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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)

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ClinicalTrials.gov Identifier: NCT04965493
Recruitment Status : Recruiting
First Posted : July 16, 2021
Last Update Posted : November 17, 2021
Sponsor:
Information provided by (Responsible Party):
Eli Lilly and Company ( Loxo Oncology, Inc. )

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.

Condition or disease Intervention/treatment Phase
Chronic Lymphocytic Leukemia Small Lymphocytic Lymphoma Drug: Pirtobrutinib Drug: Venetoclax Drug: Rituximab Phase 3

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 600 participants
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
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)
Actual Study Start Date : September 20, 2021
Estimated Primary Completion Date : October 2025
Estimated Study Completion Date : January 2027


Arm Intervention/treatment
Experimental: Arm A (PVR)
Fixed duration pirtobrutinib in combination with venetoclax and rituximab
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

Active Comparator: Arm B (VR)
Venetoclax with rituximab
Drug: Venetoclax
Oral
Other Names:
  • Venclexta
  • Venclyxto

Drug: Rituximab
Intravenous (IV)
Other Names:
  • Rituxan
  • MabThera
  • Truxima
  • Riabni
  • Ruxience




Primary Outcome Measures :
  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 Outcome Measures :
  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 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

  7. 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



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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 and/or strong P-glycoprotein (P-gp) inhibitors
  • 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04965493


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

Locations
Show Show 27 study locations
Sponsors and Collaborators
Loxo Oncology, Inc.
Investigators
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Study Director: Safi Shahda Loxo Oncology
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Responsible Party: Loxo Oncology, Inc.
ClinicalTrials.gov Identifier: NCT04965493    
Other Study ID Numbers: LOXO-BTK-20022
J2N-OX-JZNO ( Other Identifier: Eli Lilly and Company )
First Posted: July 16, 2021    Key Record Dates
Last Update Posted: November 17, 2021
Last Verified: November 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Eli Lilly and Company ( Loxo Oncology, Inc. ):
BTKi
Hematologic Disease
Lymphoma, non-Hodgkin's
Lymphoma, B-cell
Additional relevant MeSH terms:
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Lymphoma
Leukemia
Leukemia, Lymphoid
Leukemia, Lymphocytic, Chronic, B-Cell
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Leukemia, B-Cell
Rituximab
Venetoclax
Antineoplastic Agents, Immunological
Antineoplastic Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents