Clinical trial • Phase II • Oncology|Haematology
VENETOCLAX for Chronic lymphocytic leukemia|Small lymphocytic lymphoma
Phase II trial of VENETOCLAX for Chronic lymphocytic leukemia|Small lymphocytic lymphoma.
Overview
- Trial Therapeutic Area
- Oncology|Haematology
- Trial Disease
- Chronic lymphocytic leukemia|Small lymphocytic lymphoma
- Trial Stage
- Phase II
- Drug Modality
- Small molecule
- Orphan Drug
- Yes
Key dates
- Initial CTIS Submission Date
- 07-06-2024
- First CTIS Authorization Date
- 03-07-2024
Trial design
Randomised, randomization includes an arm randomized to stop treatment (arm b) versus continuation; both arms receive the combination ibrutinib + venetoclax. doses/schedule not specified in provided data.-controlled Phase II trial across 44 sites in Belgium, Netherlands, Denmark and others.
- Randomised
- Yes
- Comparator
- Randomization includes an arm randomized to stop treatment (arm B) versus continuation; both arms receive the combination ibrutinib + venetoclax. Doses/schedule not specified in provided data.
- Target Sample Size
- 230
Eligibility
Recruits 230 Vulnerable population selected (isVulnerablePopulationSelected: true). All participants must be adults (Age at least 18 years) and must provide written informed consent ("Ability and willingness to provide written informed consent and to adhere to the study visit schedule and other protocol requirements"; "Written informed consent"). Subject information and informed consent forms (ICF) and addenda are provided for multiple countries/languages (e.g. BE-NL, BE-FR, NL, DK, FI, NO, SE, ENG), and biobank consent documents are available..
- Pregnancy Exclusion
- Pregnant women and nursing mothers
- Vulnerable Population
- Vulnerable population selected (isVulnerablePopulationSelected: true). All participants must be adults (Age at least 18 years) and must provide written informed consent ("Ability and willingness to provide written informed consent and to adhere to the study visit schedule and other protocol requirements"; "Written informed consent"). Subject information and informed consent forms (ICF) and addenda are provided for multiple countries/languages (e.g. BE-NL, BE-FR, NL, DK, FI, NO, SE, ENG), and biobank consent documents are available.
Inclusion criteria
- {"criterion_text":"- Documented relapsed/refractory CLL or SLL requiring treatment according to IWCLL criteria (no limits on previous treatment lines; CD20 and steroids are not considered prior therapy lines)"}
- {"criterion_text":"- Ability and willingness to provide written informed consent and to adhere to the study visit schedule and other protocol requirements"}
- {"criterion_text":"- Written informed consent"}
- {"criterion_text":"- Age at least 18 years"}
- {"criterion_text":"- Adequate bone marrow function, unless directly attributable to CLL infiltration of the bone marrow, proven by bone marrow biopsy"}
- {"criterion_text":"- Creatinine clearance (CrCL) ≥ 30ml/min calculated according to the modified formula of Cockcroft and Gault or directly measured with 24hr urine collection."}
- {"criterion_text":"- Adequate liver function as indicated"}
- {"criterion_text":"- Negative serological testing for hepatitis B (HBsAg negative and anti-HBc negative; patients positive for anti-HBc may be included if PCR for HBV DNA is negative and HBV-DNA PCR is performed every month until 12 months after last dose), negative testing for hepatitis C RNA within 42 days prior to registration"}
- {"criterion_text":"- Male and female subjects of reproductive potential must agree to use both a highly effective method of birth control and a barrier method during the period of therapy and for 90 days after the last dose of study drug."}
- {"criterion_text":"- Negative pregnancy test at study entry (for women of childbearing potential)"}
- {"criterion_text":"- WHO/ECOG performance status 0-3 stage 3 only if attributable to CLL"}
Exclusion criteria
- {"criterion_text":"- Any prior therapy with ibrutinib and/or venetoclax"}
- {"criterion_text":"- Major surgery within 28 days prior to registration"}
- {"criterion_text":"- Use of investigational agents which might interfere with the study drug within 28 days prior to registration"}
