Safety and efficacy of venetoclax, obinutuzumab and daratumumab in adult patients with relapsed chronic lymphocytic leukemia

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What is this study about?

Adult patients with chronic lymphocytic leukemia/small lymphocytic lymphoma whose disease has come back after earlier treatment (relapsed) are being studied. The trial uses a combination of oral venetoclax, an infusion of obinutuzumab and an infusion of daratumumab. These medicines work by targeting the abnormal white blood cells that cause the leukemia.

The purpose is to find a safe dose of the three‑drug regimen and to see how well it can clear the cancer cells, especially in patients with certain genetic changes such as TP53 or IGHV. Participants will receive the medicines on a planned schedule over several months, with regular check‑ups that may include blood tests and a test called flow cytometry to measure tiny amounts of remaining cancer cells. Safety will be monitored by recording any side effects, and success will be judged by how many patients achieve “MRD negativity,” meaning very few cancer cells can be detected.

1 enrollment and baseline assessments

after you join the study, you will provide written consent and undergo baseline examinations such as blood sampling and physical evaluation to confirm eligibility.

these assessments establish a reference point for later comparison during treatment.

2 initial treatment administration

on the first day of therapy you will receive an obinutuzumab infusion, which is a medication given through a vein.

you will also receive a daratumumab infusion, another medication administered intravenously.

in addition, you will start taking venetoclax tablets (film‑coated) by mouth; the specific tablet strength and dosing schedule are defined by the study protocol.

3 ongoing oral medication

you will continue to take the prescribed venetoclax tablets each day by oral use for the duration of the treatment phase as outlined in the protocol.

the tablets are taken without food unless instructed otherwise.

4 repeated infusion cycles

at intervals specified by the study, you will receive additional infusions of obinutuzumab and daratumumab.

each infusion is performed in a clinical setting and lasts for the time required by the medication administration guidelines.

5 regular monitoring visits

throughout the study you will attend scheduled visits for blood tests and clinical evaluation to monitor the effect of the medicines and to check for side effects.

these visits allow the study team to assess response and safety.

6 final assessment and study completion

after the last scheduled dose of the study drugs, you will undergo a final evaluation that includes blood analysis and imaging as required.

the results determine the outcome of the trial for your participation.

Who Can Join the Study?

Age: You must be older than 18 years.
Liver function: Blood tests for AST and ALT must be no more than 2.5 times the normal range, and total bilirubin must be no more than 1.5 times normal (or up to 3 times if you have Gilbert’s syndrome, a mild inherited liver condition).
No active hemolytic anemia: You cannot have a breaking‑down of red blood cells that needs treatment. A positive Coombs test (a lab test that looks for antibodies on red cells) is allowed if you have no signs of anemia.
No current corticosteroids (except low‑dose prednisone < 10 mg or equivalent for non‑blood problems): Steroid medicines that suppress the immune system are not allowed.
No prior autoimmune blood problems: You must not have had conditions like autoimmune hemolytic anemia or immune thrombocytopenia (low platelets due to the immune system) that required high‑dose steroids, monoclonal‑antibody therapy, or chemotherapy.
No recent major surgery: You cannot have had a major operation within the past 4 weeks, and no minor surgery within the past 3 days before the first dose.
No recent radiotherapy: You must not have received radiation treatment within the past 4 weeks.
Tumor lysis syndrome prevention: You must be able to take a medication that prevents tumor lysis syndrome (a rapid release of cell contents), such as a xanthine oxidase inhibitor or rasburicase.
Pregnancy testing and contraception: Women who could become pregnant must have a negative pregnancy test (blood βHCG level) and agree to use two reliable birth‑control methods or abstain from sex. Men must use a latex condom with women of child‑bearing potential during the study and for 18 months after it ends.
Informed consent: You must voluntarily sign a consent form agreeing to join the study.
Willingness to follow the study: You must be able and willing to follow all study visits and procedures.
Diagnosis of CLL or SLL: You must have chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) that meets the 2018 iwCLL criteria (a set of accepted medical definitions).
Prior CLL/SLL therapy: You must have received earlier CLL treatments such as chemotherapy, a BTK inhibitor (a type of targeted drug), venetoclax, other small‑molecule drugs, or monoclonal‑antibody therapy, and you must have responded to a previous venetoclax course with the last dose at least 36 months ago.
Indication for treatment: Your doctor must determine, based on the 2018 iwCLL guidelines, that you need new treatment now.
ECOG performance status ≤ 2: You must be able to carry out normal daily activities with only slight limitation.
Adequate blood counts without extra growth factors or transfusions: Hemoglobin ≥ 9 g/dL (protein that carries oxygen), absolute neutrophil count ≥ 1.0 × 10⁹/L (type of white blood cell), and platelet count ≥ 75 × 10⁹/L (cells that help clot blood).
Kidney function: Creatinine clearance must be ≥ 30 mL/min, measured by a 24‑hour urine collection or calculated with the modified Cockcroft‑Gault equation (a formula that estimates kidney filtering ability).

