Chronic Lymphocytic Leukemia, Small Lymphocytic Lymphoma
Conditions
Keywords
BTKi, BTK Inhibitor, Hematologic Disease, Lymphoma, non-Hodgkin's, Lymphoma, B-cell
Brief summary
The purpose of this study is to compare the efficacy and safety of pirtobrutinib (LOXO-305; Arm A) compared to BR (Arm B) in patients with CLL/SLL who have not been treated. Participation could last up to five years.
Interventions
DRUGPirtobrutinib
Oral
DRUGBendamustine
IV
DRUGRituximab
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. Patients randomized to Arm B who have disease progression (PD) confirmed by independent review committee (IRC) may be eligible to crossover into Arm A.
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 * Eastern Cooperative Oncology Group (ECOG) Performance Status 0-2 * Adequate organ function * Platelets greater than or equal to (≥)75 x 10⁹/liter (L) (≥50 × 10⁹/L for patients with evidence of bone marrow infiltrate), hemoglobin ≥8 grams/deciliter (g/dL), and absolute neutrophil count ≥0.75 x 10⁹/L * Kidney function: Estimated creatinine clearance ≥40 milliliters per minute (mL/min)
Exclusion criteria
* Known or suspected Richter's transformation at any time preceding enrollment * Prior systemic therapy for CLL/SLL * Presence of 17p deletion * Central nervous system (CNS) involvement * Active uncontrolled auto-immune cytopenia (e.g., autoimmune hemolytic anemia \[AIHA\], idiopathic thrombocytopenic purpura \[ITP\]) * Significant cardiovascular disease * Active hepatitis B or hepatitis C * Active cytomegalovirus (CMV) infection * Active uncontrolled systemic bacterial, viral, fungal, or parasitic infection * Known human immunodeficiency virus (HIV) infection, regardless of cluster of differentiation 4 (CD4) count * Concurrent use of investigational agent or anticancer therapy except hormonal therapy * Patients requiring therapeutic anticoagulation with warfarin or another Vitamin K antagonist * Vaccination with a live vaccine within 28 days prior to randomization * Patients with the following hypersensitivity: * Known hypersensitivity, including anaphylaxis, to any component or excipient of pirtobrutinib or bendamustine * Prior significant hypersensitivity to rituximab
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| To evaluate progression-free survival (PFS) of pirtobrutinib (Arm A) compared to bendamustine 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 Response Criteria |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| To evaluate the effectiveness of Arm A compared to Arm B: Progression-free survival (PFS) | Up to approximately 5 years | Assessments of effectiveness include PFS, assessed by investigator |
| To evaluate the effectiveness of Arm A compared to Arm B: Overall survival (OS) | Up to approximately 5 years | Assessments of effectiveness include OS, assessed by investigator |
| To evaluate the effectiveness of Arm A compared to Arm B: Time to next treatment (TTNT) | Up to approximately 5 years | Assessments of effectiveness include TTNT, assessed by investigator |
| To evaluate the effectiveness of Arm A compared to Arm B: Overall response rate (ORR) | Up to approximately 5 years | Assessments of effectiveness include ORR, assessed by investigator and IRC |
| To evaluate the effectiveness of Arm A compared to Arm B: Duration of Response (DOR) | Up to approximately 5 years | Assessments of effectiveness include DOR, assessed by investigator and IRC |
| To evaluate the effectiveness 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 effectiveness 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, Austria, Brazil, Bulgaria, China, Czechia, France, Hungary, Italy, Japan, New Zealand, Poland, Portugal, Romania, Russia, South Korea, Spain, 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