Midostaurin in Indolent Systemic Mastocytosis
Midostaurin in Indolent Systemic Mastocytosis
Rationale: Patients with indolent or smoldering systemic mastocytosis can have severe
 disabling symptoms. Almost all patients have fatigue, a compromised quality of life,
 hampering normal functioning. Because this form of mastocytosis is not considered
 life-threatening, mast cell eradication has never been applied and patients receive only
 symptomatic therapy with histamine blockers. Midostaurin, a c-KIT inhibitor has shown
 activity regarding symptom control and decrease of malignant mast cells in patients with
 aggressive systemic mastocytosis (ASM) or mast cell leukemia
Objective:

 Primary: To study in a pilot phase II trial the efficacy of midostaurin administered at an
 oral dose of 100 mg twice daily in patients with indolent or smoldering systemic mastocytosis
 on mediator symptom reduction, documented by the Mastocytosis Symptom Assessment
 Questionnaire, measured at 3 months.

 Secondary:

 1. To study whether symptom improvement persists at 6 months, and whether midostaurin can
 reduce mast cell infiltration in the skin and bone marrow, documented by decrease of
 serum tryptase, decrease of urticaria pigmentosa and decrease of bone marrow mast cells.

 2. To assess safety and tolerability of midostaurin in the above mentioned settings

 Study design: Single arm, open label pilot phase II study.

 Study population: Adult patients (n=20) with histologically documented systemic mastocytosis,
 indolent or smoldering subtype, with severe symptoms, not controlled by histamine 1 and 2
 blockers.

 Intervention: treatment with Midostaurin, twice daily 100 mg orally for 6 months
 continuously.
Inclusion Criteria:

 -  Patients with Indolent Systemic Mastocytosis (ISM) or Smouldering Systemic
 Mastocytosis (SSM) according to the WHO criteria

 -  Presence of the D816V c-KIT mutation

 -  Serum tryptase > 20 mg/l

 -  Serious mediator-related symptoms that cannot be controlled by H1 and H2 blocking
 drugs. Symptoms will be scored by an adapted MSAF (mastocytosis symptom assessment
 form) with at least:

 -  a pre-study score of 4 or more on 3 non-related items,

 -  or a pre-study score of 5 or more on 2 non-related items.

 -  one item from the scoring list can be replaced by flushes 7 or more per week or
 anaphylactic attacks 1 or more per week.

 -  Age >18 years

 -  Willingness to apply optimal contraceptive measures (double barrier method, both men
 and women) for women below the age of 55, men at all ages; for both: if sexually
 active.

 -  Written informed consent

 Exclusion Criteria:

 -  Aggressive systemic mastocytosis, mast cell leukemia, or ASM with or without
 accompanying non-clonal related non-mast cell disorder (SM-ANHMD).

 -  Any known other present malignancy, non-melanoma skin cancers excluded

 -  History of malignancy within the last 5 years, non-melanoma skin cancers excluded

 -  Any serious comorbidity interfering with therapy compliance and follow-up compliance

 -  Pregnancy

 -  Patients not willing or who are not able to comply with contraceptive measures