Dissemination of medulloblastoma is an independent risk factor of poor prognosis. Dissemination of medulloblastoma at recurrence is nearly universally fatal. ABL1 and 2 have been recently found to mediate the dissemination of medulloblastoma. Genetically inactivating ABL1 and 2 resulted in decreased leptomeningeal medulloblastoma and improved overall survival (OS) in rodent models. Asciminib is an FDA approved for the treatment of chronic myeloid leukemia and is well tolerated, likely due to its specificity for ABL1 and ABL2. Asciminib is a P-glycoprotein (P-gp) substrate and thus may be susceptible to being pumped out of tumor cells and brain endothelial cells. It is unclear if asciminib can enter the central nervous system (CNS) and brain tumors in adequate concentration to have anti-tumor effects.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
12
Commercially available stock
Commercially available stock
Standard of care
Washington University School of Medicine/St. Louis Children's Hospital
St Louis, Missouri, United States
Tumor:plasma ratio of asciminib
Time frame: At time of surgical resection or biopsy (day 1)
Tumor:plasma ratio of asciminib with sildenafil
Time frame: At time of surgical resection or biopsy (day 1)
Change in plasma levels of asciminib
Time frame: Baseline, time of tumor resection/biopsy (day 1), and 8 (+/- 4 hours) after surgical resection or biopsy
Expression of c-MYC in brain tumor specimens
Time frame: At time of surgical resection or biopsy (day 1)
Expression of p-CRKL in brain tumor specimens
Time frame: At time of surgical resection or biopsy (day 1)
Proportion of patients with unacceptable toxicity
Time frame: From start of treatment (day 1) through 3 weeks following asciminib
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