A Study of BLU-263 in patients with Indolent Systemic Mastocytosis
- Conditions
- Indolent Systemic Mastocytosis (ISM) and monoclonal Mast Cell Activation Syndrome (mMCAS)MedDRA version: 20.1Level: LLTClassification code 10056452Term: Indolent systemic mastocytosisSystem Organ Class: 100000004864Therapeutic area: Diseases [C] - Blood and lymphatic diseases [C15]
- Registration Number
- EUCTR2020-005173-28-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
- All
- Target Recruitment
- 403
All Patients:
-1. Patient must have an Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0 to 2.
Part 1 only
-2. Patient must have moderate-to-severe symptoms based on minimum mean total symptom score (TSS) of the ISM Symptom Assessment Form
(ISM-SAF) over the 14-day eligibility screening period.
Part 1 and Part 2
• 3. Patient has confirmed diagnosis of ISM, confirmed by Central Pathology Review of BM biopsy and central review of B- and C-findings
by WHO diagnostic criteria. Archival biopsy may be used if completed within the past 12 months.
• 4. Patient must have failed to achieve adequate symptom control for 1 or more Baseline symptoms, as determined by the Investigator, with at
least 2 of the following symptomatic therapies administered: H1 blockers, H2 blockers, proton-pump inhibitors, leukotriene inhibitors, cromolyn
sodium, corticosteroids, or omalizumab.
• 5. Patients must have BSC for ISM symptom management stabilized for at least 14 days prior to starting screening procedures.
• 6. For patients receiving corticosteroids, the dose must be = 20 mg/d prednisone or equivalent, and the dose must be stable for = 14 days.
Part M
• 7. Patients must have mMCAS, confirmed by Central Pathology Review of BM biopsy. An archival biopsy may be used if completed within the
past 12 months.
• 8. Patients must have tryptase < 20 ng/mL.
• 9. Patients must have KIT D816V in peripheral blood (PB) or BM and/or CD25+ Mast cells in BM.
• 10. Patients must have symptoms consistent with mast cell activation (despite BSC) in at least two organ systems characterized by cutaneous
flushing, tachycardia, syncope, hypotension, diarrhea, nausea, vomiting and gastro-intestinal cramping) and serum blood tryptase (sBT) levels
above 8 ng/mL OR Severe (Ring and Messmer grading = II, recurrent anaphylaxis, including but not limited to hymenoptera venom, drug or
food, regardless of sBT levels.
Optional PK Group
• 11. See inclusion criteria for All patients and Part 1/Part 2
• 12. Accrual may be limited to patients who have specific disease manifestations (ie, GI involvement) or are taking acid-reducing agents
to better explore the impact of these features on PK.
Are the trial subjects under 18? yes
Number of subjects for this age range: 3
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 383
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 17
Key Exclusion Criteria:
• 1. Patient has been diagnosed with any of the following WHO systemic mastocytosis (SM) sub-classifications: cutaneous mastocytosis only, smoldering SM, SM with associated hematologic neoplasm, aggressive SM, mast cell leukemia, or mast cell sarcoma.
• 2. Patient has been diagnosed with another myeloproliferative disorder.
• 3. Patient has organ damage C-findings attributable to SM.
• 4. Patient has clinically significant, uncontrolled, cardiovascular disease
• 5. Patient has a QT interval corrected using Fridericia's formula (QTcF) > 480 msec.
• 6. Patient has previously received treatment with any targeted KIT inhibitors.
• 7. Patient has a history of a primary malignancy that has been diagnosed or required therapy within 3 years. The following prior malignancies are not exclusionary: completely resected basal cell and squamous cell skin cancer, curatively treated localized prostate cancer, and completely resected carcinoma in situ of any site.
• 8. Time since any cytoreductive therapy including mastinib and midostaurin should be at least 5 half-lives or 14 days (whichever is longer), and for
cladribine, interferon alpha, pegylated interferon, or antibody therapy <28 days or 5 half-lives of the drug (whichever is longer), before beginning the
screening period.
• 9.Patient has received radiotherapy or psoralen and ultraviolet A (PUVA) therapy < 14 days before beginning the screening period.
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