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Untreated Adult Acute Myeloid LeukemiaPhase 2NCT01806571

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

A Phase 2 study testing Cytarabine, Daunorubicin Hydrochloride and Laboratory Biomarker Analysis in people with Untreated Adult Acute Myeloid Leukemia, run by Mayo Clinic at 2 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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… Read more about this study

Who is it for?
Ages 18 to 69 years
Conditions the study is for
Untreated Adult Acute Myeloid Leukemia
What is being tested?
Cytarabine, Daunorubicin Hydrochloride and Laboratory Biomarker Analysis
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
34 participants
Where
2 sitesUnited States
Study dates
12 Mar 2015to 30 Nov 2019
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 69 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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)
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  • 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

Who cannot join

  • 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
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  • 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
  • Myocardial infarction =< 12 months prior to starting study
  • Other clinically significant uncontrolled heart disease (e.g. unstable angina, congestive heart failure or uncontrolled hypertension)
  • History of or presence of clinically significant ventricular, atrial tachyarrhythmias or ejection fraction cutoff
  • Left ventricle ejection fraction < 45%
  • History of, congestive heart failure requiring use of ongoing maintenance therapy for life-threatening ventricular arrhythmias
  • Patients currently receiving treatment with strong cytochrome P450 family 3, subfamily A, polypeptide 4 (CYP3A4) inhibitors and treatment that cannot be either discontinued or switched to a different medication prior to starting study drug; patients receiving any medications or substances that are strong or moderate inhibitors of CYP3A4
  • Use of the following strong or moderate inhibitors is prohibited < 7 days prior to registration
  • Strong inhibitors of CYP3A4/5 > 5-fold increase in the plasma area under the curve (AUC) values or more than 80% decrease in clearance
  • Boceprevir (Victrelis)
  • Clarithromycin (Biaxin, Biaxin XL)
  • Conivaptan (Vaprisol)
  • Grapefruit juice
  • Indinavir (Crixivan)
  • Itraconazole (Sporanox)
  • Ketoconazole (Nizoral)
  • Lopinavir/ritonavir (Kaletra)
  • Mibefradil
  • Nefazodone (Serzone)
  • Nelfinavir (Viracept)
  • Posaconazole (Noxafil)
  • Ritonavir (Novir, Kaletra)
  • Saquinivir (Fortovase, Invirase)
  • Telaprevir (Incivek)
  • Telithromycin (Ketek)
  • Voriconazole (Vfend)
  • Moderate inhibitors of CYP3A4/5 > 2-fold in the plasma AUC values or 50-80% decrease in clearance
  • Amprenavir (Agenerase)
  • Aprepitant (Emend)
  • Atazanavir (Reyataz)
  • Ciprofloxacin (Cipro)
  • Darunavir (Prezista)
  • Diltiazem (Cardizem, Cardizem CD, Cardizem LA, Cardizem SR, Cartia XT, Dilacor XR, Diltia XT, Taztia XT, Tiazac)
  • Erythromycin (Erythrocin, E.E.S. , Ery-Tab, Eryc, EryPed, PCE)
  • Fluconazole (Diflucan)
  • Fosamprenavir (Lexiva)
  • Imatinib (Gleevec)
  • Verapamil (Calan, Calan SR, Covera-HS, Isoptin SR, Verelan, Verelan PM)
  • Receiving any medications or substances that are inducers of CYP3A4; use of the following inducers are prohibited =< 7 days prior to registration
  • Strong inducers of CYP3A4/5 > 80% decrease in AUC
  • Avasimibe
  • Carbamazepine (Carbatrol, Epitol, Equetro, Tegretol, Tegretol-XR)
  • Phenytoin (Dilantin, Phenytek)
  • Rifampin (Rifadin)
  • St. John's wort
  • Moderate inducers of CYP3A4/5 50-80% decrease in AUC
  • Bosentan (Tracleer)
  • Efavirenz (Sustiva)
  • Etravirine (Intelence)
  • Modafinil (Provigil)
  • Nafcillin
  • Nevirapine (Viramune)
  • Phenobarbital (Luminal)
  • Rifabutin (Mycobutin)
  • Troglitazone
  • Patients currently receiving treatment with any medications that have the potential to prolong the QT interval and the treatment cannot be either discontinued or switched to a different medication prior to starting study drug
  • Impaired gastrointestinal (GI) function or GI disease that may significantly alter the absorption of study drug (e.g., ulcerative diseases, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, small bowel resection or gastric bypass surgery)
  • Acute or chronic pancreatic disease
  • Known cytopathologically confirmed central nervous system (CNS) infiltration
  • Acute or chronic liver disease or severe renal disease considered unrelated to the cancer
  • History of significant congenital or acquired bleeding disorder unrelated to cancer
  • Major surgery =< 4 weeks prior to registration of the study or who have not recovered from prior surgery
  • Treatment with other investigational agents =< 14 days of registration
  • Diagnosis of AML-M3 (or acute promyelocytic leukemia)

Trial locations and contacts

2 sites in 1 country.

