently for up to 8 doses on Day 1 of Weeks 2, 3, 5, 9, 13, 17 and 21. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Tirabrutinib | Drug | Administered orally once daily |
|
| Measure | Description | Time Frame |
|---|---|---|
| Rate of Complete Remission/Complete Remission With Incomplete Recovery of the Bone Marrow (CR/CRi), as Assessed by Investigator Using Modified International Workshop on Chronic Lymphocytic Leukemia (IWCLL) 2008 Criteria at Week 25 | Rate of CR per modified IWCLL 2008 criteria at Week 25 was defined as the percentage of participants who achieved CR/complete remission with incomplete recovery of the bone marrow (CRi) at Week 25. CR: meeting following criteria and no disease related symptoms: no lymphadenopathy > 1.5 cm/hepatomegaly/splenomegaly; lymphocytes < 4000/μL; bone marrow sample must be normocellular with 30% lymphocytes and no B-lymphoid nodules; platelets > 100,000/µL; hemoglobin > 11 g/dL; and neutrophils > 1500/µL. CRi: CR criteria (no lymphadenopathy > 1.5 cm/hepatomegaly/splenomegaly; lymphocytes < 4000/μL; bone marrow [hypocellular] with 30% lymphocytes and no B-lymphoid nodules), persistent anemia/thrombocytopenia/neutropenia unrelated to CLL but related to drug toxicity. | Week 25 |
| Measure | Description | Time Frame |
|---|---|---|
| Rate of CR With Bone Marrow Minimal Residual Disease (CR/BM MRD) Negativity, as Assessed by the Investigator Using the Modified IWCLL 2008 Criteria at Week 25 | Rate of CR/BM MRD at Week 25 was defined as percentage of participants who achieved CR/CRi per modified IWCLL 2008 criteria and also achieved BM MRD negativity at Week 25. CR: meeting following criteria and no disease related symptoms: no lymphadenopathy > 1.5 cm/hepatomegaly/splenomegaly; lymphocytes < 4000/μL; bone marrow sample must be normocellular with 30% lymphocytes and no B-lymphoid nodules; platelets > 100,000/µL; hemoglobin > 11 g/dL; and neutrophils > 1500/µL. CRi: CR criteria (no lymphadenopathy > 1.5 cm/hepatomegaly/splenomegaly; lymphocytes < 4000/μL; bone marrow [hypocellular] with 30% lymphocytes and no B-lymphoid nodules), persistent anemia/thrombocytopenia/neutropenia unrelated to CLL but related to drug toxicity. MRD response was assessed with four-color-flow cytometry (FACS) and MRD negativity was defined as one CLL cell per 10,000 leukocytes [0.01%], ie,<10^-4 and participants were defined as MRD negative if their disease burden was below this threshold. |
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Key Inclusion Criteria:
Documentation of relapsed or refractory CLL
Requiring treatment per modified International Workshop on CLL (IWCLL) 2008 criteria; adults without radiographically measureable disease (defined as ≥ 1 lesion > 1.5 centimetres (cm) in diameter as assessed by computed tomography (CT) or magnetic resonance imaging (MRI)) must have bone marrow evaluation at screening
Adequate hematologic function: platelet count ≥ 50 × 10^9/liter (L), neutrophil count ≥ 1 × 10^9/L, hemoglobin ≥ 8 grams per deciliter (g/dL) unless lower values are directly attributable to documented bone marrow burden of CLL
Creatinine clearance (CrCl) ≥ 50 milliliters per minute (mL/min)
Total bilirubin ≤ 1.5× institutional upper limit of normal (ULN) unless attributed to Gilbert's syndrome and aspartate transaminase (AST)/alanine transaminase (ALT) ≤ 2.5×ULN
Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) ≤ 2
Absence of active human immunodeficiency virus (HIV), hepatitis B virus (HBV) infection, and hepatitis C virus (HCV) infection
Satisfies the following criteria:
Able to comply with study procedures and restrictions
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 |
|---|---|---|---|---|---|---|
| Studienzentrum Aschaffenburg | Aschaffenburg | 63739 | Germany | |||
| Evangelisches Diakoniekrankenhaus Bremen Hämatologie |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| Result | Kutsch, N et al. A Prospective, Open-Label, Multicenter, Phase 2 Trial to Evaluate the Safety and Efficacy of the Combination of Tirabrutinib (ONO/GS-4059) and Entospletinib with and without Obinutuzumab in Patients with Relapsed/Refractory Chronic Lymphocytic Leukemia (CLL), Blood (2019) 134 (Supplement_1): 4297. |
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38 participants were screened. Randomization was discontinued after implementation of Protocol Amendment 3; all additional participants were enrolled to Arm: Tirabrutinib + Entospletinib + Obinutuzumab.
Participants were enrolled at study sites in Germany. The first participant was screened on 06 April 2017. The last study visit occurred on 01 October 2020.
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| ID | Title | Description |
|---|---|---|
| FG000 | Tirabrutinib + Entospletinib | Tirabrutinib 80 mg (4 x 20 mg tablets/2 x 40 mg tablets/1 x 80 mg tablet) orally once daily + entospletinib 400 mg (2 x 200 mg tablets) orally once daily for up to 104 weeks. |
| FG001 | Tirabrutinib + Entospletinib + Obinutuzumab |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Jan 15, 2019 | Jan 27, 2020 |
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| Entospletinib | Drug | Administered orally once daily |
|
|
| Obinutuzumab | Drug | Administered intravenously |
|
|
| Week 25 |
| Rate of CR With Peripheral Minimal Residual Disease (CR/PB MRD) Negativity, as Assessed by the Investigator Using the Modified IWCLL 2008 Criteria at Week 25 | Rate of CR/PB MRD at Week 25 was defined as the percentage of participants who achieved CR/CRi per modified IWCLL 2008 criteria and also achieved PB MRD negativity at Week 25. CR: meeting following criteria and no disease related symptoms: no lymphadenopathy > 1.5 cm/hepatomegaly/splenomegaly; lymphocytes < 4000/μL; bone marrow sample must be normocellular with 30% lymphocytes and no B-lymphoid nodules; platelets > 100,000/µL; hemoglobin > 11 g/dL; and neutrophils > 1500/µL. CRi: CR criteria (no lymphadenopathy > 1.5 cm/hepatomegaly/splenomegaly; lymphocytes < 4000/μL; bone marrow [hypocellular] with 30% lymphocytes and no B-lymphoid nodules), persistent anemia/thrombocytopenia/neutropenia unrelated to CLL but related to drug toxicity. MRD response was assessed with FACS and MRD negativity was defined as one CLL cell per 10,000 leukocytes [0.01%], ie,<10^-4 and participants were defined as MRD negative if their disease burden was below this threshold. | Week 25 |
| Overall Response Rate (ORR), as Assessed by the Investigator Using the Modified IWCLL 2008 Criteria at Week 25 | ORR was assessed based on modified IWCLL 2008 criteria and was defined as percentage of participants achieving a CR, CRi, partial remission (PR; including nodular partial response [nPR]), and PR with lymphocytosis (PR-L). CR and CRi: meeting all the criteria that have been defined in Outcome measures 1, 2 and 3. PR: ≥ 2 of these: ≥ 50% decrease in lymphocytes, lymphadenopathy, size of liver, size of spleen, and 50% decrease in bone marrow infiltrates; and ≥ 1 of these: neutrophils > 1500/μL or ≥ 50% increase from Baseline, platelets ≥ 100,000/µL or ≥ 50% increase from Baseline, hemoglobin >11 g/dL or ≥ 50% increase from Baseline. PR-L: meeting PR criteria; however, a lymphocytosis related to treatment may be present. nPR: All criteria for a CR/CRi were fulfilled, but the bone marrow showed lymphoid nodules. | Week 25 |
| Percentage of Participants Experiencing Any Treatment-Emergent Adverse Events (AEs) and Treatment-Emergent Serious Adverse Events (SAEs) | A treatment emergent AE is defined as an AE that occurs or worsens in severity on or after the date of the first dose of study drug but no later than 30 days after the permanent discontinuation of study drug or an AE leading to discontinuation of study drug. A SAE is defined as an event that, at any dose, resulted in any of the following: death, life-threatening, in-patient hospitalization or prolongation of existing hospitalization, persistent or significant disability/incapacity, a congenital anomaly/birth defect, or a medically important event or reaction. | First dose date up to the last dose date (maximum: 105.9 weeks) plus 30 days |
| Bremen |
| 28239 |
| Germany |
| Uniklinik Köln Klinik I für Innere Medizin | Cologne | 50937 | Germany |
| St.-Johannes-Hospital | Dortmund | D-44137 | Germany |
| University Medical Center Freiburg | Freiburg im Breisgau | 79106 | Germany |
| Onkologische Schwerpunktpraxis Lerchenfeld | Hamburg | 22081 | Germany |
| Universitätsklinikum Heidelberg, Abteilung Innere Medizin V | Heidelberg | 69120 | Germany |
| Marienhospital Herne, Dept. of Internal Medicine | Herne | 44625 | Germany |
| Universitätsklinikum Schleswig-Holstein Klinik für Innere Medizin II - Hämatologie und Onkologie | Kiel | 24105 | Germany |
| Mannheimer Onkologie Praxis | Manheim | 68161 | Germany |
| Gemeinschaftspraxis für Hämatologie und Onkologie | Münster | 48149 | Germany |
| Kreiskliniken Reutlingen GmbH Klinikum am Steinenberg | Reutlingen | 72764 | Germany |
| Praxis für Hämatologie und Onkologie | Saarbrücken | 66113 | Germany |
| Robert-Bosch-Krakenhaus | Stuttgart | 70376 | Germany |
| Universitätsklinik Ulm - Klinik für Innere Medizin III | Ulm | 89081 | Germany |
Tirabrutinib 80 mg (4 x 20 mg tablets/ 2 x 40 mg tablets/ 1 x 80 mg tablet) orally once daily + entospletinib 400 mg (2 x 200 mg tablets) orally once daily for up to 104 weeks + obinutuzumab 100 mg on Day 1, 900 mg on Day 1 or 2, and 1000 mg subsequently for up to 8 doses administered intravenously on Day 1 of Weeks 2, 3, 5, 9, 13, 17 and 21. |
| COMPLETED |
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| NOT COMPLETED |
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Full Analysis Set included all randomized or enrolled participants who received at least 1 dose of any study drug.
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| ID | Title | Description |
|---|---|---|
| BG000 | Tirabrutinib + Entospletinib | Tirabrutinib 80 mg (4 x 20 mg tablets/2 x 40 mg tablets/1 x 80 mg tablet) orally once daily + entospletinib 400 mg (2 x 200 mg tablets) orally once daily for up to 104 weeks. |
| BG001 | Tirabrutinib + Entospletinib + Obinutuzumab | Tirabrutinib 80 mg (4 x 20 mg tablets/ 2 x 40 mg tablets/ 1 x 80 mg tablet) orally once daily + entospletinib 400 mg (2 x 200 mg tablets) orally once daily for up to 104 weeks + obinutuzumab 100 mg on Day 1, 900 mg on Day 1 or 2, and 1000 mg subsequently for up to 8 doses administered intravenously on Day 1 of Weeks 2, 3, 5, 9, 13, 17 and 21. |
| BG002 | 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 = local regulators did not allow collection of ethnicity information. | Count of Participants | Participants | No |
| ||||||||||||||
| Race/Ethnicity, Customized | Not Permitted = local regulators did not allow collection of race information. | 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 | Rate of Complete Remission/Complete Remission With Incomplete Recovery of the Bone Marrow (CR/CRi), as Assessed by Investigator Using Modified International Workshop on Chronic Lymphocytic Leukemia (IWCLL) 2008 Criteria at Week 25 | Rate of CR per modified IWCLL 2008 criteria at Week 25 was defined as the percentage of participants who achieved CR/complete remission with incomplete recovery of the bone marrow (CRi) at Week 25. CR: meeting following criteria and no disease related symptoms: no lymphadenopathy > 1.5 cm/hepatomegaly/splenomegaly; lymphocytes < 4000/μL; bone marrow sample must be normocellular with 30% lymphocytes and no B-lymphoid nodules; platelets > 100,000/µL; hemoglobin > 11 g/dL; and neutrophils > 1500/µL. CRi: CR criteria (no lymphadenopathy > 1.5 cm/hepatomegaly/splenomegaly; lymphocytes < 4000/μL; bone marrow [hypocellular] with 30% lymphocytes and no B-lymphoid nodules), persistent anemia/thrombocytopenia/neutropenia unrelated to CLL but related to drug toxicity. | Full Analysis Set included all randomized or enrolled participants who received at least 1 dose of any study drug. | Posted | Number | 90% Confidence Interval | percentage of participants | Week 25 |
|
|
| ||||||||||||||||||||||||||||
| Secondary | Rate of CR With Bone Marrow Minimal Residual Disease (CR/BM MRD) Negativity, as Assessed by the Investigator Using the Modified IWCLL 2008 Criteria at Week 25 | Rate of CR/BM MRD at Week 25 was defined as percentage of participants who achieved CR/CRi per modified IWCLL 2008 criteria and also achieved BM MRD negativity at Week 25. CR: meeting following criteria and no disease related symptoms: no lymphadenopathy > 1.5 cm/hepatomegaly/splenomegaly; lymphocytes < 4000/μL; bone marrow sample must be normocellular with 30% lymphocytes and no B-lymphoid nodules; platelets > 100,000/µL; hemoglobin > 11 g/dL; and neutrophils > 1500/µL. CRi: CR criteria (no lymphadenopathy > 1.5 cm/hepatomegaly/splenomegaly; lymphocytes < 4000/μL; bone marrow [hypocellular] with 30% lymphocytes and no B-lymphoid nodules), persistent anemia/thrombocytopenia/neutropenia unrelated to CLL but related to drug toxicity. MRD response was assessed with four-color-flow cytometry (FACS) and MRD negativity was defined as one CLL cell per 10,000 leukocytes [0.01%], ie,<10^-4 and participants were defined as MRD negative if their disease burden was below this threshold. | Participants in the Full Analysis Set were analyzed. | Posted | Number | 90% Confidence Interval | percentage of participants | Week 25 |
| ||||||||||||||||||||||||||||||
| Secondary | Rate of CR With Peripheral Minimal Residual Disease (CR/PB MRD) Negativity, as Assessed by the Investigator Using the Modified IWCLL 2008 Criteria at Week 25 | Rate of CR/PB MRD at Week 25 was defined as the percentage of participants who achieved CR/CRi per modified IWCLL 2008 criteria and also achieved PB MRD negativity at Week 25. CR: meeting following criteria and no disease related symptoms: no lymphadenopathy > 1.5 cm/hepatomegaly/splenomegaly; lymphocytes < 4000/μL; bone marrow sample must be normocellular with 30% lymphocytes and no B-lymphoid nodules; platelets > 100,000/µL; hemoglobin > 11 g/dL; and neutrophils > 1500/µL. CRi: CR criteria (no lymphadenopathy > 1.5 cm/hepatomegaly/splenomegaly; lymphocytes < 4000/μL; bone marrow [hypocellular] with 30% lymphocytes and no B-lymphoid nodules), persistent anemia/thrombocytopenia/neutropenia unrelated to CLL but related to drug toxicity. MRD response was assessed with FACS and MRD negativity was defined as one CLL cell per 10,000 leukocytes [0.01%], ie,<10^-4 and participants were defined as MRD negative if their disease burden was below this threshold. | Participants in the Full Analysis Set were analyzed. | Posted | Number | 90% Confidence Interval | percentage of participants | Week 25 |
| ||||||||||||||||||||||||||||||
| Secondary | Overall Response Rate (ORR), as Assessed by the Investigator Using the Modified IWCLL 2008 Criteria at Week 25 | ORR was assessed based on modified IWCLL 2008 criteria and was defined as percentage of participants achieving a CR, CRi, partial remission (PR; including nodular partial response [nPR]), and PR with lymphocytosis (PR-L). CR and CRi: meeting all the criteria that have been defined in Outcome measures 1, 2 and 3. PR: ≥ 2 of these: ≥ 50% decrease in lymphocytes, lymphadenopathy, size of liver, size of spleen, and 50% decrease in bone marrow infiltrates; and ≥ 1 of these: neutrophils > 1500/μL or ≥ 50% increase from Baseline, platelets ≥ 100,000/µL or ≥ 50% increase from Baseline, hemoglobin >11 g/dL or ≥ 50% increase from Baseline. PR-L: meeting PR criteria; however, a lymphocytosis related to treatment may be present. nPR: All criteria for a CR/CRi were fulfilled, but the bone marrow showed lymphoid nodules. | Participants in the Full Analysis Set were analyzed. | Posted | Number | 90% Confidence Interval | percentage of participants | Week 25 |
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| Secondary | Percentage of Participants Experiencing Any Treatment-Emergent Adverse Events (AEs) and Treatment-Emergent Serious Adverse Events (SAEs) | A treatment emergent AE is defined as an AE that occurs or worsens in severity on or after the date of the first dose of study drug but no later than 30 days after the permanent discontinuation of study drug or an AE leading to discontinuation of study drug. A SAE is defined as an event that, at any dose, resulted in any of the following: death, life-threatening, in-patient hospitalization or prolongation of existing hospitalization, persistent or significant disability/incapacity, a congenital anomaly/birth defect, or a medically important event or reaction. | Safety Analysis Set included all randomized or enrolled participants who received at least 1 dose of any study drug. | Posted | Number | percentage of participants | First dose date up to the last dose date (maximum: 105.9 weeks) plus 30 days |
|
Adverse Events: First dose date up to last dose date (maximum: 105.9 weeks) plus 30 days; All-Cause Mortality: Enrollment up to 42 months
Adverse Events: Safety Analysis Set included all randomized or enrolled participants who received at least 1 dose of any study drug; All-cause mortality: All Enrolled Analysis Set included all participants who received a study participant identification number in the study after screening.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Tirabrutinib + Entospletinib | Tirabrutinib 80 mg (4 x 20 mg tablets/2 x 40 mg tablets/1 x 80 mg tablet) orally once daily + entospletinib 400 mg (2 x 200 mg tablets) orally once daily for up to 104 weeks. | 0 | 6 | 1 | 6 | 6 | 6 |
