Clinical trial • Phase III • Oncology

NEMTABRUTINIB for Small lymphocytic lymphoma (SLL) | Chronic lymphocytic leukemia (CLL)

Phase III trial of NEMTABRUTINIB for Small lymphocytic lymphoma (SLL) | Chronic lymphocytic leukemia (CLL).

Overview

Trial Therapeutic Area
Oncology
Trial Disease
Small lymphocytic lymphoma (SLL) | Chronic lymphocytic leukemia (CLL)
Trial Stage
Phase III
Drug Modality
Small molecule

Key dates

Initial CTIS Submission Date
26-03-2024
First CTIS Authorization Date
12-06-2024

Trial design

Randomised, open-label, investigator’s choice of ibrutinib or acalabrutinib (comparator arms = ibrutinib or acalabrutinib per investigator's choice); specific trial doses/schedules not specified in ctis record.-controlled Phase III trial across 42 sites in Belgium, Norway, Denmark and others.

Randomised
Yes
Open Label
Yes
Comparator
Investigator’s choice of Ibrutinib or Acalabrutinib (comparator arms = ibrutinib or acalabrutinib per investigator's choice); specific trial doses/schedules not specified in CTIS record.
Target Sample Size
948

Eligibility

Recruits 948 No vulnerable population selected. The protocol and consent documentation target adult participants only; informed consent is obtained from participants (adult main consent forms available). Assent or parental consent is not applicable..

Vulnerable Population
No vulnerable population selected. The protocol and consent documentation target adult participants only; informed consent is obtained from participants (adult main consent forms available). Assent or parental consent is not applicable.

Inclusion criteria

  • {"criterion_text":"- Confirmed diagnosis of chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) and active disease clearly documented to have a need to initiate therapy.\n- Has at least 1 marker of disease burden.\n- Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2 within 7 days before randomization.\n- Has the ability to swallow and retain oral medication.\n- Participants who are hepatitis B surface antigen (HBsAg) positive are eligible if they have received hepatitis B virus (HBV) antiviral therapy for at least 4 weeks and have undetectable HBV deoxyribonucleic acid (DNA) viral load before randomization.\n- Participants with history of hepatitis C virus (HCV) infection are eligible if HCV ribonucleic acid (RNA) viral load is undetectable at screening.\n- Participants with human immunodeficiency virus (HIV) who meet ALL eligibility criteria."}

Exclusion criteria

  • {"criterion_text":"- Has an active hepatitis B virus/ hepatitis C virus (HBV/HCV) infection.\n- Is currently being treated with p-glycoprotein (P-gp) substrates with a narrow therapeutic index, cytochrome P450 3A (CYP3A) strong or moderate inducers or CYP3A strong inhibitors.\n- Received prior radiotherapy within 2 weeks of start of study intervention, or radiation-related toxicities, requiring corticosteroids.\n- Received a live or live-attenuated vaccine within 30 days before the first dose of study intervention. Administration of killed vaccines are allowed.\n- Has received an investigational agent or has used an investigational device within 4 weeks before study intervention administration.\n- Has active infection requiring systemic therapy, including intravenous (IV) antibiotics during screening.\n- Participants who have not adequately recovered from major surgery or have ongoing surgical complications.\n- Has gastrointestinal (GI) dysfunction that may affect drug absorption.\n- Has diagnosis of Richter Transformation or active central nervous system (CNS) involvement by CLL/SLL.\n- Has had acquired immune deficiency syndrome (AIDS)-defining opportunistic infection in the past 12 months before screening.\n- Has clinically significant cardiovascular disease.\n- Has hypersensitivity to nemtabrutinib or contraindication to ibrutinib or acalabrutinib, or any of the excipients.\n- Has history of severe bleeding disorder.\n- Has known additional malignancy that is progressing or has required active treatment within the past 2 years.\n- Has received any systemic anticancer therapy for CLL/SLL."}

