TriangleNCT02561988 · CITED IN SOURCE DOCUMENTS
(EXPLORER) Study of BLU-285 in Patients With Advanced Systemic Mastocytosis (AdvSM) and Relapsed or Refractory Myeloid Malignancies
An NCI or FDA source cites this study. A citation does not establish that it applies to an individual diagnosis.
- Phase
- PHASE1
- Status at capture
- COMPLETED
- Registry last update
- 2023-03-17
This is a Phase 1, open-label, dose-escalation study designed to evaluate the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD) and antineoplastic activity of avapritinib (also known as BLU-285), administered orally (PO), in adult patients with advanced systemic mastocytosis and other relapsed or refractory myeloid malignancies. The study consists of 2 parts:, dose-escalation (Part 1) and expansion (Part 2).
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
- Inclusion Criteria: For Part 1:Patients must have one of the following diagnoses based on World Heath Organization (WHO) diagnostic criteria: * Aggressive systemic mastocytosis (ASM). * Systemic mastocytosis with an associated hematologic neoplasm (SM-AHN) and at least 1 C-finding attributable to systemic mastocytosis (SM). The AHN must be myeloid, with the following exceptions that are excluded: Acute myeloid leukemia (AML), Myelodysplastic syndrome (MDS) that is very high- or high-risk as defined by the International prognostic scoring system for myelodysplastic syndromes (IPSS-R) and Philadelphia chromosome positive malignancies. * Mast cell leukemia (MCL). * Histologically- or cytologically- confirmed myeloid malignancy that is relapsed or refractory to standard treatments. AML, MDS that is very high- or high-risk as defined by the IPSS-R, and Philadelphia chromosome positive malignancies are excluded. * Upon discussion with the sponsor, other relapsed or refractory, potentially avapritinib-responsive hematologic neoplasms (e.g., evidence of aberrant KIT or platelet derived growth factor receptor (PDGFR) signaling) may be considered for enrollment. For Part 2, patients must have one of the following diagnoses, based on WHO diagnostic criteria: * ASM. * SM-AHN. The AHN must be myeloid, with the following exceptions that are excluded: AML, MDS that is very high- or high-risk as defined by the IPSS-R, and Philadelphia chromosome positive malignancies. * MCL. For Part 2, Cohort 2, patients must have at least 1 measurable C-finding per modified IWG-MRT-ECNM criteria at Baseline, attributed to SM unless diagnosis is MCL, which does not require a C-finding. * Cytopenias: ANC \< 1.0 × 10⁹/L or hemoglobin \< 10 g/dL or platelet count \< 75 × 10⁹/L. * Symptomatic ascites or pleural effusion requiring medical intervention such as: use of diuretics (Grade 2) or ≥ 2 therapeutic paracenteses or thoracenteses (Grade 3) at least 28 days apart over the 12 weeks before study entry and 1 of the procedures is performed during the 6 weeks before study start (C1D1). * ≥ Grade 2 abnormalities in direct bilirubin (\> 1.5 × upper limit of normal \[ULN\]), aspartate aminotransferase (AST; \> 3.0 × ULN), alanine aminotransferase (ALT; \> 3.0 × ULN), or alkaline phosphatase (\> 2.5 × ULN) with 1 of the following present: ascites or clinically relevant portal hypertension or liver mast cell infiltration that is biopsy-proven or no other identified cause of abnormal liver function. * ≥ Grade 2 hypoalbuminemia (\< 3.0 g/dL). * A spleen that is palpable ≥ 5 cm below the left costal margin. * Transfusion-dependent anemia defined as: transfusion of ≥ 6 units packed red blood cells (PRBCs) in the 12 weeks before start of treatment (C1D1) and most recent transfusion occurring during the preceding 4 weeks and transfusion administered for hemoglobin ≤ 8.5 g/dL and reason for transfusion is not bleeding, hemolysis, or therapy-related. Eastern Cooperative Oncology Group (ECOG) performance status of 0-3. Exclusion Criteria: * QT interval corrected using Fridericia's formula (QTcF) \>480 milliseconds * Platelet count \<50,000/μL (within 4 weeks of the first dose of study drug) or receiving platelet transfusion(s) * Absolute neutrophil count \<500/μL * Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) \>3 x the upper limit of normal (ULN); \>5 × ULN if associated with clinically suspected liver infiltration by mastocytosis or another disease for which the patient enrolled into the study * Total bilirubin \>1.5 × ULN; \>3 × ULN if associated with liver infiltration by the disease being treated or in the presence of Gilbert's Disease (In the case of Gilbert's disease, a direct bilirubin \> 2.0 ULN would be an exclusion.) * Estimated (Cockroft-Gault formula) or measured creatinine clearance \<40 mL/min * Brain malignancy or metastases to the brain * History of a seizure disorder or requirement for anti-seizure medication * Known risk of intracranial bleeding, such as a brain aneurysm or history of subdural or subarachnoid bleeding * Eosinophilia and known positivity for the FIP1L1-PGDFRA fusion, unless the patient has demonstrated relapse or progressive disease on prior imatinib therapy
- healthy Volunteers
- false
- minimum Age
- 18 Years
- sex
- ALL
- std Ages
- ADULT
- OLDER_ADULT
Treatment arms and interventions
- arm Groups
- description
- Avapritinib tablets for oral administration. Avapritinib will be dosed daily for 28 day cycles.
