Clinical trial · Interventional
Study of LOXO-305 (Pirtobrutinib) Versus Investigator's Choice (Idelalisib Plus Rituximab or Bendamustine Plus Rituximab) in Patients With Previously Treated Chronic Lymphocytic Leukemia (CLL)/Small Lymphocytic Lymphoma (SLL)
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)
- 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)
This is a study for patients with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (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.
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 (4)
| Intervention | Type | Mapped drug | Match |
|---|---|---|---|
| Bendamustine | Drug | Bendamustine | ALIAS |
| Idelalisib | Drug | Idelalisib | ALIAS |
| Pirtobrutinib | Drug | Pirtobrutinib | ALIAS |
| Rituximab | Drug | Rituximab | ALIAS |
Design
Arms and outcomes
Arms (2)
- type
- EXPERIMENTAL
- label
- Arm A - Pirtobrutinib
- description
- Participants received 200 milligrams (mg) of pirtobrutinib administered orally once daily (QD) on Days 1 through 28 of a 28-day cycle. The treatment was continued until progressive disease, a discontinuation criterion, or unacceptable toxicity.
- interventionNames
- Drug: Pirtobrutinib
- type
- ACTIVE_COMPARATOR
- label
- Arm B - Idelalisib plus Rituximab or Bendamustine plus Rituximab
- description
- Participants received either 150 mg of idelalisib administered twice-daily (BID) orally on Days 1 through 28 of a 28-day cycle in combination with 375 milligram per square meter (mg/m\^2) of rituximab by intravenous (IV) infusion on day 1 of cycle 1, then 4 IV infusions of rituximab 500 mg/m\^2 every 2 weeks (Q2W) and 3 IV infusions of rituximab 500 mg/m\^2 every 4 weeks (Q4W) or 70 mg/m\^2 of bendamustine administered IV on day 1 and 2 of each 28-day cycle from cycles 1 to 6 in combination with 375 mg/m\^2 of rituximab IV on day 1 of cycle 1, then 500 mg/m\^2 of rituximab on day 1 of each 28-day cycle from cycles 2 to 6.
- interventionNames
Eligibility
Eligibility (as posted)
- Sex
- All
- Minimum age
- 18 Years
Show eligibility criteria text
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.
References
Publications (2)
- DERIVEDLoubert A, Creel K, Bhandari NR, Hess LM, Ruppert AS, Abada P, Regnault A, Payakachat N. Psychometric analysis of new lymphoma-specific patient-reported symptom measures derived from the EORTC item library. J Patient Rep Outcomes. 2026 Jun 22;10(1):109. doi: 10.1186/s41687-026-01126-w. PMID 42329537
- DERIVEDSharman JP, Munir T, Grosicki S, Roeker LE, Burke JM, Chen CI, Grzasko N, Follows G, Matrai Z, Sanna A, Qiu L, Feng R, Hua VM, Jurczak W, Ritgen M, Yi S, Bosch F, Coombs CC, Bao K, Patel V, Liu B, Compte L, Guntur A, Wang DY, Hill M, Leow CC, Ghia P, Barr PM. Phase III Trial of Pirtobrutinib Versus Idelalisib/Rituximab or Bendamustine/Rituximab in Covalent Bruton Tyrosine Kinase Inhibitor-Pretreated Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (BRUIN CLL-321). J Clin Oncol. 2025 Aug;43(22):2538-2549. doi: 10.1200/JCO-25-00166. Epub 2025 Jun 6. PMID 40479620