Acute Myeloid Leukemia Clinical Trial

Liposome-encapsulated Daunorubicin-Cytarabine, Fludarabine Phosphate, Cytarabine, and Filgrastim in Treating Younger Patients With Relapsed or Refractory Acute Myeloid Leukemia


This phase I/II trial studies the side effects and best dose of liposome-encapsulated daunorubicin-cytarabine when given with fludarabine phosphate, cytarabine, and filgrastim and to see how well they work in treating younger patients with acute myeloid leukemia that has come back after treatment (relapsed) or is not responding to treatment (is refractory). Liposome-encapsulated daunorubicin-cytarabine is made up of two chemotherapy drugs, cytarabine and daunorubicin hydrochloride, and works to stop cancer cell growth by blocking the cells from dividing. Drugs used in chemotherapy, such as fludarabine phosphate 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. Filgrastim may increase the production of blood cells and may help the immune system recover from the side effects of chemotherapy. Giving liposome-encapsulated daunorubicin-cytarabine followed by fludarabine phosphate, cytarabine, and filgrastim may be a better treatment for patients with relapsed acute myeloid leukemia and may cause fewer side effects to the heart, a common effect of other chemotherapy treatments for acute myeloid leukemia.

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Full Description


I. To determine a recommended phase 2 dose (RP2D) and the toxicities associated with liposome-encapsulated daunorubicin-cytarabine (CPX-351) in pediatric and young adult patients with relapsed/refractory acute myeloid leukemia (AML).

II. To estimate the response rate (complete remission [CR] plus complete remission with partial platelet recovery [CRp]) after CPX-351 (cycle 1) followed by fludarabine phosphate, cytarabine, and filgrastim (FLAG) (cycle 2) in children with AML in first relapse.


I. To estimate the response rate (CR + CRp + complete remission with incomplete blood count recovery [CRi]) after one cycle of CPX-351.

II. To describe the pharmacokinetics of plasma cytarabine and daunorubicin after CPX-351 administration to pediatric and young adult patients with relapsed/refractory AML.


I. To describe the response in biomarkers of cardiac injury to a single cycle of CPX-351.

II. To explore the effect of CPX-351 on novel biochemical and imaging markers of cardiotoxicity, including plasma micro ribonucleic acid (RNAs) (miRNA) and myocardial deformation.

III. To explore the role of rare coding variants as risk factors for anthracycline-induced cardiomyopathy.


COURSE 1: Patients receive cytarabine intrathecally (IT) on day 0 and at day 28-30 or up to 7 days prior to day 1 of course 2, and liposome-encapsulated daunorubicin-cytarabine intravenously (IV) over 90 minutes on days 1, 3, and 5. Patients without evidence of central nervous system (CNS) disease (CNS1) receive no further CNS-directed therapy in course 1. Patients with < 5 white blood cells per microliter of blood with blast cells (CNS2) disease may receive additional 4-6 doses of cytarabine IT twice weekly starting 48 hours after the third dose of liposome-encapsulated daunorubicin-cytarabine until CNS is clear at the discretion of the investigator. Patients meeting criteria for CR, CRp, and CRi may proceed to course 2.

COURSE 2: Patients receive filgrastim on days 1-5 and then on day 15 until blood count recovery, and fludarabine phosphate IV over 30 minutes and high-dose cytarabine IV over 1-3 hours once daily (QD) on days 1-5.

After completion of study treatment, patients are followed up periodically for 12 months, and then yearly for 5 years.

View Eligibility Criteria

Eligibility Criteria

Inclusion Criteria:

Patients must have had histologic verification of AML at original diagnosis

Patient must have one of the following:

Recurrent disease with >= 5% blasts in the bone marrow (M2/M3 bone marrow), with or without extramedullary disease.
Recurrent disease with an absolute blast count greater than 1,000 per microliter in the peripheral blood with or without extramedullary disease

To be eligible for the dose-finding phase: (the dose-finding phase completed in 12/2016)

Relapsed patients

Patients must be in first relapse, and
Patients must not have received prior re-induction therapy

