INCB 18424-269 (COG AALL1521), A Phase 2 Study of the JAK1/JAK2 Inhibitor Ruxolitinib With Chemotherapy in Children With De Novo High-Risk CRLF2 Rearranged and/or JAK Pathway-Mutant Acute Lymphoblastic Leukemia (CTMS# 16-0137)
- To evaluate initial safety and tolerability and to define the recommended Part 2 dose (RP2D) of ruxolitinib in combination with multi-agent chemotherapy in children and adolescents or young adults (AYA) with de novo high-risk (HR) Philadelphia chromosome like (Ph-like) cytokine receptor like factor 2 rearranged (CRLF2-R) and/or Janus kinase (JAK) pathway mutant B-cell acute lymphoblastic leukemia (B-ALL).
- To determine the efficacy of ruxolitinib in combination with chemotherapy for children and AYA with de novo HR Ph-like CRLF2-R and/or JAK pathway mutant B-ALL.
- To characterize the safety and potential toxicity of ruxolitinib combined with chemotherapy throughout the course of treatment in children and AYA with de novo HR Ph-like CRLF2-R and/or JAK pathway mutant B-ALL.
- To assess the pharmacokinetics (PK) of ruxolitinib in combination with chemotherapy in children and AYA with B-ALL.
- To assess rates of minimal residual disease (MRD) at end-Consolidation in end-Induction MRD+ subjects who are treated with ruxolitinib and chemotherapy.
- To measure pharmacodynamic (PD) signaling inhibition and biomarkers of ruxolitinib activity, for correlation with ruxolitinib PK and with efficacy measures.
- To evaluate the overall survival (OS) of all subjects receiving ruxolitinib in combination with chemotherapy.