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Effectiveness of rituximab and venetoclax in patients with relapsed or refractory chronic lymphocytic leukemia

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What is this study about?

The study involves adults whose disease has returned or did not respond to earlier therapy, specifically chronic lymphocytic leukemia or small lymphocytic lymphoma. The investigational regimen combines an antibody medication called rituximab given by infusion with an oral tablet known as Venclyxto (the brand name for venetoclax), which works by targeting a protein that helps cancer cells survive.

The purpose is to compare progression-free survival, the time patients remain free of disease progression when the oral tablet is continued for a longer period versus when it is stopped after the initial treatment phase. After six cycles of the combined therapy, participants are randomly assigned to either keep taking the tablet for additional cycles or to discontinue it, and they are monitored with regular clinic visits, blood tests, and imaging as needed. Outcomes such as overall health, quality of life, and a laboratory assessment of minimal residual disease using flow cytometry are recorded.

1 randomization

randomization assigns the patient to one of two treatment plans after joining the study. the assignment determines whether venetoclax will be continued for a longer period or stopped after a short period.

2 start rituximab treatment

the patient receives rituximab by intravenous infusion. the drug is given once every four weeks for a total of six cycles. each cycle lasts about four weeks.

3 begin venetoclax dose escalation

the patient starts oral venetoclax tablets. the first week the dose is 20 mg taken once daily. the dose is increased each week (20 mg, 50 mg, 100 mg, 200 mg, 400 mg) until the target dose of 400 mg daily is reached, usually by week five.

venetoclax tablets are available in 10 mg, 50 mg, and 100 mg film‑coated forms. the appropriate combination of tablets is used to reach the prescribed daily dose.

4 continue venetoclax for assigned duration

after reaching the target dose, the patient continues taking 400 mg venetoclax each day.

if assigned to the short‑duration arm, venetoclax is taken for a total of six cycles (approximately six months).

if assigned to the long‑duration arm, venetoclax is taken for a total of twenty‑six cycles (approximately twenty‑six months).

5 regular monitoring visits

the patient attends clinic visits roughly every four weeks. during each visit blood samples are taken to check blood counts, kidney and liver function, and the level of disease cells.

adverse events (side effects) are recorded using standard questionnaires. any severe side effect may lead to temporary or permanent stopping of venetoclax.

6 end of treatment assessment

when the assigned number of venetoclax cycles is completed, the patient stops taking the drug.

a final assessment is performed to evaluate response to treatment, including blood tests and a physical examination.

7 follow‑up period

after stopping treatment, the patient continues to be seen every three months for up to 84 weeks from the start of randomization.

follow‑up visits include the same blood tests and questionnaires used during treatment to monitor disease status and quality of life.

Who Can Join the Study?

  • Documented relapsed or refractory chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) after at least one previous systemic (whole‑body) first‑line treatment.
  • Must have had testing for TP53 mutation (a change in a gene that can affect treatment response) after the most recent therapy.
  • Must have had testing for del(17p) mutation (a specific chromosome abnormality) after the most recent therapy.
  • Must be able and willing to follow the study visit schedule and all other study requirements.
  • Must provide written informed consent (a signed document showing you understand the study and agree to take part).
  • Must be capable of giving informed consent (able to understand the information and make a decision).
  • Must need treatment according to the International Workshop on Chronic Lymphocytic Leukemia (IWCLL) 2018 criteria (a set of rules doctors use to decide when treatment is necessary).
  • Must be at least 18 years old.
  • Must have a WHO performance status of 0 to 3 (a scale that measures how well you are able to carry out daily activities), with stage 3 allowed only if it is caused by CLL/SLL.
  • Must have adequate bone‑marrow function, meaning:
    • Hemoglobin (a protein that carries oxygen) greater than 5.0 mmol/L, unless low because the disease is in the bone marrow.
    • Absolute neutrophil count (a type of white blood cell that fights infection) greater than 0.75 × 10⁹/L, unless low because the disease is in the bone marrow.
    • Platelet count (cells that help blood clot) greater than 30 × 10⁹/L, unless low because the disease is in the bone marrow.
  • Must have an estimated glomerular filtration rate (eGFR) or estimated creatinine clearance (CrCl) of at least 30 mL/min (measures of kidney function).
  • Must have adequate liver function, defined as:
    • Serum aspartate transaminase (ASAT) and alanine transaminase (ALAT) no more than three times the upper limit of normal (ULN).
    • Bilirubin (a waste product processed by the liver) no more than 1.5 times ULN, unless the increase is due to Gilbert’s syndrome or a controlled autoimmune hemolytic anemia.
  • Must test negative for hepatitis B surface antigen (HBsAg) and hepatitis B core antibody (anti‑HBc), and for hepatitis C antibody. If any of these tests are positive, a follow‑up PCR test must be negative (PCR detects active virus).
  • Must have had assessment of IGHV mutation status (a test that looks at a gene linked to disease behavior) at least once.