Refractory patients

Patients must not have received more than one attempt at remission induction, which may consist of up to two different therapy courses; Children Oncology Group (COG) AAML1031 de novo therapy including induction I and induction II is an example

Treatment-related AML (t-AML)

Patients must be previously untreated for secondary AML

To be eligible for the phase 2 efficacy phase:

Relapse patients:

Patients must be in first marrow relapse, and
Patients must not have received prior re-induction therapy; donor lymphocyte infusion (DLI) is considered a re-induction attempt
Patients must have the status of CNS1 or CNS2 only, and no clinical signs or neurologic symptoms suggestive of CNS leukemia, such as cranial palsy
Patients must have a performance status corresponding to an Eastern Cooperative Oncology Group (ECOG) scores of 0, 1 or 2; use Karnofsky for patients > 16 years of age and Lansky for patients =< 16 years of age; Note: patients who are unable to walk because of paralysis, but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score
Patients must have recovered from the acute toxic effects of all prior chemotherapy, immunotherapy, stem cell transplant or radiotherapy prior to entering this study; all prior treatment-related toxicities must have resolved to =< grade 2 prior to enrollment

Myelosuppressive chemotherapy: must not have received myelosuppressive chemotherapy within 3 weeks of entry onto this study (excluding hydroxyurea)

Cytoreduction with hydroxyurea can be initiated and continued for up to 24 hours prior to the start of CPX-351
Biologic (anti-neoplastic agent): at least 7 days since the completion of therapy with a biologic agent such as steroids, retinoids; Note: for agents that have known adverse events occurring beyond 7 days after administration (i.e. monoclonal antibodies), this period must be extended beyond the time during which acute adverse events are known to occur
Radiation therapy (RT): >= 2 weeks for local palliative RT (small port); >= 6 months must have elapsed if prior craniospinal RT or if >= 50% radiation of pelvis; >= 6 weeks must have elapsed if other substantial bone marrow (BM) radiation; Note: patients must have received =< than 13.6 Gray (Gy) prior radiation to the mediastinum

Stem cell transplant (SCT): no evidence of active graft vs. host disease for at least 4 weeks; for allogeneic SCT patients, >= 3 months must have elapsed since transplant

Must have received no more than 1 prior autologous or allogeneic stem cell transplant.
Patients must be off all systemic immunosuppressive therapy for at least 2 weeks, excluding hydrocortisone for physiologic cortisol replacement

Intrathecal cytotoxic therapy:

No waiting period is required for patients having received intrathecal cytarabine, methotrexate, and/or hydrocortisone
At least 14 days must have elapsed since receiving liposomal cytarabine (DepoCyte) by intrathecal injection

Growth factors:

Patients must not have received growth factors for 7 days prior to CPX-351
Patients must not have received pegfilgrastim for 14 days prior to CPX-351

Creatinine clearance or radioisotope glomerular filtration rate (GFR) >= 70 mL/min/1.73 m^2 or a serum creatinine based on age/gender as follows:

Age 1 to < 2 years: maximum serum creatinine 0.6 mg/dL (males and females)
Age 2 to < 6 years: maximum serum creatinine 0.8 mg/dL (males and females)
Age 6 to < 10 years: maximum serum creatinine 1.0 mg/dL (males and females)
Age 10 to < 13 years: maximum serum creatinine 1.2 mg/dL (males and females)
Age 13 to < 16 years: maximum serum creatinine 1.5 mg/dL (males) and 1.4 mg/dL (females)
Age >= 16 years: maximum serum creatinine 1.7 mg/dL (males) and 1.4 mg/dL (females)
Direct bilirubin < 1.5 x upper limit of normal (ULN) for age and institution
Serum glutamate pyruvate (SGPT) (alanine aminotransferase [ALT]) =< 3.0 x upper limit of normal (ULN) for age and institution (unless it is related to leukemic involvement)
Shortening fraction of >= 27% by echocardiogram, or
Ejection fraction of >= 50% by radionuclide angiogram or echocardiogram
Corrected QT (using Bazett's formula [QTcB]) interval < 500 msecs
Patients with seizure disorder may be enrolled if on anticonvulsants and if seizures are well controlled
Central nervous system (CNS) toxicