Ignite Creation Date:
2024-05-06 @ 3:21 AM
Last Modification Date:
2024-10-26 @ 11:32 AM
Study NCT ID:
NCT02270788
Status:
COMPLETED
Last Update Posted:
2017-10-03
First Post:
2014-10-17
Brief Title:
Crenolanib in Combination With Sorafenib in Patients With Refractory or Relapsed Hematologic Malignancies
Sponsor:
St Jude Childrens Research Hospital
Organization:
St Jude Childrens Research Hospital
Study Overview
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
Status Verified Date:
2017-10
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief 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
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
Detailed 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 trials 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
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 trials 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
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
True
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| NCI-2014-01784 | REGISTRY | NCI Clinical Trial Registration Program | None |