Who Cannot Join the Study?

  • If your CLL has changed into a more aggressive cancer known as Richter’s transformation.
  • If you are currently taking cancer‑fighting medicines (anti‑neoplastic drugs) as part of another clinical study.
  • If personal, family, mental health, or living‑away‑far issues would make it hard for you to follow the study plan and attend visits.
  • If you have taken the study drug venetoclax in the past two years, or if your disease got worse while you were on venetoclax before.
  • If cancer has spread to the brain or spinal cord (the central nervous system).
  • If you have another type of cancer that still needs whole‑body (systemic) treatment, has not been cured (curative intent), or is getting worse after treatment.
  • If you have ever had progressive multifocal leukoencephalopathy (PML), a rare brain infection.
  • If you are allergic to medicines called xanthine oxidase inhibitors or rasburicase.
  • If you have had a severe allergic reaction (hypersensitivity or anaphylaxis) to any of the study medicines.
  • If you have serious heart problems such as ongoing irregular heartbeats (arrhythmias), heart failure (congestive heart failure), or chest pain from reduced blood flow (ischemic heart disease) that are classified as severe (grade III‑IV).
  • If you have serious lung problems classified as severe (grade III‑IV) (pulmonary dysfunction).
  • If you have serious brain, nerve, or mental health conditions that are rated as severe (grade III‑IV) (neurological or psychiatric disease).
  • If you currently have a fungal, bacterial, or viral infection that needs whole‑body (systemic) medication.
  • If your liver disease is classified as Child Pugh C, which means very advanced liver dysfunction.
  • If you have another serious health problem that is not under control, such as uncontrolled diabetes, high blood pressure (hypertension), or an infection.
  • If you are known to have HIV‑positive status.
  • If you cannot swallow pills or have a stomach/intestine problem (gastrointestinal disease) that would stop the medicine from being absorbed.
  • If you are pregnant or breastfeeding (nursing mother).
  • If you are able to have children and are not using a reliable birth‑control method, or are not surgically sterile or past menopause.
  • If you have already taken part in the HO139 CLL or HO140 CLL studies and are planning to join the HO159 CLL study.

Where you can join this trial?

Verified and Recommended Sites

No sites found in this category

Verified Sites

Site Name City Country Status
Zuyderland Medisch Centrum Stichting Geleen The Netherlands

