Purpose

This is a randomized, double-blind, placebo-controlled, Phase 2/3 study comparing the efficacy and safety of elenestinib (BLU-263) + best supportive care (BSC) with placebo + BSC in patients with indolent systemic mastocytosis (ISM) whose symptoms are not adequately controlled by BSC. Parts 1 and 2 will enroll patients with ISM. Patients enrolled in Part 1 or Part 2 will roll over onto Part 3 to receive treatment with elenestinib in an open-label fashion following completion of the earlier Part. Part M will enroll patients with monoclonal mast cell activation syndrome (mMCAS). Part S will enroll participants with smoldering systemic mastocytosis (SSM). The study also includes PK groups that will enroll patients with ISM.

Conditions

Eligibility

Eligible Ages
Over 16 Years
Eligible Genders
All
Accepts Healthy Volunteers
No

Inclusion Criteria

All Patients -1. Patient must have an Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0 to 2. Part 1 and Part 2 - 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 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 < 20 ng/mL. - 9. Patients must have KIT D816V in peripheral blood (PB) or BM and/or CD25+ Mast cells in BM. - 10. Patients must have symptoms consistent with mast cell activation (despite BSC) in at least two organ systems characterized by cutaneous flushing, tachycardia, syncope, hypotension, diarrhea, nausea, vomiting and gastro-intestinal cramping) and serum blood tryptase (sBT) levels above 8 ng/mL OR Severe (Ring and Messmer grading ≥ II, recurrent anaphylaxis, including but not limited to hymenoptera venom, drug or food, regardless of sBT levels. PK Groups - 11. See inclusion criteria for All patients and Part 1/Part 2 - 12. Accrual may be limited to patients who have specific disease manifestations (ie, GI involvement) or are taking acid-reducing agents to better explore the impact of these features on PK. Part S: -13. Patient has confirmed diagnosis of SSM, confirmed by Central Pathology Review of BM biopsy and central review of B- and C-findings by WHO 2022 diagnostic criteria.

Exclusion Criteria

  • 1. Patient has been diagnosed with any of the following WHO systemic mastocytosis (SM) sub-classifications: cutaneous mastocytosis only, SM with an associated hematologic neoplasm of non-MC lineage (SM-AHN), 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.

Study Design

Phase
Phase 2/Phase 3
Study Type
Interventional
Allocation
Randomized
Intervention Model
Parallel Assignment
Intervention Model Description
In Part 1 of the study, participants with ISM will be randomly assigned to 1 of 3 doses of elenestinib + BSC or to placebo + BSC. Once the recommended dose (RD) of elenestinib is identified in Part 1, participants with ISM in Part 2 will be randomly assigned to receive elenestinib at the RD + BSC or matching placebo + BSC. Participants will be randomized 2:1 to elenestinib:placebo. In Part 3, participants who have completed treatment in Part 1 or Part 2 of the study (including those initially randomized to placebo) will participate in a long-term open-label extension, receiving elenestinib at the RD + BSC. In Part M of the study, participants with monoclonal mast cell activation syndrome will receive elenestinib + BSC at the RD in an open-label fashion. In Part S of the study, participants with smoldering systemic mastocytosis (SSM) will receive open-label elenestinib + BSC. The study also includes PK groups that will enroll patients with ISM
Primary Purpose
Treatment
Masking
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Arm Groups

ArmDescriptionAssigned Intervention
Experimental
(Part 1) Elenestinib Dose 1 + BSC
Patients will receive best supportive care (BSC) and Dose 1 of elenestinib. BSC will be determined on a per patient basis. Elenestinib will be administered orally, once daily until completion of Part 1.
  • Drug: Elenestinib
    Elenestinib oral tablet
    Other names:
    • BLU-263
Experimental
(Part 1) Elenestinib Dose 2 + BSC
Patients will receive BSC and Dose 2 of elenestinib. BSC will be determined on a per patient basis. Elenestinib will be administered orally, once daily until completion of Part 1.
  • Drug: Elenestinib
    Elenestinib oral tablet
    Other names:
    • BLU-263
Experimental
(Part 1) Elenestinib Dose 3 + BSC
Patients will receive BSC and Dose 3 of elenestinib. BSC will be determined on a per patient basis. Elenestinib will be administered orally, once daily until completion of Part 1.
  • Drug: Elenestinib
    Elenestinib oral tablet
    Other names:
    • BLU-263
Placebo Comparator
(Part 1) Placebo + BSC
Patients will receive BSC and matching placebo. BSC will be determined on a per patient basis. Placebo will be administered orally, once daily until completion of Part 1
  • Drug: Placebo
    Placebo oral tablet
Experimental
(Part 2) Elenestinib RD + BSC
Patients will receive BSC and the recommended dose (RD) of elenestinib. BSC will be determined on a per patient basis. Elenestinib will be administered orally, once daily for approximately 24 weeks
  • Drug: Elenestinib
    Elenestinib oral tablet
    Other names:
    • BLU-263
Placebo Comparator
(Part 2) Placebo + BSC
Patients will receive BSC and matching placebo. BSC will be determined on a per patient basis. Placebo will be administered orally, once daily once daily for approximately 24 weeks
  • Drug: Placebo
    Placebo oral tablet
Experimental
(Part 3) Elenestinib RD + BSC
Patients will receive open-label BSC and the RD of elenestinib for up to approximately 4 years.
  • Drug: Elenestinib
    Elenestinib oral tablet
    Other names:
    • BLU-263
Experimental
(Part M) Elenestinib RD + BSC
Patients will receive BSC and the RD of elenestinib. BSC will be determined on a per patient basis. Elenestinib will be administered orally, once daily for the duration of participation in the study.
  • Drug: Elenestinib
    Elenestinib oral tablet
    Other names:
    • BLU-263
Experimental
PK Groups (Dose 2 or Dose 3)
Patients will receive BSC and Dose 2 or Dose 3 of elenestinib. BSC will be determined on a per patient basis. Elenestinib will be administered orally for the duration of participation in the study.
  • Drug: Elenestinib
    Elenestinib oral tablet
    Other names:
    • BLU-263
Experimental
(Part S) Elenestinib + BSC
Participants with Smoldering Systemic Mastocytosis (SSM) will receive open-label BSC and elenestinib for up to approximately 4 years.
  • Drug: Elenestinib
    Elenestinib oral tablet
    Other names:
    • BLU-263

Recruiting Locations

University of Alabama at Birmingham
Birmingham, Alabama 35294

More Details

Status
Recruiting
Sponsor
Blueprint Medicines Corporation

Study Contact

Blueprint Medicines
617-714-6707
medinfo@blueprintmedicines.com

Notice

Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.