TriangleNCT03731260 · CITED IN SOURCE DOCUMENTS
(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
An NCI or FDA source cites this study. A citation does not establish that it applies to an individual diagnosis.
- Phase
- PHASE2
- Status at capture
- ACTIVE NOT RECRUITING
- Registry last update
- 2025-09-23
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.
Open the original ClinicalTrials.gov record → · Download preserved record
What did the study report?
Outcomes, safety and baseline populations are separate source sections. Quality-of-life measures appear under their original outcome titles.
No posted result sections were captured. Registered plans do not establish that a treatment works.
Who could take part
- eligibility 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.
- healthy Volunteers
- false
- minimum Age
- 18 Years
- sex
- ALL
- std Ages
- ADULT
- OLDER_ADULT
Treatment arms and interventions
- arm Groups
- description
- Avapritinib will be administered orally in continuous 28-day cycles
- intervention Names
- Drug: Avapritinib
- label
- (Part 1) Avapritinib Dose 1 + BSC
- type
- EXPERIMENTAL
- description
- Avapritinib will be administered orally in continuous 28-day cycles
- intervention Names
- Drug: Avapritinib
- label
- (Part 1) Avapritinib Dose 2 + BSC
- type
- EXPERIMENTAL
- description
- Avapritinib will be administered orally in continuous 28-day cycles
- intervention Names
- Drug: Avapritinib
- label
- (Part 1) Avapritinib Dose 3 + BSC
- type
- EXPERIMENTAL
- description
- Placebo will be administered orally in continuous 28-day cycles
- intervention Names
- Drug: Placebo
- label
- (Part 1) Placebo + BSC
- type
- PLACEBO_COMPARATOR
- description
- Avapritinib will be administered orally in continuous 28-day cycles
- intervention Names
- Drug: Avapritinib
- label
- (Part 2) Avapritinib RP2D + BSC
- type
- EXPERIMENTAL
- description
- Placebo will be administered orally in continuous 28-day cycles
- intervention Names
- Drug: Placebo
- label
- (Part 2) Placebo + BSC
- type
- PLACEBO_COMPARATOR
- description
- Avapritinib will be administered orally in continuous 28-day cycles
- intervention Names
- Drug: Avapritinib
- label
- (Part 3) Avapritinib RP2D + BSC
- type
- EXPERIMENTAL
- interventions
- arm Group Labels
- (Part 1) Avapritinib Dose 1 + BSC
- (Part 1) Avapritinib Dose 2 + BSC
- (Part 1) Avapritinib Dose 3 + BSC
- (Part 2) Avapritinib RP2D + BSC
- (Part 3) Avapritinib RP2D + BSC
- description
- Avapritinib tablet
- name
- Avapritinib
- other Names
- BLU-285
- type
- DRUG
- arm Group Labels
- (Part 1) Placebo + BSC
- (Part 2) Placebo + BSC
- description
- Placebo tablet
- name
- Placebo
- type
- DRUG
Study design
- allocation
- RANDOMIZED
- intervention Model
- PARALLEL
- 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 Info
- masking
- QUADRUPLE
- who Masked
- PARTICIPANT
- CARE_PROVIDER
- INVESTIGATOR
- OUTCOMES_ASSESSOR
- primary Purpose
- TREATMENT
Enrollment
- count
- 251
- type
- ACTUAL
Registered outcome plans (not posted results)
- primary Outcomes
- measure
- Part 1: Recommended Phase 2 dose (RP2D) in patients with ISM
- time Frame
- 9 months
- description
- 0 - 110 points (higher value represents worse symptom outcomes)
- measure
- Part 2: Mean change in ISM Symptom Assessment Form (ISM-SAF) total symptom score (TSS) as compared to placebo
- time Frame
- 6 months
- measure
- Part 3: Number of Participants with Adverse Events
- time Frame
- Up to 5 years
- secondary Outcomes
- measure
- Part 2: Proportion of patients with a ≥50% reduction in serum tryptase
- time Frame
- 6 months
- measure
- 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
- measure
- Part 2: Proportion of patients with ≥50% reduction in ISM-SAF TSS
- time Frame
- 6 months
- measure
- Part 2: Proportion of patients with ≥30% reduction in ISM-SAF TSS
- time Frame
- 6 months
- measure
- 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
- measure
- Parts 1, 2, and 3: Change in serum tryptase
- time Frame
- Up to 5 years
- measure
- Parts 1, 2, and 3: Change in KIT D816V allele burden in blood
- time Frame
- Up to 5 years
- measure
- Parts 1, 2, and 3: Change in bone marrow mast cells
- time Frame
- Up to 5 years
- measure
- Parts 1, 2, and 3: Change in best supportive care (BSC) concomitant medication usage
- time Frame
- Up to 5 years
- measure
- Parts 1, 2, and 3: Change from Baseline in ISM-SAF Score
- time Frame
- Up to 5 years
- measure
- Parts 1, 2, and 3: Change in Mastocytosis Quality of Life Questionnaire (MC-QoL)
- time Frame
- Up to 5 years
- measure
- Parts 1, 2, and 3: Change in Patient's Global Impression of Symptom Severity (PGIS)
- time Frame
- Up to 5 years
Full study description
- 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.
