Phase 3, open-label, randomized study of LOXO-305 versus investigator's choice of idelalisib plus rituximab or bendamustine plus rituximab in chronic lymphocytic leukemia/small cell lymphocytic lymphoma pretreated with BTK inhibitor (BRUIN CLL-321)

Australia, Austria, Belgium, Canada, China, Croatia, Czechia, France, Germany, Hungary, Ireland, Israel, Italy, Japan, Korea, Republic of, Poland, Russian Federation, Singapore, Spain, Switzerland, Taiwan, Turkey, United Kingdom, United States (ICTRP)

ID di studio ICTRP
NCT04666038 (ICTRP)

Titolo ufficiale (approvato dal comitato etico)
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) (BASEC)

Titolo accademico
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) (ICTRP)

Titolo pubblico
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) (ICTRP)

Malattie studiate
Chronic Lymphocytic LeukemiaSmall Lymphocytic Lymphoma (ICTRP)

Intervento studiato
Drug: PirtobrutinibDrug: IdelalisibDrug: BendamustineDrug: Rituximab (ICTRP)

Tipo di studio
Interventional (ICTRP)

Disegno dello studio
Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: None (Open Label). (ICTRP)

Criteri di inclusione/esclusione
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. (ICTRP)

non disponibile

Endpoint primari e secondari
Progression-free Survival (PFS) Assessed by Independent Review Committee (IRC) (ICTRP)

PFS Assessed by Investigator;Overall Survival (OS);Time to Next Treatment (TTNT);Event Free Survival (EFS);Percentage of Participants With Overall Response Rate (ORR) Assessed by Investigator;Time to Worsening (TTW) of CLL/SLL Related Symptoms;Time to Worsening (TTW) of Physical Function (ICTRP)

Data di registrazione
non disponibile

Inclusione del primo partecipante
non disponibile

Sponsor secondari
Eli Lilly and Company (ICTRP)

Contatti aggiuntivi
Marisa Hill, MD, Loxo Oncology, Inc. (ICTRP)

ID secondari
J2N-OX-JZNN, LOXO-BTK-20020, 18073 (ICTRP)

Risultati-Dati individuali dei partecipanti
non disponibile

Ulteriori informazioni sullo studio
https://clinicaltrials.gov/ct2/show/NCT04666038 (ICTRP)