A Study of Avapritinib in Patients with Advanced Systemic Mastocytosis

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 60

Inclusion Criteria

1. Patients who are = 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 = 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 = 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 = 14 days before C1D-8.
9. If the patient is receiving corticosteroids, the dose must be = 20 mg/d prednisone or equivalent and dose must be stable for = 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. Patient has received 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. Patient has received prior radiotherapy within 14 days before the screening BM biopsy, unless given to palliate specific sites of disease (eg, bone lesion).
4. Patient received any hematopoietic growth factor within 14 days of screening BM biopsy.
5. Patient requires therapy with a concomitant medication that is a strong inhibitor, strong inducer, or moderate inducer of CYP3A4.
6. Patient has had a 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. Patient is a candidate for allogeneic hematopoietic stem cell transplantation for treatment of SM, in the opinion of the Investigator.
8. Patient has 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. Patient has 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. Patient meets 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. Patient has a QT interval corrected using Fridericia’s formula (QTcF) > 450 msec.
12. Patient has a history of a seizure disorder (eg, epilepsy) or requirement for antiseizure medication.
13. Patient has a history of a cerebrovascular accident or transient ischemic attacks within 1 year before the first dose of study drug.
14. Patient has a known risk or recent history (within the preceding 1 year) of intracranial bleeding (eg, brain aneurysm).
15. Patient has a primary brain malignancy or metastases to the brain.
16. Patient has 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. Patient is 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 from sexual intercourse or employ highly effective contraception

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

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Blueprint Medicines Corporation

Updated 4/15/2024