(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
- Conditions
- Indolent Systemic Mastocytosis
- Interventions
- Drug: Placebo
- Registration Number
- NCT03731260
- Lead Sponsor
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 251
- 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
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description (Part 1) Placebo + BSC Placebo Placebo will be administered orally in continuous 28-day cycles (Part 1) Avapritinib Dose 1 + BSC Avapritinib Avapritinib will be administered orally in continuous 28-day cycles (Part 2) Avapritinib RP2D + BSC Avapritinib Avapritinib will be administered orally in continuous 28-day cycles (Part 2) Placebo + BSC Placebo Placebo will be administered orally in continuous 28-day cycles (Part 1) Avapritinib Dose 2 + BSC Avapritinib Avapritinib will be administered orally in continuous 28-day cycles (Part 1) Avapritinib Dose 3 + BSC Avapritinib Avapritinib will be administered orally in continuous 28-day cycles (Part 3) Avapritinib RP2D + BSC Avapritinib Avapritinib will be administered orally in continuous 28-day cycles
- Primary Outcome Measures
Name Time Method Part 1: Recommended Phase 2 dose (RP2D) in patients with ISM 9 months Part 2: Mean change in ISM Symptom Assessment Form (ISM-SAF) total symptom score (TSS) as compared to placebo 6 months 0 - 110 points (higher value represents worse symptom outcomes)
Part 3: Number of Participants with Adverse Events Up to 5 years
- Secondary Outcome Measures
Name Time Method 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 6 months Part 2: Proportion of patients with a ≥50% reduction in serum tryptase 6 months Part 2: Proportion of patients with a ≥50% reduction in bone marrow mast cells or no aggregates for patients with aggregates at Baseline 6 months Parts 1, 2, and 3: Change in best supportive care (BSC) concomitant medication usage Up to 5 years Parts 1, 2, and 3: Change in Patient's Global Impression of Symptom Severity (PGIS) Up to 5 years Part 2: Proportion of patients with ≥30% reduction in ISM-SAF TSS 6 months Parts 1, 2, and 3: Change in bone marrow mast cells Up to 5 years Parts 1, 2, and 3: Change from Baseline in ISM-SAF Score Up to 5 years Parts 1, 2, and 3: Change in Patients' Global Impression of Change (PGIC) Up to 5 years 1 - 7 (higher value represents worse symptom outcomes)
Parts 1, 2, and 3: Change in EuroQuol 5 Dimensions 5 Levels (EQ 5D-5L) Up to 5 years 0 - 100 (higher value represents better symptom outcomes)
Part 2: Proportion of patients with ≥50% reduction in ISM-SAF TSS 6 months Parts 1, 2, and 3: Change in KIT D816V allele burden in blood Up to 5 years Parts 1, 2, and 3: Change in Mastocytosis Quality of Life Questionnaire (MC-QoL) Up to 5 years Parts 1, 2, and 3: Change in 12-item Short Form Health Survey (SF-12) Up to 5 years 0 - 100 points (higher value represents better symptom outcomes)
Parts 1, 2, and 3: Safety of avapritinib as assessed by number of adverse events Up to 5 years CTCAE version 5.0
Parts 1, 2, and 3: Change in serum tryptase Up to 5 years
Trial Locations
- Locations (49)
University of Alabama at Birmingham
🇺🇸Birmingham, Alabama, United States
Mayo Clinic Hospital
🇺🇸Phoenix, Arizona, United States
Stanford Cancer Institute
🇺🇸Stanford, California, United States
Mayo Clinic Florida
🇺🇸Jacksonville, Florida, United States
H. Lee Moffitt Cancer Center
🇺🇸Tampa, Florida, United States
Winship Cancer Institute, Emory University
🇺🇸Atlanta, Georgia, United States
Rush University Medical Center
🇺🇸Chicago, Illinois, United States
University of Kansas Hospital
🇺🇸Kansas City, Kansas, United States
Brigham & Women's Hospital
🇺🇸Boston, Massachusetts, United States
Dana Farber Cancer Institute
🇺🇸Boston, Massachusetts, United States
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