A Phase 3 Open-Label, Randomized Study of LOXO-305 Versus Investigator's Choice of Idelalisib Plus Rituximab or Bendamustine Plus Rituximab in BTK Inhibitor Pretreated Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (BRUIN CLL-321)

LOXO-BTK-20020

This is a study for patients with chronic lymphocytic leukemia (CLL) or small lymphocytic leukemia (SLL) who have previously received treatment with at least a BTK inhibitor. The main purpose is to compare LOXO-305 to idelalisib plus rituximab or bendamustine plus rituximab. Participation could last up to four years, and possibly longer, if the disease does not progress.

2021-03-09

2023-11-01

2027-05-01

Active (not recruiting)

Early phase I

250

Inclusion Criteria: * Confirmed diagnosis of CLL/SLL requiring therapy as defined by iwCLL 2018 criteria. * Previously treated with a covalent BTK inhibitor. * Eastern Cooperative Oncology Group (ECOG) 0-2. * Absolute neutrophil count ≥ 0.75 × 10\^9/L without granulocyte-colony-stimulating factor support, or ≥ 0.50 × 10\^9/L in patients with documented bone marrow involvement considered to impair hematopoiesis. Granulocyte-colony-stimulating factor support is permitted in patients with documented bone marrow involvement. * Hemoglobin ≥ 8 g/dL or ≥ 6 g/dL in patients with documented bone marrow involvement considered to impair hematopoiesis. Transfusion support is permitted in patients with bone marrow involvement. * Platelets ≥ 50 × 10\^9/L. If an investigator has chosen bendamustine/rituximab as the Arm B treatment, platelets must be ≥ 75 × 10\^9/L. Patients may enroll below these thresholds if the Investigator determines the cytopenia is related to bone marrow involvement considered to impair hematopoiesis. Patients with a platelet count \< 30 x 10\^9/L are excluded. * AST and ALT ≤ 3.0 x upper limit of normal (ULN). * Total bilirubin ≤ 1.5 x ULN. * Estimated creatinine clearance of ≥ 30 mL/min. Exclusion Criteria: * Known or suspected Richter's transformation at any time preceding enrollment. * Known or suspected history of central nervous system (CNS) involvement by CLL/SLL. * Ongoing drug-induced liver injury. * Active uncontrolled auto-immune cytopenia. * Significant cardiovascular disease. * History of allogeneic or stem cell transplantation (SCT) or chimeric antigen receptor-modified T cells (CAR-T) therapy within the past 60 days. * Active hepatitis B or hepatitis C. * Known active cytomegalovirus (CMV) infection. * Active uncontrolled systemic bacterial, viral, fungal or parasitic infection. * Known Human Immunodeficiency Virus (HIV) infection, regardless of CD4 count. * Clinically significant active malabsorption syndrome or inflammatory bowel disease * Prior exposure to 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. * Vaccination with a live vaccine within 28 days prior to randomization. * Patients with the following hypersensitivity: 1. Known hypersensitivity, including anaphylaxis, to any component or excipient of LOXO-305. For patients planned to receive idelalisib, known hypersensitivity, including anaphylaxis, to any component or excipient of idelalisib. For patients planned to receive bendamustine, known hypersensitivity, including anaphylaxis, to any component or excipient of bendamustine. 2. Prior significant hypersensitivity to rituximab.

{'studyType': 'INTERVENTIONAL', 'phases': ['PHASE3'], 'designInfo': {'allocation': 'RANDOMIZED', 'interventionModel': 'PARALLEL', 'interventionModelDescription': 'Eligible patients will be randomized in 1:1 into Arm A or Arm B. Patients randomized to Arm B who have disease progression (PD) confirmed by independent review committee (IRC) may be eligible to crossover into Arm A. Patients who discontinue treatment for toxicity may still be evaluated for cross over at the time of IRC-confirmed PD.', 'primaryPurpose': 'TREATMENT', 'maskingInfo': {'masking': 'NONE'}}, 'enrollmentInfo': {'count': 250, 'type': 'ESTIMATED'}}

2024-04-26