A Study of Avapritinib in Patients with Indolent and Smoldering Systemic Mastocytosis
- Conditions
- Indolent and Smoldering Systemic Mastocytosis (ISM & SSM)MedDRA version: 20.0 Level: PT Classification code 10042949 Term: Systemic mastocytosis System Organ Class: 10005329 - Blood and lymphatic system disordersMedDRA version: 20.1 Level: LLT Classification code 10056452 Term: Indolent systemic mastocytosis System Organ Class: 10005329 - Blood and lymphatic system disordersTherapeutic area: Diseases [C] - Blood and lymphatic diseases [C15]
- Registration Number
- EUCTR2018-000588-99-ES
- Lead Sponsor
- Blueprint Medicines Corporation
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- Not specified
- Target Recruitment
- 60
1. Patients who are at least 18 years of age.
2. Patient must have SM, confirmed by Central Pathology Review of BM biopsy, and ISM or SSM subtype, as confirmed by WHO diagnostic criteria. In Part 1 of the study, only patients with a diagnosis of ISM are eligible.
3. Patient must have moderate-to-severe symptoms based on minimum mean TSS over the 14-day eligibility screening period for assessment of TSS and at least 1 symptom in skin or GI domains of the ISM-SAF at Baseline. Minimum TSS for eligibility is greater than or equal to 28.
4. Patient must have failed to achieve symptom control for 1 or more Baseline symptoms measured by ISM-SAF, as determined by the Investigator, with at least 2 of the following symptomatic therapies administered at optimal (approved) dose and for a minimum of 28 days before starting the ISM-SAF for determination of eligibility: H1 blockers, H2 blockers, proton-pump inhibitors, leukotriene inhibitors, cromolyn sodium, corticosteroids, or omalizumab.
5. Patient must have symptom management optimized with symptomatic therapies (eg, H1 and H2 blockers) and the dose must be stable for at least 14 days before starting the ISM-SAF for determination of eligibility.
6. If the patient is receiving corticosteroids, the dose must be less than or equal to 20 mg/d prednisone or equivalent, and the dose must be stable for at least 14 days before starting the ISM-SAF for determination of eligibility.
7. Patient must have an Eastern Cooperative Oncology Group Performance Status of 0 to 2.
8. Patient must give written informed consent.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 100
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 12
1. Has been diagnosed with any of the following WHO SM subclassifications: CM only, SM-AHN, ASM, MCL, MC sarcoma.
2. Has been diagnosed with another myeloproliferative disorder.
3. Has any of the following organ damage C-findings attributable to SM: Cytopenia, Hepatomegaly with ascites and impaired liver function, Palpable splenomegaly with hypersplenism, Malabsorption with hypoalbuminemia and significant weight loss, Skeletal lesions: large osteolytic lesions with pathologic fractures, Life-threatening organ damage in other organ systems that is caused by MC infiltration in tissues.
4. Meets any of the following laboratory criteria: Aspartate aminotransferase or alanine aminotransferase > 3.0 × ULN, Total bilirubin > 1.5 × ULN; > 3.0 × ULN if due to Gilbert's disease, Albumin < 1 × LLN, eGFR < 30 mL/min/1.73 m^2 or creatinine clearance calculated by Cockcroft-Gault equation < 40 mL/min, Absolute neutrophil count < 1.5 × 10^9/L, Hemoglobin < 10 g/dL, Platelet count < 100 × 10^9/L.
5. Has received any of the following medications, therapies, or procedures in the timeframes listed: Any prior treatment with avapritinib, Any TKI, including but not limited to masitinib and midostaurin, or investigational agent < 14 days before starting the ISM-SAF for determination of eligibility, Any antineoplastic drug therapy < 28 days before starting the ISM-SAF for determination of eligibility, Radiotherapy or psoralen and ultraviolet A (PUVA) therapy < 14 days before starting the ISM-SAF for determination of eligibility, Any hematopoietic growth factor < 14 days before starting the ISM-SAF for determination of eligibility, Any major surgical procedure < 14 days before starting the ISM-SAF for determination of eligibility.
6. Requires therapy with a concomitant medication that is a strong inhibitor, strong inducer, or moderate inducer of cytochrome P450 3A4 (CYP3A4).
7. Has a history of a malignancy that has been diagnosed or required therapy within 3 years before the first dose of study drug. The following are exempt from the 3-year limit: completely resected basal cell and squamous cell skin cancer, curatively treated localized prostate cancer, and completely resected carcinoma in situ of any site.
8. Has a QTcF > 450 msec.
9. Has a history of a seizure disorder (eg, epilepsy) or requires antiseizure medication.
10. Has a history of a cerebrovascular accident or transient ischemic attacks within 12 months before the first dose of study drug.
11. Has a known risk or recent history (12 months before the first dose of study drug) of intracranial bleeding (eg, brain aneurysm).
12. Has a primary brain malignancy or metastases to the brain.
13. Has clinically significant, uncontrolled cardiovascular disease, including Grade III or IV congestive heart failure according to NYHA; myocardial infarction or unstable angina within the previous 6 months; clinically significant, uncontrolled arrhythmias, or uncontrolled hypertension.
14. Is unwilling or unable to comply with scheduled visits, drug administration plan, laboratory tests, or other study procedures, including mandatory BM and skin biopsies, and study restrictions.
15. Female patients who are unwilling, if not postmenopausal or surgically sterile, to abstain from sexu
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method