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A 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

Trial Status: Active

This study will evaluate the efficacy and safety of venetoclax and obinutuzumab (VEN + G) compared with fludarabine + cyclophosphamide + rituximab or bendamustine + rituximab (FCR / BR) in FIT participants (FIT is defined by a cumulative illness rating scale [CIRS] / score of ≤6 and a normal creatinine clearance of ≥70 mL / min) with previously untreated CLL without DEL(17P) or TP53 mutation requiring treatment. Eligible participants will be randomly assigned in a 1:1 ratio to receive either VEN + G (Arm A) or FCR / BR (Arm B).

Inclusion Criteria

  • Ability to comply with the study protocol, in the investigator's judgment
  • Aged 18 years or older
  • Have previously untreated documented Chronic Lymphocytic Leukemia (CLL) according to the International Workshop on Chronic Lymphocytic Leukemia (iwCLL) criteria
  • CLL requiring treatment according to the iwCLL criteria
  • Cumulative Illness Rating Scale (CIRS) score ≤ 6 and creatinine clearance (CrCl) ≥ 70 mL/min
  • Hematology values within the following limits, unless cytopenia is caused by the underlying disease (i.e., no evidence of additional bone marrow (BM) dysfunction; e.g., myelodysplastic syndrome, hypoplastic BM):
  • Absolute neutrophil count ≥ 1.0 x 109/L, unless there is BM involvement
  • Platelet count ≥ 75 x 109/L and more than 7 days since last transfusion, or ≥ 30 x 109/L if there is BM involvement
  • Adequate liver function as indicated by a total bilirubin, aspartate aminotransferase, and Alanine transaminase ≤ 2 times the institutional upper limit of normal (ULN) value, unless directly attributable to the participant's CLL
  • Life expectancy >6 months
  • For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraception and agreement to refrain from donating eggs
  • For men: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive methods, and agreement to refrain from donating sperm

Exclusion Criteria

  • Transformation of CLL to aggressive Non-Hodgkin's Lymphoma (NHL)
  • Participants with Small Lymphocyclic Lymphoma (SLL)
  • Known central nervous system involvement
  • Participants with a history of confirmed progressive multifocal leukoencephalopathy (PML)
  • Detected del (17p) or TP53 mutation
  • 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.

New Jersey

Hackensack University Medical Center
Status: ACTIVE

Trial Phase Phase III

Trial Type Treatment

Lead Organization
Hoffmann-La Roche

  • Primary ID CO41685
  • Secondary IDs NCI-2020-09077, 2019-003327-37
  • ID NCT04285567