- intervention Names
- Drug: Avapritinib
- label
- Avapritinib (also known as BLU-285)
- type
- EXPERIMENTAL
- interventions
- arm Group Labels
- Avapritinib (also known as BLU-285)
- name
- Avapritinib
- type
- DRUG
Study design
- allocation
- NA
- intervention Model
- SINGLE_GROUP
- masking Info
- masking
- NONE
- primary Purpose
- TREATMENT
Enrollment
- count
- 86
- type
- ACTUAL
Registered outcome plans (not posted results)
- primary Outcomes
- measure
- Maximum tolerated dose (MTD) of avapritinib (also known as BLU-285)
- time Frame
- During cycle 1 (28 days) of treatment
- measure
- Number of patients with adverse and serious adverse events and changes in physical findings, vital signs, clinical laboratory results and ECG findings
- time Frame
- Approximately 24 months
- measure
- Recommended Phase 2 dose (RP2D) of avapritinib
- time Frame
- Approximately 24 months
- secondary Outcomes
- description
- Blood samples may be taken at pre-dose, and 0.5, 1, 2, 4, 8 and 24 hrs post dose (plus 10 and 48 hrs post dose in Part 2) on Cycle 1 Day 1 and Cycle 1 Day 15, Pre-dose of Cycle 2 to 4, Day 1
- measure
- Maximum plasma concentration of avapritinib
- time Frame
- Every cycle (28 days) up to cycle 4
- description
- Blood samples may be taken at pre-dose, and 0.5, 1, 2, 4, 8 and 24 hrs post dose (plus 10 and 48 hrs post dose in Part 2) on Cycle 1 Day 1 and Cycle 1 Day 15, Pre-dose of Cycle 2 to 4, Day 1
- measure
- Time to maximum plasma concentration of avapritinib
- time Frame
- Every cycle (28 days) up to cycle 4
- description
- Including complete remission (CR), CR with partial recovery of peripheral blood (CRh), partial remission (PR) and clinical improvement (CI) using modified International Working Group Myeloproliferative Neoplasms Research and Treatment (IWG-MRT) and European competence network on mastocytosis (ECNM) criteria; and duration of response (DOR)
- measure
- Overall Response Rate
- time Frame
- 8, 24, 40, 68 and every 24 weeks until patient terminates from the study (approximately 24 months)
- description
- Including morphologic complete remission (mCR), morphologic CR with partial recovery of peripheral blood (mCRh), and morphologic partial remission (mPR) based on Pure Pathologic Response
- measure
- Morphologic response
- time Frame
- ≥ 12 weeks
- measure
- Changes in levels of serum tryptase and levels of V-kit Hardy-Zuckerman 4 feline sarcoma viral oncogene homolog (KIT) D816V allele burden in blood
- time Frame
- Cycle (C)1Day (D)1, C1D15, C2D1, C3D1, C5D1, C7D1, C11D1, C18D1 every 6 cycles thereafter and at disease progression. (approximately 24 months)
- description
- Defined as change from Baseline
- measure
- Changes in patient reported symptoms and quality of life using the Patient Global Impression of Symptom Severity (PGIS) scale
- time Frame
- Part 2 only - Day 1 of Cycles 1-12
- description
- Defined as change from Baseline
- measure
- Changes in patient reported quality of life using the European Organization for Research and Treatment of Cancer Core Quality of Life Questionnaire (EORTC QLQ-C-30)
- time Frame
- Part 2 only - Day 1 of Cycles 1-12
- description
- Defined as change from Baseline
- measure
- Changes in patient reported outcomes using the advanced SM symptom assessment form (AdvSM-SAF)
- time Frame
- Part 2 only - daily from Day -7 through Cycle 12
- description
- mL
- measure
- Change in liver volume by imaging
- time Frame
- Day 1 of Cycles 5-18, and every 6 cycles thereafter (each cycle is 28 days)
- description
- mL
- measure
- Change in spleen volume by imaging
- time Frame
- Day 1 of Cycles 5-18, and every 6 cycles thereafter (each cycle is 28 days)
Full study description
- brief Summary
- This is a Phase 1, open-label, dose-escalation study designed to evaluate the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD) and antineoplastic activity of avapritinib (also known as BLU-285), administered orally (PO), in adult patients with advanced systemic mastocytosis and other relapsed or refractory myeloid malignancies. The study consists of 2 parts:, dose-escalation (Part 1) and expansion (Part 2).
