Study of Crenolanib Combined With Chemotherapy in FLT3-mutated Acute Myeloid Leukemia Patients

NCT02400281 | Completed Phase 1 Results

• 1 other identifier: ARO-010
• Study Type: interventional
• Target: 28
• Locations: 1 country
• Sites: 1

Brief Summary

This is an open label, two-arm, Phase I-II trial, non-randomized. Arm 1: crenolanib with standard chemotherapy (Idarubicin/Cytarabine, MEC;Mitoxantrone/Etoposide/Cytarabine, FLAG-Ida: Fludarabine/Cytarabine/G-CSF/Idarubicin) Arm 2: crenolanib with 5-azacitidine

Conditions

Acute Myeloid Leukemia

Outcome Measures

Primary Outcomes (1)

• Response Rate of Crenolanib Besylate Combination Therapy

  To determine the response rate to crenolanib. CR Complete remission (CR) response criteria include a post-baseline bone marrow (BM) biopsy or aspiration % blasts \<5%, absolute neutrophil count (ANC) \>1×10\^9/L and platelet count \>100×10\^9/L. CRi response included all CR criteria met, except participant did not experience either platelet recovery or ANC recovery. Morphologic Leukemia-Free State (MLFS) response included ≤5% in % blasts in the BM aspirate or biopsy. Resistant Disease (RD) was defined as the absence of CR, CRi, CRp, PR or MLFS. Death in aplasia response include deaths occurring following chemotherapy while cytopenic with an aplastic or hypoplastic BM prior to death without evidence of persistent leukemia.

  Baseline up to first documented response, persistent disease, or death (whichever occurs first), 1 year.

Study Arms (2)

Arm 1 crenolanib besylate combination

EXPERIMENTAL

Arm 1 patients will receive crenolanib besylate, combined with standard chemotherapy (Idarubicin/Cytarabine, MEC;Mitoxantrone/Etoposide/Cytarabine, FLAG-Ida: Fludarabine/Cytarabine/G-CSF/Idarubicin

Drug: Crenolanib besylate; Drug: Idarubicin; Drug: Cytarabine; Drug: Mitoxantrone; Drug: Etoposide; Drug: Fludarabine; Drug: G-CSF

Arm 2 crenolanib besylate combination

EXPERIMENTAL

Arm 2 patients will receive crenolanib besylate and azacytidine.

Drug: Crenolanib besylate; Drug: Azacytidine

Interventions

Crenolanib besylate DRUG

Also known as: CP-868,596-26

Arm 1 crenolanib besylate combination; Arm 2 crenolanib besylate combination

Idarubicin DRUG

Also known as: 4-demethoxydaunorubicin

Arm 1 crenolanib besylate combination

Cytarabine DRUG

Also known as: cytosine arabinoside

Arm 1 crenolanib besylate combination

Azacytidine DRUG

Also known as: 5-azacytidine

Arm 2 crenolanib besylate combination

Mitoxantrone DRUG

Also known as: Novantrone

Arm 1 crenolanib besylate combination

Etoposide DRUG

Also known as: etoposide phosphate

Arm 1 crenolanib besylate combination

Fludarabine DRUG

Also known as: Fludarabine phosphate

Arm 1 crenolanib besylate combination

G-CSF DRUG

Arm 1 crenolanib besylate combination

Eligibility Criteria

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

You may qualify if:

• Confirmed diagnosis of refractory/relapsed AML or high-risk MDS
• Arm 1: Subjects must have received at least one prior therapy and a maximum of three prior therapies
• Arm 2: Subjects must have received at least one prior therapy and a maximum of three prior therapies. No prior treatment with 5-Azacitidine is allowed in this arm.
• FLT3 mutation positive (ITD, TKD or other)
• ECOG PS 0-2
• Adequate liver and renal function
• Negative pregnancy test
• Extramedullary leukemia allowed except CNS disease

You may not qualify if:

• \<5% blasts in marrow or blood at time of screening
• Active HIV, hepatitis B or C
• CNS leukemia
• Clinically significant GVHD or organ dysfunction where chemotherapy specified by protocol cannot be given
• Patient with AML-M3 (APL)
• Pre-existing liver diseases (i.e. cirrhosis, chronic hepatitis B or C, nonalcoholic steatohepatitis, sclerosing cholangitis)

Sponsors & Collaborators

• Arog Pharmaceuticals, Inc.: lead

Study Sites (1)

MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

MeSH Terms

Conditions

Leukemia, Myeloid, Acute

Interventions

Idarubicin; Cytarabine; Azacitidine; Mitoxantrone; Etoposide; etoposide phosphate; fludarabine; fludarabine phosphate; Granulocyte Colony-Stimulating Factor

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Arabinonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Aza Compounds; Ribonucleosides; Anthraquinones; Anthrones; Anthracenes; Quinones; Podophyllotoxin; Tetrahydronaphthalenes; Naphthalenes; Glucosides; Colony-Stimulating Factors; Glycoproteins; Glycoconjugates; Hematopoietic Cell Growth Factors; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors

Results Point of Contact

• Title: Edward McDonald
• Organization: Arog Pharmaceuticals

emcdonald@arogpharma.com

214-593-0500

Study Officials

• Jorge Cortes, MD

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 18, 2015
• First Posted: March 27, 2015
• Study Start: September 1, 2015
• Primary Completion: July 15, 2020
• Study Completion: July 15, 2020
• Last Updated: July 3, 2024
• Results First Posted: March 20, 2024

Record last verified: 2024-06

Locations

US (1)