A Trial of Pirtobrutinib (LOXO-305) Plus Venetoclax and Rituximab (PVR) Versus Venetoclax and Rituximab (VR) in Previously Treated Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL)

ID#: NCT04965493

Age: 18 years - 66+

Gender: All

Healthy Subjects: No

Study Phase: Phase 3

Recruitment Status: Recruiting

Start Date: September 20, 2021

End Date: January 01, 2027

Contact Information:
Patient Advocacy
Summary: 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.

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