Venetoclax for Chronic lymphocytic leukaemia | Small lymphocytic lymphoma

Stratification factors

• TP53 deletion and/or mutation (present vs absent)
• IGHV mutational status (unmutated vs mutated)
• Type of lymphoma (CLL vs SLL)
• Age (≤ 65 vs > 65 years)

Inclusion criteria

• {"criterion_text":"- Documented CLL/SLL requiring treatment according to iwCLL criteria with a CLL phenotype cell count >10-2 tracked by flow cytometry at screening."}
• {"criterion_text":"- Adequate bone marrow function as indicated by: - an absolute neutrophil count ≥ 1 x 10⁹/l - a hemoglobin value ≥8.0 g/dL without transfusions during the last 7 days unless directly attributable to CLL/SLL (e.g. bone marrow infiltration) and - a platelet count ≥ 25 x 10⁹/l unless due to the CLL/SLL, in this case, platelet count should be ≥ 10.000/µl without transfusion during the last 7 days."}
• {"criterion_text":"- Adequate renal function, as indicated by a creatinine clearance ≥30ml/min calculated according to the MDRD-formula or an equally accurate method (e.g. 24 hr. urine collection)"}
• {"criterion_text":"- Adequate liver function as indicated by: - a total bilirubin≤ 2 x the institutional upper limit of normal (ULN) value, and -\tAST/ ALT ≤ 2.5 x the institutional ULN value, unless directly attributable to the patient’s CLL/SLL or to Gilbert’s Syndrome."}
• {"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 dosage of obinutuzumab), negative testing for hepatitis-C (HCV-RNA PCR) and negative HIV test within 6 weeks prior to registration"}
• {"criterion_text":"- Age ≥ 18 years"}
• {"criterion_text":"- Eastern Cooperative Oncology Group Performance Status (ECOG) performance status"}
• {"criterion_text":"- Life expectancy ≥ 6 months"}
• {"criterion_text":"- Ability and willingness to provide written informed consent and to adhere to the study visit schedule and other protocol requirements."}

Exclusion criteria

• {"criterion_text":"- Any prior CLL- or SLL-specific therapies, except for corticosteroid treatment administered due to necessary immediate intervention (within the last 10 days before start of study treatment only dose equivalents up to 20 mg prednisolone per day are permitted)."}
• {"criterion_text":"- Decompensated auto-immune cytopenia (defined as ongoing drop in hemoglobin (AIHA) or in platelets (ITP) in spite of prednisolone and/or intravenous immunoglobulins treatment)."}
• {"criterion_text":"- (Suspicion of) transformation of CLL/SLL (i.e. Richter`s transformation) or central nervous system (CNS) involvement."}
• {"criterion_text":"- (Suspicion of) progressive multifocal leukoencephalopathy (PML)."}
• {"criterion_text":"- Malignant neoplasm other than CLL/SLL unless in remission and unlikely to adversely impact on patient´s life expectancy, defined as curatively treated non-melanoma skin cancer or other neoplasias treated curatively ≥1 year ago, without signs of progression and not currently requiring systemic therapies (with the exception of ongoing anti-hormonal therapy)."}
• {"criterion_text":"- Active infection requiring systemic treatment, including HIV, HBV and HCV"}
• {"criterion_text":"- Increased risk of bleeding, e.g. due to: - known bleeding disorder - anticoagulant therapy with phenprocoumon or other vitamin K antagonists (anticoagulation with a direct oral Xa or thrombin inhibitor (DOAC) or heparin) is permitted) - major surgery ≤4 weeks prior to randomization - stroke or intracranial hemorrhage ≤ 6 months of randomization"}
• {"criterion_text":"- Any comorbidity or organ system impairment rated with a CIRS (cumulative illness rating scale) score of 4 or any other life-threatening illness, medical condition or organ system dysfunction that – in the investigator´s opinion - could compromise the patient`s safety or interfere with the absorption or metabolism of the study drugs (e.g, inability to swallow tab-lets or impaired resorption in the gastrointestinal tract)"}
• {"criterion_text":"- Pregnant women and nursing mothers (a negative pregnancy test is required for all women of childbearing potential within 7 days before start of treatment)"}
• {"criterion_text":"- Fertile men or women of childbearing potential unless: - surgically sterile or ≥ 2 years after the onset of menopause, or -\twilling to use two methods of reliable contraception including one highly effective (Pearl Index <1) and one additional effective (barrier) method during study treatment and for the required time period thereafter (at least one and up to 18 months after end of study treatment depending of study drug(s) used, see chapter 2.2.2.1 Known risks relevant with all study drugs)."}
• {"criterion_text":"- Vaccination with a live vaccine ≤ 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":"- Legal incapacity"}
• {"criterion_text":"- Prisoners or subjects who are institutionalized by regulatory or court order"}
• {"criterion_text":"- Persons who are in dependence to the sponsor or an investigator"}

Primary endpoints

• {"endpoint_text":"- Progression-free survival (PFS)","definition_or_measurement_approach":"Progression-free survival (PFS) measured as time to progression or death; primary objective: compare PFS between MRD-guided Venetoclax/Pirtobrutinib vs fixed-duration Venetoclax/Pirtobrutinib and MRD-guided Venetoclax/Pirtobrutinib vs fixed-duration Venetoclax/Obinutuzumab."}

