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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

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. Read our disclaimer for details. Identifier: NCT03580655
Recruitment Status : Active, not recruiting
First Posted : July 9, 2018
Last Update Posted : August 2, 2023
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

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Study Type : Interventional  (Clinical Trial)
Estimated 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 : November 21, 2018
Estimated Primary Completion Date : January 31, 2026
Estimated Study Completion Date : January 31, 2026

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 (IWG-MRT-ECNM) response criteria [ 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. Objective response rate [ Time Frame: 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) [ Time Frame: 10 Months ]

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

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

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

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

  8. Change in serum tryptase [ Time Frame: 10 Months ]

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

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

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

  12. Clinical benefit based on modified IWG-MRT-ECNM consensus criteria [ Time Frame: 10 Months ]
  13. Change in PGIS [ Time Frame: 10 Months ]
    0 - 10 points (higher value represents worse symptom outcomes)

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

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

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

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.

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
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.

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 identifier (NCT number): NCT03580655

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Sponsors and Collaborators
Blueprint Medicines Corporation
Additional Information:
Publications automatically indexed to this study by Identifier (NCT Number):
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Responsible Party: Blueprint Medicines Corporation Identifier: NCT03580655    
Other Study ID Numbers: BLU-285-2202
2017-004836-13 ( EudraCT Number )
First Posted: July 9, 2018    Key Record Dates
Last Update Posted: August 2, 2023
Last Verified: August 2023

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Mastocytosis, Systemic
Hematologic Neoplasms
Leukemia, Mast-Cell
Neoplasms, Connective Tissue
Neoplasms, Connective and Soft Tissue
Neoplasms by Histologic Type
Mast Cell Activation Disorders
Immune System Diseases
Neoplasms by Site
Hematologic Diseases
Leukemia, Myeloid, Acute
Leukemia, Myeloid