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Not yet recruitingRare disease

Phase 2 Trial of Vemurafenib, Venetoclax and Rituximab in Relapsed or Refractory Hairy Cell 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 focuses on patients with Hairy Cell Leukemia, a rare blood cancer that makes too many abnormal white blood cells. The treatment plan combines two oral medicines, vemurafenib and venetoclax, which target the cancer's growth signals. After this short course, patients receive an infusion of the antibody rituximab, which works by recognizing a protein called anti‑CD20 on the cancer cells and helping the immune system destroy them.

The aim of the study is to determine whether the combination of the two oral drugs can achieve a higher complete remission rate than what has been seen with each drug alone. Participants take the oral drugs for four treatment cycles, then have a blood and bone‑marrow test to check for MRD, the tiny amount of disease that can remain after therapy. If the test shows remaining disease, the antibody infusion is given to try to clear it.

During the trial, patients are monitored for side effects, overall health, and quality of life using simple questionnaires. The study also looks at how long patients stay free of measurable disease and how long they live without the cancer coming back. The trial includes patients who have already been treated with drugs that target the BRAF or BCL-2 pathways, or who could not receive standard purine analogue treatments such as cladribine or pentostatin.

The research process

The trial runs in 5 steps – from screening to follow-up. Each step says what happens and what the team monitors.

  1. Step 1

    Start Oral Targeted Therapy

    You begin taking two oral medicines at the same time. Vemurafenib is taken as film‑coated tablets that together provide a total of 1920 mg each day, usually split into two equal doses. Venetoclax is taken as film‑coated tablets that together provide 400 mg each day, taken as a single dose. Both medicines are taken by mouth every day.

    The purpose of this combined oral therapy is to treat the hair‑cell leukemia by blocking specific pathways that the cancer cells use to grow.

  2. Step 2

    Complete Four Cycles of Oral Therapy

    You continue the daily oral doses for four treatment cycles. One cycle is typically about four weeks, so the entire oral phase lasts roughly sixteen weeks (about four months).

    During each cycle you may have scheduled visits for blood tests and other routine checks, but the medication schedule itself remains the same: daily oral tablets of vemurafenib (1920 mg) and venetoclax (400 mg).

  3. Step 3

    Assess Minimal Residual Disease (MRD)

    After the four cycles of oral therapy, your doctor will evaluate the presence of any remaining cancer cells. This evaluation is called a MRD (minimal residual disease) test and may use blood samples, bone‑marrow samples, or a liquid‑biopsy of plasma.

    The MRD test determines whether the disease has been cleared at a microscopic level before any further treatment is considered.

  4. Step 4

    Receive Anti‑CD20 Immunotherapy if MRD Is Positive

    If the MRD test shows that cancer cells are still detectable, you will start an anti‑CD20 immunotherapy with rituximab. This medicine is given by IV infusion (injection into a vein).

    The dose of rituximab is 375 mg per square meter of body‑surface area per infusion. The exact number of infusions is guided by the MRD results, but they are typically administered at regular intervals (for example, once every two weeks) until the MRD test becomes negative.

  5. Step 5

    Final Evaluations and Follow‑Up

    After completing the rituximab infusions, you will have a final set of assessments, which include repeat MRD testing, blood work, and questionnaires about quality of life.

    These final evaluations help determine the overall success of the treatment and provide information for any future care decisions.

Who can join the trial?

12 criteria

  • Be 18 years old or older, male or female.
  • Use a highly effective birth‑control method during the study and for the required time after treatment (examples: intra‑uterine device, hormonal implant, tubal ligation for women; vasectomy or condom for men). Oral contraceptive pills are not considered reliable for this trial.
  • Have no medical, psychological, family, social or travel problems that would stop you from following the study schedule or affect the results.
  • Sign the informed consent form before any study procedures are done.
  • Have a confirmed diagnosis of hairy‑cell leukemia (HCL) and show the BRAF‑V600E mutation in the cancer cells, proven by a laboratory test such as a special DNA test or a staining test.
  • Fit into at least one of the following disease‑history groups: (1) did not respond to the first treatment with a purine analogue (cladribine or pentostatin), with or without an anti‑CD20 drug (rituximab or obinutuzumab); (2) the disease came back within 2 years after the first purine‑analogue treatment, or within 5 years after the first combined chemotherapy‑immunotherapy; (3) the disease came back after, or did not respond to, a second or later line of therapy; (4) was previously treated with venetoclax or a BRAF inhibitor (such as vemurafenib or dabrafenib), achieved at least a partial response, and the last dose was given more than 6 months ago; (5) had severe side effects from purine‑analogue drugs (for example, very low blood counts, infections, kidney problems, blood‑vessel inflammation, or autoimmune anemia), or the doctor considers you medically unfit for such chemotherapy, or you refuse chemotherapy, or you have an active infection that makes chemotherapy unsafe, even if you have never received treatment before.
  • Need treatment now because of at least one of the following: very low neutrophil count (< 1,000 per mm³), low hemoglobin (< 10 g/dL), low platelet count (< 100,000 per mm³), an enlarged or painful spleen, cancer spreading to other organs (such as swollen lymph nodes), or disease‑related infections or autoimmune problems.
  • Have an ECOG Performance Status of 0‑2, meaning you are fully active (0) or able to care for yourself with some limitation in physical activity (1‑2).
  • Do not have ongoing severe nausea, vomiting, problems absorbing food or medicine, a biliary (bile duct) shunt, major bowel surgery, or a neurological disorder that would stop the medicine from being absorbed properly.
  • Be able to swallow tablets.
  • Have a heart test (ECG) showing a QTc interval of 500 milliseconds or less.
  • For women who could become pregnant, have a negative pregnancy test within 14 days before starting the study. Women who are not able to become pregnant (because they have had surgery that makes them sterile or are post‑menopausal) may also join.

