Clinical trial • Phase II • Oncology

NEMTABRUTINIB for Mantle cell lymphoma | Chronic lymphocytic leukemia | Follicular lymphoma | Richter's syndrome

Phase II trial of NEMTABRUTINIB for Mantle cell lymphoma | Chronic lymphocytic leukemia | Follicular lymphoma | Richter's syndrome. open-label.

Overview

Trial Therapeutic Area
Oncology
Trial Disease
Mantle cell lymphoma | Chronic lymphocytic leukemia | Follicular lymphoma | Richter's syndrome
Trial Stage
Phase II
Drug Modality
Small molecule|ADC

Key dates

Initial CTIS Submission Date
20-12-2023
First CTIS Authorization Date
07-02-2024

Trial design

open-label Phase II trial in Estonia, Poland, Italy and others.

Open Label
Yes
Single Multiple Or Escalation Dose Combined
Yes
Target Sample Size
172

Eligibility

Recruits 172 No vulnerable populations selected; the study population is adults only. Informed consent is obtained from adult participants. Subject information and informed consent forms are available in multiple country-specific languages (examples in the dossier include English, Czech, Polish, Italian, Portuguese, Spanish, Swedish, German, Estonian)..

Vulnerable Population
No vulnerable populations selected; the study population is adults only. Informed consent is obtained from adult participants. Subject information and informed consent forms are available in multiple country-specific languages (examples in the dossier include English, Czech, Polish, Italian, Portuguese, Spanish, Swedish, German, Estonian).

Inclusion criteria

  • {"criterion_text":"- For aggressive B-cell malignancies mantle cell lymphoma (MCL) Cohort A: Has histologically confirmed biopsy according to the 2016 World Health Organization (WHO) classification of neoplasms of the hematopoietic and lymphoid tissues and has relapsed or refractory disease after at least 2 prior systemic therapies including a Bruton’s tyrosine kinase inhibition/inhibitor(s) (BTKi), and is post chimeric antigen receptor T (CAR-T) cell therapy or is ineligible for CAR-T cell therapy"}
  • {"criterion_text":"- For aggressive B-cell malignancies MCL Cohort A: Has histologically confirmed biopsy according to the 2016 World Health Organization (WHO) classification of neoplasms of the hematopoietic and lymphoid tissues and has relapsed or refractory disease after at least 1 prior systemic therapy and has no prior exposure to a non-covalent BTKi."}
  • {"criterion_text":"- For aggressive B-cell malignancies Richter transformation lymphoma (RTL): Has histologically confirmed biopsy according to the 2016 World Health Organization (WHO) classification of neoplasms of the hematopoietic and lymphoid tissues and has relapsed or refractory disease."}
  • {"criterion_text":"- For indolent B-cell malignancies follicular lymphoma (FL) and chronic lymphocytic leukemia (CLL): Has histologically confirmed biopsy and has relapsed or refractory disease after at least 2 prior systemic therapies and no other available therapy."}
  • {"criterion_text":"- 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 viral load prior to randomization/allocation."}
  • {"criterion_text":"- Have an ECOG performance status of 0 to 2 assessed within 7 days before cycle 1 day 1."}

Exclusion criteria

  • {"criterion_text":"- Has received solid organ transplant at any time."}
  • {"criterion_text":"- Has clinically significant (ie, active) cardiovascular disease: cerebral vascular accident/stroke (<6 months prior to enrollment), myocardial infarction (<6 months prior to enrollment), unstable angina (<6 months prior to enrollment), congestive heart failure (New York Heart Association Classification Class ≥II), or serious cardiac arrhythmia requiring medication."}
  • {"criterion_text":"- Has pericardial effusion or clinically significant pleural effusion."}
  • {"criterion_text":"- Has ongoing Grade >1 peripheral neuropathy."}
  • {"criterion_text":"- Has a demyelinating form of Charcot-Marie-Tooth disease."}
  • {"criterion_text":"- Has a history of a second malignancy, unless potentially curative treatment has been completed with no evidence of malignancy for 2 years."}
  • {"criterion_text":"- Participants with FL who have transformed to a more aggressive type of lymphoma."}
  • {"criterion_text":"- Has received prior systemic anticancer therapy, including investigational agents, within 5 half-lives or 4 weeks (if prior therapy was a monoclonal antibodies) or 2 weeks (small molecules like kinase inhibitors) prior to the first dose of study intervention."}
  • {"criterion_text":"- Has received prior radiotherapy within 28 days of start of study intervention. Participants must have recovered from all radiation-related toxicities."}
  • {"criterion_text":"- Has ongoing corticosteroid therapy exceeding 30 mg daily of prednisone equivalent."}
  • {"criterion_text":"- Has received a live or live-attenuated vaccine within 30 days before the first dose of study intervention."}
  • {"criterion_text":"- Has known active central nervous system (CNS) lymphoma involvement or active CNS involvement by lymphoma."}
  • {"criterion_text":"- Has an active infection requiring systemic therapy."}
  • {"criterion_text":"- Has a known history of human immunodeficiency virus (HIV) infection not well controlled on antiretroviral therapy (ART)"}
  • {"criterion_text":"- Active HBV or hepatitis C virus (HCV) infection."}
  • {"criterion_text":"- For Cohort C only: has any clinically significant gastrointestinal abnormalities that might alter absorption."}

