Clinical trial • Phase II/III • Haematology

Venetoclax for Chronic lymphocytic leukemia | Small lymphocytic lymphoma

Phase II/III trial of Venetoclax for Chronic lymphocytic leukemia | Small lymphocytic lymphoma.

Overview

Trial Therapeutic Area
Haematology
Trial Disease
Chronic lymphocytic leukemia | Small lymphocytic lymphoma
Trial Stage
Phase II/III
Drug Modality
Small molecule | Monoclonal antibody
Orphan Drug
Yes

Key dates

Initial CTIS Submission Date
19-07-2024
First CTIS Authorization Date
29-10-2024

Trial design

open-label, obinutuzumab (gazyvaro 1,000 mg concentrate for solution for infusion; iv infusion product) and acalabrutinib (calquence 100 mg film-coated tablets; oral) are the combination partners compared with venetoclax ramp-up schedules (doses/schedules for combinations not fully specified in the registration data).-controlled Phase II/III trial in France, Greece, Spain.

Open Label
Yes
Comparator
Obinutuzumab (Gazyvaro 1,000 mg concentrate for solution for infusion; IV infusion product) and Acalabrutinib (Calquence 100 mg film-coated tablets; oral) are the combination partners compared with venetoclax ramp-up schedules (doses/schedules for combinations not fully specified in the registration data).
Single Multiple Or Escalation Dose Combined
Yes
Target Sample Size
154
Trial Duration For Participant
721

Eligibility

Recruits 154 adults.

Inclusion criteria

  • {"criterion_text":"- Diagnosis of documented, previously untreated, chronic lymphocytic leukemia (CLL) requiring treatment according to the 2018 international workshop on chronic lymphocytic leukemia (iwCLL) criteria and have a life expectancy of > 6 months.\n- Previously untreated small lymphocytic lymphoma (SLL) meeting the 2018 iwCLL criteria for treatment will also be equally considered as CLL for eligibility, screening, treatment and evaluation.\n- Eastern Cooperative Oncology Group (ECOG) performance status <= 2.\n- Adequate marrow function independent of growth factor or transfusion support within 2 weeks of screening, unless cytopenia is due to marrow involvement of CLL as listed in the protocol.\n- Creatinine clearance (CrCl) >= 30 mL/min using the Cockcroft-Gault formula"}

Exclusion criteria

  • {"criterion_text":"- Active/uncontrolled infection or Richter's transformation or active immune thrombocytopenia."}

Endpoints

Primary endpoints

  • {"endpoint_text":"- Part 1: Incidence of treatment-emergent laboratory TLS or treatment-emergent hyperkalemia per Howard criteria that require a clinical intervention that has been confirmed by an IRC assessment","definition_or_measurement_approach":"Assessment using Howard criteria; events requiring clinical intervention must be confirmed by an Independent Review Committee (IRC) assessment during the venetoclax ramp-up period."}
  • {"endpoint_text":"- Reduction of Tumor Burden from Baseline","definition_or_measurement_approach":"Change in tumor burden from baseline (measurement details as per protocol; reduction assessed from baseline to after debulking where performed)."}

Secondary endpoints

  • {"endpoint_text":"- Part 1: The incidence of treatment-emergent laboratory TLS or treatment-emergent hyperkalemia per Howard criteria that require a clinical intervention that has confirmed by an IRC assessment","definition_or_measurement_approach":"Assessment using Howard criteria; interventions confirmed by IRC; assessed at each dose level and laboratory monitoring point during the ramp-up period."}
  • {"endpoint_text":"- Part 1: Incidence of Laboratory TLS per Howard criteria that require a clinical intervention that has been confirmed by an IRC assessment","definition_or_measurement_approach":"Assessment using Howard criteria; events requiring clinical intervention confirmed by IRC."}
  • {"endpoint_text":"- Part 1: Incidence of Hyperkalemia per Howard criteria that require a clinical intervention that has been confirmed by an IRC assessment","definition_or_measurement_approach":"Assessment using Howard criteria; hyperkalemia requiring clinical intervention confirmed by IRC."}
  • {"endpoint_text":"- Part 1: Incidence of Laboratory TLS per Howard criteria irrespective of clinical intervention","definition_or_measurement_approach":"Incidence based on laboratory criteria per Howard, regardless of whether clinical intervention occurred."}
  • {"endpoint_text":"- Part 1: Incidence of Hyperkalemia irrespective of clinical intervention","definition_or_measurement_approach":"Incidence of hyperkalemia per criteria irrespective of clinical intervention."}
  • {"endpoint_text":"- Part 1: Incidence of Clinical TLS per Howard criteria irrespective of clinical intervention","definition_or_measurement_approach":"Incidence of clinical TLS per Howard criteria irrespective of clinical intervention."}
  • {"endpoint_text":"- Part 1: Incidence of any single TLS-related lab abnormality requiring clinical intervention per Investigator (Hyperuricemia or Hyperphosphatemia or Hyperkalemia or Hypocalcemia)","definition_or_measurement_approach":"Investigator-reported laboratory abnormalities requiring clinical intervention (listed conditions); assessed during ramp-up."}
  • {"endpoint_text":"- Adverse Events (AE) of TLS","definition_or_measurement_approach":"Adverse events of TLS as reported by the Investigator during the venetoclax ramp-up period."}
  • {"endpoint_text":"- Reduction of tumor burden from baseline","definition_or_measurement_approach":"Change in tumor burden from baseline (assessed where TLS assessments performed at both baseline and after debulking)."}

