(PIONEER) Study to Evaluate Efficacy and Safety of Avapritinib (BLU-285), A Selective KIT Mutation-targeted Tyrosine Kinase Inhibitor, Versus Placebo in Patients With Indolent Systemic Mastocytosis
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| ClinicalTrials.gov Identifier: NCT03731260 |
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Recruitment Status :
Active, not recruiting
First Posted : November 6, 2018
Last Update Posted : September 30, 2022
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Sponsor:
Blueprint Medicines Corporation
Information provided by (Responsible Party):
Blueprint Medicines Corporation
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Brief Summary:
This is a Phase 2, randomized, double-blind, placebo-controlled study comparing the efficacy and safety of avapritinib + 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 3 parts. All patients will receive treatment with avapritinib during Part 3 including those rolling over from the placebo group.
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Indolent Systemic Mastocytosis | Drug: Avapritinib Drug: Placebo | Phase 2 |
| Study Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 251 participants |
| Allocation: | Randomized |
| Intervention Model: | Parallel Assignment |
| Intervention Model Description: | In Part 1 of the study, patients will be randomly assigned to 1 of 3 doses of avapritinib or to placebo + BSC. Once the recommended phase 2 dose (RP2D) of avapritinib is identified in Part 1, patients in Part 2 will be randomly assigned to receive avapritinib at the RP2D + BSC or matching placebo + BSC. In Part 3, patients who have completed treatment in Part 1 or Part 2 of the study (including those initially randomized to placebo) may participate in a long-term open-label extension, receiving avapritinib at the RP2D + BSC. |
| Masking: | Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor) |
| Primary Purpose: | Treatment |
| Official Title: | A 3-Part, Randomized, Double-Blind, Placebo-Controlled Phase 2 Study to Evaluate Safety and Efficacy of Avapritinib (BLU-285), a Selective KIT Mutation-Targeted Tyrosine Kinase Inhibitor, in Indolent and Smoldering Systemic Mastocytosis With Symptoms Inadequately Controlled With Standard Therapy |
| Actual Study Start Date : | April 16, 2019 |
| Actual Primary Completion Date : | June 21, 2022 |
| Estimated Study Completion Date : | January 31, 2027 |
Resource links provided by the National Library of Medicine
MedlinePlus Genetics related topics:
Systemic mastocytosis
Drug Information available for:
Avapritinib
| Arm | Intervention/treatment |
|---|---|
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Experimental: (Part 1) Avapritinib Dose 1 + BSC
Avapritinib will be administered orally in continuous 28-day cycles
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Drug: Avapritinib
Avapritinib tablet
Other Name: BLU-285 |
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Experimental: (Part 1) Avapritinib Dose 2 + BSC
Avapritinib will be administered orally in continuous 28-day cycles
|
Drug: Avapritinib
Avapritinib tablet
Other Name: BLU-285 |
|
Experimental: (Part 1) Avapritinib Dose 3 + BSC
Avapritinib will be administered orally in continuous 28-day cycles
|
Drug: Avapritinib
Avapritinib tablet
Other Name: BLU-285 |
|
Placebo Comparator: (Part 1) Placebo + BSC
Placebo will be administered orally in continuous 28-day cycles
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Drug: Placebo
Placebo tablet |
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Experimental: (Part 2) Avapritinib RP2D + BSC
Avapritinib will be administered orally in continuous 28-day cycles
|
Drug: Avapritinib
Avapritinib tablet
Other Name: BLU-285 |
|
Placebo Comparator: (Part 2) Placebo + BSC
Placebo will be administered orally in continuous 28-day cycles
|
Drug: Placebo
Placebo tablet |
|
Experimental: (Part 3) Avapritinib RP2D + BSC
Avapritinib will be administered orally in continuous 28-day cycles
|
Drug: Avapritinib
Avapritinib tablet
Other Name: BLU-285 |
Primary Outcome Measures :
- Part 1: Recommended Phase 2 dose (RP2D) in patients with ISM [ Time Frame: 9 months ]
- Part 2: Mean change in ISM Symptom Assessment Form (ISM-SAF) total symptom score (TSS) [ Time Frame: 6 months ]0 - 110 points (higher value represents worse symptom outcomes)
Secondary Outcome Measures :
- Part 2: Proportion of patients with a ≥50% reduction in serum tryptase [ Time Frame: 6 months ]
- Part 2: Proportion of patients with a ≥50% reduction in peripheral blood V-kit Hardy-Zuckerman 4 feline sarcoma viral oncogene homolog aspartate 816 valine (KIT D816V) allele fraction or undetectable for patients with detectable mutation at Baseline [ Time Frame: 6 months ]
