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)

NCT02968563 | Completed Phase 2 Results FDA Drug

• 3 other identifiers: GS-US-401-19582015-003909-42CLLRUmbrella1
• Study Type: interventional
• Target: 35
• Locations: 1 country
• Sites: 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

Outcome Measures

Primary Outcomes (1)

• Rate of Complete Response/Complete Remission (CR), 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

Secondary Outcomes (4)

• 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

  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

  Week 25

• Overall Response Rate (ORR), as Assessed by the Investigator Using the Modified IWCLL 2008 Criteria at Week 25

  Week 25

• Percentage of Participants Experiencing Any Treatment-Emergent Adverse Events (AEs) and Treatment-Emergent Serious Adverse Events (SAEs)

  First dose date up to the last dose date (maximum: 105 weeks) plus 30 days

Study Arms (2)

Tirabrutinib + Idelalisib

EXPERIMENTAL

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.

Drug: Tirabrutinib; Drug: Idelalisib

Tirabrutinib + Idelalisib + Obinutuzumab

EXPERIMENTAL

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.

Drug: Tirabrutinib; Drug: Idelalisib; Drug: Obinutuzumab

Interventions

Tirabrutinib DRUG

Tablets administered orally

Also known as: GS-4059

Tirabrutinib + Idelalisib; Tirabrutinib + Idelalisib + Obinutuzumab

Idelalisib DRUG

Tablets administered orally

Also known as: Zydelig®, GS-1101, CAL-101

Tirabrutinib + Idelalisib; Tirabrutinib + Idelalisib + Obinutuzumab

Obinutuzumab DRUG

Administered intravenously

Also known as: Gazyvaro®, Gazyva®, GA101

Tirabrutinib + Idelalisib + Obinutuzumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• Gilead Sciences: lead
• German CLL Study Group: collaborator

Study Sites (14)

Ambulante Krebszentrum Schaubstraße

Frankfurt (Oder), Brandenburg, 60596, Germany

Location

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

Augsburg, 86150, Germany

Location

Uniklinik Koln

Cologne, 50937, Germany

Location

Internistische Gemeinschaftspraxis Dres. Schliesser-Käbisch-Weber, Gießen

Giessen, 35392, Germany

Location

Uniklinik Leipzig

Leipzig, 04103, Germany

Location

Luebecker Onkologische Schwerpunktpraxis

Lübeck, 23562, Germany

Location

Universitasmtedizin Mannheim

Mannheim, 68167, Germany

Location

KH Maria Hilf-Franziskushaus, Mönchengladbach

Mönchengladbach, 41063, Germany

Location

Stauferklinikum Schwäbisch Gmünd

Mutlangen, 73557, Germany

Location

Krankenhaus München-Schwabing

München, 80804, Germany

Location

Klinikum Rechts der Isar der Technischen Universität München

München, 81675, Germany

Location

Studienzentrum Onkologie Ravensburg

Ravensburg, 88212, Germany

Location

Facharztzentrum Regensburg

Regensburg, 93053, Germany

Location

Universitätsklinikum Ulm

Ulm, 89081, Germany

Location

MeSH Terms

Conditions

Leukemia, Lymphocytic, Chronic, B-Cell

Interventions

tirabrutinib; idelalisib; obinutuzumab

Condition Hierarchy (Ancestors)

Leukemia, B-Cell; Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Results Point of Contact

• Title: Gilead Clinical Study Information Center
• Organization: Gilead Sciences

GileadClinicalTrials@gilead.com

1-833-445-3230 (GILEAD-0)

Study Officials

• Gilead Study Director

  Gilead Sciences

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 16, 2016
• First Posted: November 18, 2016
• Study Start: December 13, 2016
• Primary Completion: June 17, 2019
• Study Completion: January 14, 2021
• Last Updated: January 21, 2022
• Results First Posted: July 1, 2020

Record last verified: 2021-12

Data Sharing

• IPD Sharing: Will not share

Locations

DE (14)