A Safety and Tolerability Study of Crenolanib in Combination With Chemotherapy in Newly Diagnosed Acute Myeloid Leukemia Patients With FLT3 Mutations

Sponsor

Arog Pharmaceuticals, Inc. (Industry)

Overall Status

Completed

CT.gov ID

NCT02283177

Collaborator

(none)

Enrollment

Locations

Arms

Duration (Months)

4.9

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This pilot study is designed to evaluate the safety and tolerability of oral crenolanib besylate given sequentially during standard induction and consolidation chemotherapy in patients with newly diagnosed AML with FLT3 activating mutations.

Condition or Disease	Intervention/Treatment	Phase
Newly Diagnosed AML With FLT3 Activating Mutations	Drug: crenolanib Drug: cytarabine Drug: daunorubicin Drug: idarubicin	Phase 2

Study Design

Study Type:

Interventional

Actual Enrollment :

44 participants

Allocation:

Non-Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Safety and Tolerability Trial of Crenolanib and Chemotherapy With Cytarabine and Anthracyclines in Patients With Newly Diagnosed Acute Myeloid Leukemia With FLT3 Activating Mutations

Study Start Date :

Jan 1, 2015

Actual Primary Completion Date :

Dec 1, 2019

Actual Study Completion Date :

Dec 1, 2019

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Cohort A Patients will be given cytarabine and daunorubicin during induction therapy plus crenolanib at 100 mg TID.	Drug: crenolanib Other Names: CP-868,596-26 Drug: cytarabine Drug: daunorubicin
Experimental: Cohort B Patients will be given cytarabine and idarubicin during induction therapy plus crenolanib at 100 mg TID.	Drug: crenolanib Other Names: CP-868,596-26 Drug: cytarabine Drug: idarubicin

Arm

Intervention/Treatment

Experimental: Cohort A

Patients will be given cytarabine and daunorubicin during induction therapy plus crenolanib at 100 mg TID.

Drug: crenolanib

Other Names:

CP-868,596-26

Drug: cytarabine

Drug: daunorubicin

Experimental: Cohort B

Patients will be given cytarabine and idarubicin during induction therapy plus crenolanib at 100 mg TID.

Drug: crenolanib

Other Names:

CP-868,596-26

Drug: cytarabine

Drug: idarubicin

Outcome Measures

Primary Outcome Measures

The safety and tolerability of crenolanib in combination with chemotherapy will be determined by assessing the adverse events experienced by patients. [2 years]

Secondary Outcome Measures

Patients' serum and plasma samples will be collected and pharmacokinetic parameters including Cmax and AUC will be measured. [day 4 and day 15 of induction 1; day 7 of consolidation 1]
Response rate [day 14-28 of induction]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Unequivocal diagnosis of AML based on the WHO classification, excluding acute promyelocytic leukemia
No prior therapy for AML, except for hydroxyurea, in this setting is allowed.
Subjects with AML evolving from MDS may have received prior MDS therapy with demethylating agents
Subjects must have tested positive for FLT3-ITD and/or other FLT3 activating mutations
Age ≥18 years
ECOG PS 0 - 2
Adequate liver function, defined as normal total bilirubin, ALT ≤2.0x ULN, and AST ≤2.0x ULN measured within 24 hours prior to crenolanib commencement
Adequate renal function, defined as serum creatinine ≤1.5x ULN or GFR >50 mL/min
Negative pregnancy test (serum or urine) for women of childbearing potential (WOCBP)

• Women considered not of childbearing potential include any of the following: no menses for at least 2 years or menses within 2 years but amenorrheic for at least 2 months and luteinizing hormone (LH) and follicular stimulating hormone (FSH) values within normal range (according to definition of postmenopausal for laboratory used) or bilateral oophorectomy or radiation castration and amenorrheic for at least 3 months or with bilateral tubal ligation

WOCBP must practice contraception. Acceptable methods of contraception are double barrier methods (condoms with spermicidal jelly or foam and diaphragm with spermicidal jelly or foam), oral, depo provera, or injectable contraceptives, intrauterine devices, tubal ligations, and abstention
Male patients (except those with prior surgical contraceptive procedures) with female partners who are of childbearing potential: Recommendation is for male and partner to use effective contraceptive methods, such as latex condoms, during the study
Able and willing to provide written informed consent

Exclusion Criteria:

Pre-existing liver diseases (i.e., cirrhosis, chronic hepatitis B or C, nonalcoholic steatohepatitis, and sclerosing cholangitis, etc.)
Active CNS leukemia
Subject with concurrent severe and/or uncontrolled medical conditions that in the opinion of the investigator may impair the participation in the study or the evaluation of safety and/or efficacy
NYHA Class III-IV heart failure, myocardial infarction <6 months prior to study entry, and/or serious arrhythmia requiring anti-arrhythmic therapy
Unable to swallow pills
Major surgical procedures within 14 days of administration of crenolanib (does not include line placement as needed for chemotherapy administration).
Unwillingness or inability to comply with protocol.
Concurrent use of other investigational agents.
Subjects who are not eligible for standard chemotherapy

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	City of Hope Medical Center	Duarte	California	United States	91010
2	University of Iowa Hospitals and Clinics	Iowa City	Iowa	United States	52242
3	Dana-Farber Cancer Institute	Boston	Massachusetts	United States	02215
4	Roswell Park Cancer Institute	Buffalo	New York	United States	14263
5	Memorial Sloan Kettering Cancer Center	New York	New York	United States	10065
6	Weill Cornell Medical College	New York	New York	United States	10065
7	Cleveland Clinic	Cleveland	Ohio	United States	44195
8	University of Texas Southwestern Medical Center	Dallas	Texas	United States	75390
9	Fred Hutchinson Cancer Research Center	Seattle	Washington	United States	98195