Clinical trial • Phase III • Oncology

PIRTOBRUTINIB for Chronic lymphocytic leukemia | Small lymphocytic lymphoma

Phase III trial of PIRTOBRUTINIB for Chronic lymphocytic leukemia | Small lymphocytic lymphoma.

Overview

Trial Therapeutic Area
Oncology
Trial Disease
Chronic lymphocytic leukemia | Small lymphocytic lymphoma
Trial Stage
Phase III
Drug Modality
Small molecule | Monoclonal antibody

Key dates

Initial CTIS Submission Date
10-05-2024
First CTIS Authorization Date
04-07-2024

Trial design

Randomised, open-label, investigator's choice (arm b) of: 1) idelalisib plus rituximab; 2) bendamustine plus rituximab. (product entries list idelalisib tablets and rituximab infusion and bendamustine iv; specific dosing schedules not specified in the provided text.)-controlled Phase III trial in Belgium, Hungary, Croatia and others.

Randomised
Yes
Open Label
Yes
Comparator
Investigator's choice (Arm B) of: 1) Idelalisib plus Rituximab; 2) Bendamustine plus Rituximab. (Product entries list Idelalisib tablets and Rituximab infusion and Bendamustine IV; specific dosing schedules not specified in the provided text.)
Target Sample Size
130

Eligibility

Recruits 130 isVulnerablePopulationSelected = true. Subjects must be "Willing and capable of giving signed informed consent" as required by Section 10.1.2 Appendix 1; ICFs and subject information are provided (multiple ICF versions: Main ICF, Crossover ICF, Pregnant Partner ICF, Optional sample collection ICF, Treatment Beyond PD ICF, etc.). ICF documents are available in multiple languages (examples in the document list include English, French, German, Dutch, Hungarian, Croatian, Polish, Italian, Spanish). No specific assent procedures for minors are described (trial includes adults ≥18)..

Vulnerable Population
isVulnerablePopulationSelected = true. Subjects must be "Willing and capable of giving signed informed consent" as required by Section 10.1.2 Appendix 1; ICFs and subject information are provided (multiple ICF versions: Main ICF, Crossover ICF, Pregnant Partner ICF, Optional sample collection ICF, Treatment Beyond PD ICF, etc.). ICF documents are available in multiple languages (examples in the document list include English, French, German, Dutch, Hungarian, Croatian, Polish, Italian, Spanish). No specific assent procedures for minors are described (trial includes adults ≥18).

Inclusion criteria

  • {"criterion_text":"- Age 18 or older per local regulations at time of enrollment.\n- Confirmed diagnosis of CLL/SLL requiring therapy as defined by iwCLL 2018 criteria\n- Previously treated with a covalent BTK inhibitor\n- Eastern Cooperative Oncology Group (ECOG) 0 2\n- Absolute neutrophil count ≥ 0.75 × 10^9/L without granulocyte colony stimulating factor support, or ≥ 0.50 × 10^9/L in patients with documented bone marrow involvement considered to impair hematopoiesis. Granulocyte colony stimulating factor support is permitted in patients with documented bone marrow involvement\n- Hemoglobin ≥ 8 g/dL or ≥ 6 g/dL in patients with documented bone marrow involvement considered to impair hematopoiesis. Transfusion support is permitted in patients with bone marrow involvement\n- Platelets ≥ 50 × 10^9/L. If an investigator has chosen bendamustine/rituximab as the Arm B treatment, platelets must be ≥ 75 × 10^9/L. Patients may enroll below these thresholds if the Investigator determines the cytopenia is related to bone marrow involvement considered to impair hematopoiesis. Patients with a platelet count < 30 x 10^9/L are excluded\n- AST and ALT ≤ 3.0 x upper limit of normal (ULN)\n- Total bilirubin ≤ 1.5 x ULN\n- Estimated creatinine clearance of ≥ 30 mL/min\n- Willing and capable of giving signed informed consent as described in Section 10.1.2 Appendix 1 which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol."}

