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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00782067
Recruitment Status : Completed
First Posted : October 29, 2008
Results First Posted : June 6, 2017
Last Update Posted : July 17, 2018
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

Brief Summary:
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 or disease Intervention/treatment Phase
Leukemia Drug: Midostaurin (PKC412) Phase 2

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 116 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
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
Actual Study Start Date : October 13, 2008
Actual Primary Completion Date : December 1, 2014
Actual Study Completion Date : August 24, 2017

Arm Intervention/treatment
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.

Primary Outcome Measures :
  1. 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 :
  1. Duration of Response [ Time Frame: 5 years ]
  2. Time to Response [ Time Frame: 5 years ]
  3. Overall Survival (OS) [ Time Frame: 5 years ]

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00782067

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

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 )
First Posted: October 29, 2008    Key Record Dates
Results First Posted: June 6, 2017
Last Update Posted: July 17, 2018
Last Verified: June 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided
Plan Description:

Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.

This trial data availability is according to the criteria and process described on

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

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

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