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BRUIN-MCL-321: Study of BTK Inhibitor LOXO-305 Versus Approved BTK Inhibitor Drugs in Patients With Mantle Cell Lymphoma (MCL)

Sponsor
Loxo Oncology, Inc. (Industry)
Overall Status
Recruiting
CT.gov ID
NCT04662255
Collaborator
Eli Lilly and Company (Industry)
500
Enrollment
159
Locations
2
Arms
47.8
Anticipated Duration (Months)
3.1
Patients Per Site
0.1
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This is a study for participants with a type of blood cancer called mantle cell lymphoma (MCL). The main purpose is to compare pirtobrutinib (LOXO-305) to other drugs that work in a similar way that have already been approved by the United States Food and Drug Administration (US FDA). Participation could last up to two years, and possibly longer, if the disease does not progress.

Condition or Disease Intervention/Treatment Phase
Phase 3

Detailed Description

This is a Phase 3 global, randomized, open-label study comparing pirtobrutinib (Arm A) to investigator's choice of ibrutinib, acalabrutinib or zanubrutinib (Arm B) in MCL patients who have received 1 or more lines of therapy and are BTK inhibitor naïve.

Study Design

Study Type:
Interventional
Anticipated Enrollment :
500 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Phase 3 Open-Label, Randomized Study of LOXO-305 Versus Investigator Choice of BTK Inhibitor in Patients With Previously Treated BTK Inhibitor Naïve Mantle Cell Lymphoma (BRUIN MCL-321)
Actual Study Start Date :
Apr 8, 2021
Anticipated Primary Completion Date :
Apr 1, 2025
Anticipated Study Completion Date :
Apr 1, 2025

Arms and Interventions

Arm Intervention/Treatment
Experimental: Arm A (Pirtobrutinib)

Orally

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

    		•
    Active Comparator: Arm B (Ibrutinib, Acalabrutinib, or Zanubrutinib)

    Investigator's choice (based on local availability) of ibrutinib, acalabrutinib or zanubrutinib orally. Options are limited to those that are available/approved in the specific country.

    Drug: Ibrutinib
    Oral
    Other Names:
  • Imbruvica

    • Drug: Acalabrutinib
    Oral
    Other Names:
  • Calquence

    • Drug: Zanubrutinib
    Oral
    Other Names:
  • Brukinsa

    		•

    Outcome Measures

    Primary Outcome Measures

    1. To compare progression-free survival (PFS) of pirtobrutinib as monotherapy (Arm A) to investigator choice of covalent BTK inhibitor monotherapy (Arm B) in patients with previously treated mantle cell lymphoma (MCL) [Up to approximately 24 months]

      Assessed per Lugano criteria

    Secondary Outcome Measures

    1. To compare Event Free Survival (EFS) as monotherapy (Arm A) to investigator choice of covalent BTK inhibitor monotherapy (Arm B) treatment arms [Up to approximately 24 months]

      Defined as the time from randomization to progressive disease (PD) or start of new treatment for MCL or withdrawal from trial due to toxicity or death

    2. To compare Time to Treatment Failure (TTTF) as monotherapy (Arm A) to investigator choice of covalent BTK inhibitor monotherapy (Arm B) treatment arms [Up to approximately 24 months]

      Time from randomization to time when discontinuation criteria met

    3. Time to worsening (TTW) of MCL-related symptoms [Up to approximately 24 months]

      Using symptom questions identified from the European Organization for Research and Treatment of Cancer (EORTC) item library. The range of raw scores for these items could be from 0 to 52 with highest score being worse symptoms.

    4. Comparative Tolerability as measured by proportion of time with high side effect burden [Up to approximately 24 months]

      Using 18 items covering 10 Patient Reported Outcome- Common Terminology Criteria for Adverse Events (PRO-CTCAE) concepts for frequency (0-5 with 5 as most frequent), and/or presence (0-1 with 1 being present), or Severity (0-5 with 5 as most severe) and/or presence (0-1 with 1 being present); these selective adverse events will be framed and then overall side effect burden will be ascertained with the Functional Assessment of Cancer Therapy (FACT) - Item GP5. The range of this item is 0 -4 with 4 as most bothersome.

    5. To compare Overall Response Rate (ORR) of pirtobrutinib as monotherapy (Arm A) to investigator choice of covalent BTK inhibitor monotherapy (Arm B) treatment arms [Up to approximately 24 months]

      Assessed per Lugano criteria

    6. To compare Duration of Response (DOR) of pirtobrutinib as monotherapy (Arm A) to investigator choice of covalent BTK inhibitor monotherapy (Arm B) treatment arms [Up to approximately 24 months]

      Assessed per Lugano criteria

    7. To compare Overall Survival of pirtobrutinib as monotherapy (Arm A) to investigator choice of covalent BTK inhibitor monotherapy (Arm B) treatment arms [Up to approximately 24 months]

      Assessed by survival

    Eligibility Criteria

    Criteria

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

    • Confirmed MCL diagnosis

    • Previously treated with at least one prior line of systemic therapy for MCL

    • Measurable disease per Lugano criteria

    • Eastern Cooperative Oncology Group (ECOG) 0-2

    • Absolute neutrophil count ≥ 0.75 × 109/L without granulocyte-colony stimulating factor support within 7 days of screening

    • Hemoglobin ≥ 8 g/dL not requiring transfusion support or growth factors within 7 days of screening

    • Platelets ≥ 50 × 109/L not requiring transfusion support or growth factors within 7 days of screening.

    • AST and ALT ≤ 3.0 x upper limit of normal (ULN).

    • Total bilirubin ≤ 1.5 x ULN.

    • Creatinine clearance of ≥ 30 mL/min according to Cockcroft/Gault Formula

    Exclusion Criteria:

    • Prior treatment with an approved or investigational BTK inhibitor

    • History of bleeding diathesis

    • History of stroke or intracranial hemorrhage within 6 months of randomization

    • History of allogeneic or autologous stem cell transplant (SCT) or chimeric antigen receptor modified T-cell (CAR-T) therapy within 60 days of randomization

    • Clinically significant cardiovascular disease

    • Prolonged QT interval corrected using Fridericia's formula (QTcF) > 470 ms on 2/3 consecutive ECGs, and mean QTcF>470 ms on all 3 ECGs

    • Known HIV infection or active HBV, HCV, or CMV infections

    • Clinically significant active malabsorption syndrome or other condition likely to affect gastrointestinal (GI) absorption

    • Ongoing chronic treatment with strong cytochrome P450 3A4 (CYP3A4) inhibitors or inducers which cannot be stopped within 3-5 half lives of the CYP3A inhibitor therapy prior to start of study drug treatment.

    • Patients requiring therapeutic anticoagulation with warfarin or another Vitamin K antagonist.

    • Vaccination with live vaccine within 28 days prior to randomization

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Arizona Oncology Associates, P.C. - HOPE Phoenix Arizona United States 85016
    2 Arizona Oncology Associates, P.C. - HOPE Tucson Arizona United States 85711
    3 St. Joseph Heritage Healthcare Fullerton California United States 92835
    4 The Oncology Institute of Hope and Innovation Long Beach California United States 90805
    5 Rocky Mountain Cancer Center Aurora Colorado United States 80012
    6 Medical Oncology Hematology Consultants, PA Newark Delaware United States 19713
    7 Florida Cancer Specialists Fort Myers Florida United States 33901
    8 Mayo Clinic in Florida Jacksonville Florida United States 32224
    9 Florida Cancer Specialists Saint Petersburg Florida United States 33705
    10 Florida Cancer Specialists Tallahassee Florida United States 32308
    11 Florida Cancer Specialists East West Palm Beach Florida United States 33401
    12 University of Kentucky Markey Cancer Center Lexington Kentucky United States 40504
    13 Mercy Health-Paducah Medical Oncology and Hematology Paducah Kentucky United States 42003
    14 Hematology Oncology Clinic Baton Rouge Louisiana United States 70809
    15 Cancer Center Office of Clinical Research New Orleans Louisiana United States 70112
    16 Greenebaum Comprehensive Cancer Center Baltimore Maryland United States 21201
    17 University of Michigan Ann Arbor Michigan United States 48109
    18 Karmanos Cancer Institute Detroit Michigan United States 48201
    19 Mayo Clinic Rochester Minnesota United States 55905
    20 Health Midwest Ventures Group, Inc d/b/a HCA MidAmerica Division, LLC Kansas City Missouri United States 64132
    21 Washington University Medical School Saint Louis Missouri United States 63110
    22 Comprehensive Cancer Centers of Nevada Las Vegas Nevada United States 89169
    23 Hematology Oncology Associates Of Northern New Jersey Morristown New Jersey United States 07960
    24 Columbia University Medical Center New York New York United States 10032
    25 Memorial Sloan Kettering Cancer Center New York New York United States 10065
    26 Messino Cancer Center Asheville North Carolina United States 28806
    27 Levine Cancer Institute Charlotte North Carolina United States 28204
    28 Wake Forest University School of Medicine Winston-Salem North Carolina United States 27157
    29 Oncology Hematology Care Inc Cincinnati Ohio United States 45236
    30 Willamette Valley Cancer Institute & Research Ctr. Eugene Oregon United States 97401
    31 Oregon Oncology Specialists Salem Oregon United States 97301
    32 UPMC Hillman Cancer Center Pittsburgh Pennsylvania United States 15213
    33 Sarah Cannon Research Institute SCRI Nashville Tennessee United States 37203
    34 Texas Oncology-Austin Midtown Austin Texas United States 78705
    35 Texas Oncology - Bedford Bedford Texas United States 76022
    36 University of Texas MD Anderson Cancer Center Houston Texas United States 77030
    37 Texas Oncology - McAllen McAllen Texas United States 78503
    38 Texas Oncology - McKinney McKinney Texas United States 75071
    39 Texas Oncology - Sherman Sherman Texas United States 75090
    40 Texas Oncology - Tyler Tyler Texas United States 75702
    41 Virginia Cancer Specialists, PC Gainesville Virginia United States 20155
    42 University of Wisconsin Carbone Cancer Center Madison Wisconsin United States 53705
    43 Froedtert Memorial Lutheran Hospital Milwaukee Wisconsin United States 53226
    44 The St. George Hospital Kogarah New South Wales Australia 2217
    45 Flinders Medical Centre Bedford Park South Australia Australia 5042
    46 Royal Hobart Hospital Hobart Tasmania Australia 7000
    47 Andrew Lowe Cancer Centre Geelong Victoria Australia 3220
    48 Linear Clinical Research Ltd Nedlands Western Australia Australia WA6009
    49 Royal Perth Hospital Perth Western Australia Australia 6000
    50 Icon Cancer Care - The Wesley Medical Centre Auchenflower Australia 4066
    51 Ordensklinikum Linz GmbH Elisabethinen Linz Oberösterreich Austria 4020
    52 Uniklinikum Salzburg Salzburg Osterreich Austria 5020
    53 Universitair Ziekenhuis Gent Gent Belgium 9000
    54 Universitaire Ziekenhuizen Leuven - Campus Gasthuisberg Leuven Belgium 3000
    55 BC Cancer Vancouver Vancouver British Columbia Canada V5Z 1H6
    56 Anhui Provincial Cancer Hospital Hefei Anhui China 233004
    57 Peking University First Hospital Beijing Beijing China 100034
    58 Peking University People's Hospital Beijing Beijing China 100044
    59 Beijing ChaoYang Hospital Beijing Beijing China 100141
    60 Peking University Third Hospital Beijing Beijing China 100191
    61 Beijing Cancer hospital Haidian District Beijing China 100142
    62 Sun Yat-sen University Cancer Center Guangzhou Guangdong China 510060
    63 Southern Medical University Nanfang Hospital Guangzhou Guangdong China 510515
    64 Henan Cancer Hospital Zhengzhou Henan China 450008
    65 Wuhan Union Hospital Wuhan Hubei China 430022
    66 The First Affiliated Hospital of Soochow University Suzhou Jiangsu China 215066
    67 The First Affiliated Hospital of Nanchang University Nanchang Jiangxi China 330006
    68 Shengjing Hospital of China Medical University Shenyang Liaoning China 110004
    69 West China Hospital of Sichuan University Chengdu Sichuan China 610041
    70 Tianjin Medical University Cancer Institute and Hospital Tianjin Tianjin China 300060
    71 Affiliated Tumor Hospital of Xinjiang Medical University Urumqi Xinjiang China 830002
    72 Zhejiang Cancer Hospital Hangzhou Zhejiang China 310022
    73 Chongqing Cancer Hospital Chongqing China 400030
    74 Blood Institute of the Chinese Academy of Medical science Tianjin China 300020
    75 Fakultni nemocnice Brno Brno Czechia 62500
    76 Fakultni nemocnice Hradec Kralove Hradec Kralove Czechia 500 05
    77 Aarhus Universitetshospital, Aarhus Sygehus Aarhus N Jutland Denmark DK-8200
    78 Odense Universitetshospital Odense Denmark DK-5000
    79 Institut Bergonié - Centre Régional de Lutte Contre Le Cancer de Bordeaux et Sud Ouest Bordeaux Aquitaine France 33076
    80 Centre de Lutte Contre le Cancer - Centre Henri Becquerel Normandie Rouen Rouen Seine-Maritime France 76038
    81 CHRU De Tours Tours Tours Cedex 9 France 37044
    82 Hopital Saint Vincent De Paul Lille cedex France 59020
    83 Centre Hospitalier Universitaire de Nantes - L' Hopital l'hôtel-Dieu Nantes Cedex 1 France 44093
    84 Centre hospitalier universitaire de Haut Leveque Pessac Cedex France 33600
    85 Centre Hospitalier Lyon Sud Pierre Benite Cedex France 69495
    86 Pole Regionalde Cancérologie(CHU de Poitiers) Politiers France 86021
    87 Chu De Nancy Hop D'Adultes De Brabois Vandœuvre-lès-Nancy France 54500
    88 Klinikum der Universität München Großhadern München Bayern Germany 81377
    89 St James's Hosptial Dublin Dublin 8 Ireland D08 NHY1
    90 Bnai Zion Medical Center Haifa Israel 3339419
    91 Hadassah Medical Center Jerusalem Israel 9112001
    92 Chaim Sheba Medical Center Ramat Gan Israel
    93 Tel Aviv Sourasky Medical Center Tel Aviv Israel 6423906
    94 Presidio Ospedaliero Civile Santi Antonio e Biagio Alessandria AL Italy 15100
    95 Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori Meldola Emilia-Romagna Italy 47014
    96 Irccs Crob Rionero in Vulture Potenza Italy 85028
    97 IRCCS - AOU di Bologna Bologna Italy 40138
    98 IRCCS Ospedale Policlinico San Martino Genova Italy 16132
    99 Azienda Ospedaliera Ospedali Riuniti Papardo Piemonte Messina Italy 98158
    100 Ospedale Vincenzo Cervello Palermo Italy 90100
    101 Ospedale Santa Maria delle Croci Ravenna Italy 48020
    102 Arcispedale Santa Maria Nuova Reggio Emilia Italy 42123
    103 Nagoya Medical Center Nagoya Aichi Japan 460-0001
    104 Nagoya City University Hospital Nagoya Aichi Japan 467-8602
    105 Hokkaido University Hospital Sapporo Hokkaido Japan 060-8648
    106 Kobe City Medical Center General Hospital Kobe Hyogo Japan 650-0047
    107 Kochi Medical School Hospital Nankoku Kochi Japan 783-8505
    108 Tohoku University Hospital Sendai-shi Miyagi Japan 980-8574
    109 Kindai University Hospital Osaka Sayama-shi Osaka Japan 589 8511
    110 Saitama Medical Center Kawagoe Saitama Japan 350-8550
    111 Japanese Foundation for Cancer Research Koto Tokyo Japan 135-8550
    112 NTT Medical Center Tokyo Shinagawa-KU Tokyo Japan 141-8625
    113 Chugoku Central Hospital Hiroshima Japan 720-0001
    114 Kumamoto University Hospital Kumamoto Japan 860-8556