Exclusion criteria

  • {"criterion_text":"- Known or suspected Richter's transformation at any time preceding enrollment\n- Known Human Immunodeficiency Virus (HIV) infection, regardless of CD4 count\n- Clinically significant active malabsorption syndrome or inflammatory bowel disease\n- Prior exposure to non covalent (reversible) BTK inhibitor\n- Patients requiring therapeutic anticoagulation with warfarin or another Vitamin K antagonist\n- Current treatment with strong cytochrome P450 (CYP) 3A4 (CYP3A4) inhibitors or inducers\n- Vaccination with a live vaccine within 28 days prior to randomization\n- Patients with the following hypersensitivity: 1.\tKnown hypersensitivity, including anaphylaxis, to any component or excipient of pirtobrutinib. For patients planned to receive idelalisib, known hypersensitivity, including anaphylaxis, to any component or excipient of idelalisib. For patients planned to receive bendamustine, known hypersensitivity, including anaphylaxis, to any component or excipient of bendamustine. Prior significant hypersensitivity to rituximab\n- Known or suspected history of central nervous system (CNS) involvement by CLL/SLL\n- Ongoing drug induced liver injury\n- Active uncontrolled auto immune cytopenia\n- Significant cardiovascular disease\n- History of allogeneic or stem cell transplantation (SCT) or chimeric antigen receptor modified T cells (CAR T) therapy within the past 60 days\n- Active hepatitis B or hepatitis C\n- Known active cytomegalovirus (CMV) infection\n- Active uncontrolled systemic bacterial, viral, fungal or parasitic infection"}

Endpoints

Primary endpoints

  • {"endpoint_text":"- Assessed by Independent Review Committee (IRC): • PFS per iwCLL 2018","definition_or_measurement_approach":"Assessed by Independent Review Committee (IRC); progression-free survival (PFS) according to iwCLL 2018 criteria"}

Recruitment

Registry Or Advocacy Recruitment
True - advocacy letter(s) referenced in recruitment documents; specific advocacy organisation names are not provided in the available documents.
Digital Remote Recruitment
True - ePRO/eCOA digital methods are used (ePRO Patient Information Guide, ePRO training modules, reminder icons, eCOA handheld materials, digital participant materials such as Happify digital wellbeing content).
Planned Sample Size
130
Recruitment Window Months
71
Consent Approach
Informed consent must be signed by the participant; inclusion criterion: "Willing and capable of giving signed informed consent as described in Section 10.1.2. Appendix 1". Multiple ICF versions are provided (Main ICF, Crossover ICF, Pregnant Partner ICF, Optional sample collection ICF, Treatment Beyond PD ICF, etc.) and are available in multiple languages (examples include English, French, German, Dutch, Hungarian, Croatian, Polish, Italian, Spanish). No separate assent process for minors is described (trial enrolment restricted to ≥18).

Methods

  • Physician referral letters / Physician referral (documents: e.g. "L2_Physician Referral Letter_V02HRV01_san"). Target audience: treating physicians to identify eligible patients.
  • Advocacy engagement / Advocacy letters (documents: e.g. "K1_Advocacy Letter_V02HRV01__san"). Target audience: patient advocacy groups/communities (advocacy organisation names not specified in documents).
  • Patient-facing brochures, participant study guides and patient ID cards (multiple country-specific Patient Brochures and Participant Study Guide documents). Channels: printed materials given at sites; target audience: potential participants and caregivers.
  • ePRO / digital methods: ePRO Patient Information Guide, ePRO reminder icons, eCOA handheld materials and digital training modules (documents: ePRO Patient Information Guide, eCOA Handheld reports, ePRO Patient Guide). Target audience: enrolled participants for remote data capture and reminders.
  • Travel and reimbursement support materials (prepaid Visa / travel-expense cards) and related FAQs (documents include travel-expense cardholder FAQ and travel-expense patient brochure). Target audience: participants requiring travel assistance.
  • Happify wellbeing materials and related flyers/FAQs (documents: Happify Card, Happify Flyer, Happify FAQ). Target audience: participants (support materials).
  • Site-specific recruitment materials and recruitment placeholders exist for multiple countries (country-specific K1_Recruitment Arrangements documents).

Geography

Total Number Of Sites
47
Total Number Of Participants
130

Belgium

Earliest CTIS Part Ii Submission Date
24-05-2024
Latest Decision Or Authorization Date
11-02-2026
Processing Time Days
628
Number Of Sites
1
Number Of Participants
1

Sites

Site Name
Algemeen Ziekenhuis Delta
Department Name
Hematology
Contact Person Name
Lien Deleu
Contact Person Email
lien.deleu@azdelta.be

Hungary

Earliest CTIS Part Ii Submission Date
24-05-2024
Latest Decision Or Authorization Date
13-02-2026
Processing Time Days
630
Number Of Sites
2
Number Of Participants
4

Sites

Site Name
Del-Pesti Centrumkorhaz Orszagos Hematologiai Es Infektologiai Intezet
Department Name
Hematológiai és Őssejt-transzplantációs Osztály
Contact Person Name
Zoltán Mátrai
Contact Person Email
matraiz1@gmail.com
Site Name
University Of Debrecen
Department Name
Belgyógyászati Klinika. B épület. Hematológia
Contact Person Name
Árpád Illés
Contact Person Email
illesarpaddr@gmail.com

Croatia

Earliest CTIS Part Ii Submission Date
24-05-2024
Latest Decision Or Authorization Date
13-02-2026
Processing Time Days
630
Number Of Sites
1
Number Of Participants
1

Sites

Site Name
KBC Zagreb
Department Name
Hematology
Contact Person Name
Igor Aurer
Contact Person Email
igor.aurer@kbc-zagreb.hr

Germany

Earliest CTIS Part Ii Submission Date
24-05-2024
Latest Decision Or Authorization Date
11-02-2026
Processing Time Days
628
Number Of Sites
4
Number Of Participants
6

Sites

Site Name
Universitaetsklinikum Heidelberg AöR
Department Name
Hämatologie, Onkologie und Rheumatologie
Contact Person Name
Peter Dreger
Site Name
Universitaetsklinikum Schleswig-Holstein AöR
Department Name
Klinik für Innere Medizin II, Hämatologie und Onkologie, Im Karl-Lennert-Krebscentrum
Contact Person Name
Matthias Ritgen
Contact Person Email
matthias.ritgen@uksh.de
Site Name
Universitaetsklinikum Ulm AöR
Department Name
Klinik für Innere Medizin III
Contact Person Name
Eugen Tausch
Contact Person Email
eugen.tausch@uniklinik-ulm.de
Site Name
Luebecker Onkologische Schwerpunktpraxis
Department Name
Dres. med. Uthgenannt, Kisro, Weber
Contact Person Name
Jens Kisro
Contact Person Email
jens.kisro@t-online.de

Spain

Earliest CTIS Part Ii Submission Date
24-05-2024
Latest Decision Or Authorization Date
11-02-2026
Processing Time Days
628
Number Of Sites
4
Number Of Participants
6

Sites

Site Name
Hospital Universitario Quironsalud Madrid
Department Name
pediatria
Contact Person Name
María del Carmen Martinez Chamorro
Site Name
University Hospital Virgen Del Rocio S.L.
Department Name
Unidad de ensayos clinicos
Contact Person Name
Fatima de la Cruz Vicente
Contact Person Email
fatimadelacruzv@gmail.com
Site Name
Hospital Universitario Marques De Valdecilla
Department Name
Alergia
Contact Person Name
Lucrecia Yañez San Segundo
Contact Person Email
lucrecia@humv.es
Site Name
Hospital Universitario Infanta Leonor
Department Name
Farmacia
Contact Person Name
JOSE ANGEL HERNANDEZ RIVAS
Contact Person Email
jahernandezr@salud.madrid.org

