Safety and Efficacy of the Combination of Tirabrutinib and Entospletinib With and Without Obinutuzumab in Adults With Chronic Lymphocytic Leukemia (CLL)
NCT ID: NCT02983617
Last Updated: 2021-12-21
Study Results
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View full resultsBasic Information
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COMPLETED
PHASE2
36 participants
INTERVENTIONAL
2017-04-06
2020-10-01
Brief Summary
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Detailed Description
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Conditions
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Study Design
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NON_RANDOMIZED
PARALLEL
TREATMENT
NONE
Study Groups
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Tirabrutinib + Entospletinib
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
Administered orally once daily
Entospletinib
Administered orally once daily
Tirabrutinib + Entospletinib + Obinutuzumab
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.
Tirabrutinib
Administered orally once daily
Entospletinib
Administered orally once daily
Obinutuzumab
Administered intravenously
Interventions
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Tirabrutinib
Administered orally once daily
Entospletinib
Administered orally once daily
Obinutuzumab
Administered intravenously
Other Intervention Names
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Eligibility Criteria
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Inclusion Criteria
* 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:
* For females of childbearing potential, willingness to abstain from sexual intercourse or use a protocol-specified method of contraception as described in the study protocol
* Males of reproductive potential who engage in sexual intercourse must agree to use protocol-specified method(s) of contraception as described in the study protocol
* Able to comply with study procedures and restrictions
Exclusion Criteria
* Known central nervous system (CNS) involvement
* Progression on treatment with any inhibitor of Bruton's tyrosine kinase (BTK), spleen tyrosine kinase (SYK), phosphatidylinositol 3-kinase (PI3K), B-cell lymphoma 2 (BCL-2), or obinutuzumab. The treatment and disease response history of participants with prior treatment with agents in these classes should be reviewed by the sponsor or the German CLL Study Group office prior to enrollment to clarify sensitivity to these treatments
* Any treatment for CLL other than corticosteroids for symptomatic management within 28 days of the start of study treatment
* Participation on a concurrent therapeutic clinical trial unless all treatment is complete with only ongoing surveillance
* Diagnosis of or concern for progressive multifocal leukoencephalopathy
* History of myelodysplastic syndrome or another malignancy other than CLL, except for the following: any malignancy that has been in complete remission for 3 years, adequately treated local basal cell or squamous cell carcinoma of the skin, cervical carcinoma in situ, superficial bladder cancer, asymptomatic prostate cancer without known metastatic disease and with no requirement for therapy or requiring only hormonal therapy and with normal prostate-specific antigen for ≥1 year prior to start of study therapy
* Active infection requiring systemic therapy
* Pregnant or nursing women (a negative pregnancy test is required for all women of childbearing potential within 7 days before start of treatment and monthly during therapy)
* Active autoimmune disease or the need for higher than prednisone 10 mg daily unless for management of CLL symptoms
* History of stroke or intracranial hemorrhage within 12 months of randomization; participants requiring therapeutic anticoagulation for any indication should be discussed with the German CLL Study Group (GCLLSG) cooperating physician and/or medical monitor prior to screening
* Anticipated chronic use of strong CYP3A4/CYP2C9 inducers, moderate CYP2C9 inducers, or strong P-gp inducers while on study; use within 2 weeks of first dose of study treatment should be avoided
* Requirement for proton pump inhibitor (PPI) therapy
* Demonstration of corrected QT (QTc) interval \> 450 milliseconds or requirement for ongoing treatment with concomitant medications that prolong the QT interval
18 Years
ALL
No
Sponsors
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German CLL Study Group
OTHER
Gilead Sciences
INDUSTRY
Responsible Party
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Principal Investigators
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Gilead Study Director
Role: STUDY_DIRECTOR
Gilead Sciences
Locations
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Studienzentrum Aschaffenburg
Aschaffenburg, , Germany
Evangelisches Diakoniekrankenhaus Bremen Hämatologie
Bremen, , Germany
Uniklinik Köln Klinik I für Innere Medizin
Cologne, , Germany
St.-Johannes-Hospital
Dortmund, , Germany
University Medical Center Freiburg
Freiburg im Breisgau, , Germany
Onkologische Schwerpunktpraxis Lerchenfeld
Hamburg, , Germany
Universitätsklinikum Heidelberg, Abteilung Innere Medizin V
Heidelberg, , Germany
Marienhospital Herne, Dept. of Internal Medicine
Herne, , Germany
Universitätsklinikum Schleswig-Holstein Klinik für Innere Medizin II - Hämatologie und Onkologie
Kiel, , Germany
Mannheimer Onkologie Praxis
Manheim, , Germany
Gemeinschaftspraxis für Hämatologie und Onkologie
Münster, , Germany
Kreiskliniken Reutlingen GmbH Klinikum am Steinenberg
Reutlingen, , Germany
Praxis für Hämatologie und Onkologie
Saarbrücken, , Germany
Robert-Bosch-Krakenhaus
Stuttgart, , Germany
Universitätsklinik Ulm - Klinik für Innere Medizin III
Ulm, , Germany
Countries
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References
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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.
Provided Documents
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Document Type: Study Protocol
Document Type: Statistical Analysis Plan
Other Identifiers
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2016-002768-15
Identifier Type: EUDRACT_NUMBER
Identifier Source: secondary_id
CLLRUmbrella2
Identifier Type: OTHER
Identifier Source: secondary_id
GS-US-401-2076
Identifier Type: -
Identifier Source: org_study_id