| EG001 | Tirabrutinib + Entospletinib + Obinutuzumab | Tirabrutinib 80 mg (4 x 20 mg tablets/ 2 x 40 mg tablets/ 1 x 80 mg tablet) orally once daily + entospletinib 400 mg (2 x 200 mg tablets) orally once daily for up to 104 weeks + obinutuzumab 100 mg on Day 1, 900 mg on Day 1 or 2, and 1000 mg subsequently for up to 8 doses administered intravenously on Day 1 of Weeks 2, 3, 5, 9, 13, 17 and 21. | 4 | 30 | 15 | 30 | 29 | 30 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anaemia | Blood and lymphatic system disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Hydrocele | Congenital, familial and genetic disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Disease progression | General disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Pyrexia | General disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Bronchopulmonary aspergillosis | Infections and infestations | MedDRA 23.1 | Systematic Assessment |
| |
| Covid-19 pneumonia | Infections and infestations | MedDRA 23.1 | Systematic Assessment |
| |
| Nasopharyngitis | Infections and infestations | MedDRA 23.1 | Systematic Assessment |
| |
| Peritonsillitis | Infections and infestations | MedDRA 23.1 | Systematic Assessment |
| |
| Pneumonia | Infections and infestations | MedDRA 23.1 | Systematic Assessment |
| |
| Soft tissue infection | Infections and infestations | MedDRA 23.1 | Systematic Assessment |
| |
| Tracheobronchitis | Infections and infestations | MedDRA 23.1 | Systematic Assessment |
| |
| Urinary tract infection | Infections and infestations | MedDRA 23.1 | Systematic Assessment |
| |
| Infusion related reaction | Injury, poisoning and procedural complications | MedDRA 23.1 | Systematic Assessment |
| |
| Procedural haemorrhage | Injury, poisoning and procedural complications | MedDRA 23.1 | Systematic Assessment |
| |
| Subdural haematoma | Injury, poisoning and procedural complications | MedDRA 23.1 | Systematic Assessment |
| |
| Syncope | Nervous system disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Renal impairment | Renal and urinary disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Urethral caruncle | Renal and urinary disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Benign prostatic hyperplasia | Reproductive system and breast disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Pleural effusion | Respiratory, thoracic and mediastinal disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Pneumonitis | Respiratory, thoracic and mediastinal disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Pemphigoid | Skin and subcutaneous tissue disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Haematoma | Vascular disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Peripheral arterial occlusive disease | Vascular disorders | MedDRA 23.1 | Systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anaemia | Blood and lymphatic system disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Leukopenia | Blood and lymphatic system disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Neutropenia | Blood and lymphatic system disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Thrombocytopenia | Blood and lymphatic system disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Aortic valve incompetence | Cardiac disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Palpitations | Cardiac disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Tachycardia | Cardiac disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Ear pain | Ear and labyrinth disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Tinnitus | Ear and labyrinth disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Conjunctival haemorrhage | Eye disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Abdominal pain | Gastrointestinal disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Abdominal pain upper | Gastrointestinal disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Constipation | Gastrointestinal disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Diarrhoea | Gastrointestinal disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Dry mouth | Gastrointestinal disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Dyspepsia | Gastrointestinal disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Flatulence | Gastrointestinal disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Gastritis | Gastrointestinal disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Gastrointestinal disorder | Gastrointestinal disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Nausea | Gastrointestinal disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Stomatitis | Gastrointestinal disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Vomiting | Gastrointestinal disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Asthenia | General disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Chest pain | General disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Chills | General disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Fatigue | General disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Impaired healing | General disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Mucosal inflammation | General disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Oedema peripheral | General disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Pyrexia | General disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Bronchitis | Infections and infestations | MedDRA 23.1 | Systematic Assessment |
| |
| Conjunctivitis | Infections and infestations | MedDRA 23.1 | Systematic Assessment |
| |
| Cystitis | Infections and infestations | MedDRA 23.1 | Systematic Assessment |
| |
| Folliculitis | Infections and infestations | MedDRA 23.1 | Systematic Assessment |
| |
| Gastroenteritis | Infections and infestations | MedDRA 23.1 | Systematic Assessment |
| |
| Herpes virus infection | Infections and infestations | MedDRA 23.1 | Systematic Assessment |
| |
| Herpes zoster | Infections and infestations | MedDRA 23.1 | Systematic Assessment |
| |
| Nasopharyngitis | Infections and infestations | MedDRA 23.1 | Systematic Assessment |
| |
| Oral herpes | Infections and infestations | MedDRA 23.1 | Systematic Assessment |
| |
| Periodontitis | Infections and infestations | MedDRA 23.1 | Systematic Assessment |
| |
| Pneumonia | Infections and infestations | MedDRA 23.1 | Systematic Assessment |
| |
| Respiratory tract infection | Infections and infestations | MedDRA 23.1 | Systematic Assessment |
| |
| Rhinitis | Infections and infestations | MedDRA 23.1 | Systematic Assessment |
| |
| Root canal infection | Infections and infestations | MedDRA 23.1 | Systematic Assessment |
| |
| Sinusitis | Infections and infestations | MedDRA 23.1 | Systematic Assessment |
| |
| Upper respiratory tract infection | Infections and infestations | MedDRA 23.1 | Systematic Assessment |
| |
| Urinary tract infection | Infections and infestations | MedDRA 23.1 | Systematic Assessment |
| |
| Arthropod bite | Injury, poisoning and procedural complications | MedDRA 23.1 | Systematic Assessment |
| |
| Contusion | Injury, poisoning and procedural complications | MedDRA 23.1 | Systematic Assessment |
| |
| Infusion related reaction | Injury, poisoning and procedural complications | MedDRA 23.1 | Systematic Assessment |
| |
| Blood bilirubin increased | Investigations | MedDRA 23.1 | Systematic Assessment |
| |
| Blood glucose increased | Investigations | MedDRA 23.1 | Systematic Assessment |
| |
| Haemoglobin urine present | Investigations | MedDRA 23.1 | Systematic Assessment |
| |
| Immunoglobulins decreased | Investigations | MedDRA 23.1 | Systematic Assessment |
| |
| Lipase increased | Investigations | MedDRA 23.1 | Systematic Assessment |
| |
| Platelet count decreased | Investigations | MedDRA 23.1 | Systematic Assessment |
| |
| Red blood cells urine positive | Investigations | MedDRA 23.1 | Systematic Assessment |
| |
| Weight increased | Investigations | MedDRA 23.1 | Systematic Assessment |
| |
| Folate deficiency | Metabolism and nutrition disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Hyperkalaemia | Metabolism and nutrition disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Hypertriglyceridaemia | Metabolism and nutrition disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Muscle spasms | Musculoskeletal and connective tissue disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Musculoskeletal pain | Musculoskeletal and connective tissue disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Neck pain | Musculoskeletal and connective tissue disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Osteoarthritis | Musculoskeletal and connective tissue disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Osteoporotic fracture | Musculoskeletal and connective tissue disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Pain in extremity | Musculoskeletal and connective tissue disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Richter's syndrome | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 23.1 | Systematic Assessment |
