GIVE trial (Gazyvaro In combination with VEnetoclax in Elderly CLL)

Prior treatment

• Concurrent use of other anti-cancer agents or treatments
• Malignancies surgically treated with curative intent and with no known active disease present for 3 years before randomization
• Concurrent severe and/or uncontrolled medical condition (e.g. uncontrolled diabetes, hypertension, hyperthyroidism or hypothyroidism, etc.)
• Vaccination with a live vaccine a minimum of 28 days prior to registration
• Use of any other experimental drug or therapy within 28 days of baseline

Other illness

• History of prior malignancy, except for conditions as listed below if patients have recovered from the acute side effects incurred as a result of previous therapy
• Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease
• Adequately treated cervical carcinoma in situ without evidence of disease
• Severe cardiovascular disease (arrhythmias requiring chronic treatment, congestive heart failure or symptomatic ischemie heart disease) (CTCAE grade 111-IV)
• Severe neurological or psychiatrie disease (CTCAE grade 111-IV)
• Any psychological, familial, sociological and geographical condition potentially hampering compliance with the study protocol and follow-up schedule
• History of severe allergie or anaphylactic reactions to humanized or murine monoclonal antibodies. Known sensitivity or allergy to murine products
• Hepatitis B virus (HBV): Patients with positive serology for hepatitis B defined as positivity for hepatitis B surface antigen (HBsAg) or hepatitis B care antibody (anti-HBc).
• Hepatitis C virus (HCV): Patients with positive hepatitis C serology unless HCV- (RNA) is confirmed negative
• HIV positive patients
• Active fungal, bacterial, and/or viral infection that requires systemic therapy

Age

• Fertile men or women of childbearing potential unless: (1). surgically sterile or >= 2 years after the onset of menopause (2). willing to use a highly effective contraceptive method (Pearl Index <1) during study treatment and in female patients for 18 months after end of antibody treatment and male patients for 6 months after end of treatment

Other

• Current inclusion in other clinical trials
• Severe pulmonary dysfunction (CTCAE grade 111-IV)
• Wamen who are pregnant or lactating
• lntolerance of exogenous protein administration

• Diagnosis of symptomatic CLL (according to IWCLL guidelines)
• Negative serum or urine pregnancy test within 28 days prior to registration (all females of childbearing potential)
• Written informed consent
• Patient is capable of giving informed consent
• Patients without prior treatment for CLL (Corticoid treatment administered due to necessary immediate intervention is allowed; within the last 10 days before start of study treatment only dose equivalents of max 20 mg prednisolone are permitted)
• Patients older than 18 years, not fit tor FCR-like regimens
• Able to adhere to the study visit schedule and other protocol requirements
• WHO performance status of <= 2
• absolute neutrophil count >= 1.0 x 109/l and platelet count >= 50 x 109/l unless due to bone marrow infiltration
• creatinine clearance>= 45 ml/min
• total bilirubin <= 1,5 x ULN unless considered due to Gilbert's syndrome
• transaminases <= 3 x ULN