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

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ClinicalTrials.gov Identifier: NCT02283177
Recruitment Status : Completed
First Posted : November 5, 2014
Last Update Posted : July 20, 2020
Information provided by (Responsible Party):
Arog Pharmaceuticals, Inc.

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

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Study Type : Interventional  (Clinical Trial)
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 : January 2015
Actual Primary Completion Date : December 2019
Actual Study Completion Date : December 2019

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 Name: 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 Name: CP-868,596-26

Drug: cytarabine
Drug: idarubicin

Primary Outcome Measures :
  1. The safety and tolerability of crenolanib in combination with chemotherapy will be determined by assessing the adverse events experienced by patients. [ Time Frame: 2 years ]

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

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02283177

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United States, California
City of Hope Medical Center
Duarte, California, United States, 91010
United States, Iowa
University of Iowa Hospitals and Clinics
Iowa City, Iowa, United States, 52242
United States, Massachusetts
Dana-Farber Cancer Institute
Boston, Massachusetts, United States, 02215
United States, New York
Roswell Park Cancer Institute
Buffalo, New York, United States, 14263
Memorial Sloan Kettering Cancer Center
New York, New York, United States, 10065
Weill Cornell Medical College
New York, New York, United States, 10065
United States, Ohio
Cleveland Clinic
Cleveland, Ohio, United States, 44195
United States, Texas
University of Texas Southwestern Medical Center
Dallas, Texas, United States, 75390
United States, Washington
Fred Hutchinson Cancer Research Center
Seattle, Washington, United States, 98195
Sponsors and Collaborators
Arog Pharmaceuticals, Inc.
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Principal Investigator: Richard Stone, MD Dana-Farber Cancer Institute
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Responsible Party: Arog Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier: NCT02283177    
Other Study ID Numbers: ARO-006
First Posted: November 5, 2014    Key Record Dates
Last Update Posted: July 20, 2020
Last Verified: July 2020
Additional relevant MeSH terms:
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Leukemia, Myeloid, Acute
Neoplasms by Histologic Type
Leukemia, Myeloid
Antimetabolites, Antineoplastic
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Antiviral Agents
Anti-Infective Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antibiotics, Antineoplastic
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors