A Study Evaluating the Efficacy and Safety of Pirtobrutinib in Participants With Relapsed or Refractory Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma

Phase 2

Recruiting

• Conditions: Chronic Lymphocytic Leukemia; Small Lymphocytic Lymphoma
• Interventions: Drug: Pirtobrutinib

• Registration Number: NCT06588478
• Lead Sponsor: Loxo Oncology, Inc.

Brief Summary

The main purpose of this study is to assess the efficacy and safety of 3 dose levels of Pirtobrutinib in participants with relapsed or refractory chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL), who have received 1-3 lines of treatment including a covalent Bruton tyrosine kinase (BTK) inhibitor. The study is expected to last approximately 3 years.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2024-09-06
• Study First Submitted QC: 2024-09-06
• Study First Posted: 2024-09-19
• Study Start: 2025-01-03
• Status Verified: 2025-04
• Last Update Submitted: 2025-04-17
• Last Update Posted: 2025-04-18
• Primary Completion: 2028-06
• Study Completion: 2028-12

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 249

Inclusion Criteria

• Have confirmed diagnosis of CLL/SLL as defined by these iwCLL 2018 criteria.
• Have received prior CLL/SLL treatment
• Have received at least 1, but not more than 3 lines of prior treatment for CLL/SLL
• Have received a covalent BTK inhibitor
• Have a requirement for therapy consistent with iwCLL 2018 criteria for initiation of therapy
• Capable of swallowing oral study medication.
• Have an Eastern Cooperative Oncology Group Performance Status (ECOG) score of 0 to 2.

Exclusion Criteria

• Have received prior treatment with a BTK degrader and a noncovalent BTK inhibitor

• Have a history of greater than or equal to (>=) Grade 3 bleeding due to treatment with a BTK inhibitor

• Have known or suspected Richter's transformation

• Have known or suspected history of central nervous system involvement by CLL/SLL

• Previous or concurrent cancer distinct from CLL/SLL within 3 years before randomization. Exceptions may occur with documented sponsor approval. Examples include:

  • nonmelanoma skin cancer or lentigo maligna melanoma
  • cervical carcinoma in situ
  • localized prostate cancer undergoing active surveillance, and
  • localized (for example, lymph node negative) breast cancer with no evidence of active disease present for more than 3 years. Individual may be receiving adjuvant hormonal therapy

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Pirtobrutinib Standard Dose (Dose 1)	Pirtobrutinib	Pirtobrutinib administered orally.
Pirtobrutinib Dose 2	Pirtobrutinib	Pirtobrutinib administered orally.
Pirtobrutinib Dose 3	Pirtobrutinib	Pirtobrutinib administered orally.

Primary Outcome Measures

Name	Time	Method
Overall Response Rate	Baseline up to 3 years	Overall response rate is defined as the proportion of participants who achieve the best overall response at or before the initiation of subsequent anticancer therapy of CR, CRi, nPR, or PR. ORR will be assessed using International Workshop on Chronic Lymphocytic Leukemia (iwCLL) 2018 response criteria.

Secondary Outcome Measures

Name	Time	Method
Duration of Response	Baseline up to 3 years	Duration of response is defined as the time from the date of the first documented CR, CRi, nPR, or PR to disease progression (per iwCLL 2018) or death from any cause.

Trial Locations

Locations (136)

Ironwood Cancer & Research Centers; 🇺🇸 Chandler, Arizona, United States

City of Hope National Medical Center; 🇺🇸 Irvine, California, United States

Palo Alto Medical Foundation Research Institute (PAMFRI); 🇺🇸 Palo Alto, California, United States

Stanford Cancer Center; 🇺🇸 Palo Alto, California, United States

Rocky Mountain Cancer Center; 🇺🇸 Aurora, Colorado, United States

University of Miami Hospital and Clinics, Sylvester Cancer Center; 🇺🇸 Miami, Florida, United States

City of Hope National Medical Center, Atlanta Cancer Center; 🇺🇸 Newnan, Georgia, United States

Mission Cancer + Blood; 🇺🇸 Waukee, Iowa, United States

Saint Elizabeth Medical Center Edgewood; 🇺🇸 Edgewood, Kentucky, United States

American Oncology Partners of Maryland, PA; 🇺🇸 Bethesda, Maryland, United States

Boston Medical Center; 🇺🇸 Boston, Massachusetts, United States

Gulfport Memorial Hospital; 🇺🇸 Gulfport, Mississippi, United States

Clinical Research Alliance; 🇺🇸 Westbury, New York, United States

East Carolina University; 🇺🇸 Greenville, North Carolina, United States

Williamette Valley Cancer Institute & Research Center; 🇺🇸 Eugene, Oregon, United States

Cancer Care Associates Of York; 🇺🇸 York, Pennsylvania, United States

The West Clinic, PLLC dba West Cancer Center; 🇺🇸 Germantown, Tennessee, United States

USO-Texas Oncology-Central/South Texas; 🇺🇸 Austin, Texas, United States

Royal Hobart Hospital; 🇦🇺 Hobart, Tasmania, Australia

Sarah Cannon Research Institute/SCRI; 🇺🇸 The Woodlands, Texas, United States

USO-Virginia Oncology Associates; 🇺🇸 Hampton, Virginia, United States

USO-Northwest Cancer Specialists, PC; 🇺🇸 Vancouver, Washington, United States

Bankstown-Lidcombe Hospital; 🇦🇺 Bankstown, New South Wales, Australia

Coffs Harbour Health Campus; 🇦🇺 Coffs Harbour, New South Wales, Australia

Calvary Mater Newcastle; 🇦🇺 Waratah, New South Wales, Australia

Princess Alexandra Hospital; 🇦🇺 Woolloongabba, Queensland, Australia

Flinders Medical Centre; 🇦🇺 Adelaide, South Australia, Australia

ICON Cancer Centre - Kurralta Park; 🇦🇺 Kurralta Park, South Australia, Australia

Box Hill Hospital; 🇦🇺 Box Hill, Victoria, Australia

Latrobe Regional Health; 🇦🇺 Traralgon, Victoria, Australia

The Perth Blood Institute - West Perth; 🇦🇺 West Perth, Western Australia, Australia

Clinique Saint Pierre; 🇧🇪 Ottignies, Brabant Wallon, Belgium

Institut Jules Bordet; 🇧🇪 Anderlecht, Bruxelles-Capitale, Région De, Belgium

Groupe Jolimont; 🇧🇪 La Louvière, Hainaut, Belgium

CHR Verviers - La Tourelle; 🇧🇪 Verviers, Liège, Belgium

UZ Gent; 🇧🇪 Gent, Oost-Vlaanderen, Belgium

AZ Nikolaas; 🇧🇪 Sint-Niklaas, Oost-Vlaanderen, Belgium

UZ Leuven; 🇧🇪 Leuven, Vlaams-Brabant, Belgium

AZ Sint-Jan Brugge-Oostende AV; 🇧🇪 Brugge, West-Vlaanderen, Belgium

AZ Delta vzw; 🇧🇪 Roeselare, West-Vlaanderen, Belgium

Royal Victoria Regional Health Centre; 🇨🇦 Barrie, Ontario, Canada

CIUSSS- saguenay-Lac-Saint-Jean; 🇨🇦 Chicoutimi, Quebec, Canada

Saskatoon Cancer Centre; 🇨🇦 Saskatoon, Saskatchewan, Canada

Fakultní nemocnice Brno Bohunice; 🇨🇿 Brno, Brno-město, Czechia

Fakultni nemocnice Hradec Kralove; 🇨🇿 Hradec Kralove, Hradec Králové, Czechia

Fakultni nemocnice Kralovske Vinohrady; 🇨🇿 PRague, Praha 10, Czechia

Vseobecna fakultni nemocnice v Praze; 🇨🇿 Praha 2, Czechia

Aarhus Universitetshospital, Skejby; 🇩🇰 Aarhus, Midtjylland, Denmark

Odense Universitetshospital; 🇩🇰 Odense, Syddanmark, Denmark

Centre Antoine-Lacassagne; 🇫🇷 Nice, Alpes-Maritimes, France

Groupe Hospitalier de la Région de Mulhouse et Sud Alsace - Hôpital Emile Muller; 🇫🇷 Mulhouse, Alsace, France

Centre Hospitalier Universitaire de Caen - Hôpital Côte de Nacre; 🇫🇷 Caen, Calvados, France

Institut Universitaire du Cancer Toulouse - Oncopole - CHU de TOULOUSE; 🇫🇷 Toulouse, Haute-Garonne, France

Centre Hospitalier Régional Universitaire de Tours - Hôpital Bretonneau; 🇫🇷 Tours, Indre-et-Loire, France

Centre Hospitalier du Mans; 🇫🇷 Le Mans, Sarthe, France

Centre Hospitalier d'Argenteuil Victor Dupouy; 🇫🇷 Argenteuil, Val-d'Oise, France

Klinikum Aschaffenburg-Alzenau; 🇩🇪 Aschaffenburg, Bayern, Germany

Centrum für Hämatologie und Onkologie Bethanien; 🇩🇪 Frankfurt, Hessen, Germany

OSP Göttingen; 🇩🇪 Goettingen, Niedersachsen, Germany

Onkologisches Ambulanzzentrum Hannover; 🇩🇪 Hannover, Niedersachsen, Germany

MV-Zentrum für Onkologie und Hämatologie; 🇩🇪 Cologne, Nordrhein-Westfalen, Germany

InVO Institut für Versorgungsforschung in der Onkologie; 🇩🇪 Koblenz, Rheinland-Pfalz, Germany

Evangelismos General Hospital of Athens; 🇬🇷 Athens, Attikí, Greece

Attikon General University Hospital; 🇬🇷 Chaidari, Attikí, Greece

General Hospital of Athens "Laiko"; 🇬🇷 Αthens, Attikí, Greece

G. Papanikolaou General Hospital; 🇬🇷 Thessaloniki, Thessaloníki, Greece

Pécsi Tudományegyetem Klinikai Központ; 🇭🇺 Pécs, Baranya, Hungary

Szegedi Tudományegyetem Szent-Györgyi Albert Klinikai Központ; 🇭🇺 Szeged, Csongrád, Hungary

Semmelweis Egyetem; 🇭🇺 Budapest, Hungary

Dél-Pesti Centrumkórház; 🇭🇺 Budapest, Hungary

Azienda Ospedaliero Universitaria S.Anna; 🇮🇹 Cona, Emilia-Romagna, Italy

Fondazione Policlinico Universitario Agostino Gemelli IRCCS - Università Cattolica del Sacro Cuore; 🇮🇹 Roma, Lazio, Italy

ASST Grande Ospedale Metropolitano Niguarda; 🇮🇹 Milan, Lombardia, Italy

A.O.U.C. Policlinico di Bari; 🇮🇹 Bari, Puglia, Italy

Az. Osp. Ospedali Riuniti VILLA SOFIA-CERVELLO; 🇮🇹 Palermo, Sicilia, Italy

Azienda Ospedaliera Universitaria Careggi; 🇮🇹 Firenze, Toscana, Italy

AO Santa Maria della Misericordia; 🇮🇹 Perugia, Umbria, Italy

Azienda Ospedale - Università Padova; 🇮🇹 Padova, Veneto, Italy

Azienda Ospedaliero Universitaria Maggiore della Carità; 🇮🇹 Novara, Italy

AOU Policlinico Umberto I; 🇮🇹 Roma, Italy

Chonnam National University Hwasun Hospital; 🇰🇷 Hwasun-gun, Jeonranamdo, Korea, Republic of

Pusan National University Hospital; 🇰🇷 Busan, Pusan-Kwangyǒkshi, Korea, Republic of

Seoul National University Hospital; 🇰🇷 Seoul, Seoul-teukbyeolsi [Seoul], Korea, Republic of

Samsung Medical Center; 🇰🇷 Seoul, Seoul-teukbyeolsi [Seoul], Korea, Republic of

The Catholic Univ. of Korea Seoul St. Mary's Hospital; 🇰🇷 Seoul, Seoul-teukbyeolsi [Seoul], Korea, Republic of

The Catholic University of Korea, Yeouido St. Mary's Hospital; 🇰🇷 Seoul, Seoul-teukbyeolsi [Seoul], Korea, Republic of

Uniwersytecki Szpital Kliniczny im. Jana Mikulicza-Radeckiego we Wrocławiu; 🇵🇱 Wrocław, Dolnośląskie, Poland

IN VIVO; 🇵🇱 Bydgoszcz, Kujawsko-pomorskie, Poland

Pratia MCM Krakow; 🇵🇱 Kraków, Małopolskie, Poland

AIDPORT Sp. z o.o.; 🇵🇱 Skórzewo, Wielkopolskie, Poland

Pratia Onkologia Katowice; 🇵🇱 Katowice, Śląskie, Poland

Fundeni Clinical Institute; 🇷🇴 Bucuresti, București, Romania

Ovidius Clinical Hospital OCH; 🇷🇴 Ovidiu, Constanța, Romania

Spitalul Clinic Municipal Filantropia Craiova; 🇷🇴 Craiova, Dolj, Romania

Spitalul Clinic Colțea; 🇷🇴 București, Romania

Institutul Oncologic Cluj; 🇷🇴 Cluj, Romania

Institutul Regional de Oncologie; 🇷🇴 Iași, Romania

Fakultna nemocnica s poliklinikou F.D.Roosevelta Banska Bystrica; 🇸🇰 Banska Bystrica, Banskobystrický Kraj, Slovakia

Narodny onkologicky ustav; 🇸🇰 Bratislava, Bratislavský Kraj, Slovakia

Univerzitna Nemocnica L. Pasteura Kosice; 🇸🇰 Kosice, Košický Kraj, Slovakia

Univerzitna nemocnica Martin; 🇸🇰 Martin, Žilinský Kraj, Slovakia

Hospital Universitario Virgen Macarena; 🇪🇸 Sevilla, Andalucía, Spain

Hospital Universitario Central de Asturias; 🇪🇸 Oviedo, Asturias, Spain

Institut Català d'Oncologia (ICO) - Badalona; 🇪🇸 Badalona, Barcelona [Barcelona], Spain

Hospital Universitari Vall d'Hebron; 🇪🇸 Barcelona, Barcelona [Barcelona], Spain

Institut Català d'Oncologia - L'Hospitalet; 🇪🇸 L'Hospitalet Del Llobregat, Barcelona [Barcelona], Spain

Hospital Universitario Marqués de Valdecilla; 🇪🇸 Santander, Cantabria, Spain

Hospital Clínic de Barcelona; 🇪🇸 Barcelona, Catalunya [Cataluña], Spain

Clinica Universidad de Navarra; 🇪🇸 Madrid, Madrid, Comunidad De, Spain

Hospital Universitario Infanta Leonor; 🇪🇸 Madrid, Madrid, Comunidad De, Spain

MD Anderson Cancer Center; 🇪🇸 Madrid, Madrid, Comunidad De, Spain

Hospital Universitario Ramón y Cajal; 🇪🇸 Madrid, Madrid, Comunidad De, Spain

Hospital Universitario Puerta de Hierro Majadahonda; 🇪🇸 Majadahonda, Madrid, Comunidad De, Spain

Hospital Costa del Sol; 🇪🇸 Marbella, Málaga, Spain

Hospital Universitario 12 de Octubre; 🇪🇸 Madrid, Spain

Hospital Universitario Quironsalud Madrid; 🇪🇸 Madrid, Spain

Hospital Universitario de Salamanca - Complejo Asistencial Universitario de Salamanca; 🇪🇸 Salamanca, Spain

Hospital Universitario Virgen Del Rocio; 🇪🇸 Sevilla, Spain

Kocaeli Üniversitesi; 🇹🇷 Izmit, Kocaeli, Turkey

Sakarya University School of Medicine; 🇹🇷 Adapazarı, Sakarya, Turkey

Dr. Abdurrahman Yurtaslan Ankara Onkoloji Egitim ve Arastırma Hastanesi; 🇹🇷 Ankara, Turkey

Ankara University Health Practice and Research Hospitals; 🇹🇷 Ankara, Turkey

Memorial Antalya Hospital; 🇹🇷 Antalya, Turkey

Yeditepe Üniversitesi Koşuyolu Hastanesi; 🇹🇷 Istanbul, Turkey

Ege Universitesi Hastanesi; 🇹🇷 Izmir, Turkey

VM Medical Park Mersin Hastanesi; 🇹🇷 Mersin, Turkey

Ondokuz Mayıs Universitesi; 🇹🇷 Samsun, Turkey

Maidstone Hospital; 🇬🇧 Maidstone, Kent, United Kingdom

Lincoln County Hospital; 🇬🇧 Lincoln, Lincolnshire, United Kingdom

Northwick Park Hospital; 🇬🇧 Harrow, London, City Of, United Kingdom

Hammersmith Hospital; 🇬🇧 London, London, City Of, United Kingdom

Heartlands Hospital; 🇬🇧 Birmingham, United Kingdom

The Beatson West of Scotland Cancer Centre; 🇬🇧 Glasgow, United Kingdom

St James's University Hospital; 🇬🇧 Leeds, United Kingdom

Clatterbridge Cancer Centre - Liverpool; 🇬🇧 Liverpool, United Kingdom

Singleton Hospital; 🇬🇧 Swansea, United Kingdom