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) (BRUIN CLL-322)

• ClinicalTrials.gov Identifier: NCT04965493
• Recruitment Status: Recruiting
• First Posted: July 16, 2021
• Last Update Posted: May 13, 2024
• Sponsor: Loxo Oncology, Inc.
• Collaborator: Eli Lilly and Company
• Information provided by (Responsible Party): Eli Lilly and Company ( Loxo Oncology, Inc. )

Tracking Information

• First Submitted Date: July 15, 2021
• First Posted Date: July 16, 2021
• Last Update Posted Date: May 13, 2024
• Actual Study Start Date: September 20, 2021
• Estimated Primary Completion Date: April 2026 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: July 15, 2021)

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

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: July 15, 2021)

• 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
• 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
• 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
• 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
• 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
• To evaluate the effectiveness 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
• To evaluate the effectiveness 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

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 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)
• Official 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)
• Brief Summary: 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.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 3

Study Design

Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:

Eligible patients will be randomized 1:1 into Arm A and Arm B.

Masking: None (Open Label)
Primary Purpose: Treatment

Condition

• Chronic Lymphocytic Leukemia
• Small Lymphocytic Lymphoma

Intervention

• Drug: Pirtobrutinib
  Oral
  Other Names:

  • LOXO-305
  • LY3527727
• Drug: Venetoclax
  Oral
  Other Names:

  • Venclexta
  • Venclyxto
• Drug: Rituximab
  Intravenous (IV)
  Other Names:

  • Rituxan
  • MabThera
  • Truxima
  • Riabni
  • Ruxience

Study Arms

• Experimental: Arm A (PVR)
  Fixed duration pirtobrutinib in combination with venetoclax and rituximab
  Interventions:

  • Drug: Pirtobrutinib
  • Drug: Venetoclax
  • Drug: Rituximab
• Active Comparator: Arm B (VR)
  Venetoclax with rituximab
  Interventions:

  • Drug: Venetoclax
  • Drug: Rituximab

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: July 15, 2021): 600
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: January 2027
• Estimated Primary Completion Date: April 2026 (Final data collection date for primary outcome measure)

Eligibility Criteria

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

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

• Listed Location Countries: Australia, Belgium, Canada, China, Czechia, Denmark, France, Germany, Hungary, Ireland, Israel, Italy, Japan, Korea, Republic of, Poland, Singapore, Spain, Sweden, Switzerland, Taiwan, United Kingdom, United States

Administrative Information

• NCT Number: NCT04965493
• Other Study ID Numbers: LOXO-BTK-20022; J2N-OX-JZNO ( Other Identifier: Eli Lilly and Company )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Eli Lilly and Company ( Loxo Oncology, Inc. )
• Original Responsible Party: Same as current
• Current Study Sponsor: Loxo Oncology, Inc.
• Original Study Sponsor: Same as current
• Collaborators: Eli Lilly and Company

Investigators

• Study Director: James Pauff, MD; Loxo Oncology

• PRS Account: Eli Lilly and Company
• Verification Date: May 2024