Endpoints

Primary endpoints

  • {"endpoint_text":"- Objective Response Rate (ORR) per Chronic Lymphocytic Leukemia (iwCLL) Criteria 2018 as assessed by Blinded Independent Central Review (BICR)","definition_or_measurement_approach":"ORR per iwCLL Criteria 2018 assessed by Blinded Independent Central Review (BICR)"}
  • {"endpoint_text":"- Progression-Free Survival (PFS) per iwCLL Criteria 2018 as assessed by BICR","definition_or_measurement_approach":"PFS per iwCLL Criteria 2018 assessed by Blinded Independent Central Review (BICR)"}

Secondary endpoints

  • {"endpoint_text":"- Overall Survival (OS)","definition_or_measurement_approach":"Overall survival as recorded in trial follow-up (no further definition provided in CTIS record)"}
  • {"endpoint_text":"- Duration of Response (DOR) per iwCLL Criteria 2018 as assessed by BICR","definition_or_measurement_approach":"DOR per iwCLL Criteria 2018 assessed by BICR"}
  • {"endpoint_text":"- Number of Participants Who Experience One or More Adverse Events (AEs)","definition_or_measurement_approach":"Count of participants experiencing one or more adverse events (AE) (safety monitoring)"}
  • {"endpoint_text":"- Number of Participants Who Discontinue Study Treatment Due to an AE","definition_or_measurement_approach":"Count of participants discontinuing study treatment due to adverse events"}

Recruitment

Registry Or Advocacy Recruitment
True, Reify Health (documented role: recruitment activities) and country-specific advocacy material (e.g., K2_Recruitment Doc Advocacy Card_GRC_EL_for pub) are included.
Digital Remote Recruitment
True, includes website recruitment materials (e.g., K2_Recruitment Doc Website_POL_PL_SM03_for pub), a documented recruitment method using Iuvando (Germany), and optional Greenphire-related documents referenced in consent materials.
Planned Sample Size
948
Recruitment Window Months
99
Consent Approach
Informed consent obtained from adult participants. Main adult consent forms (L1_ICF_Main consent_*) are provided for multiple countries and languages (documents available in English, French, Dutch, Spanish, Portuguese, Polish, German, Swedish, Norwegian (NN), Czech (CS), Greek (EL) as per document list). Optional addenda and optional consent modules are provided (e.g., progression addendum, pregnancy follow-up, genetic consent, Greenphire optional). Assent/parental consent not applicable (adults only population).

Methods

  • Recruitment documents present for multiple countries including: patient brochures (K2_Recruitment Doc Patient Brochure_*), patient visit guides (K2_Recruitment Doc Patient Visit Guide_*), posters (K2_Recruitment Doc Poster_*), website recruitment material (K2_Recruitment Doc Website_POL_PL_SM03_for pub), recruitment study cards/advocacy cards (K2_Recruitment Doc Advocacy Card_GRC_EL_for pub), master tissue brochures (K2_Recruitment Doc Master Tissue Brochure_*), print advertisements (K2_Recruitment Doc Patient Print Ad_GRC_EL_for pub).
  • Country-specific K1 recruitment arrangements / IC procedure documents (K1_Recruitment Arrangements and IC Procedure_*) indicate local recruitment processes for each Member State (documents listed per country).
  • Recruitment method document referencing Iuvando platform in Germany (K2_Recruitment Doc Recruitment Method_Iuvando_DEU_DE_SM04_for pub).

Geography

Total Number Of Sites
42
Total Number Of Participants
407

Belgium

Earliest CTIS Part Ii Submission Date
14-06-2024
Latest Decision Or Authorization Date
01-07-2024
Processing Time Days
17
Number Of Sites
2
Number Of Participants
16

Sites

Site Name
UZ Leuven
Department Name
Department of Hematology
Contact Person Name
Ann Janssens
Contact Person Email
Ann.janssens@uzleuven.be
Site Name
A.Z. Sint-Maarten
Department Name
Department of Hematology
Contact Person Name
Toine Mercier
Contact Person Email
Toine.mercier@emmaus.be

Norway

Earliest CTIS Part Ii Submission Date
11-04-2024
Latest Decision Or Authorization Date
13-06-2024
Processing Time Days
63
Number Of Sites
3
Number Of Participants
30