Endpoints

Primary endpoints

  • {"endpoint_text":"- Percentage of Participants with MCL (Cohort C), FL (Cohort D), and CLL with ≥1 Adverse Event (AE)","definition_or_measurement_approach":"Measure: percentage of participants in specified cohorts experiencing ≥1 AE (safety assessment)."}
  • {"endpoint_text":"- Percentage of Participants with MCL (Cohort C), FL (Cohort D), and CLL who Discontinue from Study Therapy Due to AE","definition_or_measurement_approach":"Measure: percentage of participants in specified cohorts who discontinue study therapy because of an adverse event."}
  • {"endpoint_text":"- Percentage of Participants with MCL (Cohort C) who Experience a Dose-Limiting Toxicity (DLT)","definition_or_measurement_approach":"Measure: percentage of MCL (Cohort C) participants experiencing protocol-defined dose-limiting toxicity (DLT)."}
  • {"endpoint_text":"- Objective Response Rate (ORR) per Lugano Response Criteria as Assessed by Blinded Independent Central Review (BICR) in Participants with MCL (Cohort A), RT, and FL (Cohorts D & E))","definition_or_measurement_approach":"Measure: ORR assessed per Lugano Response Criteria by Blinded Independent Central Review (BICR) in specified cohorts."}
  • {"endpoint_text":"- ORR per Lugano Response Criteria as Assessed by Investigator in Participants with MCL (Cohort C)","definition_or_measurement_approach":"Measure: ORR in MCL Cohort C assessed by investigator using Lugano Response Criteria."}
  • {"endpoint_text":"- ORR per International Workshop on Chronic Lymphocytic Leukemia (iwCLL) Criteria as Assessed by Investigator in Participants with CLL","definition_or_measurement_approach":"Measure: ORR in CLL participants assessed by investigator using iwCLL criteria."}

Secondary endpoints

  • {"endpoint_text":"- Duration of Response (DOR) per Lugano Response Criteria as Assessed by BICR in Participants with MCL (Cohort A), RT, and FL (Cohorts D & E)","definition_or_measurement_approach":"Measure: Duration of Response per Lugano Criteria assessed by BICR."}
  • {"endpoint_text":"- DOR per Lugano Response Criteria as Assessed by Investigator in Participants with MCL (Cohort C)","definition_or_measurement_approach":"Measure: Duration of Response per Lugano Criteria assessed by investigator in MCL Cohort C."}
  • {"endpoint_text":"- DOR per iwCLL Criteria as Assessed by Investigator in Participants with CLL","definition_or_measurement_approach":"Measure: Duration of Response per iwCLL criteria assessed by investigator in CLL participants."}
  • {"endpoint_text":"- Percentage of Participants with ≥1 AE in Participants with MCL (Cohort A), RT, and FL (Cohort E)","definition_or_measurement_approach":"Measure: percentage of participants with ≥1 adverse event in specified cohorts (safety)."}
  • {"endpoint_text":"- Percentage of Participants Discontinuing from Study Therapy Due to AE in Participants with MCL (Cohort A), RT, and FL (Cohort E)","definition_or_measurement_approach":"Measure: percentage of participants in specified cohorts discontinuing therapy due to adverse events."}

Recruitment

Planned Sample Size
172
Recruitment Window Months
64
Consent Approach
Informed consent is obtained from adult participants (no assent required as only adults are eligible). Subject information and ICFs are country-specific and provided in multiple languages as documented (examples include English, Czech, Polish, Italian, Portuguese, Spanish, Swedish, German, Estonian).

