Exploring new frontiers in systemic mastocytosis

Introducing PIONEER – a clinical trial of investigational avapritinib for people with indolent systemic mastocytosis.

About the Pioneer Study

PIONEER is a phase 2 clinical trial that will compare the safety and effectiveness of an investigational medicine called avapritinib against a placebo in people with indolent systemic mastocytosis (SM) whose symptoms aren’t adequately controlled with standard therapies.

There are two subtypes of non-advanced SM – indolent SM and smoldering SM. Up to ~95% of people (Garcia-Montero AC et al. Blood. 2006;108(7):2366-2372.) have a specific mutation (genetic alteration) in a gene called KIT. The mutation, known as KIT D816V, plays a central role in the activation and accumulation of mast cells in people with systemic mastocytosis.

About indolent systemic mastocytosis

Indolent systemic mastocytosis is a rare condition caused by the accumulation of mast cells in the body’s organs, including the bone marrow and skin. Mast cells are an important type of immune cell that normally play a role in the body to help fight infection and trigger the allergic response. In systemic mastocytosis, mast cells are over-produced, leading to many unpredictable symptoms that can range in severity.

What are the symptoms of SM?

Accumulation of mast cells in systemic mastocytosis can occur in the skin, bone marrow (BM), spleen, liver, gastrointestinal (GI) tract and other organs. Some people with SM experience sudden, severe symptoms that come and go (called episodes) or are unpredictable. After these episodes, people with SM might feel sluggish because of the inappropriate amounts of mast cells that were activated.

Some common episodic and unpredictable symptoms:

  • Flushing (dry heat that is not the same as sweating)
  • Rapid heart beat
  • Lightheadedness
  • Severe allergic reactions (anaphylaxis)

Other symptoms may include:

  • Itchy skin or rashes
  • Nausea, vomiting, diarrhea
  • Brain fog (head feels fuzzy or cloudy)
  • Tiredness
  • Bone pain

If you think you or a loved one have indolent systemic mastocytosis, talk to your doctor about your symptoms. If you are interested in learning more about the Pioneer study, please contact Blueprint Medicines’ Medical Information Center for nearby study site information.

Who is eligible to participate in the PIONEER clinical trial?


Are confirmed to have indolent systemic mastocytosis

Have moderate-to-severe symptoms (assessed via a questionnaire)
Are at least 18 years old

Haven’t been able to control these symptoms using existing therapies (including H1 and H2 blockers, leukotriene inhibitors, and corticosteroids, among others)

Other eligibility criteria apply and these will be assessed and discussed at your screening.

About the investigational medicine

If you take part in the PIONEER clinical trial, you may receive investigational avapritinib. Investigational avapritinib comes in an oral tablet form that should be taken once daily. More information on how to take the study drug will be provided by the study site.

Avapritinib is currently being studied in systemic mastocytosis and is not approved by the U.S. Food & Drug Administration (FDA) or any other healthcare authority as safe or effective for use in this indication.

What does taking part in the PIONEER clinical trial involve?

The PIONEER clinical trial for indolent systemic mastocytosis takes place in three parts. Participation in Part 1 is not required for Participation in Part 2.

Part 1 (Complete) This phase was designed to determine what dose of investigational drug may be most effective while reducing potential side effects. Three dose levels of investigational avapritinib along with best supportive care* (BSC) were tested and compared to placebo (a “sugar pill” containing no active medication) and BSC. From Part 1, a Part 2 study dose of 25mg daily of investigational avapritinib was determined.

Part 2 (Currently enrolling) This phase will compare the dose identified from Part 1 and BSC against a placebo (a “sugar pill” containing no active medication) and BSC. Part 2 lasts about 24 weeks for all patients.

Part 3 After completing Part 1 or Part 2, study participants (including those on placebo and BSC) may begin Part 3, which looks into the long-term safety and effectiveness of the investigational drug avapritinib combined with best supportive care for up to 5 years. During this phase, all participants will receive the active study treatment.

*Best supportive care means other treatments to help manage symptoms and make patients more comfortable.

Screening Period

The first step in the screening process is to ensure best supportive care treatments are stable. Patients will be asked to complete a questionnaire to describe their symptoms to verify if they meet the severity criteria. If determined eligible based on symptoms, additional testing will be done to confirm other eligibility criteria for this study. The screening period varies and could take up to 14 weeks in some cases (from start of screening to your first dose of avapritinib).

Dosing period

Total duration on study treatment can be up to 5 years (through Part 3) and dosing will be daily in 28-day cycles.

Study participants will take the study treatment as a tablet. It should be swallowed whole with water once a day.

Follow Up
Follow up period

All participants must have a follow-up visit 14 days after their last dose of study treatment. One follow-up phone call will be required thereafter.

Participants will continue with the study treatment until:

*Their disease worsens * They can’t tolerate any side effects they may have *They decide to leave the trial * The trial doctor decides they should leave the trial * The trial sponsor decides to discontinue the trial.

PIONEER Trial Clinic Visits

During the trial, a variety of health assessments will be conducted to check on your systemic mastocytosis and see how you are responding to the study treatment. In most cases, these assessments will be done at a clinical site.

Health assessments will vary between visits, but may include:

MRI or CT scan and X-ray
Bone marrow biopsy
ECG and Vital signs (temperature, blood pressure, heart rate, respiration rate)
Skin Biopsy
Skin biopsy (if applicable)
Quality of life Questionnaires
Blood Test
Blood tests
Pregnancy Test
Pregnancy test (If applicable)

More information about health assessments and visit length will be found in the informed consent form, which you will need to read and sign if you decide to participate in the PIONEER clinical trial.

How often will these visits take place?*

Part 1 (Complete)

About once a week for one month, then about once a month for six to twelve months

Part 2

Once a month for six months

Part 3

Once a month for 6 months, then every 2 months for the next 6 months, then every 3 months for a total treatment duration of up to 5 years ( including treatment duration of Part 1 or Part 2)

*Please note that these numbers are approximate.


    No Results Found

Is there a PIONEER trial site in the United States near me?

If you are located in Europe, please visit the