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

NCT ID: NCT02971397

Last Updated: 2024-05-06

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 40 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-11-30
• Study Completion Date: 2018-08-08

Brief Summary

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.

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.

Conditions

Acute Myeloid Leukemia

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

Bone Marrow Aspiration and Biopsy

Intervention Type: PROCEDURE

Undergo bone marrow aspiration and biopsy

Cytarabine

Intervention Type: DRUG

Given IV

Daunorubicin Hydrochloride

Intervention Type: DRUG

Given IV

Laboratory Biomarker Analysis

Intervention Type: OTHER

Correlative studies

Interventions

Bone Marrow Aspiration and Biopsy

Undergo bone marrow aspiration and biopsy

Intervention Type: PROCEDURE

Cytarabine

Given IV

Intervention Type: DRUG

Daunorubicin Hydrochloride

Given IV

Intervention Type: DRUG

Laboratory Biomarker Analysis

Correlative studies

Intervention Type: OTHER

Other Intervention 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; Cerubidin; Cerubidine; Cloridrato de Daunorubicina; Daunoblastin; Daunoblastina; Daunoblastine; Daunomycin Hydrochloride; Daunomycin, hydrochloride; Daunorubicin.HCl; Daunorubicini Hydrochloridum; FI-6339; Ondena; RP-13057; Rubidomycin Hydrochloride; Rubilem

Eligibility Criteria

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

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

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

Wake Forest University Health Sciences

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Bayard Powell

Role: PRINCIPAL_INVESTIGATOR

Wake Forest University Health Sciences

Locations

Comprehensive Cancer Center of Wake Forest University

Winston-Salem, North Carolina, United States

Countries

United States

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Document Type: Informed Consent Form

View Document

Other Identifiers

NCI-2016-01464

Identifier Type: REGISTRY

Identifier Source: secondary_id

CCCWFU 22616

Identifier Type: OTHER

Identifier Source: secondary_id

P30CA012197

Identifier Type: NIH

Identifier Source: secondary_id

View Link

IRB00040792

Identifier Type: -

Identifier Source: org_study_id