Chronic Lymphocytic Leukemia Clinical Trial
— BRUIN CLL-322Official 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)
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.
| Status | Recruiting |
| Enrollment | 600 |
| Est. completion date | January 2027 |
| Est. primary completion date | April 2026 |
| Accepts healthy volunteers | No |
| Gender | All |
| Age group | 18 Years and older |
| Eligibility | 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 10?/liter (L), hemoglobin =8 grams/deciliter (g/dL) and absolute neutrophil count =1.0 x 10?/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 |
| Country | Name | City | State |
|---|---|---|---|
| Australia | Flinders Medical Centre | Adelaide | South Australia |
| Australia | Royal Adelaide Hospital | Adelaide | South Australia |
| Australia | Border Medical Oncology | Albury | New South Wales |
| Australia | Concord Repatriation General Hospital | Concord | New South Wales |
| Australia | St. Vincent's Hospital | Fitzroy | Victoria |
| Australia | Peninsula Private Hospital | Frankston | Victoria |
| Australia | Royal Hobart Hospital | Hobart | Tasmania |
| Australia | The Alfred Hospital | Melbourne | Victoria |
| Australia | Fiona Stanley Hospital | Murdoch | Western Australia |
| Australia | Sir Charles Gairdner Hospital | Nedlands | Western Australia |
| Belgium | Universitair Ziekenhuis Gent | Gent | |
| Belgium | Hôpital de Jolimont | Haine-Saint-Paul | |
| Belgium | CHU UCL Namur | Yvoir | |
| Canada | Foothills Medical Centre | Calgary | Alberta |
| Canada | Tom Baker Cancer Centre | Calgary | Alberta |
| Canada | Cross Cancer Institute | Edmonton | Alberta |
| Canada | CIUSSS du Centre Ouest de l'lle de Montreal | Montreal | Quebec |
| Canada | Sunnybrook Health Sciences Centre | Toronto | Ontario |
| Canada | BC Cancer Vancouver | Vancouver | British Columbia |
| Canada | CancerCare Manitoba | Winnipeg | Manitoba |
| China | Peking University First Hospital | Beijing | Beijing |
| China | Shanghai Tongren Hospital | Changning District | Shanghai |
| China | The Second Xiangya Hospital of Central South University | Changsha | Hunan |
| China | Chongqing University Cancer Hospital | Chongqing | |
| China | Fujian Cancer Hospital | Fuzhou | Fujian |
| China | Affiliated Cancer Hospital and Institute of Guangzhou Medical University | Guangzhou | Guangdong |
| China | First Affiliated Hosp of College of Med, Zhejiang University | Hangzhou | Zhejiang |
| China | The First Affiliated Hospital of Anhui Medical University | Hefei | Anhui |
| China | The First Affiliated Hospital Of University Of South China | Hengshan | Hunan |
| China | The Affiliated Hospital of Inner Mongolia Medical University | Hohhot | Inner Mongolia |
| China | The First People's Hospital of Yunnan Province | Kunming | Yunnan |
| China | Jiangxi Cancer Hospital | Nanchang | Jiangxi |
| China | Jiangsu Province Hospital | Nanjing | Nanjing |
| China | Guangxi Medical University Cancer Hospital | Nanning | Guangxi |
| China | Nantong Tumor Hospital | Nantong | Jiangsu |
| China | The Affiliated Hospital of Qingdao University | Qingdao City | Shandong |
| China | Ruijin Hospital of Shanghai Jiaotong University School of Medicine | Shanghai | Shanghai |
| China | Shengjing Hospital of China Medical University | Shenyang | Liaoning |
| China | Tianjin Medical University Cancer Institute and Hospital | Tianjin | Tianjin |
| China | Union Hospital,Tongji Medical College, Huazhong University of Science and Technology | Wuhan | Hubei |
| China | Tongji Hospital Affiliated to Tongji Medicine University | Wuhan City | Hubei |
| China | Wuxi People's Hospital | Wuxi | Jiangsu |
| China | Yichang Central People's Hospital | Yichang | Hubei |
| China | Henan Provincial People's Hospital | Zhengzhou | Henan |
| China | Zhongshan City People's Hospital | Zhongshan | Guangdong |
| Czechia | Fakultni nemocnice Brno | Brno | |
| Czechia | Fakultni nemocnice Hradec Kralove | Hradec Kralove | |
| Czechia | Fakultni nemocnice Kralovske Vinohrady | Praha 10 | |
| Czechia | Vseobecna fakultni nemocnice v Praze | Praha 2 | |
| Denmark | Rigshospitalet | Copenhagen | |
| France | Centre Hospitalier du Mans | Le Mans | |
| France | CHU de Limoges - Hôpital Dupuytren | Limoges | France Cédex |
| France | Hopital Saint Eloi | Montpellier Cedex 5 | Herault |
| France | CHU de Nantes - Hôtel-Dieu | Nantes | Cedex 1 |
| France | Groupe Hospitalier Pitie-Salpetriere | Paris | Cedex 13 |
| France | Hôpital Saint-Louis | Paris cedex 10 | Paris |
| France | Centre Hospitalier Lyon Sud | Pierre-Bénite | Cedex |
| France | CHU Poitiers - Hôpital la Milétrie | Politiers | Vienne |
| France | CHU Rennes - Hopital Pontchaillou | Rennes | Cedex 9 |
| France | Centre de Lutte Contre le Cancer - Centre Henri Becquerel Normandie Rouen | Rouen | Seine-Maritime |
| France | Institut de Cancérologie de Strasbourg Europe - ICANS | Strasbourg Cedex | Bas Rhin |
| France | Institut Universitaire du Cancer de Toulouse- IUCT-O | Toulouse | Cedex 9 |
| France | CHU Tours - Hôpital Bretonneau | Tours | Tours Cedex 9 |
| France | CHU de Nancy - Hôpital de Brabois Adultes | Vandœuvre-lès-Nancy | |
| Germany | Charité Universitaetsmedizin Berlin - Campus Benjamin Franklin | Berlin | |
| Germany | Klinikum Chemnitz gGmbH | Chemnitz | Sachsen |
| Germany | Universitaetsklinikum Koeln | Koeln | Nordrhein Westfalen |
| Germany | Universitaetsklinikum Leipzig AoeR | Leipzig | Sachsen |
| Germany | Universitaetsmedizin der Johannes Gutenberg-Universitaet Mainz | Mainz | Rheinland Pfalz |
| Germany | Muenchen Klinikum Schwabing | Muenchen | Bayern |
| Germany | Universitaetsmedizin Rostock | Rostock | Mecklenburg Vorpommern |
| Hungary | Orszagos Onkologiai Intezet | Budapest | |
| Hungary | Debreceni Egyetem | Debrecen | |
| Hungary | Somogy Varmegyei Kaposi Mor Oktato Korhaz | Kaposvar | |
| Ireland | Mater Misericordiae University Hospital | Dublin | |
| Ireland | University Hospital Waterford | Waterford | |
| Israel | Bnai Zion Medical Center | Haifa | |
| Israel | Health Corporation of Galilee Medical Center | Naharia | |
| Israel | Rabin Medical Center-Beilinson Campus | Petah-Tikva | |
| Israel | Kaplan Medical Center | Re?ovot | |
| Israel | Tel Aviv Sourasky Medical Center | Tel Aviv | |
| Italy | Azienda Ospedaliera Universitaria Policlinico Sant'Orsola Malpighi IRCCS | Bologna | |
| Italy | Azienda Ospedaliera di Catanzaro "Pugliese-Ciaccio" | Catanzaro | |
| Italy | Azienda Ospedaliera Universitaria Arcispedale Sant'Anna | Cona | |
| Italy | Azienda Ospedaliera Santa Croce e Carle | Cuneo | |
| Italy | Azienda Ospedaliera Universitaria Careggi | Firenze | |
| Italy | IRCCS Istituto Scientifico Romagnolo Per Lo Studio Dei Tumori "Dino Amadori" - IRST | Meldola | |
| Italy | Azienda Socio Sanitaria Territoriale Niguarda (Grande Ospedale Metropolitano Niguarda) | Milano | |
| Italy | Ospedale San Raffaele | Milano | |
| Italy | A.O.U. Policlinico di Modena | Modena | |
| Italy | Ospedale Maggiore di Novara | Novara | |
| Italy | Azienda Ospedaliera Universitaria Policlinico Umberto I - Università di Roma La Sapienza | Roma | |
| Italy | Fondazione Policlinico Universitario Agostino Gemelli IRCCS | Roma | |
| Italy | Azienda Ospedaliero-Universitaria Città della Salute e della Scienza di Torino | Torino | |
| Japan | National Cancer Center Hospital | Chuo-ku | Tokyo |
| Japan | University of Fukui Hospital | Fukui | |
| Japan | Saitama Medical Center | Kawagoe-shi | Saitama-Ken |
| Japan | Cancer Institute Hospital of JFCR | Koto | Tokyo |
| Japan | Kumamoto University Hospital | Kumamoto | |
| Japan | University Hospital, Kyoto Prefectural University of Medicine | Kyoto-shi | Kyoto |
| Japan | NHO Nagoya Medical Center | Nagoya | Aichi |
| Japan | Nagoya City University Hospital | Nagoya-shi | Aichi-Ken |
| Japan | Kochi Medical School Hospital | Nankoku | Kochi |
| Japan | Okayama University Hospital | Okayama | |
| Japan | Ome Municipal General Hospital | Ome | Tokyo |
| Japan | Kindai University Hospital | Osaka Sayama-shi | Osaka |
| Japan | Hokkaido University Hospital | Sapporo | Hokkaido |
| Japan | Tohoku University Hospital | Sendai-shi | Miyagi |
| Japan | NTT Medical Center Tokyo | Shinagawa-Ku | Tokyo |
| Japan | Kanagawa cancer center | Yokohama | Kanagawa |
| Korea, Republic of | The Catholic University of Korea-Seoul St. Mary's Hospital | Seocho-Gu | Seoul |
