Clinical trial NCT00782067: Efficacy and Safety of Midostaurin in Patients With Aggressive Systemic Mastocytosis or Mast Cell Leukemia
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Leukemia
Keywords: Aggressive systemic mastocytosis
mast cell leukemia
C-Findings
tyrosine kinase inhibitor
KIT mutation
AHNMD
Systemic
Aggressive
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2008-10-29
Enrollment: 116
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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).


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.

Primary outcomes:
measure: Percentage of Participants With Overall Response Rate (ORR)
timeFrame: 6 months
Secondary outcomes:
measure: Median Time to Duration of Response (DoR)
timeFrame: Up 5 years
measure: Median Time to Response (TTR)
timeFrame: Up 5 years
measure: Median Time to Progression-Free Survival (PFS)
timeFrame: Up 5 years
measure: Median Time to Overall Survival (OS)
timeFrame: Up 5 years
measure: Long-term Safety and Tolerability of Midostaurin
timeFrame: Up to 30 days after last dose of study treatment
measure: Histopathologic Response
timeFrame: Up 5 years
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: University of California at Los Angeles Dept. of Hematology Clinic
state: California
city: Stanford
country: United States
facility: Stanford University Medical Center Stanford University 2
state: California
city: Augusta
country: United States
facility: Georgia Health Sciences University Dept.ofMedicalCollegeOfGeorgia
state: Georgia
city: Boston
country: United States
facility: Dana Farber Cancer Institute Hematology / Oncology
state: Massachusetts
city: Ann Arbor
country: United States
facility: University of Michigan Comprehensive Cancer Center DeptofMichiganCancerCenter(3)
state: Michigan
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center Dept. of MSKCC (2)
state: New York
city: Portland
country: United States
facility: Oregon Health and Science University Dept. Hematologic Malignancies
state: Oregon
city: Philadelphia
country: United States
facility: University of Pennsylvania
state: Pennsylvania
city: Richmond
country: United States
facility: Virginia Commonwealth University SC
state: Virginia
city: Camperdown
country: Australia
facility: Novartis Investigative Site
state: New South Wales
city: Prahran
country: Australia
facility: Novartis Investigative Site
state: Victoria
city: Wien
country: Austria
facility: Novartis Investigative Site
city: Leuven
country: Belgium
facility: Novartis Investigative Site
city: London
country: Canada
facility: Novartis Investigative Site
state: Ontario
city: Toronto
country: Canada
facility: Novartis Investigative Site
state: Ontario
city: Amiens
country: France
facility: Novartis Investigative Site
city: Paris cedex 15
country: France
facility: Novartis Investigative Site
city: Mannheim
country: Germany
facility: Novartis Investigative Site
state: Baden-Württemberg
city: Koeln
country: Germany
facility: Novartis Investigative Site
state: Nordrhein-Westfalen
city: Berlin
country: Germany
facility: Novartis Investigative Site
city: Hamburg
country: Germany
facility: Novartis Investigative Site
city: Leipzig
country: Germany
facility: Novartis Investigative Site
city: Groningen
country: Netherlands
facility: Novartis Investigative Site
city: Oslo
country: Norway
facility: Novartis Investigative Site
city: Gdansk
country: Poland
facility: Novartis Investigative Site
city: Istanbul
country: Turkey
facility: Novartis Investigative Site
city: Glasgow - Scotland
country: United Kingdom
facility: Novartis Investigative Site
city: Liverpool
country: United Kingdom
facility: Novartis Investigative Site
city: London
country: United Kingdom
facility: Novartis Investigative Site
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References:
citation: Hartmann K, Gotlib J, Akin C, Hermine O, Awan FT, Hexner E, Mauro MJ, Menssen HD, Redhu S, Knoll S, Sotlar K, George TI, Horny HP, Valent P, Reiter A, Kluin-Nelemans HC. Midostaurin improves quality of life and mediator-related symptoms in advanced systemic mastocytosis. J Allergy Clin Immunol. 2020 Aug;146(2):356-366.e4. doi: 10.1016/j.jaci.2020.03.044. Epub 2020 May 11.
citation: Gotlib J, Kluin-Nelemans HC, George TI, Akin C, Sotlar K, Hermine O, Awan FT, Hexner E, Mauro MJ, Sternberg DW, Villeneuve M, Huntsman Labed A, Stanek EJ, Hartmann K, Horny HP, Valent P, Reiter A. Efficacy and Safety of Midostaurin in Advanced Systemic Mastocytosis. N Engl J Med. 2016 Jun 30;374(26):2530-41. doi: 10.1056/NEJMoa1513098.