(HARBOR) Study to Evaluate Efficacy and Safety of BLU-263 Versus Placebo in Patients With Indolent Systemic Mastocytosis

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Brief Title

(HARBOR) Study to Evaluate Efficacy and Safety of BLU-263 Versus Placebo in Patients With Indolent Systemic Mastocytosis

Official Title

A Randomized, Double-Blind, Placebo-Controlled Phase 2/3 Study of BLU-263 in Indolent Systemic Mastocytosis

Brief Summary

      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. The study will be conducted in 4 parts. 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
      optional PK groups that may enroll patients with ISM.
    


Study Phase

Phase 2/Phase 3

Study Type

Interventional


Primary Outcome

Part 1: Recommended Dose (RD) in patients with ISM

Secondary Outcome

 Part 1: Mean change in measures of mast cell burden

Condition

Indolent Systemic Mastocytosis

Intervention

BLU-263

Study Arms / Comparison Groups

 (Part 1) BLU-263 Dose 1 + BSC
Description:  Patients will receive best supportive care (BSC) and Dose 1 of BLU-263 tablets. BSC will be determined on a per patient basis. BLU-263 will be administered orally, once daily until completion of Part 1.

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information


Recruitment Status

Drug

Estimated Enrollment

403

Start Date

July 23, 2021

Completion Date

June 2028

Primary Completion Date

August 2023

Eligibility Criteria

        Key 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 < 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.

        Optional PK Group

          -  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.
      

Gender

All

Ages

16 Years - N/A

Accepts Healthy Volunteers

No

Contacts

, 617-714-6707, [email protected]

Location Countries

United States

Location Countries

United States

Administrative Informations


NCT ID

NCT04910685

Organization ID

BLU-263-1201


Responsible Party

Sponsor

Study Sponsor

Blueprint Medicines Corporation


Study Sponsor

, , 


Verification Date

June 2021