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(PATHFINDER) Study to Evaluate Efficacy and Safety of Avapritinib (BLU-285), A Selective KIT Mutation-targeted Tyrosine Kinase Inhibitor, in Patients With Advanced Systemic Mastocytosis

Sponsor
Blueprint Medicines Corporation (Industry)
Overall Status
Active, not recruiting
CT.gov ID
NCT03580655
Collaborator
(none)
103
Enrollment
32
Locations
1
Arm
85.4
Anticipated Duration (Months)
3.2
Patients Per Site
0
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This is an open-label, single arm, Phase 2 study evaluating the efficacy and safety of avapritinib (BLU-285) in patients with advanced systemic mastocytosis (AdvSM), including patients with aggressive SM (ASM), SM with associated hematologic neoplasm (SM-AHN), and mast cell leukemia (MCL)

Condition or Disease Intervention/Treatment Phase
Phase 2

Study Design

Study Type:
Interventional
Anticipated Enrollment :
103 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
An Open-label, Single Arm, Phase 2 Study to Evaluate Efficacy and Safety of Avapritinib (BLU-285), A Selective KIT Mutation-targeted Tyrosine Kinase Inhibitor, in Patients With Advanced Systemic Mastocytosis
Actual Study Start Date :
Nov 21, 2018
Anticipated Primary Completion Date :
Jan 1, 2026
Anticipated Study Completion Date :
Jan 1, 2026

Arms and Interventions

Arm Intervention/Treatment
Experimental: Avapritinib

Avapritinib will be administered as an immediate release tablet, orally, continuously, in 28-day cycles

Drug: Avapritinib
Avapritinib tablet
Other Names:
  • BLU-285

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Objective response rate (ORR) based on modified International Working Group-Myeloproliferative Neoplasms Research and Treatment and European Competence Network on Mastocytosis (IWG-MRT-ECNM) response criteria [10 Months]

    Secondary Outcome Measures

    1. Mean Change from Baseline in Advanced Systemic Mastocytosis-Symptom Assessment Form (AdvSM-SAF) Total Symptom Score [10 Months]

      0 - 80 points (higher value represents worse symptom outcomes)

    2. Objective response rate [Approximately 4 years after the first subjected enrolled]

      Including morphologic complete remission (mCR), morphologic CR with partial recovery of peripheral blood (mCRh), and morphologic partial remission (mPR) based on Pure Pathologic Response

    3. Time-to-response (TTR) [10 Months]

      Months

    4. Duration of Response (DOR) [10 Months]

      Months

    5. Progression-free Survival (PFS) [10 Months]

      Months

    6. Overall Survival (OS) [10 Months]

      Months

    7. Changes in bone marrow mast cells [10 Months]

      percentage

    8. Change in serum tryptase [10 Months]

      ng/mL

    9. Change in V-kit Hardy-Zuckerman 4 feline sarcoma viral oncogene homolog aspartate 816 valine (KIT D816V) mutation burden [10 Months]

      percentage

    10. Change in liver volume by imaging [10 Months]

      mL

    11. Change in spleen volume by imaging [10 Months]

      mL

    12. Clinical benefit based on modified IWG-MRT-ECNM consensus criteria [10 Months]

    13. Change in PGIS [10 Months]

      0 - 10 points (higher value represents worse symptom outcomes)

    14. Change in EORTC QLQ-C30 [10 Months]

      0 - 100 points (lower value represents worse quality of life)

    15. Safety of Avapritinib as assessed by incidence of adverse events [10 Months]

      CTCAE version 4.0

    16. Area Under Curve (0 to Tau) for Avapritinib [4 Months]

      h•ng/mL

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Key Inclusion Criteria:

    1. Patient must have a diagnosis of aggressive systemic mastocytosis (ASM), systemic mastocytosis with an associated hematologic neoplasm (SM-AHN) or mast cell leukemia (MCL) based on World Health Organization diagnostic criteria. Before enrollment, the Study Steering Committee must confirm the diagnosis of AdvSM (based on Central Pathology Laboratory assessment of bone marrow).

    2. Patient must have a serum tryptase ≥ 20 ng/mL.

    3. Patient must have Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 to 3.

    Key Exclusion Criteria:

    1. Patient has received prior treatment with avapritinib.

    2. Patient has received any cytoreductive therapy (including midostaurin and other TKIs, hydroxyurea, azacitidine) or an investigational agent less than 14 days, and for cladribine, interferon alpha, pegylated interferon and any antibody therapy (eg, brentuximab vedotin) less than 28 days before obtaining screening BM biopsy for this study.

    3. Patient has eosinophilia and known positivity for the FIP1L1 PGDFRA fusion, unless the patient has demonstrated relapse or PD on prior imatinib therapy. Patients with eosinophilia (> 1.5 × 10^9/L), who do not have a detectable KIT D816 mutation, must be tested for a PDGFRA fusion mutation by fluorescence in situ hybridization (FISH) or polymerase chain reaction (PCR).

    4. Patient has history of another primary 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.

    5. Patient has a QT interval corrected using Fridericia's formula (QTcF) > 480 msec.

    6. Patient has a known risk or recent history (12 months before the first dose of study drug) of intracranial bleeding (eg, brain aneurysm, concomitant vitamin K antagonist use).

    7. Platelet count < 50,000/μL (within 4 weeks of the first dose of study drug) or receiving platelet transfusion(s).

    8. Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) >3 x the upper limit of normal (ULN); no restriction if due to suspected liver infiltration by mast cells.

    9. Bilirubin >1.5 × ULN; no restriction if due to suspected liver infiltration by mast cells or Gilbert's disease. (In the case of Gilbert's disease, a direct bilirubin >2 × ULN would be an exclusion.)

    10. Estimated glomerular filtration rate (eGFR) < 30 mL/min/1.73m2 or creatinine > 1.5 × ULN.

    11. Patient has a primary brain malignancy or metastases to the brain.

    12. Patient has a history of a seizure disorder (eg, epilepsy) or requirement for antiseizure medication.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Stanford Cancer Institute Stanford California United States 94305
    2 Rush University Medical Center Chicago Illinois United States 60612
    3 The University of Kansas Cancer Center Westwood Kansas United States 66205
    4 Dana Farber Cancer Institute Boston Massachusetts United States 02215
    5 University of Michigan Ann Arbor Michigan United States 48109
    6 Washington University School of Medicine Saint Louis Missouri United States 63110
    7 Roswell Park Comprehensive Cancer Center Buffalo New York United States 14263
    8 Herbert Irving Comprehensive Cancer Center New York New York United States 10032
    9 University of Pennsylvania, Abramson Cancer Center Philadelphia Pennsylvania United States 19104
    10 University of Texas, MD Anderson Cancer Center Houston Texas United States 77030
    11 Mays Cancer Center San Antonio Texas United States 78229
    12 Huntsman Cancer Institute Salt Lake City Utah United States 84112
    13 Medizinische Universität Wien, Universitätsklinik für Innere Medizin I, Klinische Abteilung für Hämatologie und Hämostaseologie Vienna Austria 1090
    14 St. Michael's Hospital Toronto Ontario Canada M5B 1W8
    15 Odense University Hospital, Department of Haematology Odense Denmark DK-5000
    16 Hôpital Necker-Enfants Malades Paris France 75015
    17 CHU Toulouse - Hôpital Larrey Toulouse France 31059
    18 Uniklinik RWTH Aachen, Klinik für Hämatologie, Onkologie, Hämostaseologie und Stammzelltranslplantation Aachen Germany 52074
    19 Universitätsklinikum Hamburg-Eppendorf, Zentrum für Onkologie Hamburg Germany 20246
    20 Universitätsklinikum Leipzig, Medizinische Klinik und Poliklinik I - Hämatologie und Zelltherapie, lnternistische Onkologie, Hämostaseologie Leipzig Germany 04103
    21 Universitätsmedizin Mannheim III. Medizinische Klinik Mannheim Germany 68167
    22 Klinik und Poliklinik für Innere Medizin III, Klinikum rechts der Isar der TU München Munich Germany 81675
    23 Azienda Ospedaliero-Universitaria Careggi, CRIMM - Centro di Ricerca ed Innovazione per le Malattie Mieloproliferative Florence Italy 50134
    24 A.O. OO.RR. S.Giovanni di Dio e Ruggi d'Aragona, University of Salerno Salerno Italy 84131
    25 Centro Ricerche Cliniche di Verona - Azienda Ospedaliera Universitaria Integrata di Verona Verona Italy 37134
    26 University Medical Center Groningen (UMCG) Groningen Netherlands 9713 GZ
    27 Oslo University Hospital-Rikshospitalet, Hematology Oslo Norway 0372
    28 Uniwersyteckie Centrum Kliniczne, Klinika Hematologii i Transplantologii Gdańsk Poland 80-214
    29 Uniwersytecki Szpital Kliniczny im. Jana Mikulicza-Radeckiego we Wrocławiu, Klinice Hematologii, Nowotworów Krwi i Transplantacji Szpiku Wrocław Poland 50-367
    30 lnstituto de Estudios de Mastocitosis de Castilla la Mancha, Hospital Virgen del Valle - Complejo Hospitalario de Toledo Toledo Spain 45071
    31 Beatson West of Scotland Cancer Centre - NHS Greater Glasgow and Clyde Glasgow United Kingdom G12 0YN
    32 Guy's and St Thomas' NHS Foundation Trust - Guy's Hospital London United Kingdom SE1 9RT

    Sponsors and Collaborators

    • Blueprint Medicines Corporation

    Investigators

    None specified.

    Study Documents (Full-Text)

    None provided.

    More Information

    Additional Information:

    Publications

    None provided.
    Responsible Party:
    Blueprint Medicines Corporation
    ClinicalTrials.gov Identifier:
    NCT03580655
    Other Study ID Numbers:
    • BLU-285-2202
    • 2017-004836-13
    First Posted:
    Jul 9, 2018
    Last Update Posted:
    Mar 28, 2022
    Last Verified:
    Mar 1, 2022
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Additional relevant MeSH terms:
    Mastocytosis
    Mastocytosis, Systemic
    Hematologic Neoplasms
    Leukemia, Mast-Cell

    Study Results

    No Results Posted as of Mar 28, 2022