Study on Venetoclax, Ibrutinib, and Obinutuzumab for Chronic Lymphocytic Leukemia Patients Not in Complete Remission or with Detectable Bone Marrow Disease

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What is this study about?

This clinical trial is focused on studying the treatment of Chronic Lymphocytic Leukemia (CLL) and a related condition called Small Lymphocytic Lymphoma (SLL). The study involves the use of several medications: venetoclax (also known by its code names ABT-199 and GDC-0199), ibrutinib, and obinutuzumab. Venetoclax and ibrutinib are taken as film-coated tablets, while obinutuzumab is given as a solution for infusion, which means it is administered directly into the bloodstream through a vein.

The purpose of the study is to evaluate how effective these medications are in treating patients with CLL or SLL who have not achieved complete remission or still have detectable cancer cells in their bone marrow after initial treatment. The study will begin with an induction phase using venetoclax and ibrutinib, followed by an intensification phase with obinutuzumab for those who need further treatment. The trial aims to see if this approach can help patients achieve a state where no cancer cells are detectable in the bone marrow.

Participants in the study will receive treatment over a period of time, with regular check-ups to monitor their response to the medications. The study will track various outcomes, including the level of cancer cells in the bone marrow and overall survival rates. The trial is expected to continue until 2027, providing valuable information on the effectiveness of this treatment combination for CLL and SLL patients.

1 induction phase

The induction phase involves the administration of two medications: venetoclax and ibrutinib. These medications are taken orally.

The purpose of this phase is to initiate treatment for chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL).

2 venetoclax dosage escalation

Venetoclax is initially administered at a low dose and gradually increased to minimize side effects. The dosage starts with Venclyxto 10 mg film-coated tablets and progresses to Venclyxto 100 mg film-coated tablets.

This escalation is carefully monitored to ensure safety and effectiveness.

3 ibrutinib administration

Ibrutinib is taken as IMBRUVICA 140 mg film-coated tablets. This medication is also administered orally.

The goal is to maintain a consistent level of the drug in the body to effectively manage the condition.

4 intensification phase

If the patient is not in complete remission or has detectable minimal residual disease (MRD) in the bone marrow, the intensification phase begins.

This phase includes the administration of obinutuzumab, which is given as Gazyvaro 1,000 mg concentrate for solution for infusion. This medication is administered intravenously.

5 monitoring and evaluation

Throughout the trial, regular monitoring is conducted to assess the response to treatment. This includes evaluating the level of MRD in the bone marrow and peripheral blood.

The effectiveness of the treatment is measured at various time points, and adjustments may be made based on the patient’s response.

6 completion and follow-up

After completing the treatment phases, follow-up assessments are conducted to monitor long-term outcomes.

These assessments help determine the progression-free survival, event-free survival, and overall survival of the patient.

Who Can Join the Study?

Must have a documented diagnosis of Chronic Lymphocytic Leukemia (CLL) or Small Lymphocytic Lymphoma (SLL) that requires treatment.
Must be able and willing to follow the study visit schedule and other study requirements.
Must be capable of giving informed consent, which means understanding the study and agreeing to participate.
Must provide written informed consent.
Must have a WHO performance status of 0-3, which is a measure of general well-being and ability to perform daily activities. Stage 3 is only allowed if it is due to CLL/SLL.
Must not have had any prior treatment for CLL/SLL.
Must be at least 18 years old.
Must have adequate bone marrow (BM) function, which means:
- Hemoglobin (Hb) level greater than 5 mmol/L or 8 g/dL.
- Absolute neutrophil count (ANC) of at least 0.75 x 10⁹/L or 750/μL.
- Platelet count of at least 50 x 10⁹/L or 50,000/μL, unless low counts are directly due to CLL/SLL affecting the bone marrow, confirmed by a bone marrow biopsy.
Must have an estimated Glomerular Filtration Rate (eGFR) or creatinine clearance (CrCl) of at least 30 L/min, which measures kidney function. If eGFR or CrCl is less than 50 ml/min, the patient is considered high risk for Tumor Lysis Syndrome (TLS).
Must have adequate liver function, shown by:
- Serum aspartate transaminase (ASAT) and alanine transaminase (ALAT) levels no more than 3 times the upper limit of normal (ULN).
- Bilirubin level no more than 1.5 times the ULN, unless the increase is due to Gilbert’s syndrome or a non-liver-related cause.
Must have a Prothrombin time (PT)/International Normalized Ratio (INR) and activated partial thromboplastin time (aPTT) less than 1.5 times the ULN, which are tests that measure blood clotting.
Must test negative for hepatitis B and hepatitis C. If positive for certain hepatitis antibodies, a negative PCR test is required before joining the study. Those with a positive PCR test will be excluded.