Sites

Site Name
Oslo University Hospital HF
Department Name
Department of blood disorders
Contact Person Name
Andrea Lenartova
Contact Person Email
anlena@ous-hf.no
Site Name
Sykehuset I Vestfold HF
Department Name
Clinical Trial unit
Contact Person Name
Magnus Moksnes
Contact Person Email
magmok@siv.no
Site Name
Akershus University Hospital
Department Name
Hematology department
Contact Person Name
Hoa Tran
Contact Person Email
hoa.thi.tuyet.tran@ahus.no

Denmark

Earliest CTIS Part Ii Submission Date
19-06-2024
Latest Decision Or Authorization Date
27-06-2024
Processing Time Days
8
Number Of Sites
3
Number Of Participants
25

Sites

Site Name
Odense University Hospital
Department Name
Department of Hematology
Contact Person Name
Annika Rewes
Contact Person Email
annika.rewes@rsyd.dk
Site Name
Region Sjaelland
Department Name
Department of Hematology
Contact Person Name
Christian Poulsen
Contact Person Email
cbpo@regionsjaelland.dk
Site Name
Aalborg University Hospital
Department Name
Department of Hematology
Contact Person Name
Thor Høyer
Contact Person Email
thhc@rn.dk

Sweden

Earliest CTIS Part Ii Submission Date
14-06-2024
Latest Decision Or Authorization Date
08-07-2024
Processing Time Days
24
Number Of Sites
1
Number Of Participants
28

Sites

Site Name
Karolinska University Hospital
Department Name
ME Hematologi
Contact Person Name
Anders Österborg

Czechia

Earliest CTIS Part Ii Submission Date
11-04-2024
Latest Decision Or Authorization Date
12-06-2024
Processing Time Days
62
Number Of Sites
3
Number Of Participants
30

Sites

Site Name
University Hospital Olomouc
Department Name
Hemato-onkologická klinika
Contact Person Name
Peter Turcsányi
Contact Person Email
Peter.Turcsanyi@fnol.cz
Site Name
Fakultni Nemocnice Hradec Kralove
Department Name
Interní hematologická klinika
Contact Person Name
Martin Šimkovič
Contact Person Email
simkovicm@lfhk.cuni.cz
Site Name
Vseobecna Fakultni Nemocnice V Praze
Department Name
Interní klinika, Klinika hematologie
Contact Person Name
Marek Trněný
Contact Person Email
marek.trneny@lf1.cuni.cz

Spain

Earliest CTIS Part Ii Submission Date
11-04-2024
Latest Decision Or Authorization Date
17-06-2024
Processing Time Days
67
Number Of Sites
7
Number Of Participants
50

Sites

Site Name
Institut Catala D'oncologia
Department Name
Hematology
Contact Person Name
Eva Gonzalez Barca
Site Name
Vall D'hebron Institut De Recerca
Department Name
Hematology
Contact Person Name
Francesc Bosch
Contact Person Email
fboschct@vhio.net
Site Name
Hospital Universitario Quironsalud Madrid
Department Name
Hematology
Contact Person Name
Carmen Martinez Chamorro
Site Name
Hospital Clinic De Barcelona
Department Name
Hematology
Contact Person Name
Pablo Mozas Fernández
Contact Person Email
mozas@clinic.cat
Site Name
Hospital Universitario Puerta De Hierro De Majadahonda
Department Name
Hematology
Contact Person Name
José Antonio García Vela
Site Name
Hospital Universitario De Salamanca
Department Name
Hematology
Contact Person Name
Almudena Navarro Bailon
Site Name
University Hospital Of Canary Islands
Department Name
Hematology
Contact Person Name
Sandra Iraheta Reyes
Contact Person Email
sandrairaheta@hotmail.com

Poland

Earliest CTIS Part Ii Submission Date
12-06-2024
Latest Decision Or Authorization Date
17-07-2024
Processing Time Days
35
Number Of Sites
7
Number Of Participants
100

