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 mutatio
- Conditions
- Chronic Lymphocytic Leukemia (CLL)MedDRA version: 21.0Level: LLTClassification code 10008976Term: Chronic lymphocytic leukemiaSystem Organ Class: 100000004864Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2019-003327-37-ES
- Lead Sponsor
- F. Hoffmann-La Roche Ltd
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- All
- Target Recruitment
- 165
- Ability to comply with the study protocol, in the investigator's judgment
- Aged 18 years or older
- Have previously untreated documented CLL according to the International Workshop on Chronic Lymphocytic Leukemia (iwCLL) criteria
- CLL requiring treatment according to the iwCLL criteria
- Cumulative illness rating scale score <=6 and creatinine clearance >=70 mL/min
- Hematology values within the following limits, unless cytopenia is caused by the underlying disease (i.e., no evidence of additional BM dysfunction; e.g., myelodysplastic syndrome, hypoplastic BM):
o Absolute neutrophil count >=1.0 × 10^9/L, unless there is BM involvement
o Platelet count >=75 × 10^9/L and more than 7 days since last transfusion, or >=30 × 10^9/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 value, unless directly attributable to the patient’s CLL
- Life expectancy >6 months
- For women of childbearing potential: agreement to remain abstinent or use contraception and agreement to refrain from donating eggs, women must remain abstinent or use contraceptive methods with a failure rate of <=1% per year during the treatment period and for at least 30 days after the last dose of venetoclax or 18 months after the last dose of obinutuzumab for patients in Arm A and for at least 6 months after the last dose of bendamustine, fludarabine or cyclophosphamide or 12 months after the last dose of rituximab for patients in Arm B, whichever is later
- For men: agreement to remain abstinent or use contraceptive methods, and agreement to refrain from donating sperm, with a female partner of childbearing potential who is not pregnant, men who are not surgically sterile must remain abstinent or use a condom plus an additional contraceptive method that together result in a failure rate of <1% per year during the treatment period and for at least 90 days after the last dose of venetoclax or 18 months after the last dose of obinutuzumab for patients in Arm A, and for at least 6 months after the last dose of bendamustine, fludarabine, or cyclophosphamide or 12 months after the last dose of rituximab for patients in Arm B, whichever is later
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 99
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 66
- Transformation of CLL to aggressive non-Hodgkin’s lymphoma
- Patients with small lymphocyclic lymphoma
- Known central nervous system involvement
- Patients with a history of confirmed progressive multifocal leukoencephalopathy
- Detected del (17p) or TP53 mutation
- An individual organ/system impairment score of 4 as assessed by the CIRS definition limiting the ability to receive the treatment regimen of this trial with the exception of eyes, ears, nose, throat organ system
- Patients with uncontrolled autoimmune hemolytic anemia or immune thrombocytopenia
- History of prior malignancy
- Patients with infections requiring IV treatment (Grade 3 or 4) within the last 8 weeks prior to enrollment
- Evidence of other clinically significant uncontrolled condition(s) including but not limited to active or uncontrolled systemic infection
- 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, cycolphosphamide, rituximab, obinutuzumab, or venetoclax or to any of the excipients
- Pregnant women and nursing mothers
- Vaccination with a live vaccine <=28 days prior to randomization
- Prisoners or patients 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 infection and for hepatitis C
- Patients with known infection with HIV or Human T-Cell Leukemia Virus 1
- Any serious medical condition or abnormality in clinical laboratory tests that, in the investigator’s judgment, precludes the patient’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:
o Immunotherapy
o Radiotherapy
o Hormone therapy
o Any therapies intended for the treatment of lymphoma/leukemia whether approved or experimental
- Patients who have received the following agents:
o Strong and moderate CYP3A inhibitors and inducers within 7 days prior to the initiation of study treatment
o 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
o Consumed grapefruit, grapefruit products, 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
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method