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Phase 3 N=166 Randomized Treatment

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

Chronic Lymphocytic Leukemia (CLL)

Enrolled (actual)
166
Serious AEs
54.3%
Results posted
Apr 2025
Primary outcome: Primary: Minimal Residual Disease (MRD) Response Rate Measured in Peripheral Blood (PB) Using Next Generation Sequencing (NGS) — 81.3; 54.7 percentage of participants — p=0.0004

Study Design & Population

Study type
Interventional
Phase
Phase 3
Interventions
Obinutuzumab (Drug); Venetoclax (Drug); Fludarabine (Drug); Cyclophosphamide (Drug); Rituximab (Drug); Bendamustine (Drug)
Age
Adult, Older Adult · 18+ yrs
Sex
All
Sponsor
Hoffmann-La Roche
Primary completion
Mar 2024

Outcome Measures

OutcomeResultp-value
PRIMARY
Minimal Residual Disease (MRD) Response Rate Measured in Peripheral Blood (PB) Using Next Generation Sequencing (NGS)
81.3; 54.7 0.0004 sig
SECONDARY
Progression-free Survival (PFS)
NA; 53.3 0.3999
SECONDARY
MRD Response Rate in PB of FCR/BR Compared With VEN+G at the End of Treatment Response Visit
81.3; 60.5 0.0053 sig
SECONDARY
MRD Response Rate in Bone Marrow (BM) of FCR/BR Compared With VEN+G at the End of Treatment Response Visit
70.0; 38.4 < .0001 sig
SECONDARY
Objective Response Rate (ORR)
88.8; 79.1 0.1119
SECONDARY
CR Rate
50.0; 32.6 0.0154 sig
SECONDARY
MRD Response Rate in PB of Participants With a CR/CRi at the End of Treatment Visit
97.5; 78.6 0.0054 sig
SECONDARY
MRD Response Rate in BM of Participants With a CR/CRi at the End of Treatment Visit
87.5; 60.7 0.0038 sig
SECONDARY
Duration of Objective Response (DOR)
NA; 50.3 0.4100
SECONDARY
Best Overall Response (BOR)
93.8; 90.7 0.4199
SECONDARY
Event-free Survival (EFS)
NA; 53.3 0.2078
SECONDARY
Overall Survival (OS)
NA; NA 0.9468
SECONDARY
VEN + G: Tumor Lysis Syndrome (TLS) Risk Reduction Rate
23.8; 0
SECONDARY
VEN + G: Reduction in Mandatory Hospitalizations During Venetoclax Ramp-up
2
SECONDARY
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
76; 83; 46; 42
SECONDARY
Number of Participants With Premature Withdrawals Due to AEs
1; 5
SECONDARY
Change From Baseline in Physical Functioning Assessed Using European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core-30 (EORTC QLQC-30)
88.77; 88.33; -6.67; -0.92; 0.30; 8.89
SECONDARY
Change From Baseline in Role Functioning Assessed Using EORTC QLQC-30
85.67; 83.06; -33.33; -3.59; 3.79; 22.22
SECONDARY
Change From Baseline in GHS/QoL Assessed Using EORTC QLQC-30
73.10; 72.64; -25.00; 2.78; 1.85; 11.11
SECONDARY
Change From Baseline in Mean Core Symptom Severity Score as Measured by the M.D. Anderson Symptom Inventory (MDASI-CLL)
1.75; 1.66; 0.46; -0.43; -0.20; 0.38
SECONDARY
Change From Baseline in Mean Module Symptom Severity Score as Measured by MDASI-CLL
1.63; 1.43; -0.83; -0.67; -0.63; -0.58
SECONDARY
Change From Baseline in Mean Interference Score as Measured by MDASI-CLL
2.11; 2.17; 1.33; -0.23; -0.29; 0.17

Summary

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).

Eligibility Criteria

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) 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/indu
View full record on ClinicalTrials.gov →

Data sourced from ClinicalTrials.gov (NCT04285567). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.

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