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| Dizziness | Nervous system disorders | MedDRA 23.1 | Systematic Assessment |
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| Headache | Nervous system disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Paraesthesia | Nervous system disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Polyneuropathy | Nervous system disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Insomnia | Psychiatric disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Haematuria | Renal and urinary disorders | MedDRA 23.1 | Systematic Assessment |
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| Benign prostatic hyperplasia | Reproductive system and breast disorders | MedDRA 23.1 | Systematic Assessment |
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| Erectile dysfunction | Reproductive system and breast disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Oropharyngeal pain | Respiratory, thoracic and mediastinal disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Pleural effusion | Respiratory, thoracic and mediastinal disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Eczema | Skin and subcutaneous tissue disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Night sweats | Skin and subcutaneous tissue disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Petechiae | Skin and subcutaneous tissue disorders | MedDRA 23.1 | Systematic Assessment |
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| Pruritus | Skin and subcutaneous tissue disorders | MedDRA 23.1 | Systematic Assessment |
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| Purpura | Skin and subcutaneous tissue disorders | MedDRA 23.1 | Systematic Assessment |
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| Rash | Skin and subcutaneous tissue disorders | MedDRA 23.1 | Systematic Assessment |
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| Rash papular | Skin and subcutaneous tissue disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Urticaria | Skin and subcutaneous tissue disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Haematoma | Vascular disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Hypotension | Vascular disorders | MedDRA 23.1 | Systematic Assessment |
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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 |
| Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Jan 13, 2021 | Aug 18, 2021 | SAP_002.pdf |
| ID | Term |
|---|---|
| D015451 | Leukemia, Lymphocytic, Chronic, B-Cell |
| ID | Term |
|---|---|
| D015448 | Leukemia, B-Cell |
| D007945 | Leukemia, Lymphoid |
| D007938 | Leukemia |
| 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 |
Not provided
Not provided
| ID | Term |
|---|---|
| C000608238 | tirabrutinib |
| C000589391 | 6-(1H-indazol-6-yl)-N-(4-morpholinophenyl)imidazo(1,2-a)pyrazin-8-amine |
| C543332 | obinutuzumab |
Not provided
Not provided
Not provided
| Male |
|
| Not Hispanic or Latino |
|
| Not Permitted |
|
| Asian |
|
| Black |
|
| Native Hawaiian or Pacific Islander |
|
| White |
|
| Other |
|
| Not Permitted |
|
Tirabrutinib 80 mg (4 x 20 mg tablets/ 2 x 40 mg tablets/ 1 x 80 mg tablet) orally once daily + entospletinib 400 mg (2 x 200 mg tablets) orally once daily for up to 104 weeks + obinutuzumab 100 mg on Day 1, 900 mg on Day 1 or 2, and 1000 mg subsequently for up to 8 doses administered intravenously on Day 1 of Weeks 2, 3, 5, 9, 13, 17 and 21. |
|
|
Tirabrutinib 80 mg (4 x 20 mg tablets/ 2 x 40 mg tablets/ 1 x 80 mg tablet) orally once daily + entospletinib 400 mg (2 x 200 mg tablets) orally once daily for up to 104 weeks + obinutuzumab 100 mg on Day 1, 900 mg on Day 1 or 2, and 1000 mg subsequently for up to 8 doses administered intravenously on Day 1 of Weeks 2, 3, 5, 9, 13, 17 and 21. |
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