Title
POETIC PARPAML: A Phase 1 Protocol for Relapsed Pediatric AML to Determine the Safety and Efficacy of the PARP Inhibitor Talazoparib in Combination with Chemotherapy

Description
This is a Phase 1, open label, multicenter, dose finding study with dose expansion intended to evaluate the safety and tolerability of talazoparib in combination with conventional chemotherapy. Preliminary estimates of efficacy will be obtain through a dose expansion cohort receiving the maximum tolerated dose from the dose escalation phase of the study.

Objective
Primary Objective:

To determine a tolerable combination of talazoparib in combination with chemotherapy
(topotecan plus gemcitabine) in pediatric subjects with relapsed or refractory acute myeloid
leukemia (AML) or acute leukemia of ambiguous lineage.

Secondary Objectives:

1) To measure PK of talazoparib in combination with topotecan and gemcitabine
2) To estimate the overall response rate to the combination of talazoparib with chemotherapy in pediatric subjects with relapsed or refractory AML

Exploratory Objectives:
To determine if responders to treatment with PARP inhibitors can be predicted through biomarkers, cytogenetic features, and gene signature profiling.

Treatment This study aims to determine the safety of talazoparib in combination with conventional chemotherapy and to establish the maximum tolerated dose of all 3 drugs when given in combination. A preliminary estimate of efficacy through a dose expansion phase is a secondary aim.

Key Eligibility For full study eligibility, see this study's clinicaltrials.gov record.

Applicable Disease Sites
Leukemia

Participating Institutions
American Family Children's Hospital (AFCH); UW Health University Hospital