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

Primary Purpose

Indolent Systemic Mastocytosis, Monoclonal Mast Cell Activation Syndrome

Status
Recruiting
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
BLU-263
Placebo
Sponsored by
Blueprint Medicines Corporation
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Indolent Systemic Mastocytosis

Eligibility Criteria

16 Years - undefined (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Arm Type

Experimental

Experimental

Experimental

Placebo Comparator

Experimental

Placebo Comparator

Experimental

Experimental

Experimental

Arm Label

(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)

Arm 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.

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.

Outcomes

Primary Outcome Measures

Part 1: Recommended Dose (RD) in patients with ISM
Selection of the RD to be used in Part 2, Part 3 and Part M of the study
Part 2: Proportion of responders, defined as ≥30% reduction in ISM-Symptom in Assessment Form (ISM-SAF) Total Symptom Score (TSS)
Response rate in patients with ISM
Part 3: Long-term safety and tolerability of BLU-263 as assessed by the number of adverse events and serious adverse events
Part 3: Mean change in Indolent Systemic Mastocytosis-Symptom Assessment Form (ISM-SAF) Total Symptom Score (TSS)
The ISM-SAF has a scale of 0-110. A decrease in score corresponds to improvement in symptoms

Secondary Outcome Measures

Part 1: Mean change in measures of mast cell burden
Part 1: Mean change in Indolent Systemic Mastocytosis-Symptom Assessment Form (ISM-SAF) Total Symptom Score (TSS)
The ISM-SAF has a scale of 0-110. A decrease in score corresponds to improvement in symptoms
Part 1: Mean change in Indolent Systemic Mastocytosis-Symptom Assessment Form (ISM-SAF) individual symptom scores
Each symptom in the ISM-SAF has a scale of 0-10. A decrease in score corresponds to improvement in symptoms
Part 1: Time to achieve 30% reduction inIndolent Systemic Mastocytosis-Symptom Assessment Form (ISM-SAF) scores
Time to achieve a 30% reduction in scores generated by the ISM-SAF. The ISM-SAF uses a score from 0-110 and a lower score represents lower symptom burden
Part 2: Proportion of patients with a ≥50% reduction in serum tryptase
Part 2: The proportion of patients who achieve at least a 50% reduction in peripheral blood KIT D816V allele fraction, or a reduction to undetectable levels.
Part 2: Mean change in Indolent Systemic Mastocytosis-Symptom Assessment Form (ISM-SAF) Total Symptom Score (TSS)
The ISM-SAF has a scale of 0-110. A decrease in score corresponds to improvement in symptoms
Part 2: Proportion of patients with a ≥50% reduction in bone marrow mast cells or reduction to no aggregates for patients with aggregates at Baseline
Part 2: Mean change in measures of mast cell burden
Part 2: Change in number of best supportive care medications
Part 2: Mean change in Indolent Systemic Mastocytosis-Symptom Assessment Form (ISM-SAF) individual symptom scores
Each symptom in the ISM-SAF has a scale of 0-10. A decrease in score corresponds to improvement in symptoms
Part 2: Change in Indolent Systemic Mastocytosis-Symptom Assessment Form (ISM-SAF) leading symptom score
Each symptom in the ISM-SAF has a scale of 0-10. A decrease in score corresponds to improvement in symptoms
Part 2: Time to achieve 30% reduction in Indolent Systemic Mastocytosis-Symptom Assessment Form (ISM-SAF) scores
Time to achieve a 30% reduction in scores generated by the ISM-SAF. The ISM-SAF uses a score from 0-10 and a lower score represents lower symptom burden
Part 2: Mean change in the Mast Cell Quality of Life (MC-QoL) score
The MC-QoL has a scale of 0-100, higher numbers represent more severe impairment to quality of life.
Part 2: Safety of BLU-263 as assessed by number of adverse events and serious adverse events
Part 3: Mean change in measures of mast cell burden
Part 3: Change in number of best supportive care medications
Part 3: Mean change in Indolent Systemic Mastocytosis-Symptom Assessment Form (ISM-SAF) individual symptom score
Each symptom in the ISM-SAF has a scale of 0-10. A decrease in score corresponds to improvement in symptoms
Part 3: Change in Indolent Systemic Mastocytosis-Symptom Assessment Form (ISM-SAF) leading symptom score
Each symptom in the ISM-SAF has a scale of 0-10. A decrease in score corresponds to improvement in symptoms
Part 3: Mean change in the Mast Cell Quality of Life (MC-QoL) score
The MC-QoL has a scale of 0-100, higher numbers represent more severe impairment to quality of life.
Part 3: Time to achieve 30% reduction in Indolent Systemic Mastocytosis-Symptom Assessment Form (ISM-SAF) Scores
Time to achieve a 30% reduction in scores generated by the ISM-SAF. The ISM-SAF uses a score from 0-110 and a lower score represents lower symptom burden

