A Safety and Tolerability Study of Crenolanib in Combination With Chemotherapy in Newly Diagnosed Acute Myeloid Leukemia Patients With FLT3 Mutations
Condition: Newly Diagnosed AML With FLT3 Activating Mutations
MeSH terms: Leukemia, Myeloid, Acute
Intervention: crenolanib; cytarabine; daunorubicin; idarubicin
Intervention MeSH terms: Cytarabine; Daunorubicin; Idarubicin; Crenolanib
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 44.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

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.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Unequivocal diagnosis of AML based on the WHO classification, excluding acute
             promyelocytic leukemia

          2. No prior therapy for AML, except for hydroxyurea, in this setting is allowed.

          3. Subjects with AML evolving from MDS may have received prior MDS therapy with
             demethylating agents

          4. Subjects must have tested positive for FLT3-ITD and/or other FLT3 activating mutations

          5. Age ≥18 years

          6. ECOG PS 0 - 2

          7. 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

          8. Adequate renal function, defined as serum creatinine ≤1.5x ULN or GFR >50 mL/min

          9. 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

         10. 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

         11. 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

         12. Able and willing to provide written informed consent

        Exclusion Criteria:

          1. Pre-existing liver diseases (i.e., cirrhosis, chronic hepatitis B or C, nonalcoholic
             steatohepatitis, and sclerosing cholangitis, etc.)

          2. Active CNS leukemia

          3. 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

          4. NYHA Class III-IV heart failure, myocardial infarction <6 months prior to study entry,
             and/or serious arrhythmia requiring anti-arrhythmic therapy

          5. Unable to swallow pills

          6. Major surgical procedures within 14 days of administration of crenolanib (does not
             include line placement as needed for chemotherapy administration).

          7. Unwillingness or inability to comply with protocol.

          8. Concurrent use of other investigational agents.

          9. Subjects who are not eligible for standard chemotherapy