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NCT Number: NCT04965493

A Trial of Pirtobrutinib (LOXO-305) Plus Venetoclax and Rituximab (PVR) Versus Venetoclax and Rituximab (VR) in Previously Treated Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL)

The purpose of this study is to compare the efficacy and safety of fixed duration pirtobruitinib (LOXO-305) with VR (Arm A) compared to VR alone (Arm B) in patients with CLL/SLL who have been previously treated with at least one prior line of therapy. Participation could last up to five years.

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This study is active but is not currently recruiting participants.

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Key information

Conditions

Chronic Lymphocytic Leukemia Chronic Disease Disease Attributes Hematologic Diseases Hemic and Lymphatic Diseases Immune System Diseases Immunoproliferative Disorders Leukemia Leukemia, B-Cell Leukemia, Lymphocytic, Chronic, B-Cell Leukemia, Lymphoid Lymphatic Diseases Lymphoma Lymphoma, B-Cell Lymphoma, Non-Hodgkin Lymphoproliferative Disorders Neoplasms Neoplasms by Histologic Type Pathologic Processes Pathological Conditions, Signs and Symptoms Small Lymphocytic Lymphoma

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 3

Primary location

Royal Adelaide Hospital, Adelaide, Australia

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Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Confirmed diagnosis of CLL/SLL requiring therapy per iwCLL 2018 criteria
  • Previous treatment with at least one line of therapy that may include a covalent Bruton's tyrosine kinase (BTK) inhibitor
  • Platelets greater than or equal to (≥)50 x 10⁹/liter (L), hemoglobin ≥8 grams/deciliter (g/dL) and absolute neutrophil count ≥1.0 x 10⁹/L
  • Adequate organ function
  • Eastern Cooperative Oncology Group (ECOG) Performance Status 0-2
  • Estimated creatinine clearance ≥30 milliliters per minute (mL/min)

Exclusion criteria

  • Known or suspected Richter's transformation at any time preceding enrollment
  • Prior therapy with a 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
  • Prior therapy with venetoclax
  • Central nervous system (CNS) involvement
  • Active uncontrolled systemic bacterial, viral, fungal, or parasitic infection
  • Known human immunodeficiency virus (HIV) infection, regardless of cluster of differentiation 4 (CD4) count
  • Allogeneic stem cell transplantation (SCT) or chimeric antigen receptor (CAR)-T within 60 days
  • Active hepatitis B or hepatitis C
  • Known active cytomegalovirus (CMV) infection
  • Uncontrolled immune thrombocytopenic purpura (ITP) or autoimmune hemolytic anemia (AIHA)
  • Significant cardiovascular disease
  • Vaccination with a live vaccine within 28 days prior to randomization
  • Patients with the following hypersensitivity:
  • Known hypersensitivity to any component or excipient of pirtobrutinib and venetoclax
  • Prior significant hypersensitivity to rituximab
  • Known allergy to allopurinol and inability to take uric acid lowering agent

Treatment and study plan

Pirtobrutinib

Drug

Oral

Other names: LOXO-305, LY3527727

Venetoclax

Drug

Oral

Other names: Venclexta, Venclyxto

Rituximab

Drug

Intravenous (IV)

Other names: Rituxan, MabThera, Truxima, Riabni, Ruxience

Primary outcomes

  1. To evaluate progression-free survival (PFS) of pirtobrutinib plus venetoclax and rituximab (Arm A) compared to venetoclax and rituximab (Arm B)

    Time frame: Up to approximately 5 years

    Assessed by blinded independent review committee (IRC) per International Workshop on Chronic Lymphocytic Leukemia (iwCLL) 2018

Secondary outcomes

  1. To evaluate the efficacy of Arm A compared to Arm B: Progression-free survival (PFS)

    Time frame: Up to approximately 5 years

    Assessments of efficacy include PFS, assessed by investigator

  2. To evaluate the efficacy of Arm A compared to Arm B: Overall survival (OS)

    Time frame: Up to approximately 5 years

    Assessments of efficacy include OS

  3. To evaluate the efficacy of Arm A compared to Arm B: Time to next treatment (TTNT)

    Time frame: Up to approximately 5 years

    Assessments of efficacy include TTNT

  4. To evaluate the efficacy of Arm A compared to Arm B: Event-free survival (EFS)

    Time frame: Up to approximately 5 years

    Assessments of efficacy include EFS

  5. To evaluate the efficacy of Arm A compared to Arm B: Overall response rate (ORR)

    Time frame: Up to approximately 5 years

    Assessments of efficacy include ORR

  6. To evaluate the efficacy of Arm A compared to Arm B in patient-reported disease-related symptoms

    Time frame: Up to approximately 5 years

    Based on time to worsening of CLL/SLL-related symptoms

  7. To evaluate the efficacy of Arm A compared to Arm B in patient-reported physical functioning

    Time frame: Up to approximately 5 years

    Based on time to worsening of physical functioning

Sponsors and collaborators

Lead sponsor

Loxo Oncology, Inc.

Industry

Collaborators

  • Eli Lilly and Company

Registry information

Official study title

A Phase 3 Open-Label, Randomized Study of Fixed Duration Pirtobrutinib (LOXO-305) Plus Venetoclax and Rituximab Versus Venetoclax and Rituximab in Previously Treated Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (BRUIN CLL-322)

Acronym: BRUIN CLL-322

Important dates

Study start
2021
Primary completion
2026
Study completion
2027
First posted
Jul 16, 2021
Registry last updated
Jan 29, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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