Full Information

First Posted
May 17, 2021
Last Updated
October 20, 2023
Sponsor
Blueprint Medicines Corporation
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1. Study Identification

Unique Protocol Identification Number
NCT04910685
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
Study Type
Interventional

2. Study Status

Record Verification Date
October 2023
Overall Recruitment Status
Recruiting
Study Start Date
November 30, 2021 (Actual)
Primary Completion Date
June 30, 2028 (Anticipated)
Study Completion Date
June 30, 2028 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Blueprint Medicines Corporation

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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. 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Indolent Systemic Mastocytosis, Monoclonal Mast Cell Activation Syndrome

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2, Phase 3
Interventional Study Model
Parallel Assignment
Model Description
In Part 1 of the study, patients with ISM will be randomly assigned to 1 of 3 doses of BLU-263 + BSC or to placebo + BSC. Once the recommended dose (RD) of BLU-263 is identified in Part 1, patients with ISM in Part 2 will be randomly assigned to receive BLU-263 at the RD + BSC or matching placebo + BSC. Patients will be randomized 2:1 to BLU-263:placebo. In Part 3, patients 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 BLU-263 at the RD + BSC. In Part M of the study patients with monoclonal mast cell activation syndrome will receive BLU-263 + BSC at the RD in an open-label fashion. The study also includes PK groups that will enroll patients with ISM
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
443 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
(Part 1) BLU-263 Dose 1 + BSC
Arm Type
Experimental
Arm 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.
Arm Title
(Part 1) BLU-263 Dose 2 + BSC
Arm Type
Experimental
Arm Description
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.
Arm Title
(Part 1) BLU-263 Dose 3 + BSC
Arm Type
Experimental
Arm Description
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.
Arm Title
(Part 1) Placebo + BSC
Arm Type
Placebo Comparator
Arm Description
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
Arm Title
(Part 2) BLU-263 RD + BSC
Arm Type
Experimental
Arm Description
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
Arm Title
(Part 2) Placebo + BSC
Arm Type
Placebo Comparator
Arm Description
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
Arm Title
(Part 3) BLU-263 RD + BSC
Arm Type
Experimental
Arm Description
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.
Arm Title
(Part M) BLU-263 RD + BSC
Arm Type
Experimental
Arm Description
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.
Arm Title
PK Groups (Dose 2 or Dose 3)
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
BLU-263
Intervention Description
BLU-263 tablet
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Placebo Tablet
Primary Outcome Measure Information:
Title
Part 1: Recommended Dose (RD) in patients with ISM
Description
Selection of the RD to be used in Part 2, Part 3 and Part M of the study
Time Frame
3 months
Title
Part 2: Proportion of responders, defined as ≥30% reduction in ISM-Symptom in Assessment Form (ISM-SAF) Total Symptom Score (TSS)
Description
Response rate in patients with ISM
Time Frame
6 months
Title
Part 3: Long-term safety and tolerability of BLU-263 as assessed by the number of adverse events and serious adverse events
Time Frame
up to 5 years
Title
Part 3: Mean change in Indolent Systemic Mastocytosis-Symptom Assessment Form (ISM-SAF) Total Symptom Score (TSS)
Description
The ISM-SAF has a scale of 0-110. A decrease in score corresponds to improvement in symptoms
Time Frame
up to 5 years
Secondary Outcome Measure Information:
Title
Part 1: Mean change in measures of mast cell burden
Time Frame
3 Months
Title
Part 1: Mean change in Indolent Systemic Mastocytosis-Symptom Assessment Form (ISM-SAF) Total Symptom Score (TSS)