- {"criterion_text":"- Vaccination with live vaccines within 28 days prior to registration"}
- {"criterion_text":"- Steroid therapy within 7 days prior to registration, with the exception of inhaled steroids for asthma, topical steroids, steroids up to 25 mg of prednisolone daily to control autoimmune phenomenon’s, or replacement/stress corticosteroids"}
- {"criterion_text":"- Pregnant women and nursing mothers"}
- {"criterion_text":"- Any psychological, familial, sociological and geographical condition potentially hampering compliance with the study protocol and follow-up schedule"}
- {"criterion_text":"- Transformation of CLL (Richter’s transformation)"}
- {"criterion_text":"- Patients with a history of confirmed progressive multifocal leukoencephalopathy (PML)"}
- {"criterion_text":"- Malignancies other than CLL currently requiring systemic therapies or not being treated in curative intention before or showing signs of progression after curative treatment"}
- {"criterion_text":"- Known allergy to xanthine oxidase inhibitors and/or rasburicase if no other appropriate prevention of tumorlysis is considered feasible by the treating physician"}
- {"criterion_text":"- Known bleeding disorders (e.g., von Willebrand’s disease or hemophilia)"}
- {"criterion_text":"- Uncontrolled or active infection"}
- {"criterion_text":"- Patients requiring treatment with a strong cytochrome P450 (CYP) 3A inhibitor or anticoagulant therapy with warfarin or phenoprocoumon or other vitamin K antagonists. Please note: Patients being treated with NOACs can be included, but must be properly informed about the potential risk of bleeding under treatment with ibrutinib"}
- {"criterion_text":"- History of stroke or intracranial hemorrhage within 6 months prior to registration"}
Endpoints
Primary endpoints
- {"endpoint_text":"- Proportion of patients fulfilling the criteria for progression free survival (PFS) at 12 months after stopping therapy for patients randomized to stop treatment. In this trial, reinitiated treatment due to MRD positivity will not be considered as progression, and symptomatic CLL according to IWCLL criteria within 12 months after randomization followed by reinitiation treatment resulting in a response before or at 12 months after randomization will neither be considered as progression","definition_or_measurement_approach":"Proportion of patients meeting IWCLL criteria for PFS at 12 months after stopping therapy in the randomized-to-stop arm (reinitiation of treatment due to MRD positivity is not counted as progression). Symptomatic CLL per IWCLL criteria within 12 months followed by reinitiation resulting in response is not considered progression."}
Secondary endpoints
- {"endpoint_text":"- Minimal residual disease (MRD) at 12 months after stopping treatment (month 27) for patients randomized to stop of treatment","definition_or_measurement_approach":"MRD measured at 12 months after stopping treatment (month 27) for patients randomized to stop treatment."}
- {"endpoint_text":"- PFS of all study groups","definition_or_measurement_approach":"Progression-free survival assessed for all study groups (IWCLL criteria referenced elsewhere)."}
- {"endpoint_text":"- Time to and number of patients reinitiating treatment","definition_or_measurement_approach":"Time until and count of patients who restart treatment after stopping."}
- {"endpoint_text":"- Time to treatment failure after reinitiated treatment","definition_or_measurement_approach":"Time from reinitiation of treatment to treatment failure."}
- {"endpoint_text":"- Time to next CLL treatment","definition_or_measurement_approach":"Time from study entry or specified timepoint to initiation of next CLL-directed therapy."}
- {"endpoint_text":"- MRD after cycle 12 (PB), at day 15 of cycle 15 (PB and BM) and at later time points in PB","definition_or_measurement_approach":"MRD assessments in peripheral blood (PB) and bone marrow (BM) at specified cycles/time points."}
- {"endpoint_text":"- Overall survival (OS)","definition_or_measurement_approach":"Overall survival measured from defined baseline to death from any cause."}
