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

Primary Purpose

Acute Myeloid Leukemia

Status

Unknown status

Phase

Phase 2

Locations

United States

Study Type

Interventional

Intervention

Bone Marrow Aspiration and Biopsy

Cytarabine

Daunorubicin Hydrochloride

Laboratory Biomarker Analysis

About this trial

This is an interventional treatment trial for Acute Myeloid Leukemia

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

Comprehensive Cancer Center of Wake Forest University

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Treatment (cytarabine, daunorubicin hydrochloride, biopsy)

Arm Description

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.

Outcomes

Primary Outcome Measures

Change in 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

In addition to point estimates of these rates, 95% confidence intervals will be calculated.

Incidence of other unexpected toxicities, measured by Common Terminology Criteria for Adverse Events version 4.0

In addition to point estimates of these rates, 95% confidence intervals will be calculated.

Proportion of patients who complete the infusion therapy

Will report these proportions with 95% confidence intervals.

Proportion of patients with study-related deviations

Will report these proportions with 95% confidence intervals.

Change in 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

In addition to point estimates of these rates, 95% confidence intervals will be calculated.

Secondary Outcome Measures

Change in EF, assessed by MRI and ECHO

Will determine the correlation between ECHO and MRI assessments performed pre-chemotherapy. Will assess correlations between post-chemotherapy ECHO and MRI assessments. Will assess correlations between each of the time points. Paired t-tests will be performed to compare the actual values of each ECHO/MRI measurement to each other at each time point. Bland-Altman plots will be generated at baseline, follow-up and using the change in measure for each of the MRI/ECHO derived measures.

Change in 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 and ECHO

Change in left ventricular end diastolic volume, assessed by MRI and ECHO

Change in left ventricular end systolic volume, assessed by MRI and ECHO

Change in myocardial strain, assessed by MRI and ECHO

Disease-free survival for those patients who achieve remission

Induction death rate

Overall response rate, defined as CR + CRi

Full Information

NCT ID

NCT02971397

First Posted

October 4, 2016

Last Updated

November 1, 2018

Sponsor

Wake Forest University Health Sciences

Collaborators

National Cancer Institute (NCI)

1. Study Identification

Unique Protocol Identification Number

NCT02971397

Brief Title

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

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

November 2018

Overall Recruitment Status

Unknown status

Study Start Date

November 2016 (Actual)

Primary Completion Date

March 2018 (Actual)

Study Completion Date

March 2020 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Wake Forest University Health Sciences

Collaborators

National Cancer Institute (NCI)

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Acute Myeloid Leukemia

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

40 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Treatment (cytarabine, daunorubicin hydrochloride, biopsy)

Arm Type

Experimental

Arm Description

Intervention Type

Procedure

Intervention Name(s)

Bone Marrow Aspiration and Biopsy

Intervention Description

Undergo bone marrow aspiration and biopsy

Intervention Type

Drug

Intervention Name(s)

Cytarabine

Other Intervention Name(s)

.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

Intervention Description

Given IV

Intervention Type

Drug

Intervention Name(s)

Daunorubicin Hydrochloride

Other Intervention Name(s)

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

Intervention Description

Given IV

Intervention Type

Other

Intervention Name(s)

Laboratory Biomarker Analysis

Intervention Description

Correlative studies

Primary Outcome Measure Information:

Title

Change in 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

Description

In addition to point estimates of these rates, 95% confidence intervals will be calculated.

Time Frame

Baseline up to 3 months after last dose of study drug

Title

Incidence of other unexpected toxicities, measured by Common Terminology Criteria for Adverse Events version 4.0

Description

In addition to point estimates of these rates, 95% confidence intervals will be calculated.

Time Frame

Up to 6 months after last dose of study drug

Title

Proportion of patients who complete the infusion therapy

Description

Will report these proportions with 95% confidence intervals.

Time Frame

Up to 4 months

Title

Proportion of patients with study-related deviations

Description

Will report these proportions with 95% confidence intervals.

Time Frame

Up to 2 years

Title

Change in 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

Description

In addition to point estimates of these rates, 95% confidence intervals will be calculated.

Time Frame

Baseline up to 3 months after last dose of study drug

Secondary Outcome Measure Information:

Title

Change in EF, assessed by MRI and ECHO

Description

Time Frame

Baseline up to 6 months after last dose of study drug

Title

Change in 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 and ECHO

Description

Time Frame

Baseline up to 6 months after last dose of study drug

Title

Change in left ventricular end diastolic volume, assessed by MRI and ECHO

Description

Time Frame

Baseline up to 6 months after last dose of study drug

Title

Change in left ventricular end systolic volume, assessed by MRI and ECHO

Description

Time Frame

Baseline up to 6 months after last dose of study drug

Title

Change in myocardial strain, assessed by MRI and ECHO

Description

Time Frame

Baseline up to 6 months after last dose of study drug

Title

Disease-free survival for those patients who achieve remission

Time Frame

From the date of CR until relapse from CR or death, assessed for up to 2 years

Title

Induction death rate

Time Frame

Up to 28 days

Title

Overall response rate, defined as CR + CRi

Time Frame

Up to 2 years

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Bayard Powell

Organizational Affiliation

Wake Forest University Health Sciences

Official's Role

Principal Investigator

Facility Information:

Facility Name

Comprehensive Cancer Center of Wake Forest University

City

Winston-Salem

State/Province

North Carolina

ZIP/Postal Code

27157

Country

United States

12. IPD Sharing Statement

Learn more about this trial

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

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