Description
The ISM-SAF has a scale of 0-110. A decrease in score corresponds to improvement in symptoms
Time Frame
3 Months
Title
Part 1: Mean change in Indolent Systemic Mastocytosis-Symptom Assessment Form (ISM-SAF) individual symptom scores
Description
Each symptom in the ISM-SAF has a scale of 0-10. A decrease in score corresponds to improvement in symptoms
Time Frame
3 months
Title
Part 1: Time to achieve 30% reduction inIndolent Systemic Mastocytosis-Symptom Assessment Form (ISM-SAF) scores
Description
Time to achieve a 30% reduction in scores generated by the ISM-SAF. The ISM-SAF uses a score from 0-110 and a lower score represents lower symptom burden
Time Frame
3 months
Title
Part 2: Proportion of patients with a ≥50% reduction in serum tryptase
Time Frame
6 months
Title
Part 2: The proportion of patients who achieve at least a 50% reduction in peripheral blood KIT D816V allele fraction, or a reduction to undetectable levels.
Time Frame
6 months
Title
Part 2: Mean change in Indolent Systemic Mastocytosis-Symptom Assessment Form (ISM-SAF) Total Symptom Score (TSS)
Description
The ISM-SAF has a scale of 0-110. A decrease in score corresponds to improvement in symptoms
Time Frame
6 months
Title
Part 2: Proportion of patients with a ≥50% reduction in bone marrow mast cells or reduction to no aggregates for patients with aggregates at Baseline
Time Frame
6 months
Title
Part 2: Mean change in measures of mast cell burden
Time Frame
6 months
Title
Part 2: Change in number of best supportive care medications
Time Frame
6 Months
Title
Part 2: Mean change in Indolent Systemic Mastocytosis-Symptom Assessment Form (ISM-SAF) individual symptom scores
Description
Each symptom in the ISM-SAF has a scale of 0-10. A decrease in score corresponds to improvement in symptoms
Time Frame
6 months
Title
Part 2: Change in Indolent Systemic Mastocytosis-Symptom Assessment Form (ISM-SAF) leading symptom score
Description
Each symptom in the ISM-SAF has a scale of 0-10. A decrease in score corresponds to improvement in symptoms
Time Frame
6 months
Title
Part 2: Time to achieve 30% reduction in Indolent Systemic Mastocytosis-Symptom Assessment Form (ISM-SAF) scores
Description
Time to achieve a 30% reduction in scores generated by the ISM-SAF. The ISM-SAF uses a score from 0-10 and a lower score represents lower symptom burden
Time Frame
6 months
Title
Part 2: Mean change in the Mast Cell Quality of Life (MC-QoL) score
Description
The MC-QoL has a scale of 0-100, higher numbers represent more severe impairment to quality of life.
Time Frame
6 months
Title
Part 2: Safety of BLU-263 as assessed by number of adverse events and serious adverse events
Time Frame
up to 5 years
Title
Part 3: Mean change in measures of mast cell burden
Time Frame
approximately 5 years
Title
Part 3: Change in number of best supportive care medications
Time Frame
approximately 5 years
Title
Part 3: Mean change in Indolent Systemic Mastocytosis-Symptom Assessment Form (ISM-SAF) individual symptom score
Description
Each symptom in the ISM-SAF has a scale of 0-10. A decrease in score corresponds to improvement in symptoms
Time Frame
approximately 5 years
Title
Part 3: Change in Indolent Systemic Mastocytosis-Symptom Assessment Form (ISM-SAF) leading symptom score
Description
Each symptom in the ISM-SAF has a scale of 0-10. A decrease in score corresponds to improvement in symptoms
Time Frame
approximately 5 years
Title
Part 3: Mean change in the Mast Cell Quality of Life (MC-QoL) score
Description
The MC-QoL has a scale of 0-100, higher numbers represent more severe impairment to quality of life.
Time Frame
approximately 5 years
Title
Part 3: Time to achieve 30% reduction in Indolent Systemic Mastocytosis-Symptom Assessment Form (ISM-SAF) Scores
Description
Time to achieve a 30% reduction in scores generated by the ISM-SAF. The ISM-SAF uses a score from 0-110 and a lower score represents lower symptom burden
Time Frame
