Study to assess the safety and efficacy of Avapritinib (BLU-285) in patients with indolent and systemic mastocytosis

Belgium, Canada, Denmark, France, Germany, Italy, Netherlands, Norway, Spain, Sweden, Switzerland, United Kingdom, United States (ICTRP)

Identifiant de l'essai ICTRP
NCT03731260 (ICTRP)

Titre officiel (approuvé par le comité d'éthique)
3-teilige, randomisierte, doppelblinde, placebokontrollierte Studie der Phase II zur Beurteilung der Sicherheit und Wirksamkeit von Avapritinib (BLU 285), eines selektiven, gezielt auf die KIT-Mutation einwirkenden Tyrosinkinasehemmers, bei indolenter und schwelender systemischer Mastozytose, deren Symptome sich durch eine Standardtherapie nur unzureichend kontrollieren lassen (BASEC)

Titre académique
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 (ICTRP)

Titre public
(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 (ICTRP)

Maladie en cours d'investigation
Indolent Systemic Mastocytosis (ICTRP)

Intervention étudiée
Drug: AvapritinibDrug: Placebo (ICTRP)

Type d'essai
Interventional (ICTRP)

Plan de l'étude
Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor). (ICTRP)

Critères d'inclusion/exclusion
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. (ICTRP)

non disponible

Critères d'évaluation principaux et secondaires
Part 1: Recommended Phase 2 dose (RP2D) in patients with ISM;Part 2: Mean change in ISM Symptom Assessment Form (ISM-SAF) total symptom score (TSS) as compared to placebo;Part 3: Number of Participants with Adverse Events (ICTRP)

Part 2: Proportion of patients with a =50% reduction in serum tryptase;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;Part 2: Proportion of patients with =50% reduction in ISM-SAF TSS;Part 2: Proportion of patients with =30% reduction in ISM-SAF TSS;Part 2: Proportion of patients with a =50% reduction in bone marrow mast cells or no aggregates for patients with aggregates at Baseline;Parts 1, 2, and 3: Change in serum tryptase;Parts 1, 2, and 3: Change in KIT D816V allele burden in blood;Parts 1, 2, and 3: Change in bone marrow mast cells;Parts 1, 2, and 3: Change in best supportive care (BSC) concomitant medication usage;Parts 1, 2, and 3: Change from Baseline in ISM-SAF Score;Parts 1, 2, and 3: Change in Mastocytosis Quality of Life Questionnaire (MC-QoL);Parts 1, 2, and 3: Change in Patient's Global Impression of Symptom Severity (PGIS);Parts 1, 2, and 3: Change in 12-item Short Form Health Survey (SF-12);Parts 1, 2, and 3: Change in Patients' Global Impression of Change (PGIC);Parts 1, 2, and 3: Change in EuroQuol 5 Dimensions 5 Levels (EQ 5D-5L);Parts 1, 2, and 3: Safety of avapritinib as assessed by number of adverse events (ICTRP)

Date d'enregistrement
30.10.2018 (ICTRP)

Inclusion du premier participant
non disponible

Sponsors secondaires
non disponible

Contacts supplémentaires
Blueprint Medicines, medinfo@blueprintmedicines.com, 617-714-6707 (ICTRP)

ID secondaires
2018-000588-99, BLU-285-2203 (ICTRP)

Résultats-Données individuelles des participants
non disponible

Informations complémentaires sur l'essai
https://clinicaltrials.gov/study/NCT03731260 (ICTRP)