- {"endpoint_text":"- Complete response (CR)/ Partial Response (PR)/ Stable disease (SD) after cycle 3, 9, 12, 15 and month 27 and month 51 (3 years after stopping treatment)","definition_or_measurement_approach":"Response assessed at listed cycles/time points using response criteria (CR/PR/SD)."}
- {"endpoint_text":"- Duration of response","definition_or_measurement_approach":"Time from documentation of response to progression or death."}
- {"endpoint_text":"- Safety parameters: Type, frequency, and severity of adverse events (AEs) and adverse events of special interest (AESI) and their relationship to study treatment","definition_or_measurement_approach":"Safety assessed by recording type, frequency and severity of AEs/AESIs and causality relative to study treatment."}
- {"endpoint_text":"- Health-related quality of life (QoL) by EORTC QLQ-C30 and QLQ-CLL16 questionnaires","definition_or_measurement_approach":"Patient-reported QoL measured using EORTC QLQ-C30 and QLQ-CLL16 instruments."}
- {"endpoint_text":"- Exploratory endpoint: Evaluation of relationship between various baseline markers and clinical outcome parameters","definition_or_measurement_approach":"Exploratory analyses correlating baseline biomarkers with clinical outcomes."}
- {"endpoint_text":"- Exploratory endpoint: Various markers at time of progression","definition_or_measurement_approach":"Assessment of biomarkers at progression."}
- {"endpoint_text":"- Exploratory endpoint: Correlation between MRD in BM and PB","definition_or_measurement_approach":"Correlation analysis between MRD measurements in bone marrow and peripheral blood."}
- {"endpoint_text":"- Exploratory endpoint: Correlation between MRD in BM and PFS/OS","definition_or_measurement_approach":"Correlation analyses between bone marrow MRD and progression-free/overall survival."}
- {"endpoint_text":"- Exploratory endpoint: Correlation between MRD in PB and PFS/OS","definition_or_measurement_approach":"Correlation analyses between peripheral blood MRD and progression-free/overall survival."}
Other endpoints
- {"endpoint_text":"- Exploratory endpoint: Evaluation of relationship between various baseline markers and clinical outcome parameters","definition_or_measurement_approach":"Exploratory analyses correlating baseline markers with clinical outcomes."}
- {"endpoint_text":"- Exploratory endpoint: Various markers at time of progression","definition_or_measurement_approach":"Assessment of various biomarkers at progression."}
- {"endpoint_text":"- Exploratory endpoint: Correlation between MRD in BM and PB","definition_or_measurement_approach":"Correlation analysis between MRD in bone marrow and peripheral blood."}
- {"endpoint_text":"- Exploratory endpoint: Correlation between MRD in BM and PFS/OS","definition_or_measurement_approach":"Correlation between bone marrow MRD and progression-free/overall survival."}
- {"endpoint_text":"- Exploratory endpoint: Correlation between MRD in PB and PFS/OS","definition_or_measurement_approach":"Correlation between peripheral blood MRD and progression-free/overall survival."}
Recruitment
- Planned Sample Size
- 230
- Recruitment Window Months
- 116
- Consent Approach
- All participants are adults (≥18 years) and must provide written informed consent ("Ability and willingness to provide written informed consent"; "Written informed consent"). Subject information and informed consent forms and addenda exist for multiple countries/languages (examples: BE-NL, BE-FR, NL, DK, FI, NO, SE, ENG). Biobank consent documents are also provided.
Geography
- Total Number Of Sites
- 44
- Total Number Of Participants
- 230
Belgium
- Earliest CTIS Part Ii Submission Date
- 27-06-2024
- Latest Decision Or Authorization Date
- 11-07-2024
- Processing Time Days
- 14
- Number Of Sites
- 5
- Number Of Participants
- 18
Sites
- Site Name
- Het Ziekenhuisnetwerk Antwerpen
- Department Name
- Hematology
- Contact Person Name
- K.L. Wu
- Contact Person Email
- hovon@erasmusmc.nl
- Site Name
- Hôpital Jolimont
- Department Name
- Hematology
- Contact Person Name
- V. Delrieu
- Contact Person Email
- hovon@erasmusmc.nl
- Site Name
- UZ Leuven
- Department Name
- Hematology
- Contact Person Name
- A.M.H. Janssens
- Contact Person Email
- hovon@erasmusmc.nl
- Site Name
- Az St-Jan Brugge-Oostende A.V.
- Department Name
- Hematology
- Contact Person Name
- S. Snauwaert
- Contact Person Email
- HOVON@erasmusmc.nl
- Site Name
- Cliniques Universitaires Saint-Luc
- Department Name
- Hematology
- Contact Person Name
- M.C. Vekemans
- Contact Person Email
- HOVON@erasmusmc.nl
Netherlands
- Earliest CTIS Part Ii Submission Date
- 27-06-2024
- Latest Decision Or Authorization Date
- 03-07-2024
- Processing Time Days
- 6
- Number Of Sites
- 22
- Number Of Participants
- 112
Sites
- Site Name
- Groene Hart Ziekenhuis
- Department Name
- Hematology
- Contact Person Name
- T.H. Levenga
- Contact Person Email
- hovon@erasmusmc.nl
- Site Name
- Academisch Medisch Centrum
- Department Name
- Hematology
- Contact Person Name
- A.P. Kater
- Contact Person Email
- hovon@erasmusmc.nl
- Site Name
- Maasstad Ziekenhuis Stichting
- Department Name
- Hematology
- Contact Person Name
- Y. Sandberg
- Contact Person Email
- hovon@erasmusmc.nl
- Site Name
- Isala Klinieken Stichting
- Department Name
- Hematology
- Contact Person Name
- L. Laterveer
- Contact Person Email
- hovon@erasmusmc.nl
- Site Name
- Haga Hospital
- Department Name
- Hematology
- Contact Person Name
- S. Kersting
- Contact Person Email
- hovon@erasmusmc.nl
- Site Name
- St. Elisabeth Hospital Tilburg
- Department Name
- Hematology
- Contact Person Name
- J. Droogendijk
- Contact Person Email
- hovon@erasmusmc.nl
- Site Name
- Sint Antonius Ziekenhuis Stichting
- Department Name
- Hematology
- Contact Person Name
- H.R. Koene
- Contact Person Email
- hovon@erasmusmc.nl
- Site Name
- Reinier de Graaf Groep
- Department Name
- Hematology
- Contact Person Name
- E.F.M. Posthuma
- Contact Person Email
- hovon@erasmusmc.nl
- Site Name
- Zuyderland Medisch Centrum Stichting
- Department Name
- Hematology
- Contact Person Name
- R.J.W. van Kampen
- Contact Person Email
- hovon@erasmusmc.nl
- Site Name
- Zaans Medisch Centrum Stichting
- Department Name
- Hematology
- Contact Person Name
- K.G. van der Hem
- Contact Person Email
- hovon@erasmusmc.nl
- Site Name
- Noordwest Ziekenhuisgroep Stichting
- Department Name
- Hematology
- Contact Person Name
- H.P.J. visser
- Contact Person Email
- hovon@erasmusmc.nl
- Site Name
- Canisius Wilhelmina Hospital
- Department Name
- Hematology
- Contact Person Name
- S.D.P.W.M. de Jonge - Peeters
- Contact Person Email
- hovon@erasmusmc.nl
- Site Name
- Antonius ziekenhuis Sneek
- Department Name
- Hematology
- Contact Person Name
- G.J. Veldhuis
- Contact Person Email
- hovon@erasmusmc.nl
- Site Name
- Bernhoven B.V.
- Department Name
- Hematology
- Contact Person Name
- I. Ludwig
- Contact Person Email
- hovon@erasmusmc.nl
- Site Name
- Albert Schweitzer Ziekenhuis
- Department Name
- Hematology
- Contact Person Name
- M.D. Levin
- Contact Person Email
- hovon@erasmusmc.nl
- Site Name
- Amsterdam UMC Stichting (De Boelelaan 1117)
- Department Name
- Hematology
- Contact Person Name
- M.E.D. Chamuleau
- Contact Person Email
- hovon@erasmusmc.nl
- Site Name
- Amphia Hospital
- Department Name
- Hematology
- Contact Person Name
- M. van der Klift
- Contact Person Email
- hovon@erasmusmc.nl
- Site Name
- Universitair Medisch Centrum Utrecht
- Department Name
- Hematology
- Contact Person Name
- M. Jak
- Contact Person Email
- hovon@erasmusmc.nl
- Site Name
- Meander Medisch Centrum
- Department Name
- Hematology
- Contact Person Name
- J.C. Regelink
- Contact Person Email
- hovon@erasmusmc.nl
- Site Name
- Universitair Medisch Centrum Groningen
- Department Name
- Hematology
- Contact Person Name
- M. Bellido
- Contact Person Email
- hovon@erasmusmc.nl
- Site Name
- Rijnstate Ziekenhuis Stichting
- Department Name
- Hematology
- Contact Person Name
- E. van der Spek
- Contact Person Email
- hovon@erasmusmc.nl
- Site Name
- Erasmus Universitair Medisch Centrum Rotterdam (Erasmus MC)
- Department Name
- Hematology
- Contact Person Name
- J.K. Doorduijn
- Contact Person Email
- hovon@erasmusmc.nl
Denmark
- Earliest CTIS Part Ii Submission Date
- 27-06-2024
- Latest Decision Or Authorization Date
- 04-07-2024
- Processing Time Days
- 7
- Number Of Sites
- 7
- Number Of Participants
- 65
Sites
- Site Name
- Herlev Hospital
- Department Name
- Hematology
- Contact Person Name
- L. Enggaard
- Contact Person Email
- HOVON@erasmusmc.nl
- Site Name
- Region Sjaelland
- Department Name
- Hematology
- Contact Person Name
- C.B. Poulsen
- Contact Person Email
- HOVON@erasmusmc.nl
- Site Name
- Region Midtjylland
- Department Name
- Hematology
- Contact Person Name
- M.S. Steffensen
- Contact Person Email
- HOVON@erasmusmc.nl
- Site Name
- Odense University Hospital
- Department Name
- Hematology
- Contact Person Name
- H. Frederiksen
- Contact Person Email
- HOVON@erasmusmc.nl
- Site Name
- Aalborg University Hospital
- Department Name
- Hematology
- Contact Person Name
- S.T. Bønløkke
- Contact Person Email
- HOVON@erasmusmc.nl
- Site Name
- Rigshospitalet
- Department Name
- Hematology
- Contact Person Name
- C. Niemann
- Contact Person Email
- HOVON@erasmusmc.nl
- Site Name
- Region Midtjylland (Herning) - Hospitalsparken 15
- Department Name
- Hematology
- Contact Person Name
- M.S. Steffensen
- Contact Person Email
- HOVON@erasmusmc.nl
Finland
- Earliest CTIS Part Ii Submission Date
- 27-06-2024
- Latest Decision Or Authorization Date
- 04-07-2024
- Processing Time Days
- 7
- Number Of Sites
- 3
- Number Of Participants
- 10
Sites
- Site Name
- Tampere University Hospital
- Department Name
- Hematology
- Contact Person Name
- S. Luopajarvi
- Contact Person Email
- HOVON@erasmusmc.nl
- Site Name
- HUS-Yhtymae (Helsinki)
- Department Name
- Hematology
- Contact Person Name
- V. Lindstrom
- Contact Person Email
- HOVON@erasmusmc.nl
- Site Name
- Turku University Hospital
- Department Name
- Hematology
- Contact Person Name
- J. Ranti
- Contact Person Email
- HOVON@erasmusmc.nl
Norway
- Earliest CTIS Part Ii Submission Date
- 27-06-2024
- Latest Decision Or Authorization Date
- 16-07-2024
- Processing Time Days
- 19
- Number Of Sites
- 2
- Number Of Participants
- 7
Sites
- Site Name
- Akershus University Hospital
- Department Name
- Hematology
- Contact Person Name
- H.T.T. Tran
- Contact Person Email
- hovon@erasmusmc.nl
- Site Name
- St. Olavs Hospital HF
- Department Name
- Hematology
- Contact Person Name
- A.S. von Krogh
- Contact Person Email
- hovon@erasmusmc.nl
Sweden
- Earliest CTIS Part Ii Submission Date
- 27-06-2024
- Latest Decision Or Authorization Date
- 04-07-2024
- Processing Time Days
- 7
- Number Of Sites
- 5
- Number Of Participants
- 18
Sites
- Site Name
- Linkoping University Hospital Region Ostergotland
- Department Name
- Hematology
- Contact Person Name
- A Bergendahl Sandstedt
- Contact Person Email
- hovon@erasmusmc.nl
- Site Name
- Sunderbyns sjukhus
- Department Name
- Hematology
- Contact Person Name
- B. Lauri
- Contact Person Email
- hovon@erasmusmc.nl
- Site Name
- Sodra Alvsborg Hospital-Vastra Gotalandsregionen
- Department Name
- Hematology
- Contact Person Name
- P.O. Andersson
- Contact Person Email
- hovon@erasmusmc.nl
- Site Name
- Uppsala University Hospital
- Department Name
- Hematology
- Contact Person Name
- M. Mattsson
- Contact Person Email
- hovon@erasmusmc.nl
- Site Name
- Region Skane Skanes Universitetssjukhus
- Department Name
- Hematology
- Contact Person Name
- D. Roth
- Contact Person Email
- hovon@erasmusmc.nl
Sponsor
Primary sponsor
- Full Name
- Hemato-Oncologie voor Volwassenen Nederland (Hovon) Stichting
- Organisation Type
- Hospital/Clinic/Other health care facility
- Country Of Registered Address
- Netherlands
Third parties
- {"country":"Sweden","full_name":"Uppsala University Hospital","duties_or_roles":"sponsorDuties codes: 1","organisation_type":"Hospital/Clinic/Other health care facility"}
- {"country":"Finland","full_name":"Turku University Hospital","duties_or_roles":"sponsorDuties codes: 1","organisation_type":"Hospital/Clinic/Other health care facility"}
- {"country":"Belgium","full_name":"Clinigen Clinical Supplies Management","duties_or_roles":"sponsorDuties codes: 14","organisation_type":"Pharmaceutical company"}
- {"country":"Norway","full_name":"Akershus University Hospital","duties_or_roles":"sponsorDuties codes: 1","organisation_type":"Hospital/Clinic/Other health care facility"}
- {"country":"Netherlands","full_name":"Amsterdam UMC Stichting","duties_or_roles":"sponsorDuties codes: 4","organisation_type":"Hospital/Clinic/Other health care facility"}
- {"country":"Denmark","full_name":"Rigshospitalet","duties_or_roles":"sponsorDuties codes: 1, 15 (Collaboration partner), 4","organisation_type":"Hospital/Clinic/Other health care facility"}
Investigational products
- Investigational Product Name
- Venclyxto (venetoclax) - film-coated tablets
- Active Substance
- VENETOCLAX
- Modality
- Small molecule
- Routes Of Administration
- ORAL USE
- Route
- oral
- Authorisation Status
- Authorised (marketing authorisation numbers present: e.g. EU/1/16/1138/*)
- Orphan Designation
- Yes
- Maximum Dose
- 400 mg daily (maxDailyDoseAmount: 400 mg)
- Investigational Product Name
- IMBRUVICA (ibrutinib) - hard capsules
- Active Substance
- IBRUTINIB
- Modality
- Small molecule
- Routes Of Administration
- ORAL USE
- Route
- oral
- Authorisation Status
- Authorised (marketing authorisation number EU/1/14/945/001)
- Orphan Designation
- Yes
- Maximum Dose
- 420 mg daily (maxDailyDoseAmount: 420 mg)
- Combination Treatment
- Yes
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