| Korea, Republic of | Samsung Medical Center | Seoul | |
| Korea, Republic of | Seoul National University Hospital | Seoul | |
| Korea, Republic of | Severance Hospital, Yonsei University Health System | Seoul | Seoul-teukbyeolsi [Seoul] |
| Poland | Szpitale Pomorskie spólka z ograniczona odpowiedzialnoscia | Gdynia | Pomorskie |
| Poland | Pratia Onkologia Katowice | Katowice | |
| Poland | Pratia MCM Krakow | Krakow | |
| Poland | Wojewodzkie Wielospecjalistyczne Centrum Onkologii i Traumatologii im. M. Kopernika w Lodzi | Lódz | |
| Poland | Instytut Hematologii i Transfuzjologii | Warszawa | |
| Singapore | National Cancer Centre Singapore | Singapore | |
| Singapore | Singapore General Hospital | Singapore | |
| Spain | Hospital Universitari Vall d'Hebron | Barcelona | |
| Spain | Hospital Universitario Fundación Jiménez Díaz | Madrid | |
| Spain | Hospital Universitario Infanta Leonor | Madrid | |
| Spain | Hospital Universitario Quironsalud Madrid | Madrid | Pozuelo De Alarcón |
| Spain | Hospital Universitario Puerta de Hierro Majadahonda | Majadahonda | Madrid |
| Spain | Hospital Costa Del Sol | Marbella | Malaga |
| Spain | Hospital Universitario Central de Asturias | Oviedo | Asturias |
| Spain | Hospital Universitario de La Princesa | Salamanca | Mandrid |
| Spain | Hospital Universitario Virgen del Rocío | Sevilla | |
| Spain | Hospital Universitario Virgen Macarena | Sevilla | |
| Spain | Complejo Hospitalario de Toledo | Toledo | Castilla La Mancha |
| Spain | Hospital Universitari i Politecnic La Fe | Valencia | |
| Sweden | Skane University Hospital | Lund | |
| Sweden | Karolinska Universitetssjukhuset, Huddinge | Stockholm | |
| Sweden | Akademiska Sjukhuset | Uppsala | |
| Switzerland | Istituto Oncologico della Svizzera Italiana (IOSI)- Ente Ospedaliero Cantonale (EOC) | Bellinzona | Ticino |
| Switzerland | Luzerner Kantonsspital - Luzern | Luzern | |
| Taiwan | Chang Gung Memorial Hospital - Linkou | Guei Shan Township | Taoyuan City |
| Taiwan | National Taiwan University Hospital | Taipei | |
| United Kingdom | Birmingham Heartlands Hospital | Birmingham | West Midlands |
| United Kingdom | St James's University Hospital | Leeds | West Yorkshire |
| United Kingdom | Leicester Royal Infirmary | Leicester | England |
| United Kingdom | Churchill Hospital | Oxford | |
| United Kingdom | Derriford Hospital | Plymouth | Devon |
| United Kingdom | Royal Marsden Hospital | Surrey | |
| United States | University of Michigan | Ann Arbor | Michigan |
| United States | Memorial Sloan Kettering Cancer Center | Basking Ridge | New Jersey |
| United States | Hematology Oncology Clinic | Baton Rouge | Louisiana |
| United States | American Oncology Partners of Maryland, PA | Bethesda | Maryland |
| United States | Central Care Cancer Center | Bolivar | Missouri |
| United States | Dana-Farber Cancer Institute | Boston | Massachusetts |
| United States | Levine Cancer Institute | Charlotte | North Carolina |
| United States | Novant Health Cancer Institute - Charlotte | Charlotte | North Carolina |
| United States | University Of Virginia | Charlottesville | Virginia |
| United States | Tennessee Oncology | Chattanooga | Tennessee |
| United States | The Ohio State University Wexner Medical Center | Columbus | Ohio |
| United States | Memorial Sloan Kettering Cancer Center | Commack | New York |
| United States | Karmanos Cancer Institute | Detroit | Michigan |
| United States | Duke University Medical Center | Durham | North Carolina |
| United States | Florida Cancer Specialists-Broadway | Fort Myers | Florida |
| United States | Central Care Cancer Center | Garden City | Kansas |
| United States | Hackensack University Medical Center | Hackensack | New Jersey |
| United States | Memorial Sloan Kettering Cancer Center | Harrison | New York |
| United States | Houston Methodist Hospital Cancer Center | Houston | Texas |
| United States | University of Texas MD Anderson Cancer Center | Houston | Texas |
| United States | Cancer Specialists, LLC | Jacksonville | Florida |
| United States | Sarah Cannon Research Institute SCRI | Kansas City | Missouri |
