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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 : November 15, 2018
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

Brief 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).

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

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 116 participants
Allocation: N/A
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

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Leukemia
Drug Information available for: Midostaurin

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. Percentage of Participants With Overall Response Rate (ORR) [ Time Frame: 6 months ]

    Overall Response Rate (ORR) was defined as the percentage of participants who classified as confirmed responders (Major Response (MR) or Partial Response (PR)) by the adjudication of the SSC and based on a Modified Valent Criteria.

    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. Median Time to Duration of Response (DoR) [ Time Frame: Up 5 years ]
    The Duration of response (DoR) was defined as the time from first onset of confirmed response (MR or PR) to the date of first documented and confirmed progression or death due to ASM/MCL.

  2. Median Time to Response (TTR) [ Time Frame: Up 5 years ]
    The Time to response (TTR) was defined as the time from start of treatment until the date of onset of confirmed response (MR or PR).

  3. Median Time to Progression-Free Survival (PFS) [ Time Frame: Up 5 years ]
    The Progression-free survival (PFS) is defined as the time from start of treatment to the date of the first documented and confirmed progression or death due to any cause.

  4. Median Time to Overall Survival (OS) [ Time Frame: Up 5 years ]
    The Overall Survival (OS) is defined as the time from start of treatment to the date of death due to any cause.

  5. Long-term Safety and Tolerability of Midostaurin [ Time Frame: Up to 30 days after last dose of study treatment ]
    Analysis of frequencies for treatment emergent Adverse Event (AE), Serious Adverse Event (SAE) and Deaths by primary System Organ Class (SOC)

  6. Histopathologic Response [ Time Frame: Up 5 years ]
    Histopathologic response was summarized to demonstrate the change from baseline in percentage of mast cell infiltrations in the Bone Marrow (BM) and related serum tryptase levels.

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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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:

  • 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.

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

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United States, California
University of California at Los Angeles Dept. of Hematology Clinic
Los Angeles, California, United States, 90095
Stanford University Medical Center Stanford University 2
Stanford, California, United States, 94305-5750
United States, Georgia
Georgia Health Sciences University Dept.ofMedicalCollegeOfGeorgia
Augusta, Georgia, United States, 30912
United States, Massachusetts
Dana Farber Cancer Institute Hematology / Oncology
Boston, Massachusetts, United States, 02215
United States, Michigan
University of Michigan Comprehensive Cancer Center DeptofMichiganCancerCenter(3)
Ann Arbor, Michigan, United States, +1 48109 0944
United States, New York
Memorial Sloan Kettering Cancer Center Dept. of MSKCC (2)
New York, New York, United States, 10021
United States, Oregon
Oregon Health and Science University Dept. Hematologic Malignancies
Portland, Oregon, United States, 97239
United States, Pennsylvania
University of Pennsylvania
Philadelphia, Pennsylvania, United States, 19104
United States, Virginia
Virginia Commonwealth University SC
Richmond, Virginia, United States, 23284
Australia, New South Wales
Novartis Investigative Site
Camperdown, New South Wales, Australia, 2050
Australia, Victoria
Novartis Investigative Site
Prahran, Victoria, Australia, 3181
Novartis Investigative Site
Wien, Austria, 1090
Novartis Investigative Site
Leuven, Belgium, 3000
Canada, Ontario
Novartis Investigative Site
London, Ontario, Canada, N6A 4G4
Novartis Investigative Site
Toronto, Ontario, Canada, M5G 2M9
Novartis Investigative Site
Amiens, France, 80054
Novartis Investigative Site
Paris cedex 15, France, 75015
Novartis Investigative Site
Mannheim, Baden-Württemberg, Germany, 68305
Novartis Investigative Site
Koeln, Nordrhein-Westfalen, Germany, 50937
Novartis Investigative Site
Berlin, Germany, 13353
Novartis Investigative Site
Hamburg, Germany, 20246
Novartis Investigative Site
Leipzig, Germany, 04103
Novartis Investigative Site
Groningen, Netherlands, 9713 GZ
Novartis Investigative Site
Oslo, Norway, NO-0310
Novartis Investigative Site
Gdansk, Poland, 80-952
Novartis Investigative Site
Istanbul, Turkey, 34093
United Kingdom
Novartis Investigative Site
Glasgow - Scotland, United Kingdom, G12 OYN
Novartis Investigative Site
Liverpool, United Kingdom, L7 8XP
Novartis Investigative Site
London, United Kingdom, SE1 7EH
Sponsors and Collaborators
Novartis Pharmaceuticals
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Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
Additional Information:
Publications automatically indexed to this study by Identifier (NCT Number):
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Responsible Party: Novartis Pharmaceuticals Identifier: NCT00782067    
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: November 15, 2018
Last Verified: October 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

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