(EXPLORER) Study of BLU-285 in Patients With Advanced Systemic Mastocytosis (AdvSM) and Relapsed or Refractory Myeloid Malignancies

Completed · Phase 1

Conditions studied: Aggressive Systemic Mastocytosis, Systemic Mastocytosis-associated Hematologic Non-mast Cell Disease, Mast Cell Leukemia, Relapsed or Refractory Myeloid Malignancies

In brief

This is a Phase 1, open-label, dose-escalation study designed to evaluate the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD) and antineoplastic activity of avapritinib (also known as BLU-285), administered orally (PO), in adult patients with advanced systemic mastocytosis and other relapsed or refractory myeloid malignancies. The study consists of 2 parts:, dose-escalation (Part 1) and expansion (Part 2).

Key facts

Study ID: NCT02561988
Run by: Blueprint Medicines Corporation
People needed: 86
Starts: 2016-03-10
Expected to finish: 2023-01-19
Last updated by the study team: 2023-03-17

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

For Part 1:Patients must have one of the following diagnoses based on World Heath Organization (WHO) diagnostic criteria:
Aggressive systemic mastocytosis (ASM).
Systemic mastocytosis with an associated hematologic neoplasm (SM-AHN) and at least 1 C-finding attributable to systemic mastocytosis (SM). The AHN must be myeloid, with the following exceptions that are excluded: Acute myeloid leukemia (AML), Myelodysplastic syndrome (MDS) that is very high- or high-risk as defined by the International prognostic scoring system for myelodysplastic syndromes (IPSS-R) and Philadelphia chromosome positive malignancies.
Mast cell leukemia (MCL).
Histologically- or cytologically- confirmed myeloid malignancy that is relapsed or refractory to standard treatments. AML, MDS that is very high- or high-risk as defined by the IPSS-R, and Philadelphia chromosome positive malignancies are excluded.
Upon discussion with the sponsor, other relapsed or refractory, potentially avapritinib-responsive hematologic neoplasms (e.g., evidence of aberrant KIT or platelet derived growth factor receptor (PDGFR) signaling) may be considered for enrollment.
For Part 2, patients must have one of the following diagnoses, based on WHO diagnostic criteria:
ASM.
SM-AHN. The AHN must be myeloid, with the following exceptions that are excluded: AML, MDS that is very high- or high-risk as defined by the IPSS-R, and Philadelphia chromosome positive malignancies.
MCL.
For Part 2, Cohort 2, patients must have at least 1 measurable C-finding per modified IWG-MRT-ECNM criteria at Baseline, attributed to SM unless diagnosis is MCL, which does not require a C-finding.
Cytopenias: ANC < 1.0 × 10⁹/L or hemoglobin < 10 g/dL or platelet count < 75 × 10⁹/L.
Symptomatic ascites or pleural effusion requiring medical intervention such as: use of diuretics (Grade 2) or ≥ 2 therapeutic paracenteses or thoracenteses (Grade 3) at least 28 days apart over the 12 weeks before study entry and 1 of the procedures is performed during the 6 weeks before study start (C1D1).
≥ Grade 2 abnormalities in direct bilirubin (> 1.5 × upper limit of normal [ULN]), aspartate aminotransferase (AST; > 3.0 × ULN), alanine aminotransferase (ALT; > 3.0 × ULN), or alkaline phosphatase (> 2.5 × ULN) with 1 of the following present: ascites or clinically relevant portal hypertension or liver mast cell infiltration that is biopsy-proven or no other identified cause of abnormal liver function.
≥ Grade 2 hypoalbuminemia (< 3.0 g/dL).
A spleen that is palpable ≥ 5 cm below the left costal margin.
Transfusion-dependent anemia defined as: transfusion of ≥ 6 units packed red blood cells (PRBCs) in the 12 weeks before start of treatment (C1D1) and most recent transfusion occurring during the preceding 4 weeks and transfusion administered for hemoglobin ≤ 8.5 g/dL and reason for transfusion is not bleeding, hemolysis, or therapy-related.
Eastern Cooperative Oncology Group (ECOG) performance status of 0-3.

You may not qualify if…

QT interval corrected using Fridericia's formula (QTcF) >480 milliseconds
Platelet count <50,000/μL (within 4 weeks of the first dose of study drug) or receiving platelet transfusion(s)
Absolute neutrophil count <500/μL
Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) >3 x the upper limit of normal (ULN); >5 × ULN if associated with clinically suspected liver infiltration by mastocytosis or another disease for which the patient enrolled into the study
Total bilirubin >1.5 × ULN; >3 × ULN if associated with liver infiltration by the disease being treated or in the presence of Gilbert's Disease (In the case of Gilbert's disease, a direct bilirubin > 2.0 ULN would be an exclusion.)
Estimated (Cockroft-Gault formula) or measured creatinine clearance <40 mL/min
Brain malignancy or metastases to the brain
History of a seizure disorder or requirement for anti-seizure medication
Known risk of intracranial bleeding, such as a brain aneurysm or history of subdural or subarachnoid bleeding
Eosinophilia and known positivity for the FIP1L1-PGDFRA fusion, unless the patient has demonstrated relapse or progressive disease on prior imatinib therapy

Where it is running

Stanford Cancer Institute — Stanford, California, United States
University of Colorado Cancer Center — Denver, Colorado, United States
Emory University — Atlanta, Georgia, United States
Dana Farber Cancer Institute — Boston, Massachusetts, United States
University of Michigan Health System — Ann Arbor, Michigan, United States
Mount Sinai Hospital — New York, New York, United States
University of Pennsylvania — Philadelphia, Pennsylvania, United States
MD Anderson Cancer Center — Houston, Texas, United States
Huntsman Cancer Institute — Salt Lake City, Utah, United States
Beatson West of Scotland Cancer Centre — Glasgow, United Kingdom
Guy's Hospital — London, United Kingdom

Full record on ClinicalTrials.gov

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