Sites

Site Name
Pratia S.A.
Department Name
PRATIA MCM KRAKÓW
Contact Person Name
Wojciech Jurczak
Contact Person Email
biuro.mcm@pratia.com
Site Name
Uniwersytecki Szpital Kliniczny Nr 1 W Lublinie
Department Name
Klinika Hematologii i Transplantacji Szpiku
Contact Person Name
Marek Hus
Site Name
Narodowy Instytut Onkologii Im. Marii Sklodowskiej-Curie Panstwowy Instytut Badawczy
Department Name
Klinika Transplantacji Szpiku i Onkohematologii
Contact Person Name
Sebastian Giebel
Site Name
Uniwersyteckie Centrum Kliniczne
Department Name
Klinika Hematologii i Transplantologii
Contact Person Name
Aleksandra Wadolowska
Contact Person Email
hematologia@uck.gda.pl
Site Name
Narodowy Instytut Onkologii Im. Marii Sklodowskiej-Curie Panstwowy Instytut Badawczy (Warsaw)
Department Name
Klinika Nowotworów Układu Chłonnego
Contact Person Name
Ewa Paszkiewicz-Kozik
Site Name
Szpital Kliniczny Ministerstwa Spraw Wewnetrznych I Administracji Z Warminsko-Mazurskim Centrum Onkologii W Olsztynie
Department Name
Oddzial Kliniczny Hematologii
Contact Person Name
Janusz Hałka
Site Name
Pratia Hematologia Sp. z o.o.
Department Name
Pratia Onkologia Katowice
Contact Person Name
Sebastian Grosicki
Contact Person Email
anna.jakubiec@pratia.com

Portugal

Earliest CTIS Part Ii Submission Date
07-06-2024
Latest Decision Or Authorization Date
26-06-2024
Processing Time Days
19
Number Of Sites
6
Number Of Participants
38

Sites

Site Name
Centro Hospitalar Universitario De Lisboa Norte E.P.E.
Department Name
Department of Hematology and Bone Marrow Transplant
Contact Person Name
Daniela Alves
Site Name
Instituto Portugues De Oncologia De Lisboa Francisco Gentil E.P.E.
Department Name
Department of Hematology
Contact Person Name
Inês Coelho
Site Name
Champalimaud Clinical Centre
Department Name
Department of Hemato-Oncology
Contact Person Name
Sónia Leocádio
Site Name
Centro Hospitalar De Lisboa Ocidental E.P.E.
Department Name
Department of Clinical Hematology
Contact Person Name
Celina Alfonso
Contact Person Email
ccafonso@chlo.min-saude.pt
Site Name
Centro Hospitalar De Vila Nova De Gaia/Espinho E.P.E.
Department Name
Department of Hematology
Contact Person Name
Marta Soares
Site Name
Instituto Portugues De Oncologia Do Porto Francisco Gentil E.P.E.
Department Name
Department of Hematology and Bone Marrow Transplant
Contact Person Name
Isabel Oliveira

Germany

Earliest CTIS Part Ii Submission Date
11-04-2024
Latest Decision Or Authorization Date
13-06-2024
Processing Time Days
63
Number Of Sites
6
Number Of Participants
50

Sites

Site Name
Universitaetsklinikum Ulm AöR
Department Name
Klinik für Innere Medizin III, Sektion CCL
Contact Person Name
Christof Schneider
Site Name
Institut Fuer Versorgungsforschung In Der Onkologie GbR
Department Name
Institut Fuer Versorgungsforschung In Der Onkologie GbR
Contact Person Name
Geothy Chakupurakal
Contact Person Email
chakupurakal@invo-koblenz.de
Site Name
Dr. Vehling-Kaiser MVZ GmbH
Department Name
Dr. Vehling-Kaiser MVZ GmbH
Contact Person Name
Ursula Vehling-Kaiser
Contact Person Email
studien@vehling-kaiser.de
Site Name
Martin-Luther-Universitaet Halle-Wittenberg
Department Name
Klinikum der Medizinischen Fakultät
Contact Person Name
Kinga Ligeti
Contact Person Email
innere4@uk-halle.de
Site Name
Kliniken Maria Hilf GmbH Moenchengladbach
Department Name
Kliniken Maria Hilf GmbH Moenchengladbach
Contact Person Name
Ullrich Graeven
Contact Person Email
ullrich.graeven@mariahilf.de
Site Name
Onkologische Schwerpunktpraxis Kurfuerstendamm
Department Name
Onkologische Schwerpunktpraxis Kurfuerstendamm
Contact Person Name
Ingo Schwaner