Austria

Earliest CTIS Part Ii Submission Date
24-05-2024
Latest Decision Or Authorization Date
16-02-2026
Processing Time Days
633
Number Of Sites
2
Number Of Participants
2

Sites

Site Name
SCRI CCCIT Ges.m.b.H.
Department Name
Universitätsklinik für Innere Medizin III der PMU
Contact Person Name
Alexander Egle
Contact Person Email
a.egle@salk.at
Site Name
Ordensklinikum Linz GmbH
Department Name
Interne 1 - Hämatologie mit Stammzelltransplantation, Hämostaseologie und medizinische Onkologie
Contact Person Name
Michael Girschikofsky

Poland

Earliest CTIS Part Ii Submission Date
24-05-2024
Latest Decision Or Authorization Date
16-02-2026
Processing Time Days
633
Number Of Sites
9
Number Of Participants
40

Sites

Site Name
Szpital Uniwersytecki Nr 2 Im Dr Jana Biziela W Bydgoszczy
Department Name
Klinika Hematologii
Contact Person Name
Marta Sobas
Contact Person Email
marta.sobas@gmail.com
Site Name
Centrum Onkologii Ziemi Lubelskiej Im. Sw. Jana Z Dukli
Department Name
Oddział Hematologiczny
Contact Person Name
Adam Walter-Croneck
Contact Person Email
awalter@cozl.pl
Site Name
Wojewodzkie Wielospecjalistyczne Centrum Onkologii I Traumatologii Im M.Kopernika W Lodzi
Department Name
Oddział Hematologii z Pododdziałem Chemioterapii
Contact Person Name
Tadeusz Robak
Contact Person Email
robaktad@csk.umed.lodz.pl
Site Name
Pratia Hematologia Sp. z o.o.
Department Name
Pratia Onkologia Katowice
Contact Person Name
Sebastian Grosicki
Contact Person Email
sgrosicki@wp.pl
Site Name
Wojewodzki Szpital Specjalistyczny W Legnicy
Department Name
Oddział Hematologiczny
Contact Person Name
Jadwiga Holojda
Contact Person Email
sekretariat@szpital.legnica.pl
Site Name
Szpital Specjalistyczny W Brzozowie Podkarpacki Osrodek Onkologiczny Im.Ks.B.Markiewicza
Department Name
Oddział Hematologii Onkologicznej z Pododdziałem Transplantologii Klinicznej
Contact Person Name
Jacek Krzyzanowski
Contact Person Email
jacek.krzanowski@gmail.com
Site Name
Uniwersytecki Szpital Kliniczny Im. Jana Mikulicza-Radeckiego We Wroclawiu
Department Name
Klinika Hematologii, Terapii Komórkowych i Chorób Wewnętrznych
Contact Person Name
Tomasz Wrobel
Contact Person Email
tomasz_wrobel@wp.pl
Site Name
Instytut Hematologii I Transfuzjologii
Department Name
Klinika Hematologii
Contact Person Name
Ewa Lech-Maranda
Contact Person Email
emaranda@ihit.waw.pl
Site Name
Pratia S.A.
Department Name
Pratia MCM Krakow
Contact Person Name
Wojciech Jurczak
Contact Person Email
wojciech.jurczak@pratia.com

France

Earliest CTIS Part Ii Submission Date
24-05-2024
Latest Decision Or Authorization Date
09-02-2026
Processing Time Days
626
Number Of Sites
6
Number Of Participants
20