Geography

Total Number Of Sites
26
Total Number Of Participants
103

Estonia

Earliest CTIS Part Ii Submission Date
22-01-2024
Latest Decision Or Authorization Date
20-12-2024
Processing Time Days
333
Number Of Sites
1
Number Of Participants
3

Sites

Site Name
North Estonia Medical Centre Foundation
Department Name
Haematology Centre
Contact Person Name
Mariken Ross

Poland

Earliest CTIS Part Ii Submission Date
22-01-2024
Latest Decision Or Authorization Date
26-01-2026
Processing Time Days
735
Number Of Sites
6
Number Of Participants
28

Sites

Site Name
Narodowy Instytut Onkologii Im. Marii Sklodowskiej-Curie Panstwowy Instytut Badawczy
Department Name
Klinika Nowotworów Układu Chłonnego
Contact Person Name
Ewa Paszkiewicz-Kozik
Site Name
Centrum Onkologii Ziemi Lubelskiej Im. Sw. Jana Z Dukli
Department Name
Oddział Hematologii i Transplantacji Szpiku
Contact Person Name
Norbert Grząśko
Contact Person Email
badania.kliniczne@cozl.eu
Site Name
Szpital Kliniczny Ministerstwa Spraw Wewnetrznych I Administracji Z Warminsko-Mazurskim Centrum Onkologii W Olsztynie
Department Name
Oddział Kliniczny Hematologii
Contact Person Name
Janusz Hałka
Site Name
Swietokrzyskie Centrum Onkologii Samodzielny Publiczny Zaklad Opieki Zdrowotnej W Kielcach
Department Name
Klinika Hematologii i Transplantacji Szpiku
Contact Person Name
Paweł Steckiewicz
Site Name
Pratia S.A.
Department Name
Pratia MCM Kraków
Contact Person Name
Wojciech Jurczak
Contact Person Email
biuro.mcm@pratia.com
Site Name
Wojewodzkie Wielospecjalistyczne Centrum Onkologii I Traumatologii Im M.Kopernika W Lodzi
Department Name
Oddział Hematologii Ogólnej
Contact Person Name
Tadeusz Robak
Contact Person Email
tadeusz.robak@umed.lodz.pl

Italy

Earliest CTIS Part Ii Submission Date
22-01-2024
Latest Decision Or Authorization Date
20-01-2026
Processing Time Days
729
Number Of Sites
3
Number Of Participants
19

Sites

Site Name
Humanitas Research Hospital
Department Name
U.O. di Oncologia medica ed Ematologia
Contact Person Name
Armando Santoro
Site Name
Azienda Ospedaliero-Universitaria Di Bologna IRCCS Istituto Di Ricerca E Di Cura A Carattere Scientifico
Department Name
U.O. Ematologia
Contact Person Name
Pier Luigi Zinzani
Contact Person Email
pierluigi.zinzani@unibo.it
Site Name
Fondazione Policlinico Universitario Agostino Gemelli IRCCS
Department Name
UOC Ematologia e Trapianto di cellule staminali emopoietiche
Contact Person Name
Stefan Hohaus

Sweden

Earliest CTIS Part Ii Submission Date
22-01-2024
Latest Decision Or Authorization Date
20-01-2026
Processing Time Days
729
Number Of Sites
3
Number Of Participants
12

Sites

Site Name
Uppsala University Hospital
Department Name
Onkologkliniken
Contact Person Name
Ingrid Glimelius
Contact Person Email
ingrid.glimelius@igp.uu.se
Site Name
Sahlgrenska University Hospital-Vastra Gotalandsregionen
Department Name
KPE Hematologi
Contact Person Name
Per-Ola Andersson
Contact Person Email
per-ola.andersson@vgregion.se
Site Name
Region Skane Skanes Universitetssjukhus
Department Name
Skånes onkologiska klinik Lund
Contact Person Name
Mats Jerkeman
Contact Person Email
mats.jerkeman@skane.se

Ireland

Earliest CTIS Part Ii Submission Date
22-01-2024
Latest Decision Or Authorization Date
26-01-2026
Processing Time Days
735
Number Of Sites
1
Number Of Participants
3

Sites

Site Name
St James's Hospital
Department Name
Haematology Department
Contact Person Name
Carmel Waldron
Contact Person Email
cmwaldron@stjames.ie

Czechia

Earliest CTIS Part Ii Submission Date
22-01-2024
Latest Decision Or Authorization Date
20-01-2026
Processing Time Days
729
Number Of Sites
2
Number Of Participants
8

