Daunorubicin Hydrochloride, Cytarabine, and Nilotinib in Treating Patients With Newly Diagnosed Acute Myeloid Leukemia

NCT01806571 | Completed Phase 2 Results DMC

• 4 other identifiers: MC1284NCI-2013-0046912-006178P30CA015083
• Study Type: interventional
• Target: 34
• Locations: 1 country
• Sites: 2

Brief Summary

This phase II trial studies how well daunorubicin hydrochloride, cytarabine, and nilotinib work in treating patients newly diagnosed with acute myeloid leukemia. Drugs used in chemotherapy, such as daunorubicin hydrochloride and cytarabine, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Nilotinib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Giving daunorubicin hydrochloride with cytarabine and nilotinib may kill more cancer cells.

Conditions

Untreated Adult Acute Myeloid Leukemia

Outcome Measures

Primary Outcomes (1)

• Proportion of Complete Responses (CR or CRi) During Induction Therapy

  The proportion of successes will be estimated by the number of successes divided by the total number of evaluable patients. Confidence intervals for the true success proportion will be calculated according to the approach of Duffy and Santner.

  Up to 56 days

Secondary Outcomes (4)

• Disease Free Survival(DFS) Rate

  35 months

• Duration of Complete Response

  2 years

• Incidence of Adverse Events as Assessed by NCI CTCAE Version 4.0

  35 months

• Overall Survival(OS) Rate

  39 Months

Other Outcomes (4)

• Bone Marrow Flt3 Mutation

  Baseline

• Bone Marrow Kit Mutation Status

  Up to 3 years

• Bone Marrow Kit Mutation/Expression

  Baseline

Study Arms (1)

Treatment (nilotinib, daunorubicin hydrochloride, cytarabine)

EXPERIMENTAL

INDUCTION THERAPY: Patients receive daunorubicin hydrochloride IV over 10 minutes on days 1-3, cytarabine IV continuously on days 1-7, and nilotinib PO BID on days 4-14. Patients achieving CR or CRi proceed to consolidation therapy. Patients not achieving a significant decrease in bone marrow recovery or CR/CRi upon bone marrow recovery receive another course of induction therapy. CONSOLIDATION THERAPY: Patients receive cytarabine IV every 12 hours on days 1, 3, and 5, and nilotinib PO BID on days 4-14. Treatment repeats every 28 days for 4 courses in the absence of disease progression or unacceptable toxicity. Patients achieving CR or CRi proceed to maintenance therapy. MAINTENANCE THERAPY: Patients receive nilotinib PO BID on days 1-84. Treatment repeats every 84 days for up to 8 courses in the absence of disease progression or unacceptable toxicity.

Drug: Cytarabine; Drug: Daunorubicin Hydrochloride; Other: Laboratory Biomarker Analysis; Drug: Nilotinib; Other: Pharmacological Study

Interventions

Cytarabine DRUG

Given IV

Also known as: .beta.-Cytosine arabinoside, 1-.beta.-D-Arabinofuranosyl-4-amino-2(1H)pyrimidinone, 1-.beta.-D-Arabinofuranosylcytosine, 1-Beta-D-arabinofuranosyl-4-amino-2(1H)pyrimidinone, 1-Beta-D-arabinofuranosylcytosine, 1.beta.-D-Arabinofuranosylcytosine, 2(1H)-Pyrimidinone, 4-Amino-1-beta-D-arabinofuranosyl-, 2(1H)-Pyrimidinone, 4-amino-1.beta.-D-arabinofuranosyl-, Alexan, Ara-C, ARA-cell, Arabine, Arabinofuranosylcytosine, Arabinosylcytosine, Aracytidine, Aracytin, Aracytine, Beta-Cytosine Arabinoside, CHX-3311, Cytarabinum, Cytarbel, Cytosar, Cytosar-U, Cytosine Arabinoside, Cytosine-.beta.-arabinoside, Cytosine-beta-arabinoside, Erpalfa, Starasid, Tarabine PFS, U 19920, U-19920, Udicil, WR-28453

Treatment (nilotinib, daunorubicin hydrochloride, cytarabine)

Daunorubicin Hydrochloride DRUG

Given IV

Also known as: Cerubidin, Cerubidine, Cloridrato de Daunorubicina, Daunoblastin, Daunoblastina, Daunoblastine, Daunomycin Hydrochloride, Daunomycin, hydrochloride, Daunorubicin.HCl, Daunorubicini Hydrochloridum, FI-6339, Ondena, RP-13057, Rubidomycin Hydrochloride, Rubilem