Sites

Site Name
Assistance Publique Hopitaux De Paris
Department Name
Service d'Hématologie Biologique
Contact Person Name
Vincent LEVY
Contact Person Email
vincent.levy@aphp.fr
Site Name
Centre Hospitalier Regional Universitaire De Tours
Department Name
Service d'Hématologie et Thérapie Cellulaire
Contact Person Name
Caroline DARTIGEAS
Contact Person Email
c.dartigeas@chu-tours.fr
Site Name
Centre Hospitalier Universitaire De Poitiers
Department Name
Service d’Hématologie et Thérapie Cellulaire
Contact Person Name
Cécile GRUCHET
Contact Person Email
cecile.gruchet@chu-poitiers.fr
Site Name
Hospices Civils De Lyon
Department Name
Service d’Hématologie Clinique
Contact Person Name
Emmanuelle FERRANT
Site Name
Centre Hospitalier Departemental Vendee
Department Name
Service d’Onco-Hématologie
Contact Person Name
Bruno VILLEMAGNE
Contact Person Email
bruno.villemagne@chd-vendee.fr
Site Name
Centre Henri Becquerel
Department Name
Service d’Hématologie Clinique
Contact Person Name
Stéphane LEPRETRE

Czechia

Earliest CTIS Part Ii Submission Date
24-05-2024
Latest Decision Or Authorization Date
12-02-2026
Processing Time Days
629
Number Of Sites
2
Number Of Participants
3

Sites

Site Name
Fakultni Nemocnice Hradec Kralove
Department Name
The 4th Department of Internal Medicine – Hematology
Contact Person Name
Martin Šimkovič
Contact Person Email
martin.simkovic@fnhk.cz
Site Name
Vseobecna Fakultni Nemocnice V Praze
Department Name
1st Dep. of Medicine - Dep. of Hematology
Contact Person Name
Marek Trněný
Contact Person Email
trneny@cesnet.cz

Ireland

Earliest CTIS Part Ii Submission Date
24-05-2024
Latest Decision Or Authorization Date
10-02-2026
Processing Time Days
627
Number Of Sites
2
Number Of Participants
3

Sites

Site Name
St James's Hospital
Department Name
Haematology
Contact Person Name
Carmel Waldron
Contact Person Email
cwaldron@stjames.ie
Site Name
Beaumont Hospital
Department Name
Haematology
Contact Person Name
Philip Murphy
Contact Person Email
philipmurphy@beaumont.ie

Italy

Earliest CTIS Part Ii Submission Date
24-05-2024
Latest Decision Or Authorization Date
12-02-2026
Processing Time Days
629
Number Of Sites
13
Number Of Participants
42

Sites

Site Name
Azienda Ospedaliero-Universitaria Ss Antonio E Biagio E Cesare Arrigo
Department Name
Hematology
Contact Person Name
Danila Pietrasanta
Contact Person Email
dpietrasanta@ospedale.al.it
Site Name
IRCCS Ospedale Policlinico San Martino
Department Name
Hematology
Contact Person Name
Roberto Massimo Lemoli
Contact Person Email
roberto.lemoli@unige.it
Site Name
Careggi University Hospital
Department Name
Hematology
Contact Person Name
Alessandro Sanna
Contact Person Email
sannaa@aou-careggi.toscana.it
Site Name
Azienda Ospedaliera Papardo
Department Name
Hematology
Contact Person Name
Donato Mannina
Contact Person Email
donamanni@gmail.com
Site Name
Fondazione IRCCS Policlinico San Matteo
Department Name
Hematology
Contact Person Name
Marzia Varettoni
Contact Person Email
m.varettoni@smatteo.pv.it
Site Name
Fondazione Policlinico Universitario Agostino Gemelli IRCCS
Department Name
Hematology
Contact Person Name
Luca Laurenti
Contact Person Email
luca.laurenti@unicatt.it
Site Name
Fondazione IRCCS San Gerardo Dei Tintori
Department Name
Hematology
Contact Person Name
Carlo Gambacorti-Passerini
Contact Person Email
carlo.gambacorti@unimib.it
Site Name
ASST Grande Ospedale Metropolitano Niguarda
Department Name
Hematology
Contact Person Name
Anna Maria Frustaci
Site Name
Azienda Ospedaliera S Maria Di Terni
Department Name
Onco-Hematology
Contact Person Name
Gaetano Vaudo
Contact Person Email
vaudogaetano@gmail.com
Site Name
Azienda Socio Sanitaria Territoriale Degli Spedali Civili Di Brescia
Department Name
Hematology
Contact Person Name
Marina Motta
Site Name
Azienda Ospedaliera Universitaria Integrata Verona
Department Name
Hematology
Contact Person Name
Isacco Ferrarini
Contact Person Email
isakfer@gmail.com
Site Name
Hospital Santa Maria Della Misericordia
Department Name
Hematology
Contact Person Name
Paolo Sportoletti
Contact Person Email
paolo.sportoletti@unipg.it
Site Name
Istituto Tumori Bari Giovanni Paolo II
Department Name
Hematology
Contact Person Name
Carla Minoia
Contact Person Email
carla.minoia1@gmail.com

