(HARBOR) Study to Evaluate Efficacy and Safety of BLU-263 Versus Placebo in Patients With Indolent Systemic Mastocytosis
Indolent Systemic Mastocytosis, Monoclonal Mast Cell Activation Syndrome
About this trial
This is an interventional treatment trial for Indolent Systemic Mastocytosis
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 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.
Sites / Locations
- University of Alabama at BirminghamRecruiting
- Stanford Cancer InstituteRecruiting
- Brigham and Women's HospitalRecruiting
- Michigan Medicine University of MichiganRecruiting
- Mayo ClinicRecruiting
- Roswell Park Cancer InstituteRecruiting
- Columbia University Medical CenterRecruiting
- University of Cincinnati Medical CenterRecruiting
- The University of Texas, MD Anderson Cancer CenterRecruiting
- Huntsman Cancer Institute, University of UtahRecruiting
- Princess Alexandra HospitalRecruiting
- The Alfred HospitalRecruiting
- Kepler Universitatsklinikum, Med Campus III. Clinic of Internal Medicine 3 - Hematology and OncologyRecruiting
- Unitversitair Ziekenhuis AntwerpenRecruiting
- CHU Amiens-PicardieRecruiting
- CHU de CaenRecruiting
- CHU GrenobleRecruiting
- CHU de LimogesRecruiting
- CHU de NantesRecruiting
- Hôpital de la Pitié SalpétrièreRecruiting
- Hôpital Necker - Départementd 'HématologieA dultesRecruiting
- CHU de PoitiersRecruiting
- CHU Toulouse - Hopital LarreyRecruiting
- Universitätsklinikum RWTH Aachen Klinik für Hämatologie, Onkologie, Hämostaseologie und StammzelltransplantationRecruiting
- Charité - Universitätsmedizin Berlin Institute of AllergologyRecruiting
- University Clinic ErlangenRecruiting
- University Clinic Hamburg EppendorfRecruiting
- Universitätsmedizin Mannheim III. Medizinische Klinik Universität Heidelberg Medizinische Fakultät MannheimRecruiting
- LMU KlinikumRecruiting
- Dipartimentod i Oncoematologia Istituto Scientifico Romagnolop er lo studio e la cura dei tumori (IRST)- IRCCSRecruiting
- UOC EmatologiaRecruiting
- SOD Ematologia (Ambulatori)- AOUC Azienda Ospedaliero Universitaria CareggiRecruiting
- Unita Operativa di Ematologia AOU Policlinico S. Orsola-MalpighiRecruiting
- S.C. Ematologia Fondazione I.R.C.C.S. Policlinico San MatteoRecruiting
- S.S.D. Immunologia Clinica e Allergologia Azienda Ospedaliera Universitaria San Giovanni di Dio e Ruggi d'AragonaRecruiting
- Unità Operativa di Allergologia Azienda Ospedaliera Universitaria Integrata di VeronaRecruiting
- ErasmusMCRecruiting
- University Medical Center GroningenRecruiting
- Oslo University HospitalRecruiting
- Centro Hospitalar de Lisboa Central, E.P.E. - Hospital de Santo Antonio dos CapuchosRecruiting
- CHUPorto, EPE - Hospital de Santo AntónioRecruiting
- Centro Hospitalar Universitario Sao Joao, E.P.E.Recruiting
- Hospital Universitario Vall d'HebronRecruiting
- Hospital Universitario Ramon y CajalRecruiting
- Hospital Virgen del Valle - Instituto de Estudios de Mastocitosis de Castilla-La ManchaRecruiting
- University Hospital BaselRecruiting
- Luzerner KantonsspitalRecruiting
- University Hospital of WalesRecruiting
- Cancer and Haematology CentreRecruiting
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm 5
Arm 6
Arm 7
Arm 8
Arm 9
Experimental
Experimental
Experimental
Placebo Comparator
Experimental
Placebo Comparator
Experimental
Experimental
Experimental
(Part 1) BLU-263 Dose 1 + BSC
(Part 1) BLU-263 Dose 2 + BSC
(Part 1) BLU-263 Dose 3 + BSC
(Part 1) Placebo + BSC
(Part 2) BLU-263 RD + BSC
(Part 2) Placebo + BSC
(Part 3) BLU-263 RD + BSC
(Part M) BLU-263 RD + BSC
PK Groups (Dose 2 or Dose 3)
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.
Patients will receive best supportive care (BSC) and Dose 2 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.
Patients will receive best supportive care (BSC) and Dose 3 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.
Patients will receive best supportive care (BSC) and matching placebo tablets. BSC will be determined on a per patient basis. Placebo will be administered orally, once daily until completion of Part 1
Patients will receive best supportive care (BSC) and the recommended dose (RD) of BLU-263 tablets. BSC will be determined on a per patient basis. BLU-263 will be administered orally, once daily for approximately 24 weeks
Patients will receive best supportive care (BSC) and matching placebo tablets. BSC will be determined on a per patient basis. Placebo will be administered orally, once daily once daily for approximately 24 weeks
Patients will receive best supportive care (BSC) and the recommended dose (RD) of BLU-263 tablet in an open-label fashion for up to 5 years.
Patients will receive best supportive care (BSC) and the recommended dose (RD) of BLU-263 tablets. BSC will be determined on a per patient basis. BLU-263 will be administered orally, once daily for the duration of participation in the study.
Patients will receive best supportive care (BSC) and Dose 2 or Dose 3 of BLU-263 tablets. BSC will be determined on a per patient basis. BLU-263 will be administered orally for the duration of participation in the study.