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A Study of Avapritinib in Patients with Indolent and Smoldering Systemic Mastocytosis

Phase 1
Conditions
Indolent and Smoldering Systemic Mastocytosis (ISM & SSM)
MedDRA version: 21.1Level: PTClassification code 10042949Term: Systemic mastocytosisSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA version: 20.1Level: LLTClassification code 10056452Term: Indolent systemic mastocytosisSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Therapeutic area: Diseases [C] - Blood and lymphatic diseases [C15]
Registration Number
EUCTR2018-000588-99-IT
Lead Sponsor
BLUEPRINT MEDICINES CORPORATIO
Brief Summary

Not available

Detailed Description

Not available

Recruitment & Eligibility

Status
Authorised-recruitment may be ongoing or finished
Sex
All
Target Recruitment
60
Inclusion Criteria

1. Patients who are = 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 = 1 symptom in skin or GI
domains of the ISM-SAF at Baseline. Minimum TSS for eligibility is = 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 = 14 days before starting the ISM-SAF for
determination of eligibility.
6. If the patient is receiving corticosteroids, the dose must be = 20 mg/d prednisone or
equivalent, and the dose must be stable for = 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

Exclusion Criteria

1. Patient has been diagnosed with any of the following WHO SM subclassifications: CM
only, SM-AHN, ASM, MCL, MC sarcoma.
2. Patient has been diagnosed with another myeloproliferative disorder.
3. Patient 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. Patient 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. Patient 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. Patient requires therapy with a concomitant medication that is a strong inhibitor,
strong inducer, or moderate inducer of cytochrome P450 3A4 (CYP3A4).
7. Patient 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. Patient has a QTcF > 450 msec.
9. Patient has a history of a seizure disorder (eg, epilepsy) or requires antiseizure
medication.
10. Patient has a history of a cerebrovascular accident or transient ischemic attacks
within 12 months before the first dose of study drug.
11. Patient has a known risk or recent history (12 months before the first dose of study
drug) of intracranial bleeding (eg, brain aneurysm).
12. Patient has a primary brain malignancy or metastases to the brain.
13. 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.
14. Patient 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 sexual intercourse or employ highly effective contraception during the
study drug administ

Study & Design

Study Type
Interventional clinical trial of medicinal product
Study Design
Not specified
Primary Outcome Measures
NameTimeMethod
Secondary Outcome Measures
NameTimeMethod
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