Clinical Testing of Targeted Therapies for Children with JAK Pathway-mutant Acute Lymphoblastic Leukemia (ALL)

Sarah K. Tasian, MD and colleagues in the Children’s Oncology Group (COG) are evaluating ruxolitinib, an orally bioavailable JAK1/JAK2 inhibitor, as a new treatment for children with JAK pathway-mutant ALL in the phase 2 trial AALL1521. 

Ruxolitinib is an FDA-approved targeted therapy used to treat certain myeloproliferative neoplasms in adults. Results from the first-in-children COG phase 1 trial ADVL1011 demonstrated that ruxolitinib was well-tolerated in children with relapsed or refractory solid tumors, leukemias, and myeloproliferative neoplasms. Data from ADVL1011 also demonstrated pharmacodynamic inhibition of JAK/STAT signal transduction proteins in children treated with ruxolitinib.

The AALL1521 phase 2 trial is evaluating the tolerability and effectiveness of ruxolitinib in combination with cytotoxic chemotherapy in children, adolescents, and young adults with high-risk Philadelphia chromosome-like (Ph-like) ALL harboring CRLF2 and other JAK pathway mutations.

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