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

Summary and objectives

Acute Myeloid Leukemia (AML) is a rare cancer affecting children and adults. At present, the overall survival of children diagnosed with AML is less than 70%. Many patients who achieve a complete remission of AML will go on to relapse, and overall survival rate following relapse is less than 40%. Advancing our understanding of how to effectively treat AML is critical to improving survival outcomes, reducing relapse rates, and expanding therapeutic options for patients who currently have limited, and often toxic—treatment choices.

Talazoparib was approved by the FDA in 2018 following clinical trials demonstrating significant improvements in progression-free survival in subjects with HER2-negative breast cancer. Since then, talazoparib has been used and well tolerated in several other clinical trials for various diseases.

The objectives of this study are to determine a tolerable dose of talazoparib in combination with chemotherapy in pediatric subjects with relapsed or refractory AML or acute leukemia of ambiguous lineage, and to obtain preliminary estimates of the efficacy of the combination by evaluating the overall response rate.

Eligibility criteria

• Must be less than 21 years old
• Must have confirmed qualifying diagnosis that is considered in relapse or refractory to treatment, without evidence of acute graft vs host disease (GVHD)
• Must not have diagnosis of down syndrome, Acute Promyelocytic Leukemia (APL), Juvenile Myelomonocytic Leukemia (JMML), or Bone Marrow Failure Syndrome
• Must have adequate organ function and performance levels as determined by the study protocol
• Must not be receiving or planning to receive any concurrent cancer therapy
• Female patients of childbearing potential require a negative pregnancy test and must agree to use an effective method of birth control for the duration of the study
• Female subjects with infants must agree to abstain from breastfeeding
• Various protocol-identified comorbidities including uncontrolled infection could prevent participation in this study

Clinicaltrials.gov Study Details >