Indolent Systemic Mastocytosis (ISM) and monoclonal Mast Cell Activation Syndrome (mMCAS) MedDRA version: 20.1 Level: LLT Classification code 10056452 Term: Indolent systemic mastocytosis System Organ Class: 100000004864
Conditions
Interventions
Product Name: BLU-263
Product Code: BLU-263
Pharmaceutical Form: Tablet
INN or Proposed INN: BLU-263
CAS Number: 2505078-08-8
Current Sponsor code: BLU-263
Concentration unit: mg milligram(s)
Concent
Sponsors
Blueprint Medicines Corporation
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: All Patients -1. Patient must have an Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0 to 2. Part 1 only -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. Part 1 and Part 2 • 3. Patient has confirmed diagnosis of ISM, confirmed by Central Pathology Review of BM biopsy and central review of B- and C-findings by WHO diagnostic criteria. Archival biopsy may be used if completed within the past 12 months. • 4. Patient must have failed to achieve adequate symptom control for 1 or more Baseline symptoms, as determined by the Investigator, with at least 2 of the following symptomatic therapies administered: H1 blockers, H2 blockers, proton-pump inhibitors, leukotriene inhibitors, cromolyn sodium, corticosteroids, or omalizumab. • 5. Patients must have BSC for ISM symptom management stabilized for at least 14 days prior to starting screening procedures. • 6. For patients receiving corticosteroids, the dose must be = 20 mg/d prednisone or equivalent, and the dose must be stable for = 14 days. Part M • 7. Patients must have mMCAS, confirmed by Central Pathology Review of BM biopsy. An archival biopsy may be used if completed within the past 12 months. • 8. Patients must have tryptase =65 years) yes F.1.3.1 Number of subjects for this age range 17
Exclusion criteria
Exclusion criteria: Key Exclusion Criteria: • 1. Patient has been diagnosed with any of the following WHO systemic mastocytosis (SM) sub-classifications: cutaneous mastocytosis only, smoldering SM, SM with associated hematologic neoplasm, aggressive SM, mast cell leukemia, or mast cell sarcoma. • 2. Patient has been diagnosed with another myeloproliferative disorder. • 3. Patient has organ damage C-findings attributable to SM. • 4. Patient has clinically significant, uncontrolled, cardiovascular disease • 5. Patient has a QT interval corrected using Fridericia's formula (QTcF) > 480 msec. • 6. Patient has previously received treatment with any targeted KIT inhibitors. • 7. Patient has a history of a primary malignancy that has been diagnosed or required therapy within 3 years. The following prior malignancies are not exclusionary: completely resected basal cell and squamous cell skin cancer, curatively treated localized prostate cancer, and completely resected carcinoma in situ of any site. • 8. Time since any cytoreductive therapy including mastinib and midostaurin should be at least 5 half-lives or 14 days (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 screening period. • 9.Patient has received radiotherapy or psoralen and ultraviolet A (PUVA) therapy < 14 days before beginning the screening period.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Part 1: To determine RD of BLU-263. Part 2: To assess if treatment with BLU-263 improves outcomes compared to placebo + BSC, as assessed using the ISM-SAF. Part 3: - To assess the long-term safety and tolerability of treatment with BLU-263. - To assess the long-term efficacy of treatment with BLU-263. ;Secondary Objective: Part 1: -To assess the change in measures of mast cell burden from treatment with BLU-263 or placebo -To assess the change in ISM-SAF individual symptom scores from treatment with BLU-263 or placebo -To assess the time to achieve a 30% reduction in ISM-SAF TSS, ISM-SAF Gastrointestinal Symptom Score (GSS), ISM-SAF Skin Symptom Score (SSS), and ISM-SAF Neurocognitive Symptom Cluster Score Part 2: -To assess if treatment with BLU-263 improves outcomes compared to placebo, as assessed using serum tryptase -To assess if treatment with BLU-263 improves outcomes compared to placebo, as assessed using peripheral blood KIT D816V allele fraction -To assess if treatment with BLU-263 improves outcomes compared to placebo + BSC, as assessed using the mean change in ISM-SAF TSS from Baseline Part 3: -To assess the change in measures of mast cell burden -To assess the change in BSC usage for SM symptoms -To assess the change in ISM-SAF Individual Symptom Scores;Primary end point(s): Part 1 Safety and tolerability as determined by AEs, serious adverse events (SAEs), and changes in safety laboratory parameters, vital signs, and ECG evaluations PK and PD data The mean change in Indolent Systemic Mastocytosis-Symptom Assessment Form (ISM-SAF) Total Symptom Score (TSS) from Baseline at Week 13. Part 2 •Proportion of patients with moderate to severe ISM who achieve at least a 30% reduction in ISM-SAF TSS from Baseline at Week 25" Part 3 Safety and tolerability determined by AEs, SAEs, and changes in safety laboratory parameters, vital signs, and ECG evaluations The mean change in ISM-SAF TSS from BLU-263 Baseline (the last available observation | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Part 1: The mean change in the following measures from Baseline at Week 13: •Serum tryptase •KIT D816V allele fraction in blood •Bone marrow mast cells The mean change in ISM-SAF individual symptom scores from Baseline at Week 13 The time to achieve a 30% reduction in ISM-SAF TSS, ISM-SAF GSS, ISM-SAF SSS, and ISM-SAF Neurocognitive Symptom Cluster Score from randomization among patients who achieve such a reduction on or before Week 13 The mean change in the following measures from Baseline at Week 13: •Mastocytosis Quality of Life Questionnaire (MC-QoL) score •Patient Global Impression of Severity (PGI-S) score •Patient Global Impression of Change (PGI-C) score •Twelve-item Short Form Health Survey (SF-12) score •Five-level EuroQual 5D (EQ-5D-5L) score Additional exploratory endpoints shared across Part 1, Part 2, and Part 3 are detailed in Section 3.4 Part 2: Key Secondary Endpoint(s): - The proportion of patients who achieve at least a 50% reduction in serum tryptase from Baseline at Week 25, among patients with Baseline moderate to severe ISM and Baseline tryptase = 20 ng/mL. - The proportion of patients who achieve at least a 50% reduction in peripheral blood KIT D816V allele fraction, or a reduction to undetectable levels, from Baseline at Week 25, among patients with Baseline moderate to severe ISM and detectable mutation at Baseline. - The mean change in ISM-SAF from Baseline at Week 25, among patients with Baseline moderate to severe ISM - The proportion of patients who achieve at least a 50% reduction in bone marrow MCs, or a reduction to no aggregates, from Baseline at Week 25, among patients with Baseline moderate to severe ISM and aggregates at Baseline. Secondary Endpoint(s): - ORR, among all patients regardless of Baseline ISM-SAF TSS. - Part 2 Key Secondary Endpoints, among all patients regardless of Baseline ISM-SAF TSS. - The mean change in the following measures of MC burden from Baseline at Week 25, among patients with | — |
Countries
Australia, Austria, Belgium, Denmark, France, Germany, Italy, Netherlands, Norway, Portugal, Spain, Sweden, Switzerland, United Kingdom, United States
Contacts
Public ContactPatsy Folio
PPD
Outcome results
None listed