- Part 2: Proportion of patients with ≥50% reduction in ISM-SAF TSS [ Time Frame: 6 months ]
- Part 2: Proportion of patients with ≥30% reduction in ISM-SAF TSS [ Time Frame: 6 months ]
- Part 2: Proportion of patients with a ≥50% reduction in bone marrow mast cells or no aggregates for patients with aggregates at Baseline [ Time Frame: 6 months ]
- Change in serum tryptase [ Time Frame: Up to 5 years ]
- Change in KIT D816V allele burden in blood [ Time Frame: Up to 5 years ]
- Change in bone marrow mast cells [ Time Frame: Up to 1 year after the end of Part 1 and Part 2 ]
- Change in best supportive care (BSC) concomitant medication usage [ Time Frame: Up to 5 years ]
- Change in Mastocytosis Quality of Life Questionnaire (MC-QoL) [ Time Frame: Each study visit through Part 3 Cycle 12 (28-day cycles) ]0 - 100 points (higher value represents worse symptom outcomes)
- Change in Patient's Global Impression of Symptom Severity (PGIS) [ Time Frame: Each study visit through Part 3 Cycle 12 (28-day cycles) ]0 - 10 points (higher value represents worse symptom outcomes)
- Change in 12-item Short Form Health Survey (SF-12) [ Time Frame: Each study visit through Part 3 Cycle 12 (28-day cycles) ]0 - 100 points (higher value represents better symptom outcomes)
- Change in Patients' Global Impression of Change (PGIC) [ Time Frame: Each study visit through Part 3 Cycle 12 (28-day cycles) ]1 - 7 (higher value represents worse symptom outcomes)
- Change in EuroQuol 5 Dimensions 5 Levels (EQ 5D-5L) [ Time Frame: Each study visit through Part 3 Cycle 12 (28-day cycles) ]0 - 100 (higher value represents better symptom outcomes)
- Safety of avapritinib as assessed by number of adverse events [ Time Frame: Up to 5 years ]CTCAE version 5.0
- Part 1 and Part 2 only: Area Under Curve (0 to Tau) for avapritinib [ Time Frame: Every cycle (28 days) up to Cycle 4 (Part 1) and Cycle 7 (Part 2) ]h•ng/mL
Information from the National Library of Medicine
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
| Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Criteria
Key Inclusion Criteria:
- 1. Patient must have SM, confirmed by Central Pathology Review of BM biopsy, and central review of B- and C-findings by WHO diagnostic criteria.
- 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 must have failed to achieve adequate symptom control for 1 or more Baseline symptoms.
- 4. For patients receiving corticosteroids, the dose must be ≤ 20 mg/d prednisone or equivalent, and the dose must be stable for ≥ 14 days.
- 5. Patient must have an Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 to 2.
Key Exclusion Criteria:
- 1. Patient has been diagnosed with any of the following WHO SM subclassifications: cutaneous mastocytosis only, smoldering SM, SM with associated hematologic neoplasm, aggressive SM, mast cell leukemia, or mast cell sarcoma.
- 2. Patient must not have received prior treatment with avapritinib.
- 3. Patient must not have had any cytoreductive therapy including but not limited to masitinib and midostaurin, or investigational agent for < 14 days or 5 half-lives of the drug (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 14-day ISM-SAF eligibility TSS assessment.
- 4. Patient must not have received radiotherapy or psoralen and ultraviolet A (PUVA) therapy < 14 days before beginning the 14-day ISM-SAF eligibility TSS assessment.
- 5. Patient must not have received any hematopoietic growth factor the preceding 14 days before beginning the 14-day ISM-SAF eligibility TSS assessment.
- 6. Patient must not have a QT interval corrected using Fridericia's formula (QTcF) of > 480 msec.
Information from the National Library of Medicine
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03731260
Locations
Show 49 study locations
Sponsors and Collaborators
Blueprint Medicines Corporation
Additional Information:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
| Responsible Party: | Blueprint Medicines Corporation |
| ClinicalTrials.gov Identifier: | NCT03731260 |
| Other Study ID Numbers: |
BLU-285-2203 2018-000588-99 ( EudraCT Number ) |
| First Posted: | November 6, 2018 Key Record Dates |
| Last Update Posted: | September 30, 2022 |
| Last Verified: | September 2022 |
| Studies a U.S. FDA-regulated Drug Product: | Yes |
| Studies a U.S. FDA-regulated Device Product: | No |
Additional relevant MeSH terms:
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Mastocytosis Mastocytosis, Systemic Neoplasms, Connective Tissue Neoplasms, Connective and Soft Tissue |
Neoplasms by Histologic Type Neoplasms Mast Cell Activation Disorders Immune System Diseases |