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Rituximab and venetoclax treatment for 6 vs 26 cycles in patients with relapsed or refractory chronic lymphocytic leukemia

Verified siteRegistered drugNo placebo
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What is this trial about?

A plain-language summary of the goals, design and what participants do

The trial involves adults whose disease has come back or did not respond to earlier treatment (called “relapsed or refractory”) and who have either chronic lymphocytic leukemia or small lymphocytic lymphoma. The treatment being tested combines an intravenous antibody therapy known as rituximab, given for six cycles, with an oral tablet medication called venetoclax, which works by blocking a protein that helps cancer cells survive.

The purpose of the study is to compare how long patients stay free of disease progression when venetoclax is continued for a longer period versus stopping after the initial six‑month course. After the six cycles of the combination, participants are randomly assigned—by chance—to either keep taking venetoclax for up to about 20 cycles or to stop the drug. All participants are then monitored with regular doctor visits, blood tests, and scans to check for any return of disease or side effects. The main outcome measured is progression free survival, which counts the time from random assignment until the disease gets worse or the patient dies.

The research process

The trial runs in 8 steps – from screening to follow-up. Each step says what happens and what the team monitors.

  1. Step 1

    Baseline assessments

    After joining the study, you will undergo a series of tests to record your current health status. these may include blood tests, imaging, and a physical examination. the results establish a starting point for later comparisons.

  2. Step 2

    Randomization

    Based on the study design, you will be assigned to one of two groups. the assignment is made by the study system and is not influenced by personal choice.

  3. Step 3

    Rituximab treatment (6 cycles)

    You will receive rituximab, a medication given through a vein (intravenous or iv). it is administered once every 28 days, which defines one cycle. a total of six cycles are planned, so the treatment lasts about six months.

  4. Step 4

    Venetoclax start‑up (ramp‑up phase)

    Following the first dose of rituximab, you will begin taking venetoclax by mouth (oral) as film‑coated tablets. the dose is increased over four days:

    Day 1: 20 mg once daily,

    Day 2: 50 mg once daily,

    Day 3: 100 mg once daily,

    Day 4 onward: 400 mg once daily.

    The tablets are available in 10 mg, 50 mg, and 100 mg strengths, which are combined to reach the required dose.

  5. Step 5

    Venetoclax continuation (assigned duration)

    After the ramp‑up, you will continue the 400 mg daily dose of venetoclax for the period defined by your study arm:

    Arm a: 20 additional cycles (approximately 20 months) after the initial six cycles of rituximab,

    Arm b: 6 additional cycles (approximately 6 months) after the initial six cycles of rituximab.

    Each cycle is 28 days, so the total treatment time differs between the two arms.

  6. Step 6

    Regular monitoring visits

    Throughout the treatment period you will attend scheduled visits, usually every 28 days, for blood tests and safety checks. these visits help the study team track how the medicines are working and identify any side effects.

  7. Step 7

    End of treatment

    When the assigned number of cycles of venetoclax is completed, you will stop taking the medication. the study staff will confirm that the final dose has been taken.

  8. Step 8

    Follow‑up assessments

    After treatment ends, you will continue to be monitored for up to week 84 (approximately 2 years) from the time of randomization. follow‑up visits include blood tests and questionnaires about quality of life.

Who can join the trial?

15 criteria

  • You must have a diagnosis of relapsed (the disease has returned) or refractory (the disease did not respond) chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) after at least one previous systemic treatment.
  • Testing for the genetic changes called TP53 mutation and del17p mutation must have been done after your most recent treatment.
  • You must need treatment according to the IWCLL 2018 criteria, which are doctor‑approved guidelines for when therapy is required.
  • You must be at least 18 years old.
  • Your overall health must be measured as a WHO performance status of 0‑3 (a scale that shows how well you can do daily activities); a score of 3 is allowed only if it is caused by CLL/SLL.
  • Your bone marrow must be working well enough, which means:
    • Hemoglobin (Hb) level higher than 5.0 mmol/L, unless low because cancer is in the marrow.
    • Absolute neutrophil count (ANC) greater than 0.75 × 10⁹/L, unless low because of marrow involvement.
    • Platelet count greater than 30 × 10⁹/L, unless low because of marrow involvement.
    • Your kidney function must show an estimated glomerular filtration rate (eGFR) or creatinine clearance of at least 30 ml/min.
    • Your liver function must be within limits:
      • Aspartate transaminase (ASAT) and alanine transaminase (ALAT) no more than three times the normal upper limit.
      • Bilirubin no more than 1.5 times the normal upper limit (unless the increase is due to Gilbert’s syndrome or a controlled autoimmune hemolytic anemia).
      • You must test negative for hepatitis B surface antigen (HBsAg), hepatitis B core antibody (anti‑HBc), and hepatitis C antibody. If any of these are positive, a PCR test must be negative before you can join.
      • The status of the IGHV mutation must have been assessed at least once.
      • You must be able and willing to follow the study visit schedule and other protocol requirements.
      • You must sign a written informed consent and be capable of understanding what it means.

Who cannot join the trial?

