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Trial record 1 of 1 for:    NCT03731260
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(PIONEER) Study to Evaluate Efficacy and Safety of Avapritinib (BLU-285), A Selective KIT Mutation-targeted Tyrosine Kinase Inhibitor, Versus Placebo in Patients With Indolent Systemic Mastocytosis

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ClinicalTrials.gov Identifier: NCT03731260
Recruitment Status : Recruiting
First Posted : November 6, 2018
Last Update Posted : July 1, 2020
Sponsor:
Information provided by (Responsible Party):
Blueprint Medicines Corporation

Brief Summary:
This is a Phase 2, randomized, double-blind, placebo-controlled study comparing the efficacy and safety of avapritinib + best supportive care (BSC) with placebo + BSC in patients with indolent systemic mastocytosis (ISM) whose symptoms are not adequately controlled by BSC. The study will be conducted in 3 parts. All patients will receive treatment with avapritinib during Part 3 including those rolling over from the placebo group.

Condition or disease Intervention/treatment Phase
Indolent Systemic Mastocytosis Drug: Avapritinib Drug: Placebo Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 244 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: In Part 1 of the study, patients will be randomly assigned to 1 of 3 doses of avapritinib or to placebo + BSC. Once the recommended phase 2 dose (RP2D) of avapritinib is identified in Part 1, patients in Part 2 will be randomly assigned to receive avapritinib at the RP2D + BSC or matching placebo + BSC. In Part 3, patients who have completed treatment in Part 1 or Part 2 of the study (including those initially randomized to placebo) may participate in a long-term open-label extension, receiving avapritinib at the RP2D + BSC.
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A 3-Part, Randomized, Double-Blind, Placebo-Controlled Phase 2 Study to Evaluate Safety and Efficacy of Avapritinib (BLU-285), a Selective KIT Mutation-Targeted Tyrosine Kinase Inhibitor, in Indolent and Smoldering Systemic Mastocytosis With Symptoms Inadequately Controlled With Standard Therapy
Actual Study Start Date : April 16, 2019
Estimated Primary Completion Date : May 2021
Estimated Study Completion Date : December 2024

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: (Part 1) Avapritinib Dose 1 + BSC
Avapritinib will be administered orally in continuous 28-day cycles
Drug: Avapritinib
Avapritinib tablet
Other Name: BLU-285

Experimental: (Part 1) Avapritinib Dose 2 + BSC
Avapritinib will be administered orally in continuous 28-day cycles
Drug: Avapritinib
Avapritinib tablet
Other Name: BLU-285

Experimental: (Part 1) Avapritinib Dose 3 + BSC
Avapritinib will be administered orally in continuous 28-day cycles
Drug: Avapritinib
Avapritinib tablet
Other Name: BLU-285

Placebo Comparator: (Part 1) Placebo + BSC
Placebo will be administered orally in continuous 28-day cycles
Drug: Placebo
Placebo tablet

Experimental: (Part 2) Avapritinib RP2D + BSC
Avapritinib will be administered orally in continuous 28-day cycles
Drug: Avapritinib
Avapritinib tablet
Other Name: BLU-285

Placebo Comparator: (Part 2) Placebo + BSC
Placebo will be administered orally in continuous 28-day cycles
Drug: Placebo
Placebo tablet

Experimental: (Part 3) Avapritinib RP2D + BSC
Avapritinib will be administered orally in continuous 28-day cycles
Drug: Avapritinib
Avapritinib tablet
Other Name: BLU-285




Primary Outcome Measures :
  1. Part 1: Recommended Phase 2 dose (RP2D) in patients with ISM [ Time Frame: 9 months ]
  2. Part 2: Proportion of responders, defined as ≥30% reduction in ISM Symptom Assessment Form (ISM-SAF) total symptom score (TSS) [ Time Frame: 6 months ]
    0 - 120 points (higher value represents worse symptom outcomes)


Secondary Outcome Measures :
  1. Part 2: Proportion of patients with a ≥50% reduction in serum tryptase [ Time Frame: 6 months ]
  2. Part 2: Proportion of patients with a ≥50% reduction in peripheral blood V-kit Hardy-Zuckerman 4 feline sarcoma viral oncogene homolog aspartate 816 valine (KIT D816V) allele fraction or undetectable for patients with detectable mutation at Baseline [ Time Frame: 6 months ]
  3. Part 2: Mean change in ISM Symptom Assessment Form (ISM-SAF) total symptom score (TSS) [ Time Frame: 6 months ]
  4. Part 2: Proportion of patients with a ≥50% reduction in bone marrow mast cells or no aggregates for patients with aggregates at Baseline [ Time Frame: 6 months ]
  5. Change in serum tryptase [ Time Frame: Up to 5 years ]
  6. Change in V-kit Hardy-Zuckerman 4 feline sarcoma viral oncogene homolog aspartate 816 valine (KIT D816V) allele burden in blood [ Time Frame: Up to 5 years ]
  7. Change in bone marrow mast cells [ Time Frame: Up to 1 year after the end of Part 1 and Part 2 ]
  8. Change in best supportive care (BSC) concomitant medication usage [ Time Frame: Up to 5 years ]
  9. Change in Mastocytosis Quality of Life Questionnaire (MC-QoL) [ Time Frame: Each study visit through Part 3 Cycle 12 (28-day cycles) ]
    0 - 100 points (higher value represents worse symptom outcomes)

  10. Change in Patient's Global Impression of Symptom Severity (PGIS) [ Time Frame: Each study visit through Part 3 Cycle 12 (28-day cycles) ]
    0 - 10 points (higher value represents worse symptom outcomes)

  11. Change in 12-item Short Form Health Survey (SF-12) [ Time Frame: Each study visit through Part 3 Cycle 12 (28-day cycles) ]
    0 - 100 points (higher value represents better symptom outcomes)

  12. Change in Patients' Global Impression of Change (PGIC) [ Time Frame: Each study visit through Part 3 Cycle 12 (28-day cycles) ]
    1 - 7 (higher value represents worse symptom outcomes)

  13. Change in EuroQuol 5 Dimensions 5 Levels (EQ 5D-5L) [ Time Frame: Each study visit through Part 3 Cycle 12 (28-day cycles) ]
    0 - 100 (higher value represents better symptom outcomes)

  14. Safety of avapritinib as assessed by number of adverse events [ Time Frame: Up to 5 years ]
    CTCAE version 5.0

  15. Part 1 and Part 2 only: Area Under Curve (0 to Tau) for avapritinib [ Time Frame: Every cycle (28 days) up to Cycle 4 (Part 1) and Cycle 7 (Part 2) ]
    h•ng/mL



Information from the National Library of Medicine

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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 SM, confirmed by Central Pathology Review of BM biopsy, and central review of B- and C-findings by WHO diagnostic criteria.
  • 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.
  • 3. Patient must have failed to achieve adequate symptom control for 1 or more Baseline symptoms.
  • 4. For patients receiving corticosteroids, the dose must be ≤ 20 mg/d prednisone or equivalent, and the dose must be stable for ≥ 14 days.
  • 5. Patient must have an Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 to 2.

Key Exclusion Criteria:

  • 1. Patient has been diagnosed with any of the following WHO SM subclassifications: cutaneous mastocytosis only, smoldering SM, SM with associated hematologic neoplasm, aggressive SM, mast cell leukemia, or mast cell sarcoma.
  • 2. Patient must not have received prior treatment with avapritinib.
  • 3. Patient must not have had any cytoreductive therapy including but not limited to masitinib and midostaurin, or investigational agent for < 14 days or 5 half-lives of the drug (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 14-day ISM-SAF eligibility TSS assessment.
  • 4. Patient must not have received radiotherapy or psoralen and ultraviolet A (PUVA) therapy < 14 days before beginning the 14-day ISM-SAF eligibility TSS assessment.
  • 5. Patient must not have received any hematopoietic growth factor the preceding 14 days before beginning the 14-day ISM-SAF eligibility TSS assessment.
  • 6. Patient must not have a QT interval corrected using Fridericia's formula (QTcF) of > 480 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): NCT03731260


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

Locations
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United States, California
Stanford Cancer Institute Recruiting
Stanford, California, United States, 94305
Principal Investigator: Jason Gotlib, MD, MS         
United States, Massachusetts
Brigham & Women's Hospital Recruiting
Boston, Massachusetts, United States, 02115
Principal Investigator: Maria C. Castells, MD, PhD         
Dana Farber Cancer Institute Recruiting
Boston, Massachusetts, United States, 02215
Principal Investigator: Daniel J. DeAngelo, MD, PhD         
United States, Michigan
Michigan Medicine, University of Michigan Recruiting
Ann Arbor, Michigan, United States, 48106
Principal Investigator: Cem Akin, MD, PhD         
United States, New York
Herbert Irving Comprehensive Cancer Center Recruiting
New York, New York, United States, 10032
Principal Investigator: Mark L. Heaney, MD, PhD         
United States, Utah
Huntsman Cancer Institute Recruiting
Salt Lake City, Utah, United States, 84112
Principal Investigator: Michael Deininger, MD, PhD         
Belgium
University Hospital Antwerp Recruiting
Edegem, Belgium, 2650
Principal Investigator: Vito Sabato, PhD         
Canada, Ontario
St. Michael's Hospital Recruiting
Toronto, Ontario, Canada, M5B 1W8
Principal Investigator: Peter Vadas, MD, PhD         
Italy
A.O. OO.RR. S.Giovanni di Dio e Ruggi d'Aragona, University of Salerno Recruiting
Salerno, Italy, 84131
Principal Investigator: Massimo Triggiani, MD, PhD         
Azienda Ospedaliera Universitaria Integrata di Verona Recruiting
Verona, Italy, 37126
Principal Investigator: Patrizia Bonadonna, MD         
Netherlands
University Medical Center Groningen (UMCG) Recruiting
Groningen, Netherlands, 9713 GZ
Principal Investigator: J.N.G (Hanneke) Oude Elberink, MD, PhD         
Erasmus Medical Center Recruiting
Rotterdam, Netherlands, 3015 GD
Principal Investigator: Paulus Leon Arthur van Daele, MD         
Spain
lnstituto de Estudios de Mastocitosis de Castilla la Mancha, Hospital Virgen del Valle - Complejo Hospitalario de Toledo Recruiting
Toledo, Spain, 45071
Principal Investigator: Iván Alvarez-Twose, MD, PhD         
United Kingdom
Guy's and St Thomas' NHS Foundation Trust - Guy's Hospital Recruiting
London, United Kingdom, SE1 9RT
Principal Investigator: Deepti H. Radia, MD         
Sponsors and Collaborators
Blueprint Medicines Corporation
Additional Information:
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Responsible Party: Blueprint Medicines Corporation
ClinicalTrials.gov Identifier: NCT03731260    
Other Study ID Numbers: BLU-285-2203
2018-000588-99 ( EudraCT Number )
First Posted: November 6, 2018    Key Record Dates
Last Update Posted: July 1, 2020
Last Verified: June 2020

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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
Mastocytosis, Systemic
Neoplasms, Connective Tissue
Neoplasms, Connective and Soft Tissue
Neoplasms by Histologic Type
Neoplasms
Skin Diseases
Immune Complex Diseases
Hypersensitivity
Immune System Diseases