Secondary endpoints

• {"endpoint_text":"- Measurable residual disease (MRD) levels by different types of measurement from different materials at final restaging (performed 3 months after end of treatment in all patients - except for patients that show progression of CLL disease or Richter transformation before this point of time - which differs depending on the duration of treatment) and selected other time points during and after treatment","definition_or_measurement_approach":"MRD assessed by different measurement techniques from different sample types at final restaging (3 months after end of treatment) and at selected other time points during and after treatment."}
• {"endpoint_text":"- Overall response rate (ORR) and complete response (CR) rate at the final restaging and selected other time points","definition_or_measurement_approach":"ORR and CR assessed according to iwCLL guidelines at final restaging (3 months after end of treatment) and selected other time points."}
• {"endpoint_text":"- Duration of response (DOR)","definition_or_measurement_approach":"DOR assessed per iwCLL criteria."}
• {"endpoint_text":"- Time to next treatment (TTNT)","definition_or_measurement_approach":"Time from randomisation or end of treatment to initiation of next anti-lymphoma therapy."}
• {"endpoint_text":"- Treatment-free survival (TFS)","definition_or_measurement_approach":"Time patient remains alive and free from systemic anti-CLL therapy (definition per protocol)."}
• {"endpoint_text":"- Overall survival (OS)","definition_or_measurement_approach":"Time from randomisation to death from any cause."}
• {"endpoint_text":"- Safety parameters: Type, frequency and severity of - adverse events (AEs) -\tadverse events of particular interest (AEPI)","definition_or_measurement_approach":"Safety assessed by recording type, frequency and severity of AEs and AEPI (standard CTCAE grading expected per protocol)."}
• {"endpoint_text":"- Best response assessed until 1 year after end of treatment","definition_or_measurement_approach":"Best response as per iwCLL guidelines up to 1 year after end of treatment."}

Primary sponsor

Full Name

University Of Cologne

Organisation Type

Educational Institution

Country Of Registered Address

Germany

Contract research organisations

Name

Almac Clinical Services (Ireland) Limited

Responsibilities

duty codes [14] (as listed in sponsors.thirdParties)

Name

Almac Clinical Technologies LLC

Responsibilities

duty codes [3] (as listed in sponsors.thirdParties)

Name

Pharmaceutical Development And Services S.r.l.

Responsibilities

duty codes [1,12,2,5] (as listed in sponsors.thirdParties)

Third parties

• {"country":"Sweden","full_name":"Uppsala University Hospital","duties_or_roles":"[1,12,2,5]","organisation_type":"Hospital/Clinic/Other health care facility"}
• {"country":"Denmark","full_name":"Aarhus Universitet","duties_or_roles":"[1]","organisation_type":"Educational Institution"}
• {"country":"Denmark","full_name":"Rigshospitalet","duties_or_roles":"[12,2,5]","organisation_type":"Hospital/Clinic/Other health care facility"}
• {"country":"Germany","full_name":"University Hospital Cologne AöR","duties_or_roles":"[1]","organisation_type":"Hospital/Clinic/Other health care facility"}
• {"country":"Germany","full_name":"Universitaetsklinikum Schleswig-Holstein AöR","duties_or_roles":"[4]","organisation_type":"Hospital/Clinic/Other health care facility"}
• {"country":"Spain","full_name":"Red De Apoyo A La Investigacion Clinica En Hematologia Y Hemoterapia S.L.","duties_or_roles":"[1,12,2,5]","organisation_type":"Pharmaceutical company"}
• {"country":"Denmark","full_name":"Odense University Hospital","duties_or_roles":"[1]","organisation_type":"Hospital/Clinic/Other health care facility"}
• {"country":"Ireland","full_name":"Almac Clinical Services (Ireland) Limited","duties_or_roles":"[14]","organisation_type":"Pharmaceutical company"}
• {"country":"Italy","full_name":"Pharmaceutical Development And Services S.r.l.","duties_or_roles":"[1,12,2,5]","organisation_type":"Pharmaceutical company"}
• {"country":"France","full_name":"LYSARC","duties_or_roles":"[1,12,2,5]","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"Netherlands","full_name":"Hemato-Oncologie voor Volwassenen Nederland (Hovon) Stichting","duties_or_roles":"[1,12,2,5]","organisation_type":"Hospital/Clinic/Other health care facility"}
• {"country":"United States","full_name":"Almac Clinical Technologies LLC","duties_or_roles":"[3]","organisation_type":"Pharmaceutical company"}
• {"country":"Norway","full_name":"St. Olavs Hospital HF","duties_or_roles":"[1,12,2,5]","organisation_type":"Hospital/Clinic/Other health care facility"}
• {"country":"Poland","full_name":"Kapadi Sp. z o.o.","duties_or_roles":"[1,12,2,5]","organisation_type":"Pharmaceutical company"}
• {"country":"Czechia","full_name":"Masarykova Univerzita","duties_or_roles":"[1]","organisation_type":"Educational Institution"}
• {"country":"Czechia","full_name":"University Hospital Olomouc","duties_or_roles":"","organisation_type":"Hospital/Clinic/Other health care facility"}
• {"country":"Ireland","full_name":"Cancer Trials Ireland","duties_or_roles":"[1,12,2,5]","organisation_type":"Patient organisation/association"}