臨床研究等提出・公開システム

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 Study of LOXO-305 in Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma

Masaki Takeshi

Eli Lilly Japan K.K.

5-1-28, Isogamidori, Chuo-ku, Kobe, Hyogo

LTG_CallCenter@lists.lilly.com

IQVIA Services Japan G.K. jRCT Inquiry Contact

IQVIA Services Japan G.K.

4-10-18 Takanawa, Minato-ku, Tokyo

+81-3-6859-9500

JP_LOXO-BTK-20019_20020_CRA@iqvia.com

Not Recruiting

Aug. 24, 2021

Interventional

randomized controlled trial

open(masking not used)

active control

parallel assignment

treatment purpose

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 x 10^9/L without granulocyte-colony-stimulating factor support, or >= 0.50 x 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 x 10^9/L. If an investigator has chosen bendamustine/rituximab as the Arm B treatment, platelets must be >= 75 x 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.

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.

Both

Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma

Drug: LOXO-305
Oral LOXO-305
Other Name: Pirtobrutinib
Drug: Idelalisib
Oral
Other Name: Zydelig
Drug: Bendamustine
IV
Other Name: Treanda, Treakisym, Ribomustin, Levact
Drug: Rituximab
IV
Other Name: Rituxan, MabThera, Truxima

[Study Arms]
Experimental: Arm A (LOXO-305)
Orally
Intervention: Drug: LOXO-305
Active Comparator: Arm B (Idelalisib plus rituximab [IdelaR] or bendamustine plus rituximab [BR])
Investigator's choice of idelalisib plus rituximab (IdelaR) or bendamustine plus rituximab (BR).
Interventions:
Drug: Idelalisib
Drug: Bendamustine
Drug: Rituximab

To evaluate progression-free survival (PFS) of LOXO-305 monotherapy (Arm A) compared to investigator's choice of idelalisib plus rituximab (IdelaR) or bendamustine plus rituximab (BR) (Arm B) [ Time Frame: Up to approximately 36 months ]
Assessed per iwCLL 2018

+81-22-717-7000

Mar. 22, 2021

No

Australia/Austria/Belgium/Canada/China/Croatia/Czech Republic/France/Germany/Hungary/Ireland/Israel/Italy/Poland/Russia/Singapore/Spain/South Korea/Switzerland/Taiwan/United Kingdom/United States/Turkey