12 months
Other Pre-specified Outcome Measures:
Title
Part M: the proportion of patient who achieve at least a 30% reduction in Mast Cell Quality of Life (MC-QoL) score
Time Frame
6 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
16 Years
Accepts Healthy Volunteers
No
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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Blueprint Medicines
Phone
617-714-6707
Email
medinfo@blueprintmedicines.com
Facility Information:
Facility Name
University of Alabama at Birmingham
City
Birmingham
State/Province
Alabama
ZIP/Postal Code
35294
Country
United States
Individual Site Status
Recruiting
Facility Name
Stanford Cancer Institute
City
Palo Alto
State/Province
California
ZIP/Postal Code
94305
Country
United States
Individual Site Status
Recruiting
Facility Name
Brigham and Women's Hospital
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02115
Country
United States
Individual Site Status
Recruiting
Facility Name
Michigan Medicine University of Michigan
City
Ann Arbor
State/Province
Michigan
ZIP/Postal Code
48109
Country
United States
Individual Site Status
Recruiting
Facility Name
Mayo Clinic
City
Rochester
State/Province
Minnesota
ZIP/Postal Code
55902
Country
United States
Individual Site Status
Recruiting
Facility Name
Roswell Park Cancer Institute
City
Buffalo
State/Province
New York
ZIP/Postal Code
14263
Country
United States
Individual Site Status
Recruiting
Facility Name
Columbia University Medical Center
City
New York
State/Province
New York
ZIP/Postal Code
10032
Country
United States
Individual Site Status
Recruiting
Facility Name
University of Cincinnati Medical Center
City
Cincinnati
State/Province
Ohio
ZIP/Postal Code
45219
Country
United States
Individual Site Status
Recruiting
Facility Name
The University of Texas, MD Anderson Cancer Center
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Individual Site Status
Recruiting
Facility Name
Huntsman Cancer Institute, University of Utah
City
Salt Lake City
State/Province
Utah
ZIP/Postal Code
84112
Country
United States
Individual Site Status
Recruiting
Facility Name
Princess Alexandra Hospital
City
Woolloongabba
State/Province
Queensland
Country
Australia
Individual Site Status
Recruiting
Facility Name
The Alfred Hospital
City
Melbourne
State/Province
Victoria
ZIP/Postal Code
3004
Country
Australia
Individual Site Status
Recruiting
Facility Name
Kepler Universitatsklinikum, Med Campus III. Clinic of Internal Medicine 3 - Hematology and Oncology
City
Linz
ZIP/Postal Code
4021
Country
Austria
Individual Site Status
Recruiting
Facility Name
Unitversitair Ziekenhuis Antwerpen
City
Edegem
State/Province
Antwerpen
Country
Belgium
Individual Site Status
Recruiting
Facility Name
CHU Amiens-Picardie
City
Amiens
ZIP/Postal Code
80000
Country
France
Individual Site Status
Recruiting
Facility Name
CHU de Caen
City
Caen
Country
France
Individual Site Status
Recruiting
Facility Name
CHU Grenoble
City
Grenoble Cedex 9
ZIP/Postal Code
38043
Country
France
Individual Site Status
Recruiting
Facility Name
CHU de Limoges
City
Limoges Cedex
ZIP/Postal Code
87042
Country
France
Individual Site Status
Recruiting
Facility Name
CHU de Nantes
City
Nantes
ZIP/Postal Code
44093
Country
France
Individual Site Status
Recruiting
Facility Name
Hôpital de la Pitié Salpétrière
City
Paris
ZIP/Postal Code
75013
Country
France
Individual Site Status
Recruiting
Facility Name
Hôpital Necker - Départementd 'HématologieA dultes
City
Paris
ZIP/Postal Code
75015
Country
France
Individual Site Status
Recruiting
Facility Name
CHU de Poitiers
City
Poitiers
ZIP/Postal Code
86000
Country
France
Individual Site Status
Recruiting
Facility Name
CHU Toulouse - Hopital Larrey
City
Toulouse
Country
France
Individual Site Status
Recruiting
Facility Name
Universitätsklinikum RWTH Aachen Klinik für Hämatologie, Onkologie, Hämostaseologie und Stammzelltransplantation
City
Aachen
Country
Germany
Individual Site Status
Recruiting
Facility Name
Charité - Universitätsmedizin Berlin Institute of Allergology