Recruitment

Planned Sample Size
154
Recruitment Window Months
24

Geography

Total Number Of Sites
23
Total Number Of Participants
161

France

Earliest CTIS Part Ii Submission Date
14-10-2024
Latest Decision Or Authorization Date
04-11-2025
Processing Time Days
386
Number Of Sites
11
Number Of Participants
70

Sites

Site Name
Centre Hospitalier De La Cote Basque
Department Name
Service d'hématologie
Principal Investigator Name
Sophie Bernard
Principal Investigator Email
sbernard@ch-cotebasque.fr
Contact Person Name
Sophie Bernard
Contact Person Email
sbernard@ch-cotebasque.fr
Site Name
Assistance Publique Hopitaux De Paris
Department Name
Service d'hématologie
Principal Investigator Name
David Sibon
Principal Investigator Email
david.sibon@aphp.fr
Contact Person Name
David Sibon
Contact Person Email
david.sibon@aphp.fr
Site Name
Assistance Publique Hopitaux De Paris
Department Name
Service d'hématologie
Principal Investigator Name
Lise Willems
Principal Investigator Email
lise.willems@aphp.fr
Contact Person Name
Lise Willems
Contact Person Email
lise.willems@aphp.fr
Site Name
Centre Antoine Lacassagne
Department Name
Service d'oncologie médicale
Principal Investigator Name
Luca Inchiappa
Principal Investigator Email
inchiappal@ipc.unicancer.fr
Contact Person Name
Luca Inchiappa
Contact Person Email
inchiappal@ipc.unicancer.fr
Site Name
Centre Hospitalier Universitaire De Saint Etienne
Department Name
Service d'Hématologie Clinique et Thérapie Cellulaire
Principal Investigator Name
Ludovic Fouillet
Principal Investigator Email
ludovic.fouillet@chu-st-etienne.fr
Contact Person Name
Ludovic Fouillet
Site Name
Centre Hospitalier Universitaire D Orleans
Department Name
Service d'hématologie
Principal Investigator Name
Ochmann Marlène
Principal Investigator Email
marlene.ochmann@chu-orleans.fr
Contact Person Name
Ochmann Marlène
Contact Person Email
marlene.ochmann@chu-orleans.fr
Site Name
Centre Hospital Region Metz Thionville
Department Name
Service d'hématologie
Principal Investigator Name
Philippe Carassou
Principal Investigator Email
philippe.carassou@chr-metz-thionville.fr
Contact Person Name
Philippe Carassou
Site Name
Centre Hospitalier Universitaire Amiens Picardie
Department Name
Service d'hématologie
Principal Investigator Name
Caroline Delette
Principal Investigator Email
delette.caroline@chu-amiens.fr
Contact Person Name
Caroline Delette
Contact Person Email
delette.caroline@chu-amiens.fr
Site Name
Centre Hospitalier Metropole Savoie
Department Name
Service d'hématologie
Principal Investigator Name
Pierre Faurie
Principal Investigator Email
pierre.faurie@ch-metropole-savoie.fr
Contact Person Name
Pierre Faurie
Site Name
Centre Hospitalier Victor Dupouy
Department Name
Service d'hématologie
Principal Investigator Name
Driss Chaoui
Principal Investigator Email
driss.chaoui@ch-argenteuil.fr
Contact Person Name
Driss Chaoui
Contact Person Email
driss.chaoui@ch-argenteuil.fr
Site Name
Centre Antoine Lacassagne (duplicate site grouping in record)
Department Name
Service d'oncologie médicale
Principal Investigator Name
Luca Inchiappa
Principal Investigator Email
inchiappal@ipc.unicancer.fr
Contact Person Name
Luca Inchiappa
Contact Person Email
inchiappal@ipc.unicancer.fr

Greece

Earliest CTIS Part Ii Submission Date
14-10-2024
Latest Decision Or Authorization Date
20-10-2025
Processing Time Days
371
Number Of Sites
5
Number Of Participants
28

Sites

Site Name
University General Hospital Attikon
Department Name
2nd Department of Internal Medicine - Propaedeutic, Hematology Unit
Principal Investigator Name
Vasiliki Pappa
Principal Investigator Email
vas_pappa@yahoo.com
Contact Person Name
Vasiliki Pappa
Contact Person Email
vas_pappa@yahoo.com
Site Name
University General Hospital Of Alexandroupoli
Department Name
Department of Haematology
Principal Investigator Name
Ioannis Kotsianidis
Principal Investigator Email
ikotsian@med.duth.gr
Contact Person Name
Ioannis Kotsianidis
Contact Person Email
ikotsian@med.duth.gr
Site Name
Evangelismos S.A.
Department Name
Hematology-Lymphomas Department and BMT Unit
Principal Investigator Name
Bouzani Maria
Principal Investigator Email
mbouzani@yahoo.com
Contact Person Name
Bouzani Maria
Contact Person Email
mbouzani@yahoo.com
Site Name
Laiko General Hospital Of Athens
Department Name
Haematology Clinic and Βone Μarrow Τransplantation Unit, NKUA
Principal Investigator Name
Theodoros Vassilakopoulos
Principal Investigator Email
clinicaltrial.tvassilakopoulos@gmail.com
Contact Person Name
Theodoros Vassilakopoulos
Site Name
Olympion Therapeftirio General Clinic Of Patras S.A.
Department Name
Hematology & Oncology Clinic
Principal Investigator Name
Argiris (Anargyros) Symeonidis
Principal Investigator Email
argiris.symeonidis@yahoo.gr
Contact Person Name
Argiris (Anargyros) Symeonidis
Contact Person Email
argiris.symeonidis@yahoo.gr

Spain

Earliest CTIS Part Ii Submission Date
14-10-2024
Latest Decision Or Authorization Date
20-10-2025
Processing Time Days
371
Number Of Sites
7
Number Of Participants
63

Sites

Site Name
MD Anderson Cancer Center
Department Name
Hematology
Principal Investigator Name
Adolfo de la Fuente
Principal Investigator Email
afuente@mdanderson.es
Contact Person Name
Adolfo de la Fuente
Contact Person Email
afuente@mdanderson.es
Site Name
Clinica Universidad De Navarra
Department Name
Hematology
Principal Investigator Name
Carlos Grande García
Principal Investigator Email
ensayoscun@unav.es
Contact Person Name
Carlos Grande García
Contact Person Email
ensayoscun@unav.es
Site Name
Complexo Hospitalario Universitario De Santiago
Department Name
Hematology
Principal Investigator Name
Adrian Mosquera Orgueira
Principal Investigator Email
adrian.mosquera.orgeira@sergas.es
Contact Person Name
Adrian Mosquera Orgueira
Site Name
Hospital Universitario Puerta De Hierro De Majadahonda
Department Name
Hematology
Principal Investigator Name
Jose Antonio Garcia Vela
Principal Investigator Email
garciavela.joseantonio@gmail.com
Contact Person Name
Jose Antonio Garcia Vela
Site Name
Clinica Universidad De Navarra
Department Name
Hematology
Principal Investigator Name
Carlos Grande García
Principal Investigator Email
ensayoscun@unav.es
Contact Person Name
Carlos Grande García
Contact Person Email
ensayoscun@unav.es
Site Name
University Hospital Virgen Del Rocio S.L.
Department Name
Hematology
Principal Investigator Name
Guillermo Rodriguez García
Principal Investigator Email
grgarcia@gmail.com
Contact Person Name
Guillermo Rodriguez García
Contact Person Email
grgarcia@gmail.com
Site Name
Clinica Universidad De Navarra (Madrid site)
Department Name
Hematology
Principal Investigator Name
Carlos Grande García
Principal Investigator Email
ensayoscun@unav.es
Contact Person Name
Carlos Grande García
Contact Person Email
ensayoscun@unav.es

Sponsor

Primary sponsor

Full Name
AbbVie Deutschland GmbH & Co. KG
Organisation Type
Pharmaceutical company
Country Of Registered Address
Germany

Contract research organisations

Name
IQVIA Limited

Third parties

  • {"country":"United Kingdom","full_name":"IQVIA Limited","duties_or_roles":"","organisation_type":"Pharmaceutical company"}
  • {"country":"Switzerland","full_name":"Labcorp Central Laboratory Services Sàrl","duties_or_roles":"Lab samples storage","organisation_type":"Health care"}

Investigational products

Investigational Product Name
Venetoclax
Active Substance
Venetoclax
Modality
Small molecule
Routes Of Administration
Oral
Route
Oral
Investigational Product Name
Gazyvaro 1,000 mg concentrate for solution for infusion.
Active Substance
Obinutuzumab
Modality
Monoclonal antibody
Routes Of Administration
Intravenous infusion (solution for infusion)
Route
Intravenous infusion
Authorisation Status
Authorised (EU/1/14/937/001)
Orphan Designation
Yes
Starting Dose
1000 mg
Dose Levels
1000 mg per infusion up to 6000 mg total (as per product fields)
Maximum Dose
6000 mg total
Investigational Product Name
Calquence 100 mg film-coated tablets
Active Substance
Acalabrutinib
Modality
Small molecule
Routes Of Administration
Oral
Route
Oral
Authorisation Status
Authorised (EU/1/20/1479/004)
Starting Dose
100 mg
Frequency
Oral (daily as per product labeling)
Maximum Dose
200 mg daily
Combination Treatment
Yes

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