Safety and Efficacy of Subcutaneous Sarilumab in Improving the Quality of Life in People With Indolent Systemic Mastocytosis
Condition: Indolent Systemic Mastocytosis
MeSH terms: Mastocytosis; Mastocytosis, Systemic
Study type: Interventional
Phase: Phase 2

Summary: 
      Background:

      Mast cells help the body fight disease and heal wounds. People with indolent systemic
      mastocytosis (ISM) make too many mast cells. This causes pain, tiredness, digestive problems,
      and other symptoms. Researchers think the drug sarilumab could help.

      Objective:

      To see if sarilumab is a safe and effective treatment for people with ISM.

      Eligibility:

      Adults ages 18-75 with ISM who are enrolled in NIH study 02-I-0277

      Design:

      Participants will be screened with:

        -  Physical exam

        -  Medical history

        -  Blood and urine tests

        -  Questionnaires

        -  Bone marrow removed by a needle inserted into the hip bone

        -  Ultrasound of the abdomen

        -  Photographs of the skin

      Participants will repeat some screening tests at study visits.

      Participants will have a baseline visit in the hospital for 3 days. They will:

        -  Be assigned to get either the study drug or a placebo. They will not know which one they
           get.

        -  Have a skin punch biopsy: An instrument will remove a small piece of skin.

        -  Get their first drug dose injected under their skin

      Participants will keep a side effect and medication diary during the study.

      Participants will visit the clinic to get a drug dose every 2 weeks, for a total of 8 doses.

      Participants will have a visit 2 weeks after their final dose. It will last up to 2 days.

      Participants will have another visit 12 weeks later.

      Participants may then continue this study for 1 more year. Those who continue will get
      sarilumab, even if they previously got the placebo, every 2 weeks. They will have visits
      every 6 weeks, and then every 3 months.
    

Detailed description: 
      Systemic mastocytosis is a disorder caused by clonal mast cell proliferation and release of
      mast cell mediators including tryptase. As a result, mast cell numbers may increase and
      affect target organs including the dermis (maculopapular cutaneous mastocytosis/urticaria
      pigmentosa, flushing), gastrointestinal tract (abdominal pain, diarrhea), skeletal system
      (osteoporosis), hematological system (anemia, thrombocytopenia), and spleen and liver
      (organomegaly). Patients with indolent (non-aggressive) systemic mastocytosis (ISM) are not
      candidates for cytoreductive therapy and are generally treated with symptomatic therapy that
      only partly decreases symptoms. There is, however, a documented association between severity
      of mastocytosis and elevated serum levels of interleukin (IL)-6. Furthermore, mast cells have
      been shown to double their rate of division and exhibit increased reactivity and release of
      mediators when cultured in the presence of IL-6. In addition, in an animal model of
      mastocytosis, anti-IL-6 has been shown to slow disease progression. In this study, adults
      with ISM will thus be randomized and treated with sarilumab, a recombinant monoclonal
      antibody directed against the IL-6 receptor, or receive placebo. Sarilumab is marketed in the
      United States as Kevzara (Sanofi/Genzyme [Cambridge, MA, USA ]) and is approved by the Food
      and Drug Administration for the treatment of rheumatoid arthritis. Binding of sarilumab to
      the IL-6 receptor inhibits IL-6-associated human mast cell signaling and proliferation with a
      resultant decrease in proliferation and reactivity (decreased mediator release), and
      therefore is a rational choice for the treatment of ISM.

      In this study, participants will be randomized with approximately half of the participants
      receiving study drug, which will be administered at 200 mg via subcutaneous (SC) injection
      once every 2 weeks (Q2W) for a total of 16 weeks. The other participants will receive a
      placebo administered via SC injection Q2W for 16 weeks. Participants will return for a
      follow-up visit 2 weeks after the final dose (treatment peak), and then again 12 weeks later.
      Evaluations at study visits will include quality of life and symptom assessments and
      measurement of serum tryptase levels. Bone marrow examination will be performed at the onset
      and conclusion of the study. After the week 28 visit, all participants will have the option
      to continue sarilumab for 52 more weeks, at 200 mg administered via SC injections.
      Participants will continue to be monitored on a regular basis for safety concerns, as
      instructed in the study drug s package insert.
    

Intervention name(s): sarilumab; Placebo
Intervention type(s): Biological; Other
Intervention description(s): sarilumab is a fully human anti-IL-6R(number sign) monoclonal antibody that binds membrane-bound and soluble human IL-6R and has been shown to inhibit IL-6 signaling; Placebo
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: Cytokine; Monoclonal Therapy; Interleukin-6; Mast Cell; Bone Marrow