Efficacy and Safety of Midostaurin in Patients With Aggressive Systemic Mastocytosis or Mast Cell Leukemia
Condition: Leukemia
MeSH terms: Leukemia; Mastocytosis; Mastocytosis, Systemic; Leukemia, Mast-Cell; Aggression
Intervention: Midostaurin (PKC412)
Intervention description: Midostaurin was provided as 25 mg soft gelatin capsules for oral administration.
Intervention MeSH terms: Midostaurin
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 116.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Aggressive systemic mastocytosis; mast cell leukemia; C-Findings; tyrosine kinase inhibitor; KIT mutation; AHNMD; Systemic; Aggressive

Summary:

      The purpose of this study was to determine the efficacy and safety of twice daily (bid) oral
      midostaurin in patients with Aggressive Systemic Mastocytosis (ASM) or Mast Cell Leukemia
      (MCL) with or without an Associated Hematological clonal Non-Mast cell lineage Disease
      (AHNMD).
    

Eligibility criteria:

        Key inclusion criteria:

          -  Patients ≥ 18 years of age who provided written informed consent, Eastern Cooperative
             Oncology Group (ECOG) performance status of 0-3 and a life expectancy of >12 weeks,
             electrocardiogram with a QTcF of ≤ 450 ms, with a diagnosis of SM and sub-variants
             based on WHO criteria.

          -  Patients with ASM or MCL were to have one or more measurable clinical findings (termed
             "C-findings") and defined as those attributable to the mast cell disease component and
             not to AHNMD or any other cause.

          -  Patients with MCL were to have BM aspirate smears with ≥ 20% immature MCs. Patients
             with AHNMD were eligible if it was not life-threatening or in an acute stage.

        Key exclusion criteria:

          -  Patients with cardiovascular disease including congestive heart failure class III or
             IV according to the New York Heart Association classification, left ventricular
             ejection fraction (LVEF) of <50%, myocardial infarction within the previous 6 months,
             or poorly controlled hypertension.

          -  Patients with a heart block of any degree at screening (for Canada only).

          -  Patients with an AHNMD who required immediate cytoreductive therapy or targeted
             therapy (other than midostaurin).

          -  Patients who had demonstrated relapse after 3 or more prior regimens of SM treatment
             regardless of treatment regimen for supportive care (e.g., symptom-limiting
             therapies).

          -  Patients who had received any investigational agent, targeted therapy, chemotherapy,
             interferon-α, or 2 chlorodeoxyadenosine within 30 days prior to start of midostaurin
             treatment.

          -  Patients who had ASM with eosinophilia and known positivity for the FIP1L1- PDGFRα
             fusion unless they had demonstrated relapse or disease progression on prior imatinib
             therapy.

          -  Patients who had received any treatment with midostaurin prior to study entry.

          -  Patients who had received hematopoietic growth factor support within 14 days of Day 1
             of midostaurin treatment.

          -  Patients who had any surgical procedure, excluding central venous catheter placement
             or other minor procedures (e.g. skin biopsy) within 14 days of Day 1 of midostaurin
             treatment.

          -  Patients with any pulmonary infiltrate, including those suspected to be of infectious
             origin. In particular, patients with resolution of clinical symptoms of pulmonary
             infection but with residual pulmonary infiltrates on chest x-ray were not eligible
             until the pulmonary infiltrates had completely resolved. Exception: patients with
             ASM/MCL ± AHNMD-related pleural effusion as judged by the Investigator and approved by
             the SSC Chairperson or designee were permitted to enter the study.