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Study on Acalabrutinib, Venetoclax, and Obinutuzumab for Untreated Chronic Lymphocytic Leukemia Patients Without del(17p) or TP53 Mutation

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What is this trial about?

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

This clinical trial is focused on studying the effectiveness and safety of a new treatment approach for people with Chronic Lymphocytic Leukemia (CLL), a type of cancer that affects the blood and bone marrow. The study involves a combination of medications, including an investigational drug called acalabrutinib (also known as ACP-196), and two other drugs, venetoclax and obinutuzumab. These medications will be compared to standard chemotherapy treatments that are commonly used for CLL, such as combinations involving fludarabine, cyclophosphamide, and rituximab, or bendamustine and rituximab.

The purpose of this study is to evaluate how well the new combination of acalabrutinib, venetoclax, and obinutuzumab works compared to the traditional chemotherapy options. Participants in the study will be randomly assigned to receive either the new combination treatment or one of the standard chemotherapy treatments. The study will monitor participants over a period of time to assess the progression of the disease and any side effects experienced. The medications will be administered either orally or through intravenous infusion, depending on the specific drug.

This trial is designed for individuals who have not received prior treatment for their CLL and do not have certain genetic mutations, specifically the del(17p) or TP53 mutation. The study aims to provide valuable information on whether the new treatment combination can offer better outcomes for patients with CLL compared to existing chemotherapy options. Participants will be closely monitored by healthcare professionals throughout the study to ensure their safety and to gather data on the effectiveness of the treatments.

The research process

The trial runs in 7 steps – from screening to follow-up. Each step says what happens and what the team monitors.

  1. Step 1

    Randomization

    Upon joining the study, participants are randomly assigned to one of the treatment groups. This process ensures that each participant has an equal chance of receiving any of the treatment options being tested.

  2. Step 2

    Treatment group assignment

    Participants are assigned to one of the following treatment groups:

    Arm A: Acalabrutinib and Venetoclax, with or without Obinutuzumab.

    Arm C: Chemoimmunotherapy, which includes Fludarabine, Cyclophosphamide, and Rituximab (FCR) or Bendamustine and Rituximab (BR).

  3. Step 3

    Treatment administration

    Participants in Arm A receive Acalabrutinib and Venetoclax orally. Obinutuzumab is administered intravenously if included.

    Participants in Arm C receive Fludarabine, Cyclophosphamide, and Rituximab or Bendamustine and Rituximab intravenously.

  4. Step 4

    Treatment duration

    The duration of treatment varies depending on the specific protocol for each arm. Participants will be informed of the exact schedule and duration of their treatment regimen.

  5. Step 5

    Monitoring and assessments

    Throughout the trial, participants undergo regular monitoring and assessments to evaluate the effectiveness and safety of the treatment. This includes blood tests, imaging studies, and other necessary evaluations.

  6. Step 6

    End of treatment

    Upon completion of the treatment phase, participants will have a final assessment to determine the outcome of the treatment and any potential side effects.

  7. Step 7

    Follow-up

    Participants may be required to attend follow-up visits to monitor their health status and any long-term effects of the treatment.

Who can join the trial?

8 criteria

  • Men and women who are **18 years or older**.
  • Have an **ECOG performance status** of 0 to 2. This is a scale that measures how well a person can perform daily activities.
  • Have a diagnosis of **Chronic Lymphocytic Leukemia (CLL)** that meets specific criteria. This includes having certain types of B-cells in the blood.
  • Have **active disease** that requires treatment according to specific guidelines.
  • Meet certain **laboratory parameters**:
    • Have adequate **bone marrow function** without needing extra support like growth factors or transfusions. This includes having a certain number of white blood cells and platelets.
    • Have levels of liver enzymes (**AST and ALT**) that are not more than 2.5 times the normal limit.
    • Have a **total bilirubin** level that is not more than 2 times the normal limit, unless it is due to a condition called **Gilbert's syndrome**.
    • Have an **estimated creatinine clearance** of at least 50 mL/min. This is a measure of how well the kidneys are working.

Who cannot join the trial?

