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Phase 3 Study of Orelabrutinib with Rituximab and Bendamustine vs. Rituximab and Bendamustine in Treatment‑Naïve Mantle Cell Lymphoma Patients

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What is this trial about?

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

The study focuses on mantle cell lymphoma, a rare type of blood cancer that starts in the lymph nodes. Standard treatment usually includes rituximab, a medicine given through a vein (intravenous), and bendamustine, another intravenous chemotherapy drug. In this trial, participants receive either the standard two medicines plus an oral tablet of orelabrutinib, which blocks signals that help cancer cells grow, or the standard two medicines plus a matching tablet that contains no active drug (placebo).

The purpose of the trial is to find out whether adding orelabrutinib to the usual regimen can keep the disease from getting worse for a longer period of time. After a screening visit, participants are randomly assigned to one of the two groups, and neither the participants nor the doctors know which group they are in. Treatment is given in repeated cycles over several months, with regular check‑ups that include blood tests, heart checks, and questionnaires about quality of life. The study follows participants for several years to see how long they stay free of disease progression and to monitor safety.

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

    Randomisation

    After enrollment, the assignment to one of the two treatment groups is made by the study system.

    The patient may receive a placebo tablet that looks identical to the active oral medication; this tablet is only taken at the randomisation visit and not used later.

  2. Step 2

    Start of treatment

    The first treatment cycle begins following randomisation.

    The patient receives instructions on how to take the oral medication and on the schedule for intravenous infusions.

  3. Step 3

    Oral medication (orelabrutinib)

    The patient takes one orelabrutinib tablet containing 150 mg once daily by mouth.

    The tablet is taken at the same time each day for the entire period that the study treatment is administered.

  4. Step 4

    Intravenous infusions (rituximab and bendamustine)

    On scheduled infusion days, the patient receives an intravenous rituximab infusion at a dose of 375 mg per square meter of body‑surface area.

    On the same or subsequent infusion days, the patient receives an intravenous bendamustine infusion at a dose of 90 mg per square meter of body‑surface area.

    Each infusion is given over the time period defined by the study protocol and is repeated in each treatment cycle.

  5. Step 5

    Clinical assessments

    Before and after each infusion, the patient undergoes safety assessments that include blood laboratory tests, an electrocardiogram (ecg), vital‑sign measurements, and a performance‑status evaluation.

    These assessments are performed at each study visit to monitor the patient’s response and any side effects.

  6. Step 6

    Repeat cycles

    The patient continues to receive the oral orelabrutinib tablet daily and the scheduled intravenous infusions of rituximab and bendamustine in subsequent cycles.

    The number of cycles and total duration are determined by the study protocol and continue until the defined end of treatment, disease progression, or unacceptable toxicity.

  7. Step 7

    End of treatment

    After the final treatment cycle, the patient stops taking the oral medication and no further infusions are given.

    A final set of clinical assessments is performed to document the outcome of the study treatment.

Who can join the trial?

6 criteria

  • Be at least 65 years old, or be between 60 and 64 years old and unable to have a stem cell transplant or have chosen not to have one.
  • Have never received any prior systemic therapy (treatment that goes throughout the whole body) for mantle cell lymphoma.
  • Have disease that is classified as Modified Ann Arbor stage II‑IV; if the stage is II, the doctor must decide that you need systemic treatment.
  • Have a confirmed diagnosis of mantle cell lymphoma showing either Cyclin D1 protein or the genetic change called t(11;14) chromosomal translocation, with tissue sent to a central laboratory for verification.
  • Have at least one measurable site of disease: a lymph node that is larger than 1.5 cm in its longest direction, or an organ or tissue outside the lymph nodes that is larger than 1.0 cm.
  • Have an ECOG performance status score of 0, 1, or 2, which means you are fully active (0) or able to take care of yourself and move around most of the day (1‑2).

Who cannot join the trial?

6 criteria

  • Having any other malignant tumor (cancer) that has come back (recurrence) or spread to other parts of the body (metastasis) within the past 2 years.
  • Having heart or blood‑vessel problems that are not under control (uncontrolled or significant cardiovascular diseases).
  • Having bleeding disorders such as hemophilia A, hemophilia B, or von Willebrand disease, or needing blood‑thinning medication like warfarin (a vitamin K antagonist), or having a natural tendency to bleed (spontaneous bleeding tendency).
  • Having had a stroke or bleeding in the brain (intracranial hemorrhage) within the last 6 months.
  • Having serious stomach or intestinal problems that could affect taking or absorbing the medicine (gastrointestinal dysfunction), such as not being able to swallow (inability to swallow), chronic diarrhea, intestinal blockage (intestinal obstruction), or having had the whole stomach removed (total gastrectomy).
  • Having had a major operation (major surgery) within the past 30 days.
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Investigated drugs

  • Rituximab

    is a medicine that attaches to a protein called CD20 found on many B‑cell cancers, including mantle‑cell lymphoma. By binding to this protein, it helps the immune system destroy the cancer cells. In the trial, it is given together with bendamustine as part of the standard treatment that the new drug is being compared against.

  • Orelabrutinib

    is an oral pill that blocks an enzyme named BTK, which cancer cells use to grow and survive. By stopping this enzyme, the drug aims to slow or stop the lymphoma. In the study, patients take orelabrutinib along with rituximab and bendamustine to see if adding it improves how long they stay free of disease.

  • Bendamustine

    is a chemotherapy drug given by IV infusion. It works by damaging the DNA inside cancer cells, which stops them from multiplying. In this trial, it is used together with rituximab in both study groups, serving as the backbone of the standard treatment regimen.

What is already known about the treatment

  • Rituximab

    It is given by intravenous infusion as a clear solution. Rituximab is an approved medicine that has been used for many years in blood cancers. It works by attaching to a protein called CD20 on B‑cells, marking them for destruction by the immune system. It belongs to the class of monoclonal antibodies.

  • Orelabrutinib

    It is taken as an oral tablet. Orelabrutinib is a newer drug that is approved in some countries and is still being studied in clinical trials for mantle‑cell lymphoma. It blocks an enzyme called Bruton's tyrosine kinase, which stops signals that let cancerous B‑cells grow. It is classified as a BTK inhibitor, a type of targeted therapy.

  • Bendamustine

    It is administered by intravenous infusion as a solution for injection. Bendamustine is an established chemotherapy drug that is approved for several types of lymphoma. It works by attaching to DNA in cancer cells, causing breaks that lead to cell death. It is classified as an alkylating agent in the chemotherapy group.

Investigated diseases

Mantle cell lymphoma - Mantle cell lymphoma is a type of blood cancer that begins in a specific group of white blood cells called B‑cells, which are part of the immune system. It usually starts in lymph nodes, but can also appear in the spleen, bone marrow, or gastrointestinal tract. The disease often grows slowly at first, forming enlarged lymph nodes or a feeling of fullness in the abdomen. Over time the cancer cells can spread to other parts of the body, leading to more widespread involvement. Symptoms may increase as the disease progresses, including fatigue, weight loss, or night sweats.
Trial detailsLast updated 7 Oct 2026
Age18+ yearsPhasePhase IIITrial ID2025-524241-27-00Protocol codeICP-CL-00128Estimated enrolment476 patients

sourced from the EU Clinical Trials Register and site verification

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