Who cannot join the trial?

3 criteria

  • Taking any other cancer‑treating medicines at the same time (for example chemotherapy, other targeted drugs, or experimental medicines) – you cannot be in the study while using these other treatments.
  • Being pregnant (having a baby growing inside you) or breastfeeding (feeding a baby with breast milk) – pregnancy or lactation prevents participation.
  • Having another serious, active cancer that is expected to shorten your life to less than one year – a different advanced cancer with a short expected survival time excludes you from the trial.
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Investigated drugs

  • Rituximab

    is a medication that targets a protein called CD20, which is found on the surface of many cancerous B‑cells. By attaching to CD20, rituximab helps the immune system recognize and destroy these cells. In this trial, rituximab is given after the oral treatment to clean up any remaining cancer cells that are detected by sensitive tests (MRD‑guided therapy). It is administered through an IV infusion.

  • Venetoclax

    is a drug that blocks a protein called BCL‑2, which cancer cells use to avoid dying. By inhibiting BCL‑2, venetoclax encourages the cancer cells to undergo programmed cell death. In the study, patients take venetoclax by mouth as part of a short, all‑oral combination regimen aimed at shrinking the leukemia.

  • Vemurafenib

    is a medication that blocks a mutated form of the BRAF protein, which can drive cancer growth. By stopping this abnormal signal, vemurafenib helps slow or stop the growth of cancer cells. In the trial, vemurafenib is taken as a pill together with venetoclax, forming a targeted oral therapy designed to achieve a strong response before the follow‑up rituximab treatment.

What is already known about the treatment

  • Rituximab

    Given by intravenous infusion, this drug is an approved monoclonal antibody that targets the CD20 protein on B‑cells. It is widely used for B‑cell cancers such as certain leukemias and lymphomas, as well as some autoimmune disorders. Rituximab works by binding CD20 and triggering the immune system to destroy those B‑cells. It belongs to the class of immunomodulating monoclonal antibodies.

  • Venetoclax

    Taken as an oral film‑coated tablet, venetoclax is an approved medication for chronic lymphocytic leukemia and acute myeloid leukemia. It is a small‑molecule drug that blocks the BCL‑2 protein, allowing cancer cells to undergo programmed cell death. The drug is well described in medical literature and is considered a standard targeted therapy. Its pharmacological class is a BCL‑2 inhibitor.

  • Vemurafenib

    Administered orally as a film‑coated tablet, vemurafenib is an approved treatment for cancers that carry a BRAF V600 mutation, such as melanoma. It works by selectively inhibiting the mutant BRAF kinase, which stops the growth signal that drives tumor cells. The drug is widely studied and used in clinical practice for BRAF‑mutated cancers. It is classified as a BRAF kinase inhibitor.

Investigated diseases

Hairy cell leukemia - Hairy cell leukemia is a rare blood cancer where abnormal B‑cells build up in the bone marrow and spleen. These cells crowd out normal blood cells, causing low blood counts, an enlarged spleen, fatigue and a higher risk of infections. Over time the disease can spread to other parts of the body such as the liver and lymph nodes. It often follows a slow course but can become resistant to standard therapies after repeated treatment. Many cases are linked to a specific genetic change called the BRAF V600E mutation.
Trial detailsLast updated 5 Nov 2026
Age18+ yearsPhasePhase IITrial ID2026-527434-31-00Estimated enrolment26 patientsSponsorAzienda Ospedaliera Di Perugia

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