4 criteria

  • Patients who have already received treatment for their **Chronic Lymphocytic Leukemia** cannot participate. **Chronic Lymphocytic Leukemia** is a type of cancer that affects the blood and bone marrow.
  • Patients with a specific genetic change called **del(17p)** or a **TP53 Mutation** are not eligible. These are changes in the DNA that can affect how the disease behaves.
  • Patients who are not within the specified age range for the study cannot participate. The study has specific age requirements.
  • Patients who are part of a vulnerable population, which means they might need special protection or care, are not eligible.
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Investigated drugs

  • Acalabrutinib

    This medication is used to treat certain types of blood cancers, including chronic lymphocytic leukemia. It works by blocking a specific protein in cancer cells, which helps to stop their growth and spread.

  • Venetoclax

    This is a medication that targets and blocks a protein that helps cancer cells survive. By inhibiting this protein, venetoclax can help to kill cancer cells and slow down the progression of the disease.

  • Obinutuzumab

    This is a type of therapy known as a monoclonal antibody. It works by attaching to specific proteins on the surface of cancer cells, marking them for destruction by the immune system.

  • Fludarabine

    This medication is a type of chemotherapy used to treat certain blood cancers. It works by interfering with the DNA of cancer cells, preventing them from growing and dividing.

  • Cyclophosphamide

    This is a chemotherapy drug that works by slowing or stopping the growth of cancer cells. It is often used in combination with other medications to treat various types of cancer.

  • Rituximab

    This is a monoclonal antibody used to treat certain types of blood cancers. It works by targeting specific proteins on cancer cells, helping the immune system to recognize and destroy them.

What is already known about the treatment

  • Acalabrutinib

    Acalabrutinib is administered orally in the form of capsules. It is currently being studied in clinical trials for its effectiveness in treating chronic lymphocytic leukemia (CLL) without specific genetic mutations. The medication works by inhibiting a protein called Bruton's tyrosine kinase (BTK), which plays a role in the growth and survival of cancer cells. Acalabrutinib is classified as a targeted therapy, specifically a BTK inhibitor.

  • Venetoclax

    Venetoclax is taken orally as tablets. It is under investigation for its use in treating chronic lymphocytic leukemia (CLL) in patients without certain genetic mutations. The drug functions by blocking a protein called BCL-2, which helps cancer cells survive, thereby promoting their death. Venetoclax is classified as a BCL-2 inhibitor, a type of targeted therapy.

  • Obinutuzumab

    Obinutuzumab is administered intravenously. It is being evaluated in clinical trials for its potential to treat chronic lymphocytic leukemia (CLL) in combination with other medications. The drug targets a protein called CD20 on the surface of cancer cells, leading to their destruction. Obinutuzumab is classified as a monoclonal antibody, a form of immunotherapy.

Investigated diseases

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 lymphocytes, a type of white blood cell. These abnormal cells accumulate over time, crowding out healthy blood cells and impairing the immune system. CLL typically progresses slowly, and many individuals may not experience symptoms for years. As the disease advances, it can lead to symptoms such as fatigue, swollen lymph nodes, and frequent infections. CLL without del(17p) or TP53 mutation refers to a subtype where specific genetic abnormalities are not present, which can influence the disease's behavior and response to treatment.
Trial detailsLast updated 2 Oct 2026
Age18+ yearsPhasePhase IIITrial ID2023-509349-11-00Protocol codeACE-CL-311 (AMPLIFY)Estimated enrolment984 patientsSponsorAcerta Pharma B.V.

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On this site, “treatment” means an investigational medicine being studied in a clinical trial. Its safety and efficacy for the use being studied have not yet been confirmed, some participants may receive a placebo or a comparator medicine, and taking part does not guarantee any health benefit. The decision to take part is made by the doctor at the research site. This site is for information only and does not replace medical advice.

This service is not affiliated with the European Commission, the EMA, or the official CTIS system. Most information comes from publicly available international clinical-trial registries, supplemented by data from academic sites, national regulators and commercial sponsors. On this site, “treatment” and “therapy” mean a medicine being tested in a clinical trial. Its safety and effectiveness in the use being studied are not yet confirmed, some participants may receive a placebo or a comparator, and taking part does not guarantee a health benefit. The doctor at the research site decides who can take part. This site provides information, not medical advice. Certain content and visual elements on this website have been generated or enhanced using artificial intelligence (AI).