City
Berlin
ZIP/Postal Code
12203
Country
Germany
Individual Site Status
Recruiting
Facility Name
University Clinic Erlangen
City
Erlangen
ZIP/Postal Code
91054
Country
Germany
Individual Site Status
Recruiting
Facility Name
University Clinic Hamburg Eppendorf
City
Hamburg
ZIP/Postal Code
20246
Country
Germany
Individual Site Status
Recruiting
Facility Name
Universitätsmedizin Mannheim III. Medizinische Klinik Universität Heidelberg Medizinische Fakultät Mannheim
City
Mannheim
ZIP/Postal Code
68167
Country
Germany
Individual Site Status
Recruiting
Facility Name
LMU Klinikum
City
Munich
ZIP/Postal Code
80377
Country
Germany
Individual Site Status
Recruiting
Facility Name
Dipartimentod i Oncoematologia Istituto Scientifico Romagnolop er lo studio e la cura dei tumori (IRST)- IRCCS
City
Meldola
State/Province
Forli-Cesena
ZIP/Postal Code
47014
Country
Italy
Individual Site Status
Recruiting
Facility Name
UOC Ematologia
City
Milano
State/Province
Lombardia
ZIP/Postal Code
20122
Country
Italy
Individual Site Status
Recruiting
Facility Name
SOD Ematologia (Ambulatori)- AOUC Azienda Ospedaliero Universitaria Careggi
City
Firenze
State/Province
Toscana
ZIP/Postal Code
50134
Country
Italy
Individual Site Status
Recruiting
Facility Name
Unita Operativa di Ematologia AOU Policlinico S. Orsola-Malpighi
City
Bologna
ZIP/Postal Code
40138
Country
Italy
Individual Site Status
Recruiting
Facility Name
S.C. Ematologia Fondazione I.R.C.C.S. Policlinico San Matteo
City
Pavia
ZIP/Postal Code
27100
Country
Italy
Individual Site Status
Recruiting
Facility Name
S.S.D. Immunologia Clinica e Allergologia Azienda Ospedaliera Universitaria San Giovanni di Dio e Ruggi d'Aragona
City
Salerno
ZIP/Postal Code
84131
Country
Italy
Individual Site Status
Recruiting
Facility Name
Unità Operativa di Allergologia Azienda Ospedaliera Universitaria Integrata di Verona
City
Verona
ZIP/Postal Code
37126
Country
Italy
Individual Site Status
Recruiting
Facility Name
ErasmusMC
City
Rotterdam
State/Province
Zuid-Holland
ZIP/Postal Code
3015 GD
Country
Netherlands
Individual Site Status
Recruiting
Facility Name
University Medical Center Groningen
City
Groningen
ZIP/Postal Code
9713 GZ
Country
Netherlands
Individual Site Status
Recruiting
Facility Name
Oslo University Hospital
City
Oslo
ZIP/Postal Code
N-0424
Country
Norway
Individual Site Status
Recruiting
Facility Name
Centro Hospitalar de Lisboa Central, E.P.E. - Hospital de Santo Antonio dos Capuchos
City
Lisbon
ZIP/Postal Code
1169-050
Country
Portugal
Individual Site Status
Recruiting
Facility Name
CHUPorto, EPE - Hospital de Santo António
City
Porto
ZIP/Postal Code
4099-001
Country
Portugal
Individual Site Status
Recruiting
Facility Name
Centro Hospitalar Universitario Sao Joao, E.P.E.
City
Porto
ZIP/Postal Code
4200-139
Country
Portugal
Individual Site Status
Recruiting
Facility Name
Hospital Universitario Vall d'Hebron
City
Barcelona
Country
Spain
Individual Site Status
Recruiting
Facility Name
Hospital Universitario Ramon y Cajal
City
Madrid
ZIP/Postal Code
28034
Country
Spain
Individual Site Status
Recruiting
Facility Name
Hospital Virgen del Valle - Instituto de Estudios de Mastocitosis de Castilla-La Mancha
City
Toledo
ZIP/Postal Code
45071
Country
Spain
Individual Site Status
Recruiting
Facility Name
University Hospital Basel
City
Basel
ZIP/Postal Code
C-4031
Country
Switzerland
Individual Site Status
Recruiting
Facility Name
Luzerner Kantonsspital
City
Luzern
ZIP/Postal Code
6000
Country
Switzerland
Individual Site Status
Recruiting
Facility Name
University Hospital of Wales
City
Cardiff
State/Province
Wales
ZIP/Postal Code
CF14 4XW
Country
United Kingdom
Individual Site Status
Recruiting
Facility Name
Cancer and Haematology Centre
City
Oxford
ZIP/Postal Code
OX3 7LE
Country
United Kingdom
Individual Site Status
Recruiting

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

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

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