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)


About this study

The purpose of this study is to compare the effectiveness 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.

Participation eligibility

Participant eligibility includes age, gender, type and stage of disease, and previous treatments or health concerns. Guidelines differ from study to study, and identify who can or cannot participate. There is no guarantee that every individual who qualifies and wants to participate in a trial will be enrolled. Contact the study team to discuss study eligibility and potential participation.

Inclusion Criteria:

  • Age 18 and older at time of enrollment.
  • 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 ≥ 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 and/or strong P-glycoprotein (P-gp) inhibitors.
  • 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.

Participating Mayo Clinic locations

Study statuses change often. Please contact the study team for the most up-to-date information regarding possible participation.

Mayo Clinic Location Status Contact

Rochester, Minn.

Mayo Clinic principal investigator

Yucai Wang, M.D., Ph.D.

Open for enrollment

Contact information:

Cancer Center Clinical Trials Referral Office


Scottsdale/Phoenix, Ariz.

Mayo Clinic principal investigator

Jose Leis, M.D., Ph.D.

Open for enrollment

Contact information:

Cancer Center Clinical Trials Referral Office

(855) 776-0015

More information


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