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Trial record 1 of 1 for:    2016-002768-15
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Safety and Efficacy of the Combination of Tirabrutinib and Entospletinib With and Without Obinutuzumab in Adults With Chronic Lymphocytic Leukemia (CLL)

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ClinicalTrials.gov Identifier: NCT02983617
Recruitment Status : Active, not recruiting
First Posted : December 6, 2016
Last Update Posted : September 16, 2019
Sponsor:
Collaborator:
German CLL Study Group
Information provided by (Responsible Party):
Gilead Sciences

Brief Summary:

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).

The secondary objective is evaluation of safety and evaluation of additional parameters of efficacy. The treatment period is adaptive, with a duration of active treatment up to two years and a total follow-up on study for up to 30 days post end of treatment, or up to Week 25 should a participant discontinue treatment prior to Week 25 for reasons other than disease progression. The study has a 6 patient per arm safety run-in to evaluate safety prior to the enrollment of subsequent participants.


Condition or disease Intervention/treatment Phase
Chronic Lymphocytic Leukemia Drug: Tirabrutinib Drug: Entospletinib Drug: Obinutuzumab Phase 2

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 36 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Prospective, Randomized, Open-Label, Multicenter, Phase 2 Trial to Evaluate the Safety and Efficacy of the Combination of Tirabrutinib (GS-4059) and Entospletinib With and Without Obinutuzumab in Subjects With Chronic Lymphocytic Leukemia
Actual Study Start Date : April 6, 2017
Actual Primary Completion Date : February 20, 2019
Estimated Study Completion Date : September 2020


Arm Intervention/treatment
Experimental: Tirabrutinib + entospletinib
Participants will receive tirabrutinib and entospletinib for up to 104 weeks.
Drug: Tirabrutinib
80 mg (1 x 80 mg or 4 x 20 mg or 2 x 40 mg) tablets administered orally once daily
Other Name: GS-4059

Drug: Entospletinib
400 mg (2 x 200 mg) tablets administered orally once daily
Other Name: GS-9973

Experimental: Tirabrutinib + entospletinib + obinutuzumab
Participants will receive obinutuzumab over 21 weeks and the combination of tirabrutinib and entospletinib for up to 104 weeks.
Drug: Tirabrutinib
80 mg (1 x 80 mg or 4 x 20 mg or 2 x 40 mg) tablets administered orally once daily
Other Name: GS-4059

Drug: Entospletinib
400 mg (2 x 200 mg) tablets administered orally once daily
Other Name: GS-9973

Drug: Obinutuzumab
1000 mg/40 mL single-use vials administered intravenously for a total of 8 doses over 21 weeks
Other Names:
  • Gazyvaro®
  • Gazyva®
  • GA101




Primary Outcome Measures :
  1. Rate of Complete Remission (CR) as Assessed by the Investigator Using the Modified International Workshop on CLL (IWCLL) 2008 criteria [ Time Frame: After the completion of 24 weeks of treatment ]

Secondary Outcome Measures :
  1. Rate of CR with Bone Marrow Minimal Residual Disease (MRD) Negativity [ Time Frame: After the completion of 24 weeks of treatment ]
  2. Rate of CR with Peripheral Blood MRD Negativity [ Time Frame: After the completion of 24 weeks of treatment ]
  3. Overall Response Rate (ORR) [ Time Frame: After the completion of 24 weeks of treatment ]
  4. Percentage of Participants Experiencing Treatment-Emergent Adverse Events (AE) and Treatment-EmergentSerious AEs [ Time Frame: Up to 104 weeks plus 30 days, or up to Week 25 should a participant discontinue treatment prior to Week 25 for reasons other than disease progression ]


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Key Inclusion Criteria:

  • Documentation of relapsed or refractory CLL
  • Requiring treatment per modified IWCLL 2008 criteria; adults without radiographically measureable disease (defined as ≥ 1 lesion > 1.5 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/L, neutrophil count ≥ 1 × 10^9/L, hemoglobin ≥ 8 g/dL unless lower values are directly attributable to documented bone marrow burden of CLL
  • Creatinine clearance (CrCl) ≥ 50 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 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

Key Exclusion Criteria:

  • Known transformation of CLL (ie, Richter's transformation, prolymphocytic leukemia)
  • 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; subjects 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

Note: Other protocol defined Inclusion/Exclusion criteria may apply.


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02983617


Locations
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Germany
Studienzentrum Aschaffenburg
Aschaffenburg, Germany, 63739
Evangelisches Diakoniekrankenhaus Bremen Hämatologie
Bremen, Germany, 28239
St.-Johannes-Hospital
Dortmund, Germany, D-44137
University Medical Center Freiburg
Freiburg, Germany, 79106
Onkologische Schwerpunktpraxis Lerchenfeld
Hamburg, Germany, 22081
Universitätsklinikum Heidelberg, Abteilung Innere Medizin V
Heidelberg, Germany, 69120
Marienhospital Herne, Dept. of Internal Medicine
Herne, Germany, 44625
Universitätsklinikum Schleswig-Holstein Klinik für Innere Medizin II - Hämatologie und Onkologie
Kiel, Germany, 24105
Uniklinik Köln Klinik I für Innere Medizin
Köln, Germany, 50937
Mannheimer Onkologie Praxis
Manheim, Germany, 68161
Gemeinschaftspraxis für Hämatologie und Onkologie
Münster, Germany, 48149
Kreiskliniken Reutlingen GmbH Klinikum am Steinenberg
Reutlingen, Germany, 72764
Praxis für Hämatologie und Onkologie
Saarbrücken, Germany, 66113
Robert-Bosch-Krakenhaus
Stuttgart, Germany, 70376
Universitätsklinik Ulm - Klinik für Innere Medizin III
Ulm, Germany, 89081
Sponsors and Collaborators
Gilead Sciences
German CLL Study Group
Investigators
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Study Director: Gilead Study Director Gilead Sciences

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Responsible Party: Gilead Sciences
ClinicalTrials.gov Identifier: NCT02983617     History of Changes
Other Study ID Numbers: GS-US-401-2076
2016-002768-15 ( EudraCT Number )
CLLRUmbrella2 ( Other Identifier: German CLL Study Group )
First Posted: December 6, 2016    Key Record Dates
Last Update Posted: September 16, 2019
Last Verified: September 2019

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: Yes
Additional relevant MeSH terms:
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Leukemia
Leukemia, Lymphoid
Leukemia, Lymphocytic, Chronic, B-Cell
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Leukemia, B-Cell
Obinutuzumab
Antineoplastic Agents, Immunological
Antineoplastic Agents