| United States | Memorial Sloan Kettering Cancer Center | Middletown | New Jersey |
| United States | Memorial Sloan Kettering Cancer Center | Montvale | New Jersey |
| United States | Carol G Simon Cancer Center | Morristown | New Jersey |
| United States | SCRI - Tennessee Oncology | Nashville | Tennessee |
| United States | Columbia University Medical Center | New York | New York |
| United States | Icahn School of Medicine at Mount Sinai | New York | New York |
| United States | Memorial Sloan Kettering Cancer Center | New York | New York |
| United States | Westchester Medical College | New York | New York |
| United States | University of California Irvine Medical Center | Orange | California |
| United States | Mayo Clinic Arizona | Phoenix | Arizona |
| United States | Pikeville Medical Center, Inc. | Pikeville | Kentucky |
| United States | Virginia Commonwealth University (VCU) Massey Cancer Center | Richmond | Virginia |
| United States | Mayo Clinic- Rochester | Rochester | Minnesota |
| United States | Baylor Scott & White Health | Round Rock | Texas |
| United States | Florida Cancer Specialists North | Saint Petersburg | Florida |
| United States | Scripps Mercy Hospital | San Diego | California |
| United States | Sharp Memorial Hospital | San Diego | California |
| United States | Providence Medical Foundation | Santa Rosa | California |
| United States | Swedish Cancer Institute | Seattle | Washington |
| United States | MultiCare Health System Institute for Research and Innovation | Spokane | Washington |
| United States | Hematology Oncology, P.C. | Stamford | Connecticut |
| United States | SUNY Upstate Medical Center | Syracuse | New York |
| United States | Florida Cancer Specialists Panhandle | Tallahassee | Florida |
| United States | University of Arizona Cancer Center | Tucson | Arizona |
| United States | Memorial Sloan Kettering Cancer Center | Uniondale | New York |
| United States | Carle Clinic Association, P.C. | Urbana | Illinois |
| United States | UW Cancer Center at ProHealth Care | Waukesha | Wisconsin |
| United States | Florida Cancer Specialists East | West Palm Beach | Florida |
| Lead Sponsor | Collaborator |
|---|---|
| Loxo Oncology, Inc. | Eli Lilly and Company |
United States, Australia, Belgium, Canada, China, Czechia, Denmark, France, Germany, Hungary, Ireland, Israel, Italy, Japan, Korea, Republic of, Poland, Singapore, Spain, Sweden, Switzerland, Taiwan, United Kingdom,
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Primary | To evaluate progression-free survival (PFS) of pirtobrutinib plus venetoclax and rituximab (Arm A) compared to venetoclax and rituximab (Arm B) | Assessed by blinded independent review committee (IRC) per International Workshop on Chronic Lymphocytic Leukemia (iwCLL) 2018 | Up to approximately 5 years | |
| Secondary | To evaluate the efficacy of Arm A compared to Arm B: Progression-free survival (PFS) | Assessments of efficacy include PFS, assessed by investigator | Up to approximately 5 years | |
| Secondary | To evaluate the efficacy of Arm A compared to Arm B: Overall survival (OS) | Assessments of efficacy include OS | Up to approximately 5 years | |
| Secondary | To evaluate the efficacy of Arm A compared to Arm B: Time to next treatment (TTNT) | Assessments of efficacy include TTNT | Up to approximately 5 years | |
| Secondary | To evaluate the efficacy of Arm A compared to Arm B: Event-free survival (EFS) | Assessments of efficacy include EFS | Up to approximately 5 years | |
| Secondary | To evaluate the efficacy of Arm A compared to Arm B: Overall response rate (ORR) | Assessments of efficacy include ORR | Up to approximately 5 years | |
| Secondary | To evaluate the effectiveness of Arm A compared to Arm B in patient-reported disease-related symptoms | Based on time to worsening of CLL/SLL-related symptoms | Up to approximately 5 years | |
| Secondary | To evaluate the effectiveness of Arm A compared to Arm B in patient-reported physical functioning | Based on time to worsening of physical functioning | Up to approximately 5 years |
| Status | Clinical Trial | Phase | |
|---|---|---|---|
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