BRUIN CLL-322: 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)

Sponsor
Loxo Oncology, Inc. (Industry)
Overall Status
Recruiting
CT.gov ID
NCT04965493
Collaborator
(none)
600
Enrollment
27
Locations
2
Arms
63.4
Anticipated Duration (Months)
22.2
Patients Per Site
0.4
Patients Per Site Per Month

Study Details

Study Description

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.

Study Design

Study Type:
Interventional
Anticipated 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.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 :
Sep 20, 2021
Anticipated Primary Completion Date :
Oct 1, 2025
Anticipated Study Completion Date :
Jan 1, 2027

Arms and Interventions

ArmIntervention/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
  • Outcome Measures

    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) [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) [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) [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) [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) [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) [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 [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

    • 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

    Contacts and Locations

    Locations

    SiteCityStateCountryPostal Code
    1Florida Cancer SpecialistsFort MyersFloridaUnited States33916
    2Cancer Specialists of North Florida -St AugustineJacksonvilleFloridaUnited States32256
    3Florida Cancer SpecialistsSaint PetersburgFloridaUnited States33705
    4Florida Cancer SpecialistsTallahasseeFloridaUnited States32308
    5Florida Cancer Specialists EastWest Palm BeachFloridaUnited States33401
    6Hematology Oncology ClinicBaton RougeLouisianaUnited States70809
    7Research Medical CenterKansas CityMissouriUnited States63142
    8Memorial Sloan Kettering Cancer CenterBasking RidgeNew JerseyUnited States07920
    9Memorial Sloan Kettering Cancer CenterMiddletownNew JerseyUnited States07748
    10Memorial Sloan Kettering Cancer CenterMontvaleNew JerseyUnited States07645
    11Memorial Sloan Kettering Cancer CenterCommackNew YorkUnited States11725
    12Memorial Sloan Kettering Cancer CenterHarrisonNew YorkUnited States10604
    13Memorial Sloan Kettering Cancer CenterNew YorkNew YorkUnited States10021
    14Memorial Sloan Kettering Cancer CenterUniondaleNew YorkUnited States11553
    15Sarah Cannon Research Institute SCRIChattanoogaTennesseeUnited States37404
    16Tennessee Oncology PLLCNashvilleTennesseeUnited States37203
    17Universitair Ziekenhuis GentGentBelgium900
    18Hopital de la Pitie SalpetriereParisCedex 13France75651
    19CHU de Nantes - Hôtel-DieuNantesCedex 1France44093
    20CHRU De ToursToursTours Cedex 9France37044
    21Centre Hospitalier du MansLe MansFrance72000
    22Hopital Saint EloiMontpellierFrance34295
    23Centre Henri BecquerelRouen CedexFrance76038
    24Chu De Nancy Hop D'Adultes De BraboisVandœuvre-lès-NancyFrance54500
    25Nagoya Medical CenterNagoyaAichiJapan460-0001
    26National Cancer Center HospitalChuo-kuTokyoJapan104-0045
    27Kumamoto University HospitalKumamotoJapan860-8556

    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:
    NCT04965493
    Other Study ID Numbers:
    • LOXO-BTK-20022
    • J2N-OX-JZNO
    First Posted:
    Jul 16, 2021
    Last Update Posted:
    Nov 17, 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 17, 2021