Study to Evaluate the Safety and Efficacy of the Combination of Tirabrutinib and Idelalisib With and Without Obinutuzumab in Adults With Relapsed or Refractory Chronic Lymphocytic Leukemia (CLL)

NCT ID: NCT02968563

Last Updated: 2022-01-21

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 35 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-12-13
• Study Completion Date: 2021-01-14

Brief Summary

The primary objective of this study is to determine the preliminary efficacy of the combination of tirabrutinib and idelalisib with obinutuzumab in adults with relapsed or refractory chronic lymphocytic leukemia (CLL).

The study has a 6 participant per arm safety run-in to evaluate safety prior to the enrollment of subsequent participants. 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.

Conditions

Chronic Lymphocytic Leukemia

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Tirabrutinib + Idelalisib

Tirabrutinib 80 mg (4 x 20 mg tablets/2 x 40 mg tablets/1 x 80 mg tablet) once daily + idelalisib 100 mg (1 x 100 mg tablet) once daily for up to 104 weeks.

Group Type: EXPERIMENTAL

Tirabrutinib

Intervention Type: DRUG

Tablets administered orally

Idelalisib

Intervention Type: DRUG

Tablets administered orally

Tirabrutinib + Idelalisib + Obinutuzumab

Tirabrutinib 80 mg (4 x 20 mg tablets/ 2 x 40 mg tablets/ 1 x 80 mg tablet) once daily + idelalisib 100 mg (1 x 100 mg tablet) 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 on Day 1 of Weeks 2, 3, 5, and then every 4 weeks through Week 21.

Group Type: EXPERIMENTAL

Tirabrutinib

Intervention Type: DRUG

Tablets administered orally

Idelalisib

Intervention Type: DRUG

Tablets administered orally

Obinutuzumab

Intervention Type: DRUG

Administered intravenously

Interventions

Tirabrutinib

Tablets administered orally

Intervention Type: DRUG

Idelalisib

Tablets administered orally

Intervention Type: DRUG

Obinutuzumab

Administered intravenously

Intervention Type: DRUG

Other Intervention Names

GS-4059; Zydelig®; GS-1101; CAL-101; Gazyvaro®; Gazyva®; GA101

Eligibility Criteria

Inclusion Criteria

• Documentation of relapsed or refractory CLL
• Requiring treatment per modified International Workshop on CLL (IWCLL) 2008 criteria; individuals without radiographically measurable disease (defined as ≥ 1 lesion > 1.5 centimetre (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 grams per decilitre (g/dL) unless lower values are directly attributable to documented bone marrow burden of CLL
• Creatinine clearance (CrCl) ≥ 50 milliliter 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, hepatitis C virus (HCV) infection, and cytomegalovirus (CMV) 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 including mandatory prophylaxis for Pneumocystis jirovecii pneumonia (PJP)

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 individuals with prior treatment with agents in these classes should be reviewed by the sponsor or the German CLL Study Group (GCLLSG) study 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
• Treatment or prophylaxis for CMV within the past 28 days
• History of stroke or intracranial hemorrhage within 12 months of randomization; patients requiring therapeutic anticoagulation for any indication should be discussed with the GCLLSG cooperating physician and/or medical monitor prior to screening.
• Use of a strong CYP3A4 or a strong P-glycoprotein (P-gp) inducer within 2 weeks of first dose of study treatment or anticipated chronic use while on study
• Demonstration of corrected QT (QTc) interval > 450 milliseconds or requirement for ongoing treatment with concomitant medications that prolong the QT interval

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

German CLL Study Group

OTHER

Sponsor Role: collaborator

Gilead Sciences

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Gilead Study Director

Role: STUDY_DIRECTOR

Gilead Sciences

Locations

Ambulante Krebszentrum Schaubstraße

Frankfurt (Oder), Brandenburg, Germany

Hämatologische-onkologische Gem.-Praxis Dres. Brudler-Heinrich-Bangerter, Augsburg

Augsburg, , Germany

Uniklinik Koln

Cologne, , Germany

Internistische Gemeinschaftspraxis Dres. Schliesser-Käbisch-Weber, Gießen

Giessen, , Germany

Uniklinik Leipzig

Leipzig, , Germany

Luebecker Onkologische Schwerpunktpraxis

Lübeck, , Germany

Universitasmtedizin Mannheim

Mannheim, , Germany

KH Maria Hilf-Franziskushaus, Mönchengladbach

Mönchengladbach, , Germany

Stauferklinikum Schwäbisch Gmünd

Mutlangen, , Germany

Krankenhaus München-Schwabing

München, , Germany

Klinikum Rechts der Isar der Technischen Universität München

München, , Germany

Studienzentrum Onkologie Ravensburg

Ravensburg, , Germany

Facharztzentrum Regensburg

Regensburg, , Germany

Universitätsklinikum Ulm

Ulm, , Germany

Countries

Germany

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

2015-003909-42

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

CLLRUmbrella1

Identifier Type: OTHER

Identifier Source: secondary_id

GS-US-401-1958

Identifier Type: -

Identifier Source: org_study_id