Clinical trial · Interventional
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)
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)
NCT04965493CI-TRIAL-00102006BRUIN CLL-322active not recruitingPhase 3ClinicalTrials.gov clinicaltrialsProvenance
- Source
- ClinicalTrials.gov
- Retrieved
- Sep 8, 2026
- Layer
- normalized (units and labels harmonized; values unchanged)
- Run
- ING-CLINICALTRIALS-20260908-000001
Summary
Brief summary (as posted)
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.
Conditions
Conditions (2)
Free-text conditions as registered, with the CancerIndex entity they were reconciled to and the match type.
| Condition (as posted) | Mapped entity | Match | Confidence |
|---|---|---|---|
| Chronic Lymphocytic Leukemia | Chronic Lymphocytic Leukemia | ONTOLOGY_EXACT | 0.98 |
| Small Lymphocytic Lymphoma | Small Lymphocytic Lymphoma | ONTOLOGY_EXACT | 0.98 |
Interventions
Interventions (3)
| Intervention | Type | Mapped drug | Match |
|---|---|---|---|
| Pirtobrutinib | Drug | Pirtobrutinib | ALIAS |
| Rituximab | Drug | Rituximab | ALIAS |
| Venetoclax | Drug | Venetoclax | ALIAS |
Design
Arms and outcomes
Arms (2)
- type
- EXPERIMENTAL
- label
- Arm A (PVR)
- description
- Fixed duration pirtobrutinib in combination with venetoclax and rituximab
- interventionNames
- Drug: Pirtobrutinib
- Drug: Venetoclax
- Drug: Rituximab
- type
- ACTIVE_COMPARATOR
- label
- Arm B (VR)
- description
- Venetoclax with rituximab
- interventionNames
- Drug: Venetoclax
- Drug: Rituximab
Primary outcomes (1)
- measure
- To evaluate progression-free survival (PFS) of pirtobrutinib plus venetoclax and rituximab (Arm A) compared to venetoclax and rituximab (Arm B)
Eligibility
Eligibility (as posted)
- Sex
- All
- Minimum age
- 18 Years
Show eligibility criteria text
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
References
Publications (1)
- DERIVEDDavids MS, Eyre TA, Woyach JA, Roeker LE, Ferrajoli A, Wang Y, Tam CS, Jurczak W, Zinzani PL, Simkovic M, Li JY, Bosch F, Roos-Weil D, Cramer P, Osterborg A, Islam P, Jacobs R, Skarbnik A, Bhat SA, Kang S, Chen M, Nguyen B, McNeely SC, Chung KL, Oliveira JM, Ito R, Ghia P, Wierda WG. Fixed-duration pirtobrutinib plus venetoclax-rituximab versus venetoclax-rituximab for patients with previously treated chronic lymphocytic leukaemia or small lymphocytic lymphoma (BRUIN CLL-322): an open-label, multicentre, randomised, controlled, phase 3 trial. Lancet. 2026 Aug 1;408(10553):453-470. doi: 10.1016/S0140-6736(26)01204-3. Epub 2026 Jul 9. PMID 42425121