Gene Therapy Clinical Trials
(HARBOR) Study to Evaluate Efficacy and Safety of BLU-263 Versus Placebo in Patients With Indolent Systemic Mastocytosis
This is a randomized, double-blind, placebo-controlled, Phase 2/3 study comparing the efficacy and safety of 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 BLU-263 in an open-label fashion following completion of the earlier Part. Part M will enroll patients with monoclonal mast cell activation syndrome (mMCAS). The study also includes PK groups that will enroll patients with ISM.
Stanford is currently accepting patients for this trial.
Intervention(s):
- drug: BLU-263
- drug: Placebo
Eligibility
Key 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.
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.
Ages Eligible for Study
16 Years - N/A
Genders Eligible for Study
All
Now accepting new patients
Contact Information
Stanford University
School of Medicine
300 Pasteur Drive
Stanford,
CA
94305
Joanna Denise De Vore
denised@stanford.edu
Recruiting