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

NCT02283177 | Completed Phase 2 Results

• 1 other identifier: ARO-006
• Study Type: interventional
• Target: 44
• Locations: 1 country
• Sites: 9

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.

Conditions

Newly Diagnosed AML With FLT3 Activating Mutations

Outcome Measures

Primary Outcomes (1)

• Clinical Response to Crenolanib With Standard Induction Chemotherapy

  To determine the response rate to crenolanib. Complete remission (CR) response criteria includes a post-baseline bone marrow (BM) biopsy or aspiration % blasts \<5%, the absence of Auer rods and extramedullary leukemia, absolute neutrophil count (ANC) \>1×10\^9/L and platelet count \>100×10\^9/L. Complete remission with incomplete blood count recovery (CRi) response includes all CR criteria met, except participant do not achieve either platelet or ANC recovery. Composite Complete CR response includes all subjects who achieve a CR and CRi. Partial Response (PR) response includes all CR criteria met except a decrease of ≥50% in % blasts in the BM aspirate or biopsy from baseline but within 5-25% or bone marrow blasts \<5% with persistent Auer rods. Refractory Disease response includes subjects who do not satisfy the criteria for CR, CRi or PR.

  2 years

Secondary Outcomes (1)

• 3-Year Overall Survival

  3 years

Study Arms (2)

Cohort A

EXPERIMENTAL

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

Drug: crenolanib; Drug: cytarabine; Drug: daunorubicin

Cohort B

EXPERIMENTAL

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

Drug: crenolanib; Drug: cytarabine; Drug: idarubicin

Interventions

crenolanib DRUG

Also known as: CP-868,596-26

Cohort A; Cohort B

cytarabine DRUG

Cohort A; Cohort B

daunorubicin DRUG

Cohort A

idarubicin DRUG

Cohort B

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Arog Pharmaceuticals, Inc.: lead

Study Sites (9)

City of Hope Medical Center

Duarte, California, 91010, United States

Location

University of Iowa Hospitals and Clinics

Iowa City, Iowa, 52242, United States

Location

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

Roswell Park Cancer Institute

Buffalo, New York, 14263, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

Weill Cornell Medical College

New York, New York, 10065, United States

Location

Cleveland Clinic

Cleveland, Ohio, 44195, United States

Location

University of Texas Southwestern Medical Center

Dallas, Texas, 75390, United States

Location

Fred Hutchinson Cancer Research Center

Seattle, Washington, 98195, United States

Location

Related Publications (1)

• Wang ES, Goldberg AD, Tallman M, Walter RB, Karanes C, Sandhu K, Vigil CE, Collins R, Jain V, Stone RM. Crenolanib and Intensive Chemotherapy in Adults With Newly Diagnosed FLT3-Mutated AML. J Clin Oncol. 2024 May 20;42(15):1776-1787. doi: 10.1200/JCO.23.01061. Epub 2024 Feb 7.

  PMID: 38324741 DERIVED

MeSH Terms

Interventions

crenolanib; Cytarabine; Daunorubicin; Idarubicin

Intervention Hierarchy (Ancestors)

Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Arabinonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates

Results Point of Contact

• Title: Edward McDonald
• Organization: Arog Pharmaceuticals

emcdonald@arogpharma.com

214-593-0500

Study Officials

• Richard Stone, MD

  Dana-Farber Cancer Institute

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 29, 2014
• First Posted: November 5, 2014
• Study Start: January 1, 2015
• Primary Completion: December 1, 2019
• Study Completion: December 1, 2019
• Last Updated: February 2, 2024
• Results First Posted: February 2, 2024

Record last verified: 2024-01

Locations

US (9)