Chronic Lymphocytic Leukemia, Small Lymphocytic Lymphoma
Conditions
Keywords
BTKi, Hematologic Disease, Lymphoma, non-Hodgkin's, Lymphoma, B-cell
Brief summary
The purpose of this study is to compare the efficacy and safety of fixed duration pirtobruitinib (LOXO-305) with VR (Arm A) compared to VR alone (Arm B) in patients with CLL/SLL who have been previously treated with at least one prior line of therapy. Participation could last up to five years.
Interventions
DRUGPirtobrutinib
Oral
DRUGVenetoclax
Oral
DRUGRituximab
Intravenous (IV)
Sponsors
Loxo Oncology, Inc.
Eli Lilly and Company
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Eligible patients will be randomized 1:1 into Arm A and Arm B.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Confirmed diagnosis of CLL/SLL requiring therapy per iwCLL 2018 criteria * Previous treatment with at least one line of therapy that may include a covalent Bruton's tyrosine kinase (BTK) inhibitor * Platelets greater than or equal to (≥)50 x 10⁹/liter (L), hemoglobin ≥8 grams/deciliter (g/dL) and absolute neutrophil count ≥1.0 x 10⁹/L * Adequate organ function * Eastern Cooperative Oncology Group (ECOG) Performance Status 0-2 * Estimated creatinine clearance ≥30 milliliters per minute (mL/min)
Exclusion criteria
* Known or suspected Richter's transformation at any time preceding enrollment * Prior therapy with a 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 * Prior therapy with venetoclax * Central nervous system (CNS) involvement * Active uncontrolled systemic bacterial, viral, fungal, or parasitic infection * Known human immunodeficiency virus (HIV) infection, regardless of cluster of differentiation 4 (CD4) count * Allogeneic stem cell transplantation (SCT) or chimeric antigen receptor (CAR)-T within 60 days * Active hepatitis B or hepatitis C * Known active cytomegalovirus (CMV) infection * Uncontrolled immune thrombocytopenic purpura (ITP) or autoimmune hemolytic anemia (AIHA) * Significant cardiovascular disease * Vaccination with a live vaccine within 28 days prior to randomization * Patients with the following hypersensitivity: * Known hypersensitivity to any component or excipient of pirtobrutinib and venetoclax * Prior significant hypersensitivity to rituximab * Known allergy to allopurinol and inability to take uric acid lowering agent
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| To evaluate progression-free survival (PFS) of pirtobrutinib plus venetoclax and rituximab (Arm A) compared to venetoclax and rituximab (Arm B) | Up to approximately 5 years | Assessed by blinded independent review committee (IRC) per International Workshop on Chronic Lymphocytic Leukemia (iwCLL) 2018 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| To evaluate the efficacy of Arm A compared to Arm B: Progression-free survival (PFS) | Up to approximately 5 years | Assessments of efficacy include PFS, assessed by investigator |
| To evaluate the efficacy of Arm A compared to Arm B: Overall survival (OS) | Up to approximately 5 years | Assessments of efficacy include OS |
| To evaluate the efficacy of Arm A compared to Arm B: Time to next treatment (TTNT) | Up to approximately 5 years | Assessments of efficacy include TTNT |
| To evaluate the efficacy of Arm A compared to Arm B: Event-free survival (EFS) | Up to approximately 5 years | Assessments of efficacy include EFS |
| To evaluate the efficacy of Arm A compared to Arm B: Overall response rate (ORR) | Up to approximately 5 years | Assessments of efficacy include ORR |
| To evaluate the efficacy of Arm A compared to Arm B in patient-reported disease-related symptoms | Up to approximately 5 years | Based on time to worsening of CLL/SLL-related symptoms |
| To evaluate the efficacy of Arm A compared to Arm B in patient-reported physical functioning | Up to approximately 5 years | Based on time to worsening of physical functioning |
Countries
Australia, Belgium, Canada, China, Czechia, Denmark, France, Germany, Hungary, Ireland, Israel, Italy, Japan, Norway, Poland, Singapore, South Korea, Spain, Sweden, Switzerland, Taiwan, United Kingdom, United States
Contacts
STUDY_DIRECTORCall 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST)
Eli Lilly and Company
Outcome results
None listed