A Phase 3 Study of LOXO-305 in Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma

JRCT ID: jRCT2021210031

Registered date:24/08/2021

Basic Information

• Recruitment status: Not Recruiting
• Health condition(s) or Problem(s) studied: Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma
• Date of first enrollment: 14/02/2022
• Target sample size: 250
• Countries of recruitment: Australia,Japan,Austria,Japan,Belgium,Japan,Canada,Japan,China,Japan,Croatia,Japan,Czech Republic,Japan,France,Japan,Germany,Japan,Hungary,Japan,Ireland,Japan,Israel,Japan,Italy,Japan,Poland,Japan,Russia,Japan,Singapore,Japan,Spain,Japan,South Korea,Japan,Switzerland,Japan,Taiwan,Japan,United Kingdom,Japan,United States,Japan,Turkey,Japan
• Study type: Interventional

Intervention(s)

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

Outcome(s)

Primary Outcome

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

Key inclusion & exclusion criteria

• Age minimum: >= 18age old
• Age maximum: Not applicable
• Gender: Both

Include 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 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.

Exclude 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.

Related Information

• Primary Sponsor: Masaki Takeshi