Sites

Site Name
Fakultni Nemocnice Brno
Department Name
Interní hematologická a onkologická klinika
Contact Person Name
David Šálek
Contact Person Email
salek.david@fnbrno.cz
Site Name
Fakultni Nemocnice Ostrava
Department Name
Klinika hematoonkologie
Contact Person Name
Roman Hájek
Contact Person Email
roman.hajek@fno.cz

Portugal

Earliest CTIS Part Ii Submission Date
22-01-2024
Latest Decision Or Authorization Date
26-01-2026
Processing Time Days
735
Number Of Sites
2
Number Of Participants
9

Sites

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
Cláudia Moreira
Site Name
Champalimaud Clinical Centre
Department Name
Department of Hemato-Oncology
Contact Person Name
Paulo Lúcio

Spain

Earliest CTIS Part Ii Submission Date
22-01-2024
Latest Decision Or Authorization Date
21-01-2026
Processing Time Days
730
Number Of Sites
6
Number Of Participants
12

Sites

Site Name
Bellvitge University Hospital
Department Name
Servicio de Hematología
Contact Person Name
Eva González Barca
Contact Person Email
e.gonzalez@iconcologia.net
Site Name
MD Anderson Cancer Center
Department Name
Servicio de Hematología
Contact Person Name
Adolfo De la Fuente Burguera
Contact Person Email
afuente@mdanderson.es
Site Name
Hospital Universitario De Salamanca
Department Name
Servicio de Hematología
Contact Person Name
Ramón García Sanz
Contact Person Email
rgarcias@usal.es
Site Name
Clinica Universidad De Navarra
Department Name
Servicio de Hematología
Contact Person Name
Miguel ángel Canales Albendea
Contact Person Email
macanales@unav.es
Site Name
Hospital Clinico San Carlos
Department Name
Comité ético de investigación clínica
Contact Person Name
Mar García Arenillas
Contact Person Email
ceic.hcsc@salud.madrid.org
Site Name
Hospital Universitari Vall D Hebron
Department Name
Servicio de Hematología
Contact Person Name
Ana Marín-Niebla
Contact Person Email
ana.marinniebla@vallhebron.cat

Germany

Earliest CTIS Part Ii Submission Date
22-01-2024
Latest Decision Or Authorization Date
23-01-2026
Processing Time Days
732
Number Of Sites
2
Number Of Participants
9

Sites

Site Name
University Hospital Cologne AöR
Department Name
Klinik I für Innere Medizin
Contact Person Name
Ron Jachimowicz
Contact Person Email
ron.jachimowicz@uk-koeln.de
Site Name
Universitaetsklinikum Ulm AöR
Department Name
Klinik für Innere Medizin III
Contact Person Name
Stephan Stilgenbauer

Sponsor

Primary sponsor

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

Contract research organisations

Name
Clario
Responsibilities
Central imaging
Name
Almac
Responsibilities
3
Name
Medidata Solutions Inc.
Responsibilities
7
Name
Labcorp Central Laboratory Services S.a.r.l.
Responsibilities
4
Name
Parexel International Corp.
Responsibilities
EUB services (call center and medical services)
Name
Icon Clinical Research LLC
Responsibilities
Central ECG

Third parties

  • {"country":"United States","full_name":"Clario","duties_or_roles":"Central imaging","organisation_type":"Health care"}
  • {"country":"United States","full_name":"Almac","duties_or_roles":"3","organisation_type":"Pharmaceutical company"}
  • {"country":"United States","full_name":"Medidata Solutions Inc.","duties_or_roles":"7","organisation_type":"Non-Pharmaceutical company"}
  • {"country":"Switzerland","full_name":"Labcorp Central Laboratory Services S.a.r.l.","duties_or_roles":"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":"Icon Clinical Research LLC","duties_or_roles":"Central ECG","organisation_type":"Pharmaceutical company"}

Investigational products

Investigational Product Name
Nemtabrutinib
Active Substance
NEMTABRUTINIB
Modality
Small molecule
Routes Of Administration
ORAL USE
Route
ORAL USE
Authorisation Status
Authorised
Investigational Product Name
Zilovertamab vedotin
Active Substance
ZILOVERTAMAB VEDOTIN
Modality
ADC
Routes Of Administration
INTRAVENOUS INFUSION
Route
INTRAVENOUS INFUSION
Authorisation Status
Authorised
Combination Treatment
Yes

Related trials

Other published trials that may interest you.