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

NCT ID: NCT02283177

Last Updated: 2024-02-02

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 44 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-01-31
• Study Completion Date: 2019-12-31

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

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Cohort A

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

Group Type: EXPERIMENTAL

crenolanib

Intervention Type: DRUG

cytarabine

Intervention Type: DRUG

daunorubicin

Intervention Type: DRUG

Cohort B

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

Group Type: EXPERIMENTAL

crenolanib

Intervention Type: DRUG

cytarabine

Intervention Type: DRUG

idarubicin

Intervention Type: DRUG

Interventions

crenolanib

Intervention Type: DRUG

cytarabine

Intervention Type: DRUG

daunorubicin

Intervention Type: DRUG

idarubicin

Intervention Type: DRUG

Other Intervention Names

CP-868,596-26

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Arog Pharmaceuticals, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Richard Stone, MD

Role: PRINCIPAL_INVESTIGATOR

Dana-Farber Cancer Institute

Locations

City of Hope Medical Center

Duarte, California, United States

University of Iowa Hospitals and Clinics

Iowa City, Iowa, United States

Dana-Farber Cancer Institute

Boston, Massachusetts, United States

Roswell Park Cancer Institute

Buffalo, New York, United States

Memorial Sloan Kettering Cancer Center

New York, New York, United States

Weill Cornell Medical College

New York, New York, United States

Cleveland Clinic

Cleveland, Ohio, United States

University of Texas Southwestern Medical Center

Dallas, Texas, United States

Fred Hutchinson Cancer Research Center

Seattle, Washington, United States

Countries

United States

References

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.

Reference Type: DERIVED

PMID: 38324741 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

ARO-006

Identifier Type: -

Identifier Source: org_study_id