Acute Myeloid Leukemia
Conditions
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.
Interventions
PROCEDUREBone Marrow Aspiration and Biopsy
Undergo bone marrow aspiration and biopsy
DRUGCytarabine
Given IV
DRUGDaunorubicin Hydrochloride
Given IV
OTHERLaboratory Biomarker Analysis
Correlative studies
Sponsors
Wake Forest University Health Sciences
National Cancer Institute (NCI)
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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 | Baseline up to 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. |
| 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 | Unexpected toxicities (exclude hematologic and infectious) ≥ grade 3, as measured by CTCAE v 4.0 |
| Proportion of Patients Who Complete the Infusion Therapy | 72 hours | Will report these proportions with 95% confidence intervals. |
| Proportion of Patients With Study-related Deviations | Approximately 1 year, 5 months | Will report these proportions with 95% confidence intervals. |
| 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 | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| EF, Assessed by MRI and ECHO | Baseline and 3 months | Ejection Fraction at baseline, 3 months, and change from baseline to 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 | Baseline up to 6 months after last dose of study drug | 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. |
| Change in Left Ventricular End Diastolic Volume, Assessed by MRI and ECHO | Baseline up to 6 months after last dose of study drug | Left ventricular end diastolic volume assessed by MRI and ECHO at baseline, 3 months, and change from baseline to 3 months. |
| Left Ventricular End Systolic Volume, Assessed by MRI and ECHO | Baseline, 3 months | Left ventricular end systolic volume assessed by MRI and ECHO at baseline, 3 months, and change from baseline to 3 months. |
| Myocardial Strain, Assessed by MRI and ECHO | Baseline and 3 months | 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. |
| Disease-free Survival for Those Patients Who Achieve Remission | From the date of CR until relapse from CR or death, approximately 1 year, 9 months | 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. |
| Induction Death Rate | Up to 28 days | Number of patients who had an induction death |
| Overall Response Rate, Defined as CR + CRi | Approximately 1 year and 9 months | 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. |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORBayard Powell
Wake Forest University Health Sciences
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | 60.1 years STANDARD_DEVIATION 15.5 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 40 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 7 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 33 Participants |
| Sex: Female, Male Female | 22 Participants |
| Sex: Female, Male Male | 18 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 9 / 40 |
| other Total, other adverse events | 40 / 40 |
| serious Total, serious adverse events | 40 / 40 |
Outcome results
None listed