Who Cannot Join the Study?

Patients with other types of cancer besides Chronic Lymphocytic Leukemia cannot participate.
Patients who have had a heart attack or stroke in the past 6 months are excluded.
Patients with uncontrolled high blood pressure are not eligible.
Patients with severe liver or kidney disease cannot join the study.
Patients who are pregnant or breastfeeding are not allowed to participate.
Patients with active infections that require treatment are excluded.
Patients who have received another experimental treatment in the last 30 days cannot participate.
Patients with a history of allergic reactions to the study drugs are not eligible.
Patients with mental health conditions that might affect their ability to follow study instructions are excluded.
Patients who are unable to give informed consent are not allowed to join the study.

Where you can join this trial?

Verified and Recommended Sites

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Verified Sites

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Other Sites

Site Name	City	Country
Catharina Ziekenhuis Stichting	Eindhoven	The Netherlands
Meander Medical Center	Amersfoort	The Netherlands
Universitair Medisch Centrum Groningen	Groningen	The Netherlands
Ziekenhuis Gelderse Vallei Stichting	Ede	The Netherlands
Haga Hospital	Hague	The Netherlands
Rigshospitalet	Copenhagen	Denmark
Groene Hart Ziekenhuis	Gouda	The Netherlands
Tergooiziekenhuizen	Hilversum	The Netherlands
Albert Schweitzer Ziekenhuis	Dordrecht	The Netherlands
Spaarne Gasthuis	Hoofddorp	The Netherlands
Maxima Medisch Centrum	Veldhoven	The Netherlands
Flevoziekenhuis Stichting	Almere	The Netherlands
ZorgSaam Ziekenhuis	Terneuzen	The Netherlands
Ikazia Ziekenhuis	Rotterdam	The Netherlands
Bernhoven B.V.	Uden	The Netherlands
Slb Eljniumsv Hqysfpnb Trcyipj	Tilburg	The Netherlands
Alqqarnsn Urr	Amsterdam	The Netherlands

Trial status

Country	Status	Recruitment Start
Denmark	Not recruiting	15.10.2020
The Netherlands	Not recruiting	15.10.2020

Trial locations

Investigated drugs:

Ibrutinib is a medication used in this trial to help treat patients with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL). It works by blocking a protein that helps cancer cells grow, which may slow down or stop the progression of the disease.

Venetoclax is another medication used in the trial. It targets a specific protein in cancer cells that helps them survive. By blocking this protein, venetoclax can help kill cancer cells and reduce the number of cancer cells in the body.

Obinutuzumab is a type of therapy called a monoclonal antibody. It is used in this trial to help the immune system recognize and attack cancer cells. Obinutuzumab binds to a specific protein on the surface of cancer cells, marking them for destruction by the immune system.

Chronic Lymphocytic Leukemia – Chronic Lymphocytic Leukemia (CLL) is a type of cancer that affects the blood and bone marrow. It is characterized by the production of an excessive number of abnormal white blood cells called lymphocytes. These abnormal cells accumulate over time, crowding out healthy blood cells and impairing the immune system. CLL typically progresses slowly and may not cause symptoms for years. As the disease advances, it can lead to symptoms such as fatigue, swollen lymph nodes, and frequent infections. The progression of CLL varies among individuals, with some experiencing a more aggressive form of the disease.

Trial ID:

2022-502808-72-00

Protocol code:

HO158

NCT ID:

NCT04639362

Trial Phase:

Therapeutic exploratory (Phase II)

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Study on Venetoclax, Ibrutinib, and Obinutuzumab for Chronic Lymphocytic Leukemia Patients Not in Complete Remission or with Detectable Bone Marrow Disease

What is this study about?

Who Can Join the Study?

Who Cannot Join the Study?