Source references
- references
- citation
- Reiter A, Gotlib J, Alvarez-Twose I, Radia DH, Lubke J, Bobbili PJ, Wang A, Norregaard C, Dimitrijevic S, Sullivan E, Louie-Gao M, Schwaab J, Galinsky IA, Perkins C, Sperr WR, Sriskandarajah P, Chin A, Sendhil SR, Duh MS, Valent P, DeAngelo DJ. Efficacy of avapritinib versus best available therapy in the treatment of advanced systemic mastocytosis. Leukemia. 2022 Aug;36(8):2108-2120. doi: 10.1038/s41375-022-01615-z. Epub 2022 Jul 5.
- pmid
- 35790816
- type
- DERIVED
- citation
- Reiter A, Schwaab J, DeAngelo DJ, Gotlib J, Deininger MW, Pettit KM, Alvarez-Twose I, Vannucchi AM, Panse J, Platzbecker U, Hermine O, Dybedal I, Lin HM, Rylova SN, Ehlert K, Dimitrijevic S, Radia DH. Efficacy and safety of avapritinib in previously treated patients with advanced systemic mastocytosis. Blood Adv. 2022 Nov 8;6(21):5750-5762. doi: 10.1182/bloodadvances.2022007539.
- pmid
- 35640224
- type
- DERIVED
- citation
- DeAngelo DJ, Radia DH, George TI, Robinson WA, Quiery AT, Drummond MW, Bose P, Hexner EO, Winton EF, Horny HP, Tugnait M, Schmidt-Kittler O, Evans EK, Lin HM, Mar BG, Verstovsek S, Deininger MW, Gotlib J. Safety and efficacy of avapritinib in advanced systemic mastocytosis: the phase 1 EXPLORER trial. Nat Med. 2021 Dec;27(12):2183-2191. doi: 10.1038/s41591-021-01538-9. Epub 2021 Dec 6.
- pmid
- 34873347
- type
- DERIVED
Source notices and limitations
Discovery and provenance
- release id
- ctgov-registry-7ad944f6deaf1f5cd6122126
- edge id
- nct-edge-3cd88a8c2a3ed094849f
- requested nct id
- NCT02561988
- primary nct id
- NCT02561988
- source kind
- fda_spl_label
- source record id
- beacc534-14e1-4fd2-978f-5646edd537f0
- source file sha256
- a9df7a5786dc51557d38f2a0881b5b5e9ae02ae396a6798e39ac96f586bcc5e6
- payload sha256
- 352e15f8e1d3fd6467c1b664535c4854408f31327de4de4d094fe22abe55ebb4
- payload
- application numbers
- NDA212608
- clinical indication matching status
- not_inferred
- end exclusive
- true
- id
- nct-edge-3cd88a8c2a3ed094849f
- link basis
- explicit_NCT_identifier_in_acquired_source
- nct id
- NCT02561988
- occurrences
- context exact
- se were followed < 6 months from onset of response. 22 (61%) 20 (59%) 14.2 Advanced Systemic Mastocytosis The efficacy of AYVAKIT was demonstrated in EXPLORER (NCT02561988) and PATHFINDER (NCT03580655), two multi-center, single-arm, open-label clinical trials. Response-evaluable patients include those with a confirmed diagnosis o
- end
- 3002
- exact text
- NCT02561988
- start
- 2991
- offset unit
- unicode_code_points
- source file
- /tmp/cancer-full-research/indications/raw/labels-00600.json
- source file sha256
- a9df7a5786dc51557d38f2a0881b5b5e9ae02ae396a6798e39ac96f586bcc5e6
- source json pointer
- /results/40/clinical_studies/0
- source kind
- fda_spl_label
- source record id
- beacc534-14e1-4fd2-978f-5646edd537f0
- source string basis
- parsed_JSON_string_unmodified
- source string sha256
- ace6d9bb70d9cdd769257a9e26931b79d9233fdd2be2d01b8f2cb7491c309f26
- spl effective time
- 20260805
- spl set id
- 645c887c-8cd4-4623-8da9-ac223d71a8b9
Preserved source evidence · Not medical advice