Source references
- references
- citation
- Siebenhaar F, Broesby-Olsen S, Castells M, George TI, Livideanu CB, Alvarez-Twose I, Panse J, Barete S, Reiter A, Dybedal I, Akin C, Van Daele P, Radia DH, Cerquozzi S, Ustun C, Sabato V, Gotlib J, Rafferty M, DeAngelo DJ, Schafhausen P, Ungerstedt J, Ogbogu PU, Florell S, Wada DA, Rets A, Lin HM, Bidollari I, Hong J, Shaheen D, Lampson B, Hartmann K. Avapritinib improves cutaneous involvement in patients with indolent systemic mastocytosis: Results from the randomized, phase 2, interventional PIONEER study. J Am Acad Dermatol. 2026 Jun;94(6):1705-1713. doi: 10.1016/j.jaad.2026.02.025. Epub 2026 Feb 12.
- pmid
- 41690487
- type
- DERIVED
- citation
- Worth S, George TI, Shaheen DJ, Roche M, Vachhani P. Chronic Anaphylaxis With Indolent Systemic Mastocytosis: A Case Report. Case Rep Hematol. 2025 Nov 6;2025:9562195. doi: 10.1155/crh/9562195. eCollection 2025.
- pmid
- 41244098
- type
- DERIVED
- citation
- Gotlib J, Castells M, Elberink HO, Siebenhaar F, Hartmann K, Broesby-Olsen S, George TI, Panse J, Alvarez-Twose I, Radia DH, Tashi T, Bulai Livideanu C, Sabato V, Heaney M, Van Daele P, Cerquozzi S, Dybedal I, Reiter A, Pongdee T, Barete S, Ustun C, Schwartz L, Ward BR, Schafhausen P, Vadas P, Bose P, DeAngelo DJ, Rein L, Vachhani P, Triggiani M, Bonadonna P, Rafferty M, Butt NM, Oh ST, Wortmann F, Ungerstedt J, Guilarte M, Taparia M, Kuykendall AT, Arana Yi C, Ogbogu P, Gaudy-Marqueste C, Mattsson M, Shomali W, Giannetti MP, Bidollari I, Lin HM, Sulllivan E, Mar B, Scherber R, Roche M, Akin C, Maurer M. Avapritinib versus Placebo in Indolent Systemic Mastocytosis. NEJM Evid. 2023 Jun;2(6):EVIDoa2200339. doi: 10.1056/EVIDoa2200339. Epub 2023 May 23.
- pmid
- 38320129
- type
- DERIVED
- citation
- Padilla B, Shields AL, Taylor F, Li X, Mcdonald J, Green T, Boral AL, Lin HM, Akin C, Siebenhaar F, Mar B. Psychometric evaluation of the Indolent Systemic Mastocytosis Symptom Assessment Form (ISM-SAF) in a phase 2 clinical study. Orphanet J Rare Dis. 2021 Oct 18;16(1):434. doi: 10.1186/s13023-021-02037-3.
- pmid
- 34663404
- type
- DERIVED
Source notices and limitations
Discovery and provenance
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- ith MCL, the efficacy of AYVAKIT was based on complete remission (CR). 14.3 Indolent Systemic Mastocytosis The efficacy of AYVAKIT was demonstrated in PIONEER (NCT03731260), a randomized, double-blind, placebo-controlled trial conducted in adult patients with Indolent Systemic Mastocytosis (ISM) based on World Health Organization
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Preserved source evidence · Not medical advice