United States2 sites

  • Mayo Clinic

    Rochester, Minnesota, 55905

  • Mayo Clinic in Arizona

    Scottsdale, Arizona, 85259

Other trials in United States

About this study

Official title: A Phase II Study of Combination Daunorubicin and Cytarabine (Ara-c) and Nilotinib (Tasigna) (DATA) in Patients Newly Diagnosed With Acute Myeloid Leukemia and KIT Overexpression

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.

Read the detailed description

PRIMARY OBJECTIVES:

  1. To determine the complete response rates of combination nilotinib, cytarabine, and daunorubicin (daunorubicin hydrochloride) in patients newly diagnosed with acute myeloid leukemia (AML) and v-kit Hardy-Zuckerman 4 feline sarcoma viral oncogene homolog (Kit) overexpression.

SECONDARY OBJECTIVES:

  1. Determine the 2-year overall survival (OS) and disease-free survival (DFS) rates.

II. Determine the complete response duration in patients treated with this regimen.

III. Assess the safety and toxicity of this regimen based on National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.

TERTIARY OBJECTIVES:

  1. Assess the prognostic and predictive factors (Kit mutation/expression level, fms-related tyrosine kinase 3 [Flt3] mutation) for patients treated with this regimen.

II. Assess the patterns of molecular response and relapse for Kit. III. Assess the effect on minimal residual disease (MRD) by polymerase chain reaction (PCR) or flow cytometry.

OUTLINE:

INDUCTION THERAPY: Patients receive daunorubicin hydrochloride intravenously (IV) over 10 minutes on days 1-3, cytarabine IV continuously on days 1-7, and nilotinib orally (PO) twice daily (BID) on days 4-14. Patients achieving complete remission (CR) or complete remission with incomplete blood count recovery (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.

After completion of study treatment, patients are followed up every 6 months for up to 3 years.

Being tested
Cytarabine, Daunorubicin Hydrochloride, Laboratory Biomarker Analysis, Nilotinib, Pharmacological Study

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • CytarabineDrug

    Also called .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

    Given IV

  • Daunorubicin HydrochlorideDrug

    Also called Cerubidin, Cerubidine, Cloridrato de Daunorubicina, Daunoblastin

    Given IV

  • Laboratory Biomarker AnalysisOther

    Correlative studies

  • NilotinibDrug

    Also called AMN 107, Tasigna

    Given PO

  • Pharmacological StudyOther

    Correlative studies

Study groups in NCT01806571
Study groupRoleWhat they receive
Treatment (nilotinib, daunorubicin hydrochloride, cytarabine)ExperimentalINDUCTION 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.
Receives: Drug: Cytarabine; Drug: Daunorubicin Hydrochloride; Other: Laboratory Biomarker Analysis; Drug: Nilotinib; Other: Pharmacological Study

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: Up to 56 days

Secondary outcomes (4)

  1. Disease Free Survival(DFS) Rate

    Disease free survival time is defined for all evaluable patients who have achieved a CR or CRi as the time from registration to relapse or death due to any cause. The distribution of disease-free survival will be estimated using the method of Kaplan-Meier.

    Measured: 35 months

  2. Duration of Complete Response

    The distribution of duration of complete response will be estimated using the method of Kaplan-Meier.

    Measured: 2 years

  3. Incidence of Adverse Events as Assessed by NCI CTCAE Version 4.0

    The maximum grade for each type of adverse event will be recorded for each patient, and frequency tables will be reviewed to determine patterns. Additionally, the relationship of the adverse event(s) to the study treatment will be taken into consideration. This data will be reported in the Adverse Events section of the results.

    Measured: 35 months

  4. Overall Survival(OS) Rate

    Overall survival time is defined as the time from registration to death due to any cause. The distribution of survival time will be estimated using the method of Kaplan-Meier(Kaplan E 1958).

    Measured: 39 Months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted7 Mar 2013 (estimated)
  2. Study start12 Mar 2015
  3. Primary completion31 Jul 2017
  4. Study completion30 Nov 2019

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
34 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01806571
Sponsor's protocol ID
MC1284
Other IDs
NCI-2013-00469, 12-006178, MC1284, P30CA015083
Status last verified
May 2023
First submitted
25 Feb 2013
Last updated
31 May 2023
Data monitoring committee
Yes

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Cytarabine, Daunorubicin Hydrochloride and Laboratory Biomarker Analysis in people with Untreated Adult Acute Myeloid Leukemia, run by Mayo Clinic at 2 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 15 inclusion and 78 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 31 May 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 14 Nov 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Proportion of Complete Responses (CR or CRi) During Induction Therapy (time frame: Up to 56 days). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01806571.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 31 May 2023.

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