ClinicalTrials.gov
ClinicalTrials.gov Menu
Trial record 1 of 3 for:    advanced SM, blueprint medicines
Previous Study | Return to List | Next Study

(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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT03580655
Recruitment Status : Recruiting
First Posted : July 9, 2018
Last Update Posted : November 14, 2018
Sponsor:
Information provided by (Responsible Party):
Blueprint Medicines Corporation

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
Advanced Systemic Mastocytosis Aggressive Systemic Mastocytosis Systemic Mastocytosis With an Associated Hematologic Neoplasm Mast Cell Leukemia Drug: Avapritinib Phase 2

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 60 participants
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
Estimated Study Start Date : November 2018
Estimated Primary Completion Date : December 2020
Estimated Study Completion Date : November 2023


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 Name: BLU-285




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 consensus response criteria in patients with AdvSM treated with avapritinib. [ Time Frame: 10 Months ]

Secondary Outcome Measures :
  1. Mean Change from Baseline in Advanced Systemic Mastocytosis-Symptom Assessment Form (AdvSM-SAF) Total Symptom Score [ Time Frame: 10 Months ]
    0 - 80 points (higher value represents worse symptom outcomes)

  2. Time-to-response (TTR) [ Time Frame: 10 Months ]
    Months

  3. Duration of Response (DOR) [ Time Frame: 10 Months ]
    Months

  4. Progression-free Survival (PFS) [ Time Frame: 10 Months ]
    Months

  5. Overall Survival (OS) [ Time Frame: 10 Months ]
    Months

  6. Changes in bone marrow mast cells [ Time Frame: 10 Months ]
    percentage

  7. Change in serum tryptase [ Time Frame: 10 Months ]
    ng/mL

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

  9. Change in liver volume by imaging [ Time Frame: 10 Months ]
    mL

  10. Change in spleen volume by imaging [ Time Frame: 10 Months ]
    mL

  11. Clinical benefit based on modified International Working Group-Myeloproliferative Neoplasms Research and Treatment and European Competence Network on Mastocytosis (IWG-MRT-ECNM) consensus criteria [ Time Frame: 10 Months ]
  12. Change in PGIS [ Time Frame: 10 Months ]
    0 - 10 points (higher value represents worse symptom outcomes)

  13. Change in EORTC QLQ-C30 [ Time Frame: 10 Months ]
    0 - 100 points (lower value represents worse quality of life)

  14. Safety of Avapritinib as assessed by incidence of adverse events [ Time Frame: 10 Months ]
    CTCAE version 4.0

  15. Area Under Curve (0 to Tau) for Avapritinib [ Time Frame: 4 Months ]
    h•ng/mL



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.
  2. Patient must have at least 1 of the measurable C-finding per IWG-MRT-ECNM criteria indicative of organ damage, attributed to SM and evaluable for response assessment unless diagnosis is MCL, which does not require a C-finding.
  3. Patient must have a serum tryptase ≥ 20 ng/mL.

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, should 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) > 450 msec.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03580655


Contacts
Contact: Blueprint Medicines 617-714-6707 SM@blueprintmedicines.com

Locations
United States, California
Stanford Cancer Institute Recruiting
Stanford, California, United States, 94305
United States, Massachusetts
Dana Farber Cancer Institute Recruiting
Boston, Massachusetts, United States, 02215
United States, New York
Herbert Irving Comprehensive Cancer Center Recruiting
New York, New York, United States, 10032
United States, Utah
Huntsman Cancer Institute Recruiting
Salt Lake City, Utah, United States, 84112
Sponsors and Collaborators
Blueprint Medicines Corporation

Additional Information:
Responsible Party: Blueprint Medicines Corporation
ClinicalTrials.gov Identifier: NCT03580655     History of Changes
Other Study ID Numbers: BLU-285-2202
First Posted: July 9, 2018    Key Record Dates
Last Update Posted: November 14, 2018
Last Verified: November 2018

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
Neoplasms, Connective Tissue
Neoplasms, Connective and Soft Tissue
Neoplasms by Histologic Type
Neoplasms
Skin Diseases
Neoplasms by Site
Hematologic Diseases
Leukemia
Leukemia, Myeloid, Acute
Leukemia, Myeloid