PARPAML: A Phase I Protocol for Relapsed Pediatric AML to Determine the Safety and Efficacy of the PARP Inhibitor Talazoparib in Combination with Chemotherapy

Summary:

Currently, the survival of children diagnosed with AML sits at less than 70%. Despite 80 to 90% of patients achieving first complete remission, 30 to 40% will relapse and outcomes remain dismal as the overall survival rate is less than 40%. Outcomes are even worse for patients with high-risk features (subtype, genetic alterations, etc). Preclinical data suggests that AML harboring high risk cytogenetic features are sensitive to PARP inhibitors. Talazoparib, a PARP inhibitor, prevents cancer cells from repairing themselves such as after exposure to chemotherapy, causing them to die. Normally PARP, a cellular protein, would repair any DNA damage a cell has endured. Thus, this phase I study will assess the safety and tolerability of talazoparib in combination with conventional chemotherapy in pediatric patients with relapsed or refractory (resistant) AML and ALAL.

Trial Registration: ClinicalTrials.gov Identifier: NCT05101551