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)
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)
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.
This is a Phase 3 global, randomized, open-label study comparing LOXO-305 (Arm A) to investigator's choice of either idelalisib plus rituximab or bendamustine plus rituximab (Arm B) in CLL/SLL patients who have been treated with at least a covalent BTK inhibitor (BTKi). Patients may have discontinued the prior covalent BTKi due to disease progression (PD) or intolerance. Patients who have received venetoclax are eligible for the study. Eligible patients will be randomized in 1:1 to Arm A or Arm B.
Inclusion Criteria:
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:
Xicheng District, Beijing Municipality 100053, China
Zagreb, Croatia
Politiers, Politiers 86021, France
Rouen, Seine-Maritime 76038, France
Bordeaux, 33076, France
Kerpener, Köln 50937, Germany
Langenbeckstraße 1, Mainz D- 55131, Germany
Koelner Platz 1, München 80804, Germany
Viale Orazio Flacco, Bari 70124, Italy
Monza (MB) -Settore E, Piano 2 20900, Italy
Roma, 00168, Italy
Ogaki-shi, Gifu 503-8502, Japan
Osaka Sayama-shi, Osaka 589 8511, Japan
Koto, Tokyo 135-8550, Japan
Shinagawa-Ku, Tokyo 141-8625, Japan
Fukoka-ken, 806 8501, Japan
Iwaszkiewicza 5, Legnica 59-220, Poland
Brzozów, 36-200, Poland
Bydgoszcz, 85-168, Poland
Warsaw, 02-781, Poland
Wałbrzych, 58-309, Poland
Omsk, Omsk Oblast 644013, Russia
Saint Petersburg, 191024, Russia
Saint Petersburg, 197022, Russia
Namdong-gu, Incheon-gwangyeoksi [Incheon] 21565, South Korea
Seocho-Gu, Seoul 06591, South Korea
Seoul, Seoul-teukbyeolsi [Seoul] 03722, South Korea
Santiago de Compostela, La Coruna 15706, Spain
Bellinzona, Svizzera 6500, Switzerland
Taipei City, Taipei 114, Taiwan
Faith, Istanbul, Turkey (Türkiye)