VENETOCLAX for Chronic lymphocytic leukemia|Small lymphocytic lymphoma

Inclusion criteria

• {"criterion_text":"- Documented CLL or SLL requiring treatment according to IWCLL criteria, including minimal required markers (CD5/CD19/CD23 triple positive with light chain restriction)"}
• {"criterion_text":"- Ability and willingness to adhere to the study visit schedule and other protocol requirements."}
• {"criterion_text":"- Patient is capable of giving informed consent."}
• {"criterion_text":"- Written informed consent."}
• {"criterion_text":"- WHO performance status 0-3 stage 3 only if attributable to CLL/SLL"}
• {"criterion_text":"- No prior treatment for CLL/SLL"}
• {"criterion_text":"- Age at least 18 years"}
• {"criterion_text":"- Adequate BM function defined as: - Hb > 5 mmol/l or Hb > 8 g/dL. - Absolute neutrophil count (ANC) ≥ 0.75 x 109/L or 750/μL. - Platelet count ≥ 50 x 109/L or 50,000 /μL; Unless directly attributable to CLL/SLL infiltration of the BM, proven by BM biopsy."}
• {"criterion_text":"- Estimated Glomerular Filtration Rate (eGFR) (MDRD) or estimated creatinine clearance (CrCl) ≥ 30 l/min (Cockcroft-Gault); Please note: in case eGFR or CrCl is <50ml/min the patient needs to be considered high risk for TLS"}
• {"criterion_text":"- Adequate liver function as indicated: - Serum aspartate transaminase (ASAT) and alanine transaminase (ALAT) ≤ 3.0 x ULN. - Bilirubin ≤1.5 x ULN (unless bilirubin rise is due to Gilbert's syndrome or of nonhepatic origin)"}
• {"criterion_text":"- Prothrombin time (PT)/International normal ratio (INR) <1.5 x ULN and activated partial thromboplastin time (aPTT) <1.5 x ULN"}
• {"criterion_text":"- Negative serological testing for hepatitis B virus (Hepatitis B surface antigen (HBsAg) negative and hepatitis B core antibody (anti-HBc) negative) and hepatitis C virus (hepatitis C antibody). Subjects who are positive for hepatitis B core antibody, hepatitis B surface antigen, or hepatitis C antibody must have a negative PCR result before enrollment. Those who are PCR positive will be excluded."}

Exclusion criteria

• {"criterion_text":"- Transformation of CLL (Richter's transformation)"}
• {"criterion_text":"- Patient requiring treatment with a strong cytochrome P450 (CYP) 3A inhibitor or anticoagulant therapy with warfarin or phenoprocoumon or other vitamin K antagonists"}
• {"criterion_text":"- History of stroke or intracranial hemorrhage within 6 months prior to registration"}
• {"criterion_text":"- Severe cardiovascular disease (arrhythmias requiring chronic treatment, congestive heart failure or symptomatic ischemic heart disease) (CTCAE grade IIIIV);"}
• {"criterion_text":"- Severe pulmonary dysfunction (CTCAE grade III-IV)"}
• {"criterion_text":"- Patient with Child Pugh C"}
• {"criterion_text":"- Severe neurological or psychiatric disease (CTCAE grade III-IV);"}
• {"criterion_text":"- Vaccination with live vaccines within 28 days prior to registration"}
• {"criterion_text":"- Use of any other experimental drug or therapy within 28 days prior to registration"}
• {"criterion_text":"- Major surgery within 28 days prior to registration"}
• {"criterion_text":"- Steroid therapy within 10 days prior to registration, with the exception of inhaled steroids for asthma, topical steroids, steroids up to 20 mg of dose equivalents of prednisolone daily to control autoimmune phenomenon's, or replacement/stress corticosteroids"}
• {"criterion_text":"- Malignancies other than CLL/SLL currently requiring systemic therapy or not being treated incurative intention before or showing signs of progression after curative treatment"}
• {"criterion_text":"- Vaccination with live vaccines within 28 days prior to registration"}
• {"criterion_text":"- Pregnant women and nursing mothers"}
• {"criterion_text":"- Fertile men or women of childbearing potential unless: (1) surgically sterile or ≥ 2 years after the onset of menopause, and/or (2) willing to use a highly effective contraceptive method such as oral contraceptives, intrauterine device, sexual abstinence or barrier method of contraception in conjunction with spermicidal jelly during study treatment and in female patients for 3 months after end of induction treatment and 18 months after end of treatment with obinutuzumab and male patients for 6 months after end of treatment"}
• {"criterion_text":"- Current participation in other clinical trial;"}
• {"criterion_text":"- Any psychological, familial, sociological and geographical condition potentially hampering compliance with the study protocol and follow-up schedule"}
• {"criterion_text":"- Patient with CNS involvement"}
• {"criterion_text":"- Known allergy to xanthine oxidase inhibitors and/or rasburicase"}
• {"criterion_text":"- Intolerance of exogenous protein administration"}
• {"criterion_text":"- History of severe allergic or anaphylactic reactions to humanized or murine monoclonal antibodies. Known sensitivity or allergy to murine products"}
• {"criterion_text":"- Active fungal, bacterial, and/or viral infection that requires systemic therapy"}
• {"criterion_text":"- Concurrent severe and/or uncontrolled medical condition (e.g. uncontrolled: infection, auto-immune hemolysis, immune thrombocytopenia, diabetes, hypertension, hyperthyroidism or hypothyroidism etc.)"}
• {"criterion_text":"- Patient known to be HIV-positive"}

Primary endpoints

• {"endpoint_text":"- BM uMRD CR 3 months after end of intensification with ibrutinib/obinutuzumab in patients who were not in CR or who had detectable MRD on combination ibrutinib and venetoclax.","definition_or_measurement_approach":""}

Secondary endpoints

• {"endpoint_text":"- BM uMRD CR 9 months after registration 2 in all subjects","definition_or_measurement_approach":""}
• {"endpoint_text":"- Best BM MRD level during on protocol","definition_or_measurement_approach":""}
• {"endpoint_text":"- MRD level in BM and PB at different time points on protocol and in follow up","definition_or_measurement_approach":""}
• {"endpoint_text":"- Best response by IWCLL on protocol","definition_or_measurement_approach":""}
• {"endpoint_text":"- Response by IWCLL at different time points","definition_or_measurement_approach":""}
• {"endpoint_text":"- Response by Deauville criteria on PET scan at different time points","definition_or_measurement_approach":""}
• {"endpoint_text":"- Progression free survival (PFS), defined as time from registration 1 and from registration 2 to progression or death from any cause, whichever comes first","definition_or_measurement_approach":"PFS defined in protocol: time from registration 1 and from registration 2 to progression or death from any cause, whichever comes first"}
• {"endpoint_text":"- Event free survival (EFS), defined as time from registration 1 and from registration 2 to start new CLL treatment, progression or death, whichever comes first","definition_or_measurement_approach":"EFS defined in protocol: time from registration 1 and from registration 2 to start new CLL treatment, progression or death, whichever comes first"}
• {"endpoint_text":"- Overall survival (OS), defined as time from registration 1 and from registration 2 to death from any cause","definition_or_measurement_approach":"OS defined in protocol: time from registration 1 and from registration 2 to death from any cause"}
• {"endpoint_text":"- Treatment free interval (TFI), defined as date of last protocol treatment to start date of first CLL treatment off protocol, or death from any cause whichever comes first","definition_or_measurement_approach":"TFI defined in protocol: date of last protocol treatment to start date of first CLL treatment off protocol, or death from any cause whichever comes first"}
• {"endpoint_text":"- Predictive value of prognostic markers at diagnosis on uMRD and ORR by IWCLL and Deauville criteria at end of ibrutinib/venetoclax and ibrutinib/obinutuzumab;","definition_or_measurement_approach":""}
• {"endpoint_text":"- CTCAE grade ≥2 toxicities","definition_or_measurement_approach":""}
• {"endpoint_text":"- IWCLL hematological grade ≥ 2 toxicities","definition_or_measurement_approach":""}
• {"endpoint_text":"- Exploratory: MRD level in BM and PB at different time points on protocol and in follow up by novel techniques","definition_or_measurement_approach":""}
• {"endpoint_text":"- Exploratory: Quantification of lesions on 18F-FDG PET-CT at different time points","definition_or_measurement_approach":""}
• {"endpoint_text":"- Exploratory: Amount of CLL cells in LN biopsy and FNA","definition_or_measurement_approach":""}
• {"endpoint_text":"- Exploratory: Immune cell subsets and function at different time points","definition_or_measurement_approach":""}
• {"endpoint_text":"- Exploratory: QoL at different time points on protocol and in follow up","definition_or_measurement_approach":""}

Netherlands

Earliest CTIS Part Ii Submission Date

03-09-2024

Latest Decision Or Authorization Date

11-09-2024

Processing Time Days

8

Number Of Sites

17

Number Of Participants

75

Denmark

Earliest CTIS Part Ii Submission Date

03-09-2024

Latest Decision Or Authorization Date

13-09-2024

Processing Time Days

10

Number Of Sites

1

Number Of Participants

10

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":"Denmark","full_name":"Frederiksberg Hospital","duties_or_roles":"","organisation_type":"Hospital/Clinic/Other health care facility"}
• {"country":"Netherlands","full_name":"Amsterdam UMC Stichting","duties_or_roles":"MRD, biomarker and immunological studies","organisation_type":"Hospital/Clinic/Other health care facility"}
• {"country":"Netherlands","full_name":"VUmc Stichting","duties_or_roles":"imaging review","organisation_type":"Hospital/Clinic/Other health care facility"}
• {"country":"Belgium","full_name":"Clinigen Clinical Supplies Management","duties_or_roles":"Packaging, storage and distribution of trial medication","organisation_type":"Pharmaceutical company"}