A Study of BLU-263 in patients with Indolent Systemic Mastocytosis

Phase 1

• Conditions: Indolent Systemic Mastocytosis (ISM) and monoclonal Mast Cell Activation Syndrome (mMCAS); MedDRA version: 20.1Level: LLTClassification code 10056452Term: Indolent systemic mastocytosisSystem Organ Class: 100000004864; Therapeutic area: Diseases [C] - Blood and lymphatic diseases [C15]

• Registration Number: EUCTR2020-005173-28-IT
• Lead Sponsor: BLUEPRINT MEDICINES CORPORATIO

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2021-10-18
• Last Update Posted: 2 March 2022

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 403

Inclusion Criteria

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:
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

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