J2N-OX-JZNN - 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)

Studio Clinico

Patologia: Linfomi, Neoplasie ematologiche

Osservazionale-Sperimentale: Sperimentale

Monocentrico-Multicentrico: Multicentrico

Randomizzato: Sì

Fase di studio: III

Linee di trattamento: Seconda linea

Criteri di inclusione: 

- 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 × 109/L without granulocyte-colony stimulating factor support Hemoglobin ≥ 8 g/dL not requiring transfusion support or growth factors within 14 days of Cycle 1 Day 1
- Platelets ≥ 50 × 109/L not requiring transfusion support or growth factors within 14 days of C1D1. If an investigator has chosen bendamustine/rituximab as the Arm B treatment, platelets must be ≥ (75 × 109/L).
- AST and ALT ≤ 3.0 x upper limit of normal (ULN).
- Total bilirubin ≤ 1.5 x ULN.
- Estimated creatinine clearance of ≥ 30 mL/min.

Criteri di esclusione: 

- 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 and/or strong P-glycoprotein (P-gp) inhibitors
- 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, idelalisib, and bendamustine
    2. Prior significant hypersensitivity to rituximab.

Trattamento sperimentale: 

Pirtobrutinib (Loxo 305)

Trattamento di controllo: 

idelalisib plus rituximab or bendamustine plus rituximab

Centri partecipanti

Nord Italia

Centro Italia

Sud Italia e isole

Informazioni Generali

Protocollo

Numero di iscrizione a registro: 2020-004554-30

Data di inserimento: 02.08.2022

Promotore

Loxo Oncology, Inc.

Principal Investigator ITALIA

IRCCS Ospedale San Raffaele, Milano

Riferimento: Prof. Paolo Prospero Ghia

Telefono: 00000

Email: segreteriallc@hsr.it

Localita: Milano