BRUIN CLL-313: A Study of Pirtobrutinib (LOXO-305) Versus Bendamustine Plus Rituximab (BR) in Untreated Patients With Chronic Lymphocytic Leukemia (CLL)/Small Lymphocytic Lymphoma (SLL)

Sponsor
Loxo Oncology, Inc. (Industry)
Overall Status
Recruiting
CT.gov ID
NCT05023980
Collaborator
(none)
250
Enrollment
3
Locations
2
Arms
57.2
Anticipated Duration (Months)
83.3
Patients Per Site
1.5
Patients Per Site Per Month

Study Details

Study Description

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.

Study Design

Study Type:
Interventional
Anticipated Enrollment :
250 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Intervention Model Description:
Eligible patients will be randomized 1:1 into Arm A and 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.Eligible patients will be randomized 1:1 into Arm A and 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.
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Phase 3 Open-Label, Randomized Study of Pirtobrutinib (LOXO-305) Versus Bendamustine Plus Rituximab in Untreated Patients With Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma
Actual Study Start Date :
Sep 23, 2021
Anticipated Primary Completion Date :
Nov 1, 2024
Anticipated Study Completion Date :
Jul 1, 2026

Arms and Interventions

ArmIntervention/Treatment
Experimental: Arm A (Pirtobrutinib)

Pirtobrutinib administered orally

Drug: Pirtobrutinib
Oral
Other Names:
  • LOXO-305
  • LY3527727
  • Active Comparator: Arm B (BR)

    Bendamustine plus rituximab administered intravenously (IV)

    Drug: Bendamustine
    IV
    Other Names:
  • Treanda
  • Treakisym
  • Ribomustin
  • Levact
  • Drug: Rituximab
    IV
    Other Names:
  • Rituxan
  • MabThera
  • Truxima
  • Riabni
  • Ruxience
  • Outcome Measures

    Primary Outcome Measures

    1. 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

    1. 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

    2. 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

    3. 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

    4. 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

    5. 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

    6. To evaluate the effectiveness of Arm A compared to Arm B in patient-reported disease-related symptoms [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 [Up to approximately 5 years]

      Based on time to worsening of physical functioning

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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

    Contacts and Locations

    Locations

    SiteCityStateCountryPostal Code
    1California Research InstituteLos AngelesCaliforniaUnited States90027
    2Nagoya Medical CenterNagoyaAichiJapan460-0001
    3Fukui Medical University HospitalYoshida-GunFukuiJapan910-1193

    Sponsors and Collaborators

    • Loxo Oncology, Inc.

    Investigators

    • Study Director: Safi Shahda, Loxo Oncology

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Loxo Oncology, Inc.
    ClinicalTrials.gov Identifier:
    NCT05023980
    Other Study ID Numbers:
    • LOXO-BTK-20023
    • J2N-OX-JZNP
    First Posted:
    Aug 27, 2021
    Last Update Posted:
    Nov 11, 2021
    Last Verified:
    Nov 1, 2021
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Keywords provided by Loxo Oncology, Inc.
    Additional relevant MeSH terms:

    Study Results

    No Results Posted as of Nov 11, 2021