NCT02676323

Panobinostat With Fludarabine and Cytarabine for Treatment of Children With Acute Myeloid Leukemia or Myelodysplastic Syndrome

A Phase I and Dose Expansion Cohort Study of Panobinostat in Combination With Fludarabine and Cytarabine in Pediatric Patients With Refractory or Relapsed Acute Myeloid Leukemia or Myelodysplastic Syndrome

• Status: Terminated
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 19 (actual)
• Sponsor: St. Jude Children's Research Hospital · Academic / Other
• Sex: All
• Age: 24 Years
• Healthy volunteers: Not accepted

Summary

Cancer is the uncontrolled growth of human cells. The growth of normal human cells is controlled by multiple mechanisms. Panobinostat belongs to a class of chemotherapy drugs called "histone deacetylase (HDAC) inhibitors." HDAC inhibitors like panobinostat block enzymes known as histone deacetylases, which stops cancer cells from dividing and causes them to die. Fludarabine and cytarabine are chemotherapy drugs that are commonly used to treat pediatric patients with refractory or relapsed acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS). The purpose of this study is to test the safety of panobinostat and to find the highest dose of panobinostat that can be given safely when it is combined with fludarabine and cytarabine. This pilot study will be done in two parts: The goal of Part 1 of the study is to find the highest tolerable dose of panobinostat that can be given to patients with AML or MDS, when it is combined with fludarabine and cytarabine. Once that dose is determined, participants will be enrolled on Part 2: Dose Expansion, to look at the effect of the panobinostat/fludarabine/cytarabine combination in patients with leukemia/MDS. PRIMARY OBJECTIVE: * Determine a tolerable dose of panobinostat when given in combination with fludarabine and cytarabine in pediatric patients with relapsed or refractory AML or MDS. SECONDARY OBJECTIVES: * Characterize the pharmacokinetics of panobinostat after the first dose and at steady-state. * Estimate the overall response rate to the combination of panobinostat, fludarabine, and cytarabine.

Detailed description

STUDY PART 1: Dose Escalation Cohort During the dose escalation phase (Part 1), participants will receive one course of panobinostat plus fludarabine and cytarabine. The starting dose of panobinostat will be 10 mg/m\^2/dose, with 2 additional dose levels of 15 and 20, depending on tolerability. Each course is 12 days STUDY PART 2: Dose Expansion Cohort The recommended phase 2 dose (RP2D) will be chosen based on the maximum tolerated dose (MTD) and the totality of data obtained from study Part 1. Additional patients will be enrolled, if needed, so that at least 6 patients are treated with the recommended RP2D to confirm the MTD of panobinostat to be given in study Part 2. After final MTD determination, 12 additional participants will be treated at this dose level for further evaluation of tolerability and response, including more complete toxicity data and estimation of the response rate to the combination of panobinostat, fludarabine, and cytarabine.

Conditions

• Acute Myeloid Leukemia
• Myelodysplastic Syndrome

Interventions

Type	Name	Description
DRUG	Panobinostat	Panobinostat will be given orally (PO) on days 1, 3, 5, 8, 10, and 12.
DRUG	Fludarabine	Fludarabine will be given intravenously (IV), 30 mg/m\^2/dose over 30 minutes, daily for 5 days (days 8-12).
DRUG	Cytarabine	Cytarabine will be given IV, 2 gram/m\^2/dose over 4 hours, daily for 5 days (days 8-12).
DRUG	Intrathecal Triples	Given intrathecally (IT).
DRUG	Leucovorin	Leucovorin (5 mg/m\^2/dose, max 5 mg) may be given PO or IV at 24 and 30 hours after each ITMHA.

Timeline

• Start date: 2016-05-03
• Primary completion: 2018-04-09
• Completion: 2018-04-09
• First posted: 2016-02-08
• Last updated: 2018-11-14

Locations

7 sites across 1 country: United States

Regulatory

• FDA-regulated drug study