Greece

Earliest CTIS Part Ii Submission Date
11-04-2024
Latest Decision Or Authorization Date
22-07-2024
Processing Time Days
102
Number Of Sites
4
Number Of Participants
40

Sites

Site Name
Laiko General Hospital Of Athens
Department Name
A' Department of Internal Medicine, University of Athens
Contact Person Name
Panagiotis Diamantopoulos
Contact Person Email
pandiamantopoulos@gmail.com
Site Name
University General Hospital Of Alexandroupoli
Department Name
Hematology Department
Contact Person Name
Ioannis Kotsianidis
Contact Person Email
jankots@yahoo.gr
Site Name
University General Hospital Of Ioannina
Department Name
Hematology Department
Contact Person Name
Eleftheria Hatzimichael
Contact Person Email
ehatzim@uoi.gr
Site Name
Evangelismos S.A.
Department Name
Hematology and Lymphoma Department Bone Marrow Transplantation Unit
Contact Person Name
Maria Bouzani
Contact Person Email
mbouzani@yahoo.com

Sponsor

Primary sponsor

Full Name
Merck Sharp & Dohme LLC
Organisation Type
Pharmaceutical company
Country Of Registered Address
United States

Contract research organisations

Name
IQVIA Limited
Responsibilities
sponsorDuties code: 4
Name
Parexel International Corp.
Responsibilities
EUB services (call center and medical services)
Name
Bioclinica Inc.
Responsibilities
Central Imaging
Name
Reify Health
Responsibilities
recruitment activities
Name
Signant Health Management Limited
Responsibilities
sponsorDuties code: 7
Name
Signant Health LLC
Responsibilities
sponsorDuties code: 3

Third parties

  • {"country":"United Kingdom","full_name":"IQVIA Limited","duties_or_roles":"sponsorDuties code: 4","organisation_type":"Pharmaceutical company"}
  • {"country":"United Kingdom","full_name":"Signant Health Management Limited","duties_or_roles":"sponsorDuties code: 7","organisation_type":"Pharmaceutical company"}
  • {"country":"United States","full_name":"Neogenomics Inc.","duties_or_roles":"sponsorDuties code: 4","organisation_type":"Laboratory/Research/Testing facility"}
  • {"country":"United States","full_name":"Signant Health LLC","duties_or_roles":"sponsorDuties code: 3","organisation_type":"Pharmaceutical company"}
  • {"country":"United States","full_name":"Foundation Medicine Inc.","duties_or_roles":"sponsorDuties code: 4","organisation_type":"Pharmaceutical company"}
  • {"country":"United States","full_name":"Parexel International Corp.","duties_or_roles":"EUB services (call center and medical services)","organisation_type":"Pharmaceutical company"}
  • {"country":"United States","full_name":"Bioclinica Inc.","duties_or_roles":"Central Imaging","organisation_type":"Laboratory/Research/Testing facility"}
  • {"country":"United States","full_name":"Reify Health","duties_or_roles":"recruitment activities","organisation_type":"Industry"}

Investigational products

Investigational Product Name
Nemtabrutinib
Active Substance
NEMTABRUTINIB
Modality
Small molecule
Routes Of Administration
ORAL USE
Route
ORAL USE
Authorisation Status
1
Maximum Dose
65 mg
Investigational Product Name
Acalabrutinib
Active Substance
ACALABRUTINIB
Modality
Small molecule
Routes Of Administration
ORAL USE
Route
ORAL USE
Authorisation Status
2
Maximum Dose
200 mg
Investigational Product Name
Ibrutinib
Active Substance
IBRUTINIB
Modality
Small molecule
Routes Of Administration
ORAL USE
Route
ORAL USE
Authorisation Status
2
Maximum Dose
420 mg

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