Efficacy and Safety of Midostaurin in Patients With Aggressive Systemic Mastocytosis or Mast Cell Leukemia - Full Text View

Sponsor:	Novartis Pharmaceuticals
Information provided by (Responsible Party):	Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:	NCT00782067

Purpose

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
Leukemia	Drug: Midostaurin	Phase II

Study Type:	Interventional
Study Design:	Endpoint Classification: Safety/Efficacy Study Intervention Model: Single Group Assignment Masking: 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

Resource links provided by NLM:

Genetics Home Reference related topics: Help Me Understand Genetics

MedlinePlus related topics: Cancer Leukemia

Drug Information available for: Cgp 41251

U.S. FDA Resources

Further study details as provided by Novartis:

Primary Outcome Measures:

Overall response rate according to established criteria by assessing clinical findings at the end of 6 cycles [ Time Frame: at the end of 6 cycles ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Duration of response [ Time Frame: throughout the study ] [ Designated as safety issue: No ]
Time to response [ Time Frame: throughout the study ] [ Designated as safety issue: No ]
Adverse event rate [ Time Frame: throughout the study ] [ Designated as safety issue: Yes ]
Overall survival (OS) [ Time Frame: throughout the study ] [ Designated as safety issue: No ]
KIT mutational status at diagnosis and after 6 cycles of therapy [ Time Frame: at diagnosis and after 6 cycles of therapy ] [ Designated as safety issue: No ]

Estimated Enrollment:	80
Study Start Date:	October 2008
Estimated Primary Completion Date:	March 2013 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Midostaurin	Drug: Midostaurin

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

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
Patients who would be suitable for imatinib therapy (e.g. having ASM with eosinophilia and known positivity for the FIP1L1-PDGFRα fusion or known to be KIT D816V negative) unless they have demonstrated relapse or disease progression on prior imatinib therapy

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 failed more than two prior SM therapies (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 would be suitable for imatinib therapy (e.g. having ASM with eosinophilia and known positivity for the FIP1L1-PDGFRα fusion) unless they have demonstrated relapse or disease progression on prior imatinib therapy

Other protocol-defined inclusion/exclusion criteria may apply

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00782067

Contacts

Contact: Novartis Pharmaceuticals	+1-862-778-8300
Contact: Novartis Pharmaceuticals	+41 61 324 1111

Show 34 Study Locations

Sponsors and Collaborators

Novartis Pharmaceuticals

Investigators

Study Director:

Novartis Pharmaceuticals

More Information

Additional Information:

Visit NovartisClinicalTrials.com: Pre-qualify for a trial, and view a list of trials and participating study centers. This link exits the ClinicalTrials.gov site

Related Info This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party:	Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:	NCT00782067 History of Changes
Other Study ID Numbers:	CPKC412D2201
Study First Received:	October 28, 2008
Last Updated:	November 4, 2011
Health Authority:	United States: Food and Drug Administration; Australia: Department of Health and Ageing Therapeutic Goods Administration; Belgium: Directorate general for the protection of Public health: Medicines; Canada: Health Canada; France: Direction Générale de la Santé; Germany: Federal Institute for Drugs and Medical Devices; Italy: Ministry of Health; Netherlands: Ministry of Health, Welfare and Sport; United Kingdom: Medicines and Healthcare Products Regulatory Agency

Keywords provided by Novartis:

Aggressive systemic mastocytosis
mast cell leukemia
C-Findings
tyrosine kinase inhibitor

KIT mutation
AHNMD
Systemic
Aggressive

Additional relevant MeSH terms:

Aggression
Leukemia
Leukemia, Mast-Cell
Mastocytosis
Urticaria Pigmentosa
Mastocytoma
Mastocytosis, Systemic
Behavioral Symptoms
Neoplasms by Histologic Type
Neoplasms
Leukemia, Myeloid, Acute
Leukemia, Myeloid

Neoplasms, Connective Tissue
Neoplasms, Connective and Soft Tissue
Skin Diseases
Mastocytosis, Cutaneous
Pigmentation Disorders
4'-N-benzoylstaurosporine
Staurosporine
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on February 07, 2012