20 criteria

  • If your CLL has changed into a more aggressive form called Richter’s transformation (a fast‑growing type of lymphoma).
  • If you are currently receiving cancer‑fighting medicines (called anti‑neoplastic drugs) as part of another study.
  • If you have mental health issues, family problems, social circumstances, or live far away that would make it hard for you to follow study visits and rules.
  • If you have taken the study drug venetoclax in the past 2 years, or if your disease got worse while you were on venetoclax before.
  • If your disease has spread to the central nervous system (brain or spinal cord).
  • If you have another cancer besides CLL/SLL that still needs overall (systemic) treatment, isn’t being treated to cure, or is getting worse after treatment meant to cure it.
  • 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 (anaphylaxis) or strong sensitivity to any of the study medicines.
  • If you have serious heart problems such as ongoing irregular heartbeats (arrhythmias), congestive heart failure, or chest pain from poor blood flow (ischemic heart disease) that are classified as moderate to severe (CTCAE grade III‑IV).
  • If you have serious lung problems that are moderate to severe (CTCAE grade III‑IV).
  • If you have serious brain or mental health disorders that are moderate to severe (CTCAE grade III‑IV).
  • If you currently have a fungal, bacterial, or viral infection that needs overall (systemic) medicine treatment.
  • If your liver disease is classified as Child‑Pugh C, which means very poor liver function.
  • If you have another serious health problem that is not under control, such as uncontrolled diabetes, infection, high blood pressure, etc.
  • If you are known to have HIV infection.
  • If you cannot swallow pills or have stomach/intestine problems that would stop the medicine from being absorbed.
  • If you are pregnant or are breastfeeding.
  • If you can become pregnant (fertile) and are not using reliable birth control, unless you are permanently unable to have children, have been post‑menopause for at least 2 years, or agree to use a strong contraceptive method (like birth‑control pills, an intrauterine device, or abstaining from sex) during the study and for the required time after treatment.
  • If you have already taken part in the HO139 or HO140 CLL studies and are also being asked to join the HO159 CLL study.
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Investigated drugs

  • Venetoclax

    is an oral medication taken as a tablet. It works by blocking a protein that helps cancer cells survive, which can cause the leukemia cells to die. In this study, patients receive venetoclax after an initial course of another drug, and the length of treatment (either a shorter or longer number of cycles) is being compared to see which plan keeps the disease from getting worse for a longer time.

  • Rituximab

    is a medicine given by infusion into a vein. It targets a specific marker on the surface of certain white blood cells, helping the immune system recognize and destroy the leukemia cells. In this trial, all participants receive six cycles of rituximab at the start of treatment, and it is combined with venetoclax to see how well the two drugs work together.

What is already known about the treatment

  • Venclyxto 10 mg film-coated tablets

    It is taken by mouth as a film‑coated tablet, providing an oral form of the medicine. Venetoclax is an approved drug that is well documented in medical research for treating blood cancers. It is mainly used for patients with relapsed or refractory chronic lymphocytic leukemia and small lymphocytic lymphoma. The drug works by blocking the BCL‑2 protein, which helps cancer cells survive, so the cells can die; it is classified as a BCL‑2 inhibitor.

  • Venclyxto 50 mg film-coated tablets

    This medication is also an oral, film‑coated tablet that patients swallow. Venetoclax has a solid track record in the scientific literature and is approved for use in certain blood cancers. It is indicated for relapsed or refractory chronic lymphocytic leukemia and small lymphocytic lymphoma. It stops the BCL‑2 protein from protecting cancer cells, allowing them to die, and belongs to the BCL‑2 inhibitor drug class.

  • Venclyxto 100 mg film-coated tablets

    The drug comes as a film‑coated tablet taken by mouth, providing a convenient oral dosage. Venetoclax is an established, FDA‑approved therapy with extensive study in medical journals. It is prescribed for relapsed or refractory chronic lymphocytic leukemia and small lymphocytic lymphoma. By inhibiting the BCL‑2 protein, it triggers death of cancer cells and is categorized as a BCL‑2 inhibitor.

Investigated diseases

  • Relapsed or refractory small lymphocytic lymphoma

    This is a type of blood‑cell cancer that starts in the lymph nodes and can spread to the spleen or bone marrow. “Relapsed” means the disease has returned after previous treatment, and “refractory” means it did not respond to that treatment. The cancer cells continue to grow, causing the lymph nodes to become larger over time. As the disease progresses, it may affect the blood and bone marrow, leading to reduced blood cell production. The condition can slowly worsen if not controlled.

  • Relapsed or refractory chronic lymphocytic leukemia

    This is a cancer of white blood cells that begins in the bone marrow and circulates in the bloodstream. “Relapsed” indicates the disease has come back after earlier therapy, while “refractory” means it did not respond to that therapy. The abnormal cells increase in number, gradually crowding out normal blood cells. Over time, the disease may cause fatigue, frequent infections, and enlarged lymph nodes or spleen. The cancer can continue to expand if it is not managed.

Trial detailsLast updated 7 Oct 2026
Age18+ yearsPhasePhase IIITrial ID2025-524283-38-00Protocol codeHOVON 182 CLLEstimated enrolment456 patientsSponsorHemato-Oncologie voor Volwassenen Nederland (Hovon) Stichting

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