    115 Kyoto Furitsu Medical University Hospital Kyoto-shi Japan 602 8566
    116 Okayama University Hospital Okayama Japan 700-8558
    117 Gachon University Gil Hospital Namdong-gu Incheon-gwangyeoksi [Incheon] Korea, Republic of 21565
    118 Kosin University Gospel Hospital Busan Seogu Korea, Republic of 49267
    119 Seoul National University Hospital Seoul Seoul, Korea Korea, Republic of 03080
    120 Severance Hospital, Yonsei University Health System Seoul Seoul-teukbyeolsi [Seoul] Korea, Republic of 03722
    121 Asan Medical Center Seoul Seoul-teukbyeolsi [Seoul] Korea, Republic of 05505
    122 Samsung Medical Center Seoul Seoul-teukbyeolsi [Seoul] Korea, Republic of 06351
    123 The Catholic University of Korea-Seoul St. Mary's Hospital Seocho-Gu Seoul Korea, Republic of 06591
    124 Ziekenhuisapotheek HagaZiekenhuis Den Haag Netherlands 2545 AA
    125 Bravis Ziekenhuis Roosendaal Netherlands 4708 AE
    126 Erasmus Medisch Centrum Rotterdam Netherlands 3015 AA
    127 Middlemore Clinical Trials Papatoetoe Auckland New Zealand 2025
    128 Christchurch Hospital Christchurch New Zealand 8011
    129 Centrum Onkologii Ziemi Lubelskiej Lublin Lubelskie Poland 20-081
    130 Uniwersyteckie Centrum Kliniczne Gdańsk Pomorskie Poland 80-214
    131 Pratia MCM Krakow Krakow Poland 30-510
    132 IPOFG - Lisboa Lisboa Portugal 1099-035
    133 Champalimaud Foundation Lisboa Portugal 1400-038
    134 Budgetary Healthcare Institution of Omsk Region "Clinical Oncology Dispensary" Omsk Omskaya Oblast' Russian Federation 644013
    135 GUZ of Moscow City Clinical Hospital n.a. S.P. Botkin Moscow Russian Federation 125101
    136 Federal State Budgetary Institution "Russian Scientific and Research Institute of Hematology and Transfusiology of Federal Medico-Biological Agency Saint Petersburg Russian Federation 191024
    137 State Medical University named after I.P. Pavlov Saint-Petersburg Russian Federation 197022
    138 Hospital Duran I Reynals Hospitalet De Llobregat Barcelona Spain 08908
    139 Hospital Universitari Vall d'Hebron Barcelona Spain 08035
    140 Hospital General Universitario Gregorio Marañon Madrid Spain 28007
    141 Hospital Infanta Leonor Madrid Spain 28031
    142 Hospital Universitario Fundación Jiménez Díaz Madrid Spain 28040
    143 Hospital Universitario 12 de Octubre Madrid Spain 28041
    144 Kantonsspital Luzern Luzern 16 Luzern Switzerland 6000
    145 Ospedale Regionale Bellinzona e Valli Bellinzona Switzerland CH-6500
    146 Tri-Service General Hospital Taipei City Taipei Taiwan 114
    147 Chang Gung Memorial Hospital - Chiayi Chiayi County Taiwan 61363
    148 Kaohsiung Medical University Chung-Ho Memorial Hospital Kaohsiung Taiwan 80756
    149 China Medical University Hospital Taichung Taiwan 40447
    150 National Cheng-Kung Uni. Hosp. Tainan Taiwan 704
    151 National Taiwan University Hospital Taipei Taiwan 10002
    152 Taipei Veterans General Hospital Taipei Taiwan 11217
    153 Chang Gung Memorial Hospital - Linkou Taoyuan City Taiwan 333
    154 Aberdeen Royal Infirmary Aberdeen Aberdeen City United Kingdom AB25 2ZN
    155 Churchill Hospital Headington Oxford United Kingdom OX3 7LE
    156 GenesisCare Cambridge Newmarket United Kingdom CB8 7XN
    157 City Hospital, Nottingham University Hospitals Nottingham United Kingdom NG5 1PB
    158 Derriford Hospital Plymouth United Kingdom Pl6 8DH
    159 New Cross Hospital Wolverhampton United Kingdom WV10 0QP

    Sponsors and Collaborators

    • Loxo Oncology, Inc.
    • Eli Lilly and Company

    Investigators

    • Study Director: Patient Advocacy, Loxo Oncology, Inc.

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Loxo Oncology, Inc.
    ClinicalTrials.gov Identifier:
    NCT04662255
    Other Study ID Numbers:
    • LOXO-BTK-20019
    • J2N-OX-JZNM
    First Posted:
    Dec 10, 2020
    Last Update Posted:
    Aug 17, 2022
    Last Verified:
    Aug 1, 2022
    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.
    Bruton's Tyrosine Kinase Inhibitor
    BTKi
    Hematologic Disease
    Lymphoma, non-Hodgkin's
    Lymphoma, B-Cell
    Lymphoma
    pirtobrutinib
    Additional relevant MeSH terms:
    Lymphoma
    Lymphoma, Mantle-Cell
    Acalabrutinib
    Zanubrutinib

    Study Results

    No Results Posted as of Aug 17, 2022