Other Sites

Site Name City Country Status
Ziekenhuis Gelderse Vallei Stichting Ede The Netherlands
Haga Hospital Hague The Netherlands
Universitair Medisch Centrum Utrecht Utrecht The Netherlands
Maasstad Ziekenhuis Stichting Rotterdam The Netherlands
St. Antonius Ziekenhuis Nieuwegein The Netherlands
Deventer Ziekenhuis Deventer The Netherlands
Reinier de Graaf Groep Delft The Netherlands
Stichting Treant Ziekenhuiszorg Emmen The Netherlands
Bravis Ziekenhuis Roosendaal The Netherlands
Slingeland Ziekenhuis Doetinchem The Netherlands
Noordwest Ziekenhuisgroep Stichting Alkmaar The Netherlands
Isala Klinieken Stichting Zwolle The Netherlands
Groene Hart Ziekenhuis Gouda The Netherlands
Jeroen Bosch Ziekenhuis Stichting s-Hertogenbosch The Netherlands
Amphia Hospital Breda The Netherlands
Albert Schweitzer Ziekenhuis Dordrecht The Netherlands
Ziekenhuis Rivierenland Tiel The Netherlands
Spaarne Gasthuis Hoofddorp The Netherlands
Medisch Spectrum Twente Enschede The Netherlands
Diakonessenhuis Stichting Utrecht The Netherlands
Elkerliek Ziekenhuis Helmond The Netherlands
ZorgSaam Ziekenhuis Terneuzen The Netherlands
Ziekenhuis St Jansdal Harderwijk The Netherlands
Ikazia Ziekenhuis Rotterdam The Netherlands
Het Van Weel-Bethesda Ziekenhuis Dirksland The Netherlands
Bernhoven B.V. Uden The Netherlands
Rode Kruis Ziekenhuis B.V. Beverwijk The Netherlands
Lymitwdzbo Zfjuboefyc Rrbthdxw Roermond The Netherlands
Mluxkpckcucfnf Pfafrmu Bzse Beugen The Netherlands
Scvqcae Geldrop The Netherlands
Sbd Eiuvhfwaj Hxzuvmot Ttzkbgq Tilburg The Netherlands
Rfejxpitb Zhammcfqok Sjjgdteqa Arnhem The Netherlands
Schxrdqsh Mesjmyw Zevebvdxtg Groningen The Netherlands
Bnetwyw Zvmwheoelg Gorinchem The Netherlands

Want to learn more about this study or check if you can participate? Contact us.

Trial status

Country Status Recruitment Start
The Netherlands The Netherlands
Not yet recruiting
15.06.2026

Trial locations

Investigated drugs:

Venetoclax is an oral medication taken as a tablet. It works by helping the body’s immune system kill certain cancer cells that cause chronic lymphocytic leukemia (CLL). In this study, patients receive venetoclax after an initial course of another drug, and the trial compares continuing venetoclax for many cycles versus stopping it early. The drug is taken by mouth and is meant to keep the leukemia from growing.

Rituximab is given by an intravenous (IV) infusion, meaning it is injected into a vein. It is a type of antibody that attaches to a protein on the surface of CLL cells, marking them for destruction by the immune system. In the trial, all participants receive six cycles of rituximab together with venetoclax at the start of treatment. This combination is intended to reduce the number of leukemia cells before the study evaluates how long the patients stay free of disease progression.

Investigated diseases:

Relapsed or refractory small lymphocytic lymphoma – Small lymphocytic lymphoma is a slow‑growing cancer of a type of white blood cell called a B‑lymphocyte, which mainly builds up in the lymph nodes and spleen. When it returns after treatment (relapsed) or does not respond to treatment (refractory), the abnormal cells continue to increase in number. The disease may cause the lymph nodes to become larger and can spread to the bone marrow. Over time, more blood cells can be affected, leading to a gradual rise in abnormal cells in the blood. The condition usually progresses slowly, with the number of cancer cells slowly increasing.
Relapsed or refractory chronic lymphocytic leukemia – Chronic lymphocytic leukemia is a blood cancer where a type of white blood cell called a B‑cell grows abnormally and accumulates in the blood and bone marrow. In the relapsed or refractory setting, the disease either comes back after treatment or does not respond to therapy, causing the number of abnormal cells to keep rising. This leads to larger amounts of these cells in the bloodstream and can affect the bone marrow’s ability to make normal blood cells. As the disease advances, the abnormal cells may spread to the spleen and lymph nodes. The overall pattern is a slow but steady increase in cancer cells over time.

Trial ID:
2025-524283-38-00
Protocol code:
HOVON 182 CLL
Trial Phase:
Therapeutic confirmatory (Phase III)

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