Crenolanib in Combination With Sorafenib in Patients With Refractory or Relapsed Hematologic Malignancies

Acute Myeloid Leukemia Clinical Trial

Official title: A Phase I Pharmacokinetic, Pharmacodynamic and Feasibility Study of Crenolanib in Combination With Sorafenib in Patients With Refractory or Relapsed Hematologic Malignancies (ARO-008)

Status Completed

Clinical Trial Summary

PRIMARY OBJECTIVE:

This is a pilot study to characterize the toxicity profile, to determine the maximum tolerated dose of the combination of crenolanib and sorafenib, and to determine the feasibility of administering these drugs in patients with relapsed or refractory hematologic malignancies, including acute myeloid leukemia (AML), AML with prior myelodysplastic syndrome (MDS), and myeloperoxidase (MPO)-positive mixed phenotype acute leukemia with FLT3-internal tandem duplication (ITD) and tyrosine kinase domain (TKD) mutations.

The study will include two phases:

• The dose-escalation phase will characterize the dose-limiting toxicities (DLTs) and determine the maximum tolerated dose (MTD) or recommended phase 2 dose (RP2D) of crenolanib when given in combination with sorafenib.

• The dose-expansion cohort will further assess the safety and explore the efficacy of this combination.

Clinical Trial Description

Each course of therapy will be 28 days (±5 days), unless disease progression is seen while on the combination of crenolanib with sorafenib. Patients may receive subsequent courses (up to a total of 365 days) if there is no disease progression or unacceptable toxicity.

In Day 1 of Course 1, crenolanib is given once in the morning followed by characterization of the pharmacokinetic profile over the following 24-hour period. Starting with day 2 of Course 1, crenolanib will be given 3 times per day through day 28. On Days 8 to 28 of Course 1, sorafenib will be given once per day. Inter-patient dose escalation or de-escalation of crenolanib will be performed based on tolerability and toxicity.

Response will be assessed on days 8 and at end of course. If disease progresses prior to day 8, then sorafenib can be given before day 8.

In subsequent courses (up to 365 days), crenolanib and sorafenib are given on days 1 through

28. The treating physician may increase or decrease the sorafenib dose and frequency of administration per the trial's dosing table on the basis of effects and tolerability. If necessary, the crenolanib dose can be decreased per protocol.

Maintenance therapy must start no sooner than 30 days and no later than 120 days after hematopoietic stem cell therapy (HSCT). Single agent crenolanib will start at the last dose tolerated prior to HSCT. Crenolanib maintenance can be given for up to 365 days and additional therapy can be provided after discussion after discussion with the PI, in patients who continue to benefit after 1 year. ;

Related Conditions & MeSH terms

• Acute Myeloid Leukemia
• Leukemia, Myeloid, Acute

• NCT number: NCT02270788
• Study type: Interventional
• Source: St. Jude Children's Research Hospital
• Status: Completed
• Phase: Phase 1
• Start date: April 2, 2015
• Completion date: October 17, 2016