Treatment (nilotinib, daunorubicin hydrochloride, cytarabine)

Laboratory Biomarker Analysis OTHER

Correlative studies

Treatment (nilotinib, daunorubicin hydrochloride, cytarabine)

Nilotinib DRUG

Given PO

Also known as: AMN 107, Tasigna

Treatment (nilotinib, daunorubicin hydrochloride, cytarabine)

Pharmacological Study OTHER

Correlative studies

Treatment (nilotinib, daunorubicin hydrochloride, cytarabine)

Eligibility Criteria

• Age: 18 Years - 69 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Untreated, histological confirmed acute myeloid leukemia (AML) based on World Health Organization (WHO) 2008 criteria with Kit expression (cluster of differentiation \[CD\] 117) of myeloblasts \>= 20% by flow cytometry from bone marrow aspirate at diagnosis
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0, 1, or 2
• Magnesium within normal limits (WNL)
• Potassium WNL
• Phosphorus WNL
• Serum amylase =\< 1.5 x upper limit of normal (ULN)
• Serum lipase =\< 1.5 x ULN
• Total bilirubin =\< 1.5 x ULN (does not apply to patients with isolated hyperbilirubinemia \[e.g., Gilbert's disease\], in that case direct bilirubin should be =\< 2 x ULN)
• Alkaline phosphatase =\< 3 x ULN
• Serum glutamic-oxaloacetic transaminase (SGOT) (aspartate aminotransferase \[AST\]) =\< 3 x ULN
• Creatinine =\<1.5 x ULN
• Negative pregnancy test done =\< 7 days prior to registration, for women of childbearing potential only
• Provide informed written consent
• Willing to return to consenting Mayo Clinic (Mayo Clinic's campus in Rochester, Mayo Clinic's campus in Arizona, or Mayo Clinic's campus in Florida) institution for follow-up during the active monitoring phase of the study
• Willing to provide bone marrow aspirate and blood samples for correlative research purposes

You may not qualify if:

• Any of the following because this study involves investigational agent(s) whose genotoxic, mutagenic and teratogenic effects on the developing fetus and newborn are unknown
• Pregnant women
• Nursing women
• Men or women of childbearing potential who are unwilling to employ adequate contraception throughout the study and for 3 months after completion of study treatment
• Co-morbid systemic illnesses or other severe concurrent disease which, in the judgment of the investigator, would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens
• Immunocompromised patients (other than that related to the use of corticosteroids) including patients known to be human immunodeficiency virus (HIV) positive
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, or psychiatric illness/social situations that would limit compliance with study requirements
• Receiving any other investigational agent which would be considered as a treatment for the primary neoplasm
• Other active malignancy =\< 3 years prior to registration; EXCEPTIONS: non-melanotic skin cancer or carcinoma-in-situ of the cervix
• Previous treatment with chemotherapy or any other tyrosine kinase inhibitor for a hematological disorder; Exceptions: patients with prior diagnosis of myelodysplastic syndrome (MDS) and/or treatment with hypomethylating agent (azacytidine or decitabine) are not excluded, prior hydroxyurea allowed
• Impaired cardiac function including any one of the following:
• Inability to monitor the QT interval on electrocardiogram (ECG)
• Congenital long QT syndrome or a known family history of long QT syndrome
• Clinically significant resting brachycardia (\< 50 beats per minute)
• Corrected QT (QTc) \> 450 msec on baseline ECG; if QTc \> 450 msec and electrolytes are not within normal ranges, electrolytes should be corrected and then the patient re-screened for QTc

Sponsors & Collaborators

• Mayo Clinic: lead
• National Cancer Institute (NCI): collaborator

Study Sites (2)

Mayo Clinic in Arizona

Scottsdale, Arizona, 85259, United States

Location

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

MeSH Terms

Interventions

Cytarabine; Daunorubicin; nilotinib

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: Aref Al-Kali, M.D.
• Organization: Mayo Clinic

alkali.aref@mayo.edu

(507) 538-0591

Study Officials

• Aref Al-Kali

  Mayo Clinic

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 25, 2013
• First Posted: March 7, 2013
• Study Start: March 12, 2015
• Primary Completion: July 31, 2017
• Study Completion: November 30, 2019
• Last Updated: May 31, 2023
• Results First Posted: November 14, 2019

Record last verified: 2023-05

Locations

US (2)