CRISTALLO: This phase III trial is comparing the safety and effectiveness of two combinations of treatment for patients who have not yet received treatment for chronic lymphocytic leaukaemiaA Prospective, Open-Label, Multicenter Randomized Phase III Study to Compare The Efficacy and Safety of A Combined Regimen of Venetoclax and Obinutuzumab Versus Fludarabine, Cyclophosphamide, and Rituximab (FCR)/Bendamustine and Rituximab (BR) in FIT Patients With Previously Untreated Chronic Lymphocytic Leukemia (CLL) Without DEL(17P) or TP53 Mutation

Exclusion

• Transformation of CLL to aggressive Non-Hodgkin's Lymphoma (NHL)
• Participants with Small Lymphocyclic Lymphoma (SLL) only
• Known central nervous system involvement
• Participants with a history of confirmed progressive multifocal leukoencephalopathy (PML)
• Detected del(17p) or TP53 mutation (valid test within 6-months from screening is required for randomisation)
• An individual organ/system impairment score of 4 as assessed by the Cumulative Illness Rating Scale (CIRS) definition limiting the ability to receive the treatment regimen of this trial with the exception of eyes, ears, nose, throat organ system
• Participants with uncontrolled autoimmune hemolytic anemia or immune thrombocytopenia
• History of prior malignancy
• Participants with infections requiring IV treatment (Grade 3 or 4) within the last 8 weeks prior to enrollment
• Evidence of other clinically significant uncontrolled conditions including but not limited to active or uncontrolled systemic infection (e.g., viral, bacterial, or fungal)
• History of severe allergic or anaphylactic reactions to humanized or murine monoclonal antibodies or known sensitivity or allergy to murine products
• Hypersensitivity to fludarabine, bendamustine, cyclophosphamide, rituximab, obinutuzumab, or venetoclax or to any of the excipients (e.g., trehalose)
• Pregnant women and nursing mothers
• Vaccination with a live vaccine ≤ 28 days prior to randomization
• Prisoners or participants who are institutionalized by regulatory or court order or persons who are in dependence to the Sponsor or an investigator
• History of illicit drug or alcohol abuse within 12 months prior to screening, in the investigator's judgment
• Positive test results for chronic hepatitis B virus (HBV) infection (defined as positive hepatitis B surface antigen [HBsAg] serology)
• Positive test result for hepatitis C (hepatitis C virus [HCV] antibody serology testing)
• Participants with known infection with HIV or Human T-Cell Leukemia Virus 1 (HTLV-1)
• Any serious medical condition or abnormality in clinical laboratory tests that, in the investigator's judgment, precludes the participant's safe participation in and completion of the study

• Received any of the following agents within 28 days prior to the first dose of study treatment:

  • Immunotherapy
  • Radiotherapy
  • Hormone therapy
  • Any therapies intended for the treatment of lymphoma/leukemia whether approved or experimental

• Participants who have received the following agents:

  • Strong and moderate CYP3A inhibitors/inducers within 7 days prior to the initiation of study treatment
  • Steroid therapy for anti-neoplastic intent with the exception of inhaled steroids for asthma, topical steroids, or replacement/stress corticosteroids within 7 days prior to the first dose of study drug administration
  • Consumed grapefruit, grapefruit products, Seville oranges(including marmalade containing Seville oranges), or star fruit within 3 days prior to the first dose of study drug and throughout venetoclax administration
• Inability to swallow a large number of tablets.