A Study of Avapritinib in Patients with Advanced Systemic Mastocytosis

Phase 1

• Conditions: Advanced Systemic Mastocytosis (AdvSM); MedDRA version: 20.0 Level: LLT Classification code 10056453 Term: Aggressive systemic mastocytosis System Organ Class: 100000004851; Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2017-004836-13-ES
• Lead Sponsor: Blueprint Medicines Corporation

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2018-11-23
• Last Update Posted: 28 February 2019

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: Not specified
• Target Recruitment: 60

Inclusion Criteria

1. Patients who are at least 18 years of age.
2. Patients must have 1 of the following diagnoses as confirmed by World Health Organization (WHO) diagnostic criteria. Before enrollment, the SSC must confirm the diagnosis of AdvSM (based on Central Pathology Laboratory assessment of BM).
• ASM.
• SM-AHN. The AHN must be myeloid, with additional criteria defined in the protocol.
• MCL.
3. Patients with SM-AHN should have received prior treatment for the AHN component of disease if, in the opinion of the Investigator, such therapy was appropriate.
4. Patient must have a BM biopsy available to be shipped to the Central Pathology Laboratory at least 21 days before initiation of study treatment (C1D1).
5. Patient must have at least 1 measurable C-finding per modified IWG-MRT-ECNM, attributed to SM and evaluable for response assessment unless diagnosis is MCL, which does not require a C-finding. Laboratory abnormality C-findings should not be assessed until the required time period from last cytoreductive therapy has been met.
6. Patient must have a serum tryptase greater than or equal to 20 ng/mL.
7. Patients with cytoreductive therapy within the preceding 12 weeks must have discontinued therapy due to disease progression, refractory disease, lack of efficacy, or intolerance.
8. Patient must have symptom management optimized with nonantineoplastic therapies (ie, BSC; eg, H1 and H2 blockers). Dose must be stable for at least 14 days before C1D-8.
9. If the patient is receiving corticosteroids, the dose must be less than or equal to 20 mg/d prednisone or equivalent and dose must be stable for at least 14 days before C1D-8.
10. Patient has an Eastern Cooperative Oncology Group Performance Status of 0 to 3.
11. 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 36
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 24

Exclusion Criteria

1. Patient has received prior treatment with avapritinib.
2. Any cytoreductive therapy (including midostaurin and other TKIs, hydroxyurea, azacitidine) or an investigational agent less than 14 days, and for cladribine, interferon alpha, pegylated interferon and any antibody therapy (eg, brentuximab vedotin) less than 28 days before obtaining screening BM biopsy for this study.
3. Prior radiotherapy within 14 days before the screening BM biopsy, unless given to palliate specific sites of disease (eg, bone lesion).
4. Any hematopoietic growth factor within 14 days of screening BM biopsy.
5. Concomitant medication that is a strong inhibitor, strong inducer, or moderate inducer of CYP3A4.
6. Major surgical procedure within 14 days of the first dose of study drug. Surgical procedures such as central venous catheter placement, BM biopsy, and feeding tube placement are considered minor surgical procedures.
7. Candidate for allogeneic hematopoietic stem cell transplantation for treatment of SM, in the opinion of the Investigator.
8. Eosinophilia and known positivity for the FIP1L1-PGDFRA fusion, unless the patient has demonstrated relapse or PD on prior imatinib therapy. Patients with eosinophilia (> 1.5 × 10^9/L), who do not have a detectable KIT D816 mutation, should be tested for a PDGFRA fusion mutation by fluorescence in situ hybridization (FISH) or polymerase chain reaction (PCR).
9. History of another primary 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.
10. Any of the following laboratory criteria:
o AST or ALT > 3.0 × ULN; no restriction if due to suspected liver infiltration by MCs.
o Bilirubin > 1.5 × ULN; no restriction if due to suspected liver infiltration by MCs or Gilbert’s disease.
o Estimated glomerular filtration rate (eGFR) < 30 mL/min/1.73m^2 or creatinine clearance calculated by Cockcroft-Gault equation < 40 mL/min.
11. QT interval corrected using Fridericia’s formula (QTcF) > 450 msec.
12. History of a seizure disorder (eg, epilepsy) or requirement for antiseizure medication.
13. History of a cerebrovascular accident or transient ischemic attacks within 1 year before the first dose of study drug.
14. Known risk or recent history (within the preceding 1 year) of intracranial bleeding (eg, brain aneurysm).
15. Primary brain malignancy or metastases to the brain.
16. Clinically significant, uncontrolled cardiovascular disease, including Grade III or IV congestive heart failure according to the New York Heart Association classification; myocardial infarction or unstable angina within the previous 6 months; clinically significant, uncontrolled arrhythmias; or uncontrolled hypertension.
17. Unwilling or unable to comply with scheduled visits, drug administration plan, laboratory tests, or other study procedures and study restrictions.
18. Female patients who are unwilling, if not postmenopausal or surgically sterile, to abstain fr

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified