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

Cytarabine Plus Continuous Infusion Daunorubicin Induction Therapy for Adults With Acute Myeloid Leukemia: A Feasibility Study With Cardiac MRI Monitoring

This pilot clinical trial studies the side effects of cytarabine and daunorubicin hydrochloride and to see how well they work in treating patients with newly diagnosed acute myeloid leukemia. Drugs used in chemotherapy, such as cytarabine and daunorubicin hydrochloride, 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, and may be safer for the heart.

Study Overview

• Status: Completed
• Conditions: Acute Myeloid Leukemia
• Intervention / Treatment: Other: Laboratory Biomarker Analysis; Drug: Cytarabine; Drug: Daunorubicin Hydrochloride; Procedure: Bone Marrow Aspiration and Biopsy

Detailed Description

PRIMARY OBJECTIVES:

I. To assess the safety (at 3 months) and feasibility of administering daunorubicin hydrochloride (daunorubicin) as continuous infusion under the proposed treatment regimen.

SECONDARY OBJECTIVES:

I. To assess the safety (at 6 months) of administering daunorubicin as continuous infusion under the proposed treatment regimen.

II. To assess treatment outcomes (including complete remission [CR] and complete remission with incomplete recovery [CRi]) in patients with acute myeloid leukemia (AML) under the proposed treatment regimen.

III. To compare the concordance between magnetic resonance imaging (MRI) and echocardiogram (ECHO) in identifying cardiac toxicity, ie a reduction in left ventricular ejection fraction (LVEF) of >= 10% and ejection fraction (EF) =< 50% compared to baseline LVEF.

OUTLINE:

INDUCTION: Patients receive cytarabine intravenously (IV) continuously over 24 hours on days 1-7 and daunorubicin hydrochloride IV continuously over 24 hours on days 1-3 in the absence of disease progression or unacceptable toxicity. Patients then undergo bone marrow aspirate and biopsy on day 14. Patients with bone marrow cellularity >= 10% and > 5% leukemic blasts, may receive a second induction of cytarabine IV continuously over 24 hours on days 1-5 and daunorubicin hydrochloride IV continuously over 24 hours on days 1-2 in the absence of disease progression or unacceptable toxicity.

CONSOLIDATION: Patients achieving remission receive cytarabine IV over 3 hours every 12 hours on days 1, 3, and 5. Treatment repeats every 28 days for up to 3 courses in the absence of disease progression or unacceptable toxicity. Patients with core-binding factor (CBF) AML may receive 4 courses of therapy.

After completion of study treatment, patients are followed up for a minimum of 30 days, at 3 and 6 months, and then every 3 months thereafter.

• Study Type: Interventional
• Enrollment (Actual): 40
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • North Carolina
    • Winston-Salem, North Carolina, United States, 27157
      • Comprehensive Cancer Center of Wake Forest University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Patients must have morphologically confirmed newly diagnosed acute myelogenous leukemia (AML) with blood or bone marrow disease; patients with only extramedullary disease in the absence of bone marrow or blood involvement are eligible; note: this protocol uses World Health Organization (WHO) diagnostic criteria for AML; patients with acute promyelocytic leukemia (APL, French-American-British Classification [FAB], M3) or blastic transformation of chronic myelogenous leukemia (CML) are not eligible
• Eastern Cooperative Oncology Group (ECOG) performance status 0-3
• Patients with ECHO EF >= 45% within 28 days prior to registration
• Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately
• Ability to understand and the willingness to sign an Institutional Review Board (IRB)-approved informed consent document

Exclusion Criteria:

• Patients who have received prior induction chemotherapy for AML or myelodysplastic syndrome (MDS); temporary prior measures such as apheresis or hydroxyurea are allowed; patients who have received a limited and short-term exposure of ATRA (all trans retinoic acid) while AML-M3 (acute promyelocytic leukemia) was being ruled out, and which has been discontinued, will be eligible
• Patients receiving any other investigational agents
• Patients with prolonged corrected QT (QTc) interval (> 500 msec) determined by electrocardiogram (EKG) within 28 days prior to registration

• Patients not suitable for cardiac MRI; contraindications include:

  • Intracranial metal, pacemakers, defibrillators, functioning neurostimulator devices, or other implanted electronic devices
  • Ferromagnetic cerebral aneurysm clips, or other intraorbital/intracranial metal
  • Allergy to gadolinium or other severe drug allergies
  • Claustrophobia
  • Congestive heart failure (New York Heart Association [NYHA] class III or IV)
  • Significant valvular disease, or significant pulmonary disease requiring supplemental oxygen therapy
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to daunorubicin or cytarabine
• Patients with documented central nervous system (CNS) involvement

• Patients who are known to be human immunodeficiency virus (HIV) positive (+) may be eligible providing they meet all of the following additional criteria within 28 days prior to registration:

  • CD4 cells >= 500/mm^3
  • Viral load of < 50 copies HIV messenger ribonucleic acid (mRNA)/mm^3 if on combination antiretroviral therapy (cART) or < 25,000 copies HIV mRNA if not on cART
  • No zidovudine or stavudine as part of cART Patients who are HIV+ and do not meet all of these criteria are not eligible for this study
• Patients with other uncontrolled intercurrent illness or psychiatric illness/social situations that would limit compliance with study requirements
• Pregnant women are excluded from this study; breastfeeding should be discontinued prior to beginning treatment

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Treatment (cytarabine, daunorubicin hydrochloride, biopsy); INDUCTION: Patients receive cytarabine IV continuously over 24 hours on days 1-7 and daunorubicin hydrochloride IV continuously over 24 hours on days 1-3 in the absence of disease progression or unacceptable toxicity. Patients then undergo bone marrow aspirate and biopsy on day 14. Patients with bone marrow cellularity >= 10% and > 5% leukemic blasts, may receive a second induction of cytarabine IV continuously over 24 hours on days 1-5 and daunorubicin hydrochloride IV continuously over 24 hours on days 1-2 in the absence of disease progression or unacceptable toxicity. CONSOLIDATION: Patients achieving remission receive cytarabine IV over 3 hours every 12 hours on days 1, 3, and 5. Treatment repeats every 28 days for up to 3 courses in the absence of disease progression or unacceptable toxicity. Patients with CBF AML may receive 4 courses of therapy.

Other: Laboratory Biomarker Analysis; Correlative studies; Drug: Cytarabine; Given IV; Other Names: .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; Drug: Daunorubicin Hydrochloride; Given IV; Other Names: Cerubidin; Cerubidine; Cloridrato de Daunorubicina; Daunoblastin; Daunoblastina; Daunoblastine; Daunomycin Hydrochloride; Daunomycin, hydrochloride; Daunorubicin.HCl; Daunorubicini Hydrochloridum; FI-6339; Ondena; RP-13057; Rubidomycin Hydrochloride; Rubilem; Procedure: Bone Marrow Aspiration and Biopsy; Undergo bone marrow aspiration and biopsy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Cardiac Toxicity, Defined as Reduction in LVEF of >= 10% Compared to Baseline LVEF and EF =< 50% on the Follow-up Scan, Assessed Using MRI	Incidence of cardiac toxicity, defined as reduction in LVEF of >= 10% compared to baseline LVEF and EF =< 50% on the follow-up scan, assessed using MRI.	Baseline up to 3 months
Unexpected Toxicities (Exclude Hematologic and Infectious) ≥ Grade 3, as Measured by CTCAE v 4.0	Unexpected toxicities (exclude hematologic and infectious) ≥ grade 3, as measured by CTCAE v 4.0	Up to 30 days after last dose of study drug
Proportion of Patients Who Complete the Infusion Therapy	Will report these proportions with 95% confidence intervals.	72 hours
Proportion of Patients With Study-related Deviations	Will report these proportions with 95% confidence intervals.	Approximately 1 year, 5 months
Incidence of Cardiac Toxicity, Defined as Reduction in LVEF of >= 10% Compared to Baseline LVEF and EF =< 50% on the Follow-up Scan, Assessed Using ECHO	Incidence of cardiac toxicity, defined as reduction in LVEF of >= 10% compared to baseline LVEF and EF =< 50% on the follow-up scan, assessed using ECHO.	Baseline up to 3 months after last dose of study drug

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
EF, Assessed by MRI and ECHO	Ejection Fraction at baseline, 3 months, and change from baseline to 3 months	Baseline and 3 months
Incidence of Cardiac Toxicity, Defined as Reduction in LVEF of >= 10% Compared to Baseline LVEF and EF =< 50% on the Follow-up Scan, Assessed Using MRI	Incidence of cardiac toxicity, defined as reduction in LVEF of >= 10% compared to baseline LVEF and EF =< 50% on the follow-up scan, assessed using MRI.	Baseline up to 6 months after last dose of study drug
Change in Left Ventricular End Diastolic Volume, Assessed by MRI and ECHO	Left ventricular end diastolic volume assessed by MRI and ECHO at baseline, 3 months, and change from baseline to 3 months.	Baseline up to 6 months after last dose of study drug
Left Ventricular End Systolic Volume, Assessed by MRI and ECHO	Left ventricular end systolic volume assessed by MRI and ECHO at baseline, 3 months, and change from baseline to 3 months.	Baseline, 3 months
Myocardial Strain, Assessed by MRI and ECHO	Myocardial strain (Global Longitudinal Strain %) assessed by ECHO at baseline, 3 months, and change from baseline to 3 months. GLS was not measured with MRI.	Baseline and 3 months
Disease-free Survival for Those Patients Who Achieve Remission	Disease-free survival is calculated for patients who achieve CR and measured from the date of CR until relapse from CR or death. Observation is censored at the date of last follow-up for patients last known to be alive without report of relapse.	From the date of CR until relapse from CR or death, approximately 1 year, 9 months
Induction Death Rate	Number of patients who had an induction death	Up to 28 days
Overall Response Rate, Defined as CR + CRi	Overall response rate, defined as CR + CRi. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.", or similar definition that is accurate and appropriate.	Approximately 1 year and 9 months

Collaborators and Investigators

• Sponsor: Wake Forest University Health Sciences
• Collaborators: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Bayard Powell, Wake Forest University Health Sciences

Study record dates

Study Major Dates

• Study Start (Actual): November 1, 2016
• Primary Completion (Actual): March 1, 2018
• Study Completion (Actual): August 8, 2018

Study Registration Dates

• First Submitted: October 4, 2016
• First Submitted That Met QC Criteria: November 18, 2016
• First Posted (Estimated): November 23, 2016

Study Record Updates

• Last Update Posted (Actual): March 23, 2026
• Last Update Submitted That Met QC Criteria: March 2, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Histologic Type; Hematologic Diseases; Leukemia, Myeloid; Leukemia; Hemic and Lymphatic Diseases; Leukemia, Myeloid, Acute; Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Investigative Techniques; Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Surgical Procedures, Operative; Cytological Techniques; Nucleic Acids, Nucleotides, and Nucleosides; Cytodiagnosis; Hydrocarbons; Hydrocarbons, Cyclic; Carbohydrates; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Polycyclic Compounds; Glycosides; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Diagnostic Techniques, Surgical; Nucleosides; Arabinonucleosides; Anthracyclines; Naphthacenes; Aminoglycosides; Cytarabine; Daunorubicin; Biopsy
• Other Study ID Numbers: IRB00040792; P30CA012197 (U.S. NIH Grant/Contract); NCI-2016-01464 (Registry Identifier: CTRP (Clinical Trial Reporting Program)); CCCWFU 22616 (Other Identifier: Comprehensive Cancer Center of Wake Forest University)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No