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A Study of Pirtobrutinib (LOXO-305) Versus Bendamustine Plus Rituximab (BR) in Untreated Patients With Chronic Lymphocytic Leukemia (CLL)/Small Lymphocytic Lymphoma (SLL)

Phase 3
Active, not recruiting
Conditions
Chronic Lymphocytic Leukemia
Small Lymphocytic Lymphoma
Interventions
Registration Number
NCT05023980
Lead Sponsor
Loxo Oncology, Inc.
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.

Detailed Description

Not available

Recruitment & Eligibility

Status
ACTIVE_NOT_RECRUITING
Sex
All
Target Recruitment
309
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

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Arm B (BR)RituximabBendamustine plus rituximab administered intravenously (IV)
Arm A (Pirtobrutinib)PirtobrutinibPirtobrutinib administered orally
Arm B (BR)BendamustineBendamustine plus rituximab administered intravenously (IV)
Primary Outcome Measures
NameTimeMethod
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 Outcome Measures
NameTimeMethod
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 in patient-reported disease-related symptomsUp 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: 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 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: 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 physical functioningUp to approximately 5 years

Based on time to worsening of physical functioning

Trial Locations

Locations (108)

California Research Institute

🇺🇸

Los Angeles, California, United States

Innovative Clinical Research Institute

🇺🇸

Whittier, California, United States

Oncology-Hematology Associates of West Broward

🇺🇸

Coral Springs, Florida, United States

New Jersey Center for Cancer Research

🇺🇸

Brick, New Jersey, United States

Clinical Research Alliance, Inc.

🇺🇸

Westbury, New York, United States

Liverpool Hospital

🇦🇺

Liverpool, New South Wales, Australia

Westmead Hospital

🇦🇺

Wentworthville, New South Wales, Australia

Peninsula Private Hospital

🇦🇺

Frankston, Victoria, Australia

Uniklinikum Salzburg

🇦🇹

Salzburg, Austria

Klinik Ottakring

🇦🇹

Vienna, Austria

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California Research Institute
🇺🇸Los Angeles, California, United States

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