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

Summary

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. 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.

Eligibility

Age range

Up to 21 years

Sex

All

Healthy volunteers

No

Interventions

• Drug
  Talazoparib

  Talazoparib will be administered in escalating doses based on current dose level. * Dose Level 1: 400 µg/m2/dose once daily * Dose Level 2: 600 µg/m2/dose BID on Day 1, then daily on Days 2 to 5 * Dose Level 3: 600 µg/m2/dose BID on Day 1, then daily on Days 2 to 5 * Dose Level 4: 600 µg/m2/dose BID on Day 1, then daily on Days 2 to 5 * Dose Level 5: 600 ug/m2/dose BID on Day 1, then daily on Days 2 to 5 and 15 to19

• Drug
  Topotecan

  Administered IV route on Days 1 to 5 * Dose Level -2: 1 mg/m2/dose once daily by IV days 1 to 5 * Dose Level -1: 2 mg/m2/dose once daily by IV days 1 to 5 * Dose Level 1: 2 mg/m2/dose once daily by IV days 1 to 5 * Dose Level 2: 2 mg/m2/dose once daily by IV days 1 to 5 * Dose Level 3: 3 mg/m2/dose once daily by IV days 1 to 5 * Dose Level 4: 4 mg/m2/dose once daily by IV days 1 to 5 * Dose Level 5: 4 mg/m2/dose once daily by IV days 1 to 5

• Drug
  Gemcitabine

  Single dose (IV) of gemcitabine on Day 1 of each 28 day cycle for 1 cycle. * Dose Level -2: 600 mg/m2/dose once daily by IV days 1 * Dose Level -1: 600 mg/m2/dose once daily by IV days 1 * Dose Level 1: 1200 mg/m2/dose once daily by IV days 1 * Dose Level 2: 1200 mg/m2/dose once daily by IV days 1 * Dose Level 3: 1200 mg/m2/dose once daily by IV days 1 * Dose Level 4: 1200 mg/m2/dose once daily by IV days 1 * Dose Level 5: 1200 mg/m2/dose once daily by IV days 1

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