Who Cannot Join the Study?

Having Richter’s transformation (a type of aggressive lymphoma) confirmed by a tissue biopsy.
Testing positive for HIV (human immunodeficiency virus), because the study medicines may interact with HIV medicines.
Having an active hepatitis C infection, meaning hepatitis C virus is detectable in the blood.
Being pregnant or breastfeeding.
Having a condition that stops the drug from being taken by mouth, such as a severe malabsorption syndrome.
Having severe problems in any organ system that score 4 on the CIRS (Cumulative Illness Rating Scale), which means the organ cannot work well enough to follow the treatment.
Having any other serious medical, psychiatric, or laboratory problem that the doctor thinks makes the study unsafe or could affect the results.
Receiving a live vaccine (such as measles, mumps, rubella) less than 28 days before the first dose of study medication.
Using strong or moderate CYP3A inhibiting or inducing medicines within 7 days before the first dose of venetoclax, or eating grapefruit, Seville oranges, or star fruit within 3 days before the first dose.
Needing the blood thinner warfarin (unless it can be stopped and replaced with another anticoagulant).
Having moderate to severe heart failure (New York Heart Association class III or IV).
Having had a heart attack, unstable chest pain, or acute coronary syndrome within the last 6 months.
Having an infection that needed systemic (whole‑body) treatment and still on antibiotics; antibiotics must be stopped at least 14 days before the first study dose.
Having had an ischemic (clot‑related) or hemorrhagic (bleeding) stroke, or a transient ischemic attack (mini‑stroke) within the last 6 months.
Testing positive for hepatitis B surface antigen (HBsAg) or having hepatitis B core antibody (HBcAb) with detectable hepatitis B DNA, indicating an active hepatitis B infection.
Having cancer involvement in the brain or spinal fluid (central nervous system involvement of CLL).
Having moderate to severe chronic obstructive pulmonary disease (COPD), defined as a forced expiratory volume in 1 second (FEV1) less than 50 % of the predicted normal value.
Having persistent or poorly controlled asthma within the past 2 years (only mild or intermittent asthma is allowed).
Having other cancers that could interfere with the study, unless they were treated only with surgery, are in remission for at least 2 years, and are not expected to affect the trial.
Having an active systemic infection (viral, bacterial, or fungal) at the time of screening.

Where you can join this trial?

Verified and Recommended Sites

Site Name	City	Country	Status
Samodzielny Publiczny Szpital Kliniczny Nr 4 W Lublinie	Lublin	Poland

Verified Sites

Site Name	City	Country	Status
Uniwersytecki Szpital Kliniczny Im Jana Mikulicza Radeckiego We Wroclawiu	Wroclaw	Poland

Other Sites

Site Name	City	Country
Szpital Uniwersytecki Nr 2 Im Dr Jana Biziela W Bydgoszczy	Bydgoszcz	Poland
Samodzielny Publiczny Szpital Kliniczny Nr 1 W Lublinie	Lublin	Poland
Uniwersyteckie Centrum Kliniczne Warszawskiego Uniwersytetu Medycznego	Warsaw	Poland
Wzucghbndxd Wqezxidxmuixilkxkavv Cyuxuho Ophnbvdpb I Txroudfnlpahu Iy Mhcmjtysxqw W Loqsn	Lodz	Poland

Trial status

Country	Status	Recruitment Start
Poland	Not yet recruiting	01.03.2026

Trial locations

Investigated drugs:

Venetoclax is a pill taken by mouth that helps kill cancer cells in chronic lymphocytic leukaemia. In this study it is given together with other medicines to see how safely it can be combined and how well it works to clear the disease.

Obinutuzumab is a medicine given through an IV infusion. It is a type of antibody that attaches to the cancer cells and helps the immune system destroy them. In the trial it is used together with venetoclax to test how effectively the two drugs can eliminate leukaemia cells.

Daratumumab is a drug given as an injection. It is also an antibody that targets a protein on the surface of certain cancer cells, helping the body’s immune system to attack them. In this study it is added to the venetoclax‑obinutuzumab combination to find the safest dose and to see if it improves treatment results.

Investigated diseases:

Chronic lymphocytic leukemia / Small lymphocytic lymphoma – It is a type of blood cancer that starts in the bone marrow and spreads to the blood and lymph nodes. It develops slowly, and many patients have few symptoms for years. Over time, the abnormal B‑cells increase in number and can crowd out normal blood cells, causing fatigue, infections, or swollen lymph nodes. The disease can shift from a low‑risk stage to a higher‑risk stage as the number of cancer cells grows. Some patients may experience a sudden increase in disease activity called a relapse after a period of stability.

Trial ID:

2024-513917-11-01

Protocol code:

2023/ABM/01/00072

Trial Phase:

Human Pharmacology (Phase I) – Other

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Safety and efficacy of venetoclax, obinutuzumab and daratumumab in adult patients with relapsed chronic lymphocytic leukemia

What is this study about?

Who Can Join the Study?

Who Cannot Join the Study?