A Randomized, Double-Blind, Placebo-Controlled Phase 2/3 Study of BLU-263 in Indolent Systemic Mastocytosis

Phase 2

Recruiting

• Conditions: myeloproliferatieve aandoening; Mast cell disease - systemic mastocytosis

• Registration Number: NL-OMON56049
• Lead Sponsor: Blueprint Medicines Corporation

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Last Update Posted: 15 April 2024

Recruitment & Eligibility

• Status: Recruiting
• Sex: Not specified
• Target Recruitment: 10

Inclusion Criteria

All Patients
• Patient must have an Eastern Cooperative Oncology Group Performance Status
(ECOG PS) of 0 to 2.

Part 1 and Part 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
• 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.
• 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.
• Patients must have BSC for ISM symptom management stabilized for at least 14
days prior to starting screening procedures.
• 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
• 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.
• Patients must have tryptase < 20 ng/mL.
• Patients must have KIT D816V in peripheral blood (PB) or BM and/or CD25+ Mast
cells in BM.
• 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.

PK Groups
• See inclusion criteria for All patients and Part 1/Part 2
• 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.

For the full list of inclusion criteria we would like to refer you to page
66-67 of the protocol.

Exclusion Criteria

• 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.
• Patient has been diagnosed with another myeloproliferative disorder.
• Patient has organ damage C-findings attributable to SM.
• Patient has clinically significant, uncontrolled, cardiovascular disease
• Patient has a QT interval corrected using Fridericia's formula (QTcF) > 480
msec.
• Patient has previously received treatment with any targeted KIT inhibitors.
• 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.
• 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.
• Patient has received radiotherapy or psoralen and ultraviolet A (PUVA)
therapy < 14 days before beginning the screening period.
- pregnant or not willing to use highly effective contraception methods

For an overview of all exclusion criteria we would like to refer you to page
67-70 of the protocol.

Study & Design

• Study Type: Interventional
• Study Design: Not specified