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)
This is a study for patients with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) who have previously received treatment with at least a BTK inhibitor. The main purpose is to compare LOXO-305 to idelalisib plus rituximab or bendamustine plus rituximab. Participation could last up to four years, and possibly longer, if the disease does not progress.
Eligibility
Sex
ALL
Min age
18 Years
Max age
—
Healthy volunteers
No
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.
Primary outcome measure(s)
Progression-free Survival (PFS) Assessed by Independent Review Committee (IRC) — Randomization to Disease Progression or Death Due to Any Cause (Up to 29 Months) PFS is defined as the time from the date of randomization to the date of first documentation of progressive disease (PD) or death from any cause, as evaluated by an IRC according to International Workshop on Chronic Lymphocytic Leukemia (iwCLL) 2018.
Trial sites (232)
Facility
City
Region
Status
Southern Cancer Center, P.C.
Daphne
Alabama
Mitchell Cancer Institute -University of South Alabama
Mobile
Alabama
Palo Verde Hematology Oncology
Glendale
Arizona
Arizona Oncology Associates, P.C. - HOPE
Tucson
Arizona
Orange Coast Memorial Medical Center
Fountain Valley
California
California Research Institute
Los Angeles
California
Rocky Mountain Cancer Center
Aurora
Colorado
Medical Oncology Hematology Consultants, PA
Newark
Delaware
Boca Raton Regional Hospital
Boca Raton
Florida
Cancer Specialists of North Florida -St Augustine
Jacksonville
Florida
Oncology-Hematology Associates of West Broward
Tamarac
Florida
WellStar Health System
Marietta
Georgia
Rush University Medical Center
Chicago
Illinois
Illinois Cancer Specialists-Niles
Niles
Illinois
Community Health Network
Indianapolis
Indiana
Arnett Cancer Center
Lafayette
Indiana
University of Kentucky Markey Cancer Center
Lexington
Kentucky
Norton Cancer Institute
Louisville
Kentucky
Mercy Health-Paducah Medical Oncology and Hematology
Paducah
Kentucky
Cancer Center Office of Clinical Research
New Orleans
Louisiana
Greenebaum Comprehensive Cancer Center
Baltimore
Maryland
Saint Joseph Mercy Hospital
Ann Arbor
Michigan
Ascension St. John Hospital
Grosse Pointe Woods
Michigan
Minnesota Oncology/Hematology PA
Saint Paul
Minnesota
St. Vincent Frontier Cancer Center
Billings
Montana
Nebraska Hematology-Oncology
Lincoln
Nebraska
New Jersey Center for Cancer Research
Brick
New Jersey
Memorial Sloan Kettering Cancer Center
New York
New York
University of Rochester
Rochester
New York
Clinical Research Alliance, Inc.
Westbury
New York
Oncology Hematology Care Inc
Cincinnati
Ohio
Willamette Valley Cancer Institute and Research Center
Eugene
Oregon
Carolina Blood and Cancer Care Associates
Rock Hill
South Carolina
Texas Oncology - Amarillo
Amarillo
Texas
Texas Oncology Cancer Center
Austin
Texas
Texas Oncology - Medical City Dallas
Dallas
Texas
Texas Oncology - Dallas Presbyterian Hospital
Dallas
Texas
Brooke Army Medical Center
Fort Sam Houston
Texas
Texas Oncology Fort Worth
Fort Worth
Texas
The Center for Cancer and Blood Disorders
Fort Worth
Texas
+ 192 more sites — see the full list on the official registry below.
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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