Clinical trial NCT04695431: Retrospective Study Assessing the Effect of Avapritinib Versus Best Available Therapy in Patients With AdvSM
Official title: An External Control, Observational, Retrospective Study Assessing the Effect of Avapritinib Compared With Best Available Therapy for Patients With Advanced Systemic Mastocytosis
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Advanced Systemic Mastocytosis
Aggressive Systemic Mastocytosis
Systemic Mastocytosis With an Associated Hematological Neoplasm
Mast Cell Leukemia
Lead sponsor: Blueprint Medicines Corporation
Sponsor class: INDUSTRY
Collaborators: name: Analysis Group, Inc.
First posted: 2021-01-05
Enrollment: 317
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: RETROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Patients age 18 or older with a diagnosis of advanced SM.

Brief summary: BLU-285-2405 is a multi-center, synthetic control, observational and retrospective study designed to compare clinical outcomes for avapritinib compared with best available therapy for patients with AdvSM.


Eligibility criteria: Inclusion Criteria for Patients in the External Control Arm:

1. Diagnosed with AdvSM, with known subtype including SM-AHN, ASM, or MCL
2. Received at least one line of systemic therapy for AdvSM, which may include but not limited to regimens containing:

   Midostaurin Cytoreductive therapy: cladribine, interferon alpha, azacitidine, decitabine Selective TKIs: imatinib, nilotinib, dasatinib Hydroxyurea Antibody therapy: brentuximab vedotin
3. Adult (≥18 years of age) at the initiation of first systemic line of therapy at the participating site
4. Had an index date at least 3 months prior to the start of data collection (in order to include patients with at least 3 months of follow-up after index date), unless date of death occurred less than three months from index date
5. Had an approved waiver of informed consent or signed informed consent for participation in the retrospective chart review study, if no institutional waiver from the site was granted

Exclusion Criteria for Patients in the External Control Arm

1. Malignancy that is not in remission at time of SM diagnosis, or new non-hematological malignancy diagnosed after SM diagnosis, except for: completely resected basal cell and squamous cell skin cancer, curatively treated localized prostate cancer, and completely resected carcinoma in situ of any site
2. Among patients with SM-AHN, presence of either of the following:

   * Patients in whom the SM component is consistent with an indolent systemic mastocytosis (ISM) or SSM or,
   * the AHN component is a lymphoid malignancy, or one of the following myeloid malignancies: acute myeloid leukemia (AML), myelodysplastic syndrome (MDS) that is very high-or high-risk as defined by the IPSS-R, or a Philadelphia chromosome positive malignancy or,
   * there is a known FIP1L1/PDGFRA fusion gene (including those with CHIC-2 deletion and partial deletion of PDGFRA), independent of KIT mutational status
3. Received avapritinib as the first line of systemic therapy for AdvSM at participating site, or prior to initiation of first systemic therapy at participating site.

Primary outcomes:
measure: Comparative evaluation of overall survival (OS) between patients receiving best available therapy versus avapritinib in BU-285-2101 and BLU-285-2202
timeFrame: up to 12 years
Secondary outcomes:
measure: Comparative evaluation between patients receiving best available therapy versus avapritinib of duration of treatment (DOT)
timeFrame: Up to 12 years
measure: Comparative evaluation between patients receiving best available therapy versus avapritinib and time to next treatment line (TtNTL)
timeFrame: Up to 12 years
measure: Comparative evaluation of change in serum tryptase concentration in patients receiving best available therapy versus avapritinib
timeFrame: Up to 12 years
measure: To characterize the safety profile and conduct comparative evaluation of safety between patients receiving best available therapy vs. avapritinib
timeFrame: Up to 12 years
Other outcomes:
Locations:
city: Palo Alto
country: United States
facility: Standford Cancer Center
state: California
city: Boston
country: United States
facility: Dana Farber Cancer Institute
state: Massachusetts
city: Vienna
country: Austria
facility: Medizinische Universitat Wien
city: Mannheim
country: Germany
facility: Universitatmedizin Mannheim
state: Baden-Württemberg
city: Toledo
country: Spain
facility: Hospital Virgen del Valle
city: London
country: United Kingdom
facility: Guy's and St. Thomas' NHS Foundation Trust
state: England
Study officials:
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.