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Efficacy and Safety of Midostaurin in Patients With Aggressive Systemic Mastocytosis or Mast Cell Leukemia

This study is ongoing, but not recruiting participants.
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals ) Identifier:
First received: October 28, 2008
Last updated: March 8, 2017
Last verified: March 2017
This study will investigate if the drug midostaurin taken orally twice daily is effective and safe in treating patients with aggressive systemic mastocytosis or mast cell leukemia with or without an additional hematological neoplasm.

Condition Intervention Phase
Drug: Midostaurin (PKC412)
Phase 2

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: No masking
Primary Purpose: Treatment
Official Title: A Single Arm, Phase II, Open-Label Study to Determine the Efficacy of 100mg Twice Daily Oral Dosing of Midostaurin Administered to Patients With Aggressive Systemic Mastocytosis or Mast Cell Leukemia +/- an Associated Hematological Clonal Non-Mast Cell Lineage Disease

Resource links provided by NLM:

Further study details as provided by Novartis:

Primary Outcome Measures:
  • Overall response rate (ORR) [ Time Frame: 6 months ]
    The ORR was defined as the percentage of participants who classified as confirmed responders (major response (MR) or partial response (PR). A major responder had complete resolution of at least one C-Finding and no progression in other C-Findings. A partial responder showed a measurable improvement in one or more C-Finding(s) without confirmed progression in other C-Findings. A C-Finding was a Clinical Finding, which was considered by the investigator and corroborated by the Study Steering Committee (SSC) Chairperson or designee, attributable to the mast cell disease component and not the associated hematological clonal non-mast cell lineage disease (AHNMD) component or any other cause.

Secondary Outcome Measures:
  • Duration of response [ Time Frame: 5 years ]
  • Time to response [ Time Frame: 5 years ]
  • Overall survival (OS) [ Time Frame: 5 years ]

Enrollment: 116
Actual Study Start Date: October 13, 2008
Estimated Study Completion Date: July 10, 2017
Estimated Primary Completion Date: July 10, 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Midostaurin (PKC412)
Midostaurin was administered at a dose of 100 mg twice daily (bid) in continuous cycles of 28 days until disease progression, intolerable toxicity or withdrawal due to any cause, whichever occurred first.
Drug: Midostaurin (PKC412)
Midostaurin was provided as 25 mg soft gelatin capsules for oral administration.


Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Key Inclusion Criteria:

  • Confirmed diagnosis of aggressive systemic mastocytosis (ASM) or mast cell leukemia (MCL) according to WHO criteria for SM and established criteria for ASM and MCL (Valent et al 2003), presenting with at least one measurable C-Finding.
  • ECOG performance status of 0-3
  • Life expectancy > 12 weeks
  • ECG: QTc interval ≤ 450 ms
  • Meeting the following laboratory values:
  • AST and ALT must be ≤ 5 x Upper Limit of Normal (ULN) if this elevation is solely due to ASM/MCL, otherwise AST, ALT must be ≤ 2.5 x ULN
  • Serum Bilirubin must be ≤ 3 x Upper Limit of Normal (ULN) if this elevation is solely due to ASM/MCL, otherwise serum bilirubin must be

    • 1.5 x ULN
  • Serum Creatinine ≤ 2.0 mg/dL

Key Exclusion Criteria:

  • Any other concurrent severe known disease (except carcinoma in-situ) concurrent severe and/or uncontrolled medical condition including congestive heart failure grade III or IV according to the NYHA classification or with ejection fraction < 50%, etc.
  • Patients with any pulmonary infiltrate including those suspected to be of infectious origin. Exception: Patients with a pleural effusion related to the disease under study as confirmed by the investigator are permitted to enter the study
  • Patients who have demonstrated relapse to 3 or more prior regimens of SM treatment (not including those given for supportive care)
  • Patients who have received any investigational agent, chemotherapy, interferon-α, or 2-chlorodeoxyadenosine (2-CdA, cladribine) within 30 days prior to first dose
  • Patients who have ASM with eosinophilia and known positivity for the FIP1L1-PDGFRα fusion unless they have demonstrated relapse or disease progression on prior imatinib therapy
  Contacts and Locations
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Please refer to this study by its identifier: NCT00782067

  Show 31 Study Locations
Sponsors and Collaborators
Novartis Pharmaceuticals
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
  More Information

Additional Information:
Publications automatically indexed to this study by Identifier (NCT Number):
Responsible Party: Novartis Pharmaceuticals Identifier: NCT00782067     History of Changes
Other Study ID Numbers: CPKC412D2201
2008-000280-42 ( EudraCT Number )
Study First Received: October 28, 2008
Last Updated: March 8, 2017

Keywords provided by Novartis:
Aggressive systemic mastocytosis
mast cell leukemia
tyrosine kinase inhibitor
KIT mutation

Additional relevant MeSH terms:
Leukemia, Mast-Cell
Mastocytosis, Systemic
Neoplasms by Histologic Type
Behavioral Symptoms
Leukemia, Myeloid, Acute
Leukemia, Myeloid
Neoplasms, Connective Tissue
Neoplasms, Connective and Soft Tissue
Skin Diseases
Antineoplastic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action processed this record on April 24, 2017