A Phase I and Expansion Cohort Study of Venetoclax and Selinexor in Combination with Chemotherapy in Pediatric Patients with Refractory or Relapsed Acute Myeloid Leukemia

Pediatric Blood Cancer
Jeffrey Rubnitz, MD, PhD
St. Jude Children's Research Hospital


Survival rates for children with AML are greater than 60%; however, the outcome for patients with relapsed or refractory disease remains poor with less than 40% becoming long term survivors. Treatment regimens for relapsed disease are conventional chemotherapeutic agents and hematopoietic stem cell transplant (HSCT). The investigators in this phase I study suggest utilizing two targeted therapies to combat AML. The first is selinexor, a drug that targets and inhibits exportin 1, a protein responsible for exporting oncoproteins (proteins that promote tumor growth and proliferation) out of cells. The second is venetoclax a drug that targets and inhibits a family of proteins called BCL2. Overexpression of BCL2 prevents cancer cells from being killed by immune cells as they inhibit a process called apoptosis (or programmed cell death) and this is associated with resistance to chemotherapy and worsened clinical outcomes. Thus, this phase I study will determine the recommended phase 2 dosing of the combination of selinexor and venetoclax in pediatric patients with relapsed or refractory (resistant) AML or ALAL.

Trial Registration: ClinicalTrials.gov Identifier: NCT04898894