Clinical trial NCT02968563: 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)
Official title: A Prospective, Open-Label, Multicenter, Phase 2 Trial to Evaluate the Safety and Efficacy of the Combination of Tirabrutinib (GS-4059) and Idelalisib With and Without Obinutuzumab in Subjects With Chronic Lymphocytic Leukemia
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Chronic Lymphocytic Leukemia
Lead sponsor: Gilead Sciences
Sponsor class: INDUSTRY
Collaborators: name: German CLL Study Group
First posted: 2016-11-18
Enrollment: 35
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: Key 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)

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 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

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

Primary outcomes:
measure: 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
timeFrame: Week 25
Secondary outcomes:
measure: 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
timeFrame: Week 25
measure: 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
timeFrame: Week 25
measure: Overall Response Rate (ORR), as Assessed by the Investigator Using the Modified IWCLL 2008 Criteria at Week 25
timeFrame: Week 25
measure: Percentage of Participants Experiencing Any Treatment-Emergent Adverse Events (AEs) and Treatment-Emergent Serious Adverse Events (SAEs)
timeFrame: First dose date up to the last dose date (maximum: 105 weeks) plus 30 days
Other outcomes:
Locations:
city: Frankfurt
country: Germany
facility: Ambulante Krebszentrum Schaubstraße
state: Brandenburg
city: Augsburg
country: Germany
facility: Hämatologische-onkologische Gem.-Praxis Dres. Brudler-Heinrich-Bangerter, Augsburg
city: Gießen
country: Germany
facility: Internistische Gemeinschaftspraxis Dres. Schliesser-Käbisch-Weber, Gießen
city: Köln
country: Germany
facility: Uniklinik Koln
city: Leipzig
country: Germany
facility: Uniklinik Leipzig
city: Luebeck
country: Germany
facility: Luebecker Onkologische Schwerpunktpraxis
city: Mannheim
country: Germany
facility: Universitasmtedizin Mannheim
city: Mutlangen
country: Germany
facility: Stauferklinikum Schwäbisch Gmünd
city: Mönchengladbach
country: Germany
facility: KH Maria Hilf-Franziskushaus, Mönchengladbach
city: München
country: Germany
facility: Krankenhaus München-Schwabing
city: München
country: Germany
facility: Klinikum Rechts der Isar der Technischen Universität München
city: Ravensburg
country: Germany
facility: Studienzentrum Onkologie Ravensburg
city: Regensburg
country: Germany
facility: Facharztzentrum Regensburg
city: Ulm
country: Germany
facility: Universitätsklinikum Ulm
Study officials:
affiliation: Gilead Sciences
name: Gilead Study Director
role: STUDY_DIRECTOR
References: