The purpose of Part 1 of this study is to compare the efficacy and safety of pirtobruitinib (LOXO-305) to ibrutinib in participants with CLL/SLL; participants may or may not have already had treatment for their cancer. The purpose of Part 2 of this study evaluates pirtobrutinib monotherapy in treatment-naïve participants with CLL/SLL with 17p deletions. Participation could last up to six years for Part 1. Participation could last up to 2 years for Part 2.
Eligibility
Sex
ALL
Min age
18 Years
Max age
—
Healthy volunteers
No
Inclusion Criteria:
* Confirmed diagnosis of CLL/SLL requiring therapy per iwCLL 2018 criteria
* Part 1 - Known 17p deletion status (wildtype or deleted). Part 2 - Must have deletion of 17p as determined by FISH testing
* Eastern Cooperative Oncology Group (ECOG) Performance Status 0-2
* Adequate organ function
* Platelets greater than or equal to ≥ 50 x 10⁹/liter (L) or ≥30 x 10⁹/L in participants with documented bone marrow involvement considered to impair hematopoiesis,
* Hemoglobin ≥8 grams/deciliter (g/dL) or ≥6 g/dL in participants with documented bone marrow involvement considered to impair hematopoiesis
* Absolute neutrophil count ≥0.75 x 10⁹/L or ≥0.50 × 10⁹/L in participants with documented bone marrow involvement considered to impair hematopoiesis
* Kidney function: Estimated creatinine clearance ≥30 milliliters per minute (mL/min)
Exclusion Criteria:
* Known or suspected Richter's transformation to diffuse large B-cell lymphoma (DLBCL), prolymphocytic leukemia, or Hodgkin's lymphoma at any time preceding enrollment
* Known or suspected central nervous system (CNS) involvement
* A significant history of renal, neurologic, psychiatric, endocrine, metabolic or immunologic disease
* Active uncontrolled auto-immune cytopenia (e.g., autoimmune hemolytic anemia \[AIHA\], idiopathic thrombocytopenic purpura \[ITP\])
* Significant cardiovascular disease including ejection fraction \< 40% and any grade ongoing atrial fibrillation or atrial flutter
* Hepatitis B or hepatitis C testing indicating active/ongoing infection, based on Screening laboratory tests
* Active cytomegalovirus (CMV) infection
* Active uncontrolled systemic bacterial, viral, or fungal infection
* Known human immunodeficiency virus (HIV) infection, regardless of cluster of differentiation 4 (CD4) count
* Clinically significant active malabsorption syndrome or other condition likely to affect GI absorption of the oral-administered study treatments
* Ongoing inflammatory bowel disease
* Previous treatment for CLL/SLL - Part 1: Treatment-naïve and previously treated, except prior exposure to BTK inhibitor (covalent or noncovalent).
Part 2: participants must be treatment naïve
* Concurrent use of investigational agent or anticancer therapy except hormonal therapy
* Participants requiring therapeutic anticoagulation with warfarin or another Vitamin K antagonist
* Use of \> 20 mg prednisone daily or equivalent dose of steroid at the time of first dose of study drug
* Vaccination with a live vaccine within 28 days prior to randomization
* Participants receiving chronic therapy with a strong cytochrome P450 (CYP)3A inhibitor (except posaconazole and voriconazole) which cannot be stopped within 3-5 half lives of the CYP3A inhibitor therapy prior to start of study drug treatment
* Participants with known hypersensitivity, including anaphylaxis, to any component or excipient of pirtobrutinib or ibrutinib
Primary outcome measure(s)
Percentage of Participants Achieving Complete Response (CR), Complete Remission with Incomplete Hematologic Recovery (Cri), Nodular Partial Remission (nPR) or Partial Response (PR): Overall Response Rate (ORR) Part 1 — Baseline to best overall response the best response recorded from Cycle 1 Day 1 until data cutoff date, PD, or start of new anticancer treatment, whichever is the earliest] (approximately 3 years and 5 months) ORR as assessed by independent review committee (IRC) per International Workshop on Chronic Lymphocytic Leukemia (iwCLL) 2018 criteria
Percentage of Participants Achieving Complete Response (CR), Complete Remission with Incomplete Hematologic Recovery (CRi), Nodular Partial Remission (nPR) or Partial Response (PR): Overall Response Rate (ORR) Part 2 — Baseline to best overall response the best response recorded from Cycle 1 Day 1 until data cutoff date, PD, or start of new anticancer treatment, whichever is the earliest (Approximately 2 years and 3 months) ORR as assessed by independent review committee (IRC) per International Workshop on Chronic Lymphocytic Leukemia (iwCLL) 2018 criteria
Trial sites (143)
Facility
City
Region
Status
Pacific Cancer Medical Center, Inc
Anaheim
California
Recruiting
TOI Clinical Research
Cerritos
California
Recruiting
Stanford School of Medicine-Cancer Clinical Trials Office
Palo Alto
California
Recruiting
California Cancer Associates for Research and Excellence
San Marcos
California
Active Not Recruiting
Florida Cancer Specialists
Fort Myers
Florida
Recruiting
Cancer Specialists of North Florida -St Augustine
Saint Augustine
Florida
Recruiting
Florida Cancer Specialists East
West Palm Beach
Florida
Recruiting
Hematology Oncology Clinic
Baton Rouge
Louisiana
Active Not Recruiting
Tulane Cancer Center Office of Clinical Research
New Orleans
Louisiana
Active Not Recruiting
American Oncology Partners of Maryland, PA
Bethesda
Maryland
Recruiting
St. Vincent Frontier Cancer Center
Billings
Montana
Recruiting
Cancer Care Associates Of York
York
Pennsylvania
Active Not Recruiting
Prisma Health Cancer Institute
Greenville
South Carolina
Active Not Recruiting
Sarah Cannon Research Institute SCRI
Nashville
Tennessee
Recruiting
Kelsey Research Foundation
Houston
Texas
Active Not Recruiting
Lumi Research
Kingwood
Texas
Recruiting
Virginia Cancer Institute
Richmond
Virginia
Recruiting
Medical Oncology Associates, PS
Spokane
Washington
Recruiting
MultiCare Health System Institute for Research and Innovation
Spokane
Washington
Active Not Recruiting
Alexander Fleming
Ciudad Autónoma de Buenos Aire
Argentina
Recruiting
Hospital Privado De Comunidad
Mar del Plata
Argentina
Active Not Recruiting
Clínica de Nefrología, Urología y Enfermedades Cardiovasculares
This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.
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