Purpose

This is a study for patients with chronic lymphocytic leukemia (CLL) or small lymphocytic leukemia (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.

Conditions

Eligibility

Eligible Ages
Over 18 Years
Eligible Genders
All
Accepts 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 × 109/L without granulocyte-colony stimulating factor support - Hemoglobin ≥ 8 g/dL not requiring transfusion support or growth factors within 14 days of Cycle 1 Day 1 - Platelets ≥ 50 × 109/L not requiring transfusion support or growth factors within 14 days of C1D1. If an investigator has chosen bendamustine/rituximab as the Arm B treatment, platelets must be ≥ (75 × 109/L). - 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 and/or strong P-glycoprotein (P-gp) inhibitors - 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, idelalisib, and bendamustine 2. Prior significant hypersensitivity to rituximab

Study Design

Phase
Phase 3
Study Type
Interventional
Allocation
Randomized
Intervention Model
Parallel Assignment
Intervention Model Description
Eligible patients will be randomized in 1:1 into Arm A or 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.
Primary Purpose
Treatment
Masking
None (Open Label)

Arm Groups

ArmDescriptionAssigned Intervention
Experimental
Arm A (LOXO-305)
Orally
  • Drug: LOXO-305
    Oral LOXO-305
    Other names:
    • Pirtobrutinib
Active Comparator
Arm B (Idelalisib plus rituximab [IdelaR] or bendamustine plus rituximab [BR])
Investigator's choice of idelalisib plus rituximab (IdelaR) or bendamustine plus rituximab (BR).
  • Drug: Idelalisib
    Oral
    Other names:
    • Zydelig
  • Drug: Bendamustine
    IV
    Other names:
    • Treanda, Treakisym, Ribomustin, Levact
  • Drug: Rituximab
    IV
    Other names:
    • Rituxan, MabThera, Truxima

Recruiting Locations

Tulane University School of Medicine
New Orleans, Louisiana 70112

More Details

Status
Recruiting
Sponsor
Loxo Oncology, Inc.

Study Contact

Patient Advocacy
1-855-LOXO-305
clinicaltrials@loxooncology.com

Detailed Description

This is a Phase 3 global, randomized, open-label study comparing LOXO-305 (Arm A) to investigator's choice of either idelalisib plus rituximab or bendamustine plus rituximab (Arm B) in CLL/SLL patients who have been treated with at least a covalent BTK inhibitor (BTKi). Patients may have discontinued the prior covalent BTKi due to disease progression (PD) or intolerance. Patients who have received venetoclax are eligible for the study. Eligible patients will be randomized in 1:1 to Arm A and Arm B.

Notice

Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.