HO182 CLL: Treatment of patients with chronic lymphocytic leukemia (CLL) with 6 cycles of rituximab in combination with 6 or 26 cycles of venetoclax upon recurrence of the disease after previous treatment

Trial details

Who runs it

Hemato-Oncologie voor Volwassenen Nederland (Hovon) Stichting

Trial code

EU 2025-524283-38-00

Record updated

2026. augusztus 28.

Original description

To compare progression free survival (PFS) from the time of randomization between continuation of treatment with venetoclax for 20 cycles (Arm A) versus discontinuation of treatment (Arm B), in patients treated with 6 cycles Ven-R.Read full original descriptionShow less

HOVON 182 CLL: Prospective randomized phase 3 study of treatment with rituximab (6 cycles) in combination with 6 or 26 cycles of venetoclax in patients with relapsed or refractory chronic lymphocytic leukemia RED RIVER CLL study: Reduced Duration Rituximab VEnetoclax in Relapsed/refractory CLL

To compare progression free survival (PFS) from the time of randomization between continuation of treatment with venetoclax for 20 cycles (Arm A) versus discontinuation of treatment (Arm B), in patients treated with 6 cycles Ven-R.

Inclusion: Documented relapsed or refractory CLL or SLL following at least one systemic 1st-line treatment; TP53 mutation status tested after last treatment; Del17p mutation status tested after last treatment; Patient is able and willing to adhere to the study visit schedule and other protocol requirements; Written informed consent; Patient is capable of giving informed consent; Requiring treatment according to IWCLL 2018 criteria; Age at least 18 years; WHO performance status 0-3; stage 3 only if attributable to CLL/SLL; Adequate BM function defined as:  Hemoglobin (Hb) > 5.0 mmol/l, unless low Hb is directly attributable to CLL/SLL infiltration of the BM;  Absolute neutrophil count (ANC) > 0.75 x 109/L (1,000/μL), unless low ANC is directly attributable to CLL/SLL infiltration of the BM;  Platelet count > 30 x 109/L (30,000/μL), unless low platelets is directly attributable to CLL/SLL infiltration in the BM; Estimated Glomerular Filtration Rate (eGFR) (MDRD) or estimated creatinine clearance (CrCl) ≥ 30ml/min (Cockcroft-Gault); Adequate liver function as indicated:  serum aspartate transaminase (ASAT) and alanine transaminase (ALAT) ≤ 3.0 x upper limit of normal (ULN); bilirubin ≤ 1.5 x ULN (unless bilirubin rise is due to Gilbert's syndrome or controlled autoimmune hemolytic anemia); Negative serological testing for hepatitis B virus (Hepatitis B surface antigen (HBsAg) negative and hepatitis B core antibody (anti-HBc) negative) and hepatitis C virus (hepatitis C antibody). Patients who are positive for anti-HBc, HBsAg, or hepatitis C antibody must have a negative PCR result before enrollment. Those who are PCR positive will be excluded; IGHV mutation status assessed at least once.

Exclusion: Active treatment with anti-neoplastic drugs in another clinical trial; Patient received prior venetoclax treatment within 24 months of registration OR patient had progressed during previous venetoclax treatment; Malignancies other than CLL/SLL currently requiring systemic therapy, not treated with curative intent, or showing signs of progression after curative treatment; Concurrent severe and/or uncontrolled medical condition (e.g. uncontrolled diabetes, infection, hypertension, etc.); Previous participation in the HO139 CLL or HO140 CLL trial, and eligible for and willingness to participate in the HO159 CLL trial; Any psychological, familial, sociological and geographical condition potentially hampering compliance with the study protocol and follow-up schedule; Patient with a history of confirmed progressive multifocal leukoencephalopathy (PML); Known allergy to xanthine oxidase inhibitors and/or rasburicase; History of drug-specific hypersensitivity or anaphylaxis to any study drug; Severe cardiovascular disease (arrhythmias requiring chronic treatment, congestive heart failure or symptomatic ischemic heart disease) (CTCAE grade III-IV); Severe neurological or psychiatric disease (CTCAE grade III-IV); Active fungal, bacterial, and/or viral infection that requires systemic therapy; Patient known to be HIV-positive; Patient who has difficulty with or are unable to swallow oral medication, or have significant gastrointestinal disease that would limit absorption of oral medication; Fertile men or women of childbearing potential unless: (1) surgically sterile or ≥ 2 years after the onset of menopause; (2) willing to use a highly effective contraceptive method such as oral contraceptives, intrauterine device or sexual abstinence during study treatment and for 30 days after last dose of venetoclax and/or 12 months after the last dose of rituximab; Transformation of CLL (Richter’s transformation); Patient with central nervous system involvement; Severe pulmonary dysfunction (CTCAE grade III-IV); Patient with Child Pugh C; Pregnant women and nursing mothers.

EU CTIS 2025-524283-38-00