Clinical trial · Interventional
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
A 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
- Source
- ClinicalTrials.gov
- Retrieved
- Sep 8, 2026
- Layer
- normalized (units and labels harmonized; values unchanged)
- Run
- ING-CLINICALTRIALS-20260908-000001
Summary
Brief summary (as posted)
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).
Conditions
Conditions (1)
Free-text conditions as registered, with the CancerIndex entity they were reconciled to and the match type.
| Condition (as posted) | Mapped entity | Match | Confidence |
|---|---|---|---|
| Chronic Lymphocytic Leukemia (CLL) | Chronic Lymphocytic Leukemia | ALIAS | 0.90 |
Interventions
Interventions (6)
| Intervention | Type | Mapped drug | Match |
|---|---|---|---|
| Bendamustine | Drug | Bendamustine | ALIAS |
| Cyclophosphamide | Drug | Cyclophosphamide | ALIAS |
| Fludarabine | Drug | Fludarabine | ALIAS |
| Obinutuzumab | Drug | Obinutuzumab | ALIAS |
| Rituximab | Drug | Rituximab | ALIAS |
| Venetoclax | Drug | Venetoclax | ALIAS |
Design
Arms and outcomes
Arms (2)
- type
- EXPERIMENTAL
- label
- VEN + G
- description
- Participants will receive 12 cycles of treatment (each cycle is 28 days). Venetoclax (VEN) will be administered orally, daily, with a 5-week ramp-up period, starting on Cycle 1, Day 22 and administration will continue until the end of Cycle 12. Obinutuzumab (G) will be administered intravenously (IV) on Days 1 (and 2), 8, and 15 of Cycle 1 and on Day 1 of Cycles 2-6.
- interventionNames
- Drug: Obinutuzumab
- Drug: Venetoclax
- type
- ACTIVE_COMPARATOR
- label
- FCR/BR
- description
- Participants will receive 6 cycles of Fludarabine + Cyclophosphamide + Rituximab (FCR) consisting of a single cycle of a single infusion of rituximab on Day 1 and fludarabine and cyclophosphamide infusions on Days 1-3 of each 28-day cycle or bendamustine (B) as infusions on Days 1 and 2 and a single cycle of rituximab on Day 1 of each 28-day cycle.
- interventionNames
- Drug: Fludarabine
- Drug: Cyclophosphamide
Eligibility
Eligibility (as posted)
- Sex
- All
- Minimum age
- 18 Years
Show eligibility criteria text
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/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.
References
Publications (1)
- DERIVEDSharman JP, Laurenti L, Ferrant E, Casado Montero LF, Mulligan SP, Harrup R, Opat S, Ibatici A, Marasca R, Sportoletti P, Thadani-Mulero M, Cazares O, Huang W, Jiang Y, Clark E, Jin HY, Boyer M, Morschhauser F. Fixed-duration VenO vs FCR/BR in fit patients with untreated CLL: primary analysis of the phase 3 CRISTALLO trial. Blood. 2026 Jun 11;147(24):2895-2904. doi: 10.1182/blood.2025030630. PMID 41770817