Sponsor

Primary sponsor

Full Name
Loxo Oncology Inc.
Organisation Type
Pharmaceutical company
Country Of Registered Address
United States

Contract research organisations

Name
IQVIA Limited
Responsibilities
IVRS - treatment randomisation; other operational trial support (multiple sponsorDuties codes listed)
Name
Iqvia Laboratories Limited
Responsibilities
clinical haematology

Third parties

  • {"country":"United Kingdom","full_name":"Iqvia Laboratories Limited","duties_or_roles":"clinical haematology","organisation_type":"Non-Pharmaceutical company"}
  • {"country":"United States","full_name":"Unisphere Travel Ltd. Inc.","duties_or_roles":"Patient travel assistance","organisation_type":"Non-Pharmaceutical company"}
  • {"country":"United Kingdom","full_name":"IQVIA Limited","duties_or_roles":"IVRS - treatment randomisation; multiple operational roles (codes present)","organisation_type":"Pharmaceutical company"}
  • {"country":"United States","full_name":"Perceptive Informatics Inc.","duties_or_roles":"Medical image analysis/ review - X-ray, MRI, ultrasound","organisation_type":"Pharmaceutical company"}
  • {"country":"United States","full_name":"Eli Lilly & Co.","duties_or_roles":"","organisation_type":"Pharmaceutical company"}
  • {"country":"United States","full_name":"Neogenomics Laboratories Inc.","duties_or_roles":"Correlative studies (17p FISH, Bone Marrow Aspirate for complex karyotype, IGHV)","organisation_type":"Laboratory/Research/Testing facility"}
  • {"country":"United States","full_name":"Infinity Biologix LLC","duties_or_roles":"Correlative studies (bone marrow biopsy and aspirate, optional saliva DNA, MRD, cfDNA, PBMC)","organisation_type":"Pharmaceutical company"}
  • {"country":"Germany","full_name":"Azenta Germany GmbH","duties_or_roles":"Storage for all correlative studies (IGHV, bone marrow biopsy and aspirate, optional saliva DNA, MRD)","organisation_type":"Pharmaceutical company"}
  • {"country":"United States","full_name":"Alturas Analytics Inc.","duties_or_roles":"Pharmacokinetics testing and storage","organisation_type":"Pharmaceutical company"}
  • {"country":"Canada","full_name":"Cellcarta Biosciences Inc.","duties_or_roles":"Lab kit creation","organisation_type":"Pharmaceutical company"}

Investigational products

Investigational Product Name
PIRTOBRUTINIB
Active Substance
PIRTOBRUTINIB
Modality
Small molecule
Routes Of Administration
ORAL
Route
ORAL
Maximum Dose
200 mg (max daily dose amount listed as 200 mg)
Combination Treatment
Yes

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