A Phase 3 Open-Label, Randomized Study of Fixed Duration Pirtobrutinib (LOXO-305) Plus Venetoclax and Rituximab Versus Venetoclax and Rituximab in Previously Treated Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (BRUIN CLL-322)

LOXO-BTK-20022

The purpose of this study is to compare the efficacy and safety of fixed duration pirtobruitinib (LOXO-305) with VR (Arm A) compared to VR alone (Arm B) in patients with CLL/SLL who have been previously treated with at least one prior line of therapy. Participation could last up to five years.

2021-09-20

2025-10-01

2027-01-01

Recruiting

Early phase I

600

Inclusion Criteria: * Confirmed diagnosis of CLL/SLL requiring therapy per iwCLL 2018 criteria * Previous treatment with at least one line of therapy that may include a covalent Bruton's tyrosine kinase (BTK) inhibitor * Platelets greater than or equal to (≥)50 x 10⁹/liter (L), hemoglobin ≥8 grams/deciliter (g/dL) and absolute neutrophil count ≥1.0 x 10⁹/L * Adequate organ function * Eastern Cooperative Oncology Group (ECOG) Performance Status 0-2 * Estimated creatinine clearance ≥30 milliliters per minute (mL/min) Exclusion Criteria: * Known or suspected Richter's transformation at any time preceding enrollment * Prior therapy with a non-covalent (reversible) BTK inhibitor * Patients requiring therapeutic anticoagulation with warfarin or another Vitamin K antagonist * Current treatment with strong cytochrome P450 (CYP) 3A4 (CYP3A4) inhibitors or inducers * Prior therapy with venetoclax * Central nervous system (CNS) involvement * Active uncontrolled systemic bacterial, viral, fungal, or parasitic infection * Known human immunodeficiency virus (HIV) infection, regardless of cluster of differentiation 4 (CD4) count * Allogeneic stem cell transplantation (SCT) or chimeric antigen receptor (CAR)-T within 60 days * Active hepatitis B or hepatitis C * Known active cytomegalovirus (CMV) infection * Uncontrolled immune thrombocytopenic purpura (ITP) or autoimmune hemolytic anemia (AIHA) * Significant cardiovascular disease * Vaccination with a live vaccine within 28 days prior to randomization * Patients with the following hypersensitivity: * Known hypersensitivity to any component or excipient of pirtobrutinib and venetoclax * Prior significant hypersensitivity to rituximab * Known allergy to allopurinol and inability to take uric acid lowering agent

{'studyType': 'INTERVENTIONAL', 'phases': ['PHASE3'], 'designInfo': {'allocation': 'RANDOMIZED', 'interventionModel': 'PARALLEL', 'interventionModelDescription': 'Eligible patients will be randomized 1:1 into Arm A and Arm B.', 'primaryPurpose': 'TREATMENT', 'maskingInfo': {'masking': 'NONE'}}, 'enrollmentInfo': {'count': 600, 'type': 'ESTIMATED'}}

2024-01-26