First line treatment with VeNEtoclaX and ibruTinib induction followed by obinutuzumab intenSificaTion Exclusively in CLL/SLL Patients not in complete remission and/or with detectable bone marrow minimal residual disease (NEXT STEP trial)

Korábbi kezelés

• Patient requiring treatment with a strong cytochrome P450 (CYP) 3A inhibitor or anticoagulant therapy with warfarin or phenoprocoumon or other vitamin K antagonists
• History of stroke or intracranial hemorrhage within 6 months prior to registration
• Vaccination with live vaccines within 28 days prior to registration
• Use of any other experimental drug or therapy within 28 days prior to registration
• Major surgery within 28 days prior to registration
• 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
• 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
• Concurrent severe and/or uncontrolled medical condition (e.g. uncontrolled: infection, auto-immune hemolysis, immune thrombocytopenia, diabetes, hypertension, hyperthyroidism or hypothyroidism etc.)

Más betegség

• Severe cardiovascular disease (arrhythmias requiring chronic treatment, congestive heart failure or symptomatic ischemic heart disease) (CTCAE grade IIIIV);
• Severe neurological or psychiatric disease (CTCAE grade III-IV);
• Malignancies other than CLL/SLL currently requiring systemic therapy or not being treated incurative intention before or showing signs of progression after curative treatment
• Any psychological, familial, sociological and geographical condition potentially hampering compliance with the study protocol and follow-up schedule
• Known allergy to xanthine oxidase inhibitors and/or rasburicase
• History of severe allergic or anaphylactic reactions to humanized or murine monoclonal antibodies. Known sensitivity or allergy to murine products
• Active fungal, bacterial, and/or viral infection that requires systemic therapy
• Patient known to be HIV-positive

Egyéb

• Transformation of CLL (Richter's transformation)
• Severe pulmonary dysfunction (CTCAE grade III-IV)
• Patient with Child Pugh C
• Pregnant women and nursing mothers
• Current participation in other clinical trial;
• Patient with CNS involvement
• Intolerance of exogenous protein administration

• Documented CLL or SLL requiring treatment according to IWCLL criteria, including minimal required markers (CD5/CD19/CD23 triple positive with light chain restriction)
• Ability and willingness to adhere to the study visit schedule and other protocol requirements.
• Patient is capable of giving informed consent.
• Written informed consent.
• WHO performance status 0-3 stage 3 only if attributable to CLL/SLL
• No prior treatment for CLL/SLL
• Age at least 18 years
• 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.
• 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
• 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)
• Prothrombin time (PT)/International normal ratio (INR) <1.5 x ULN and activated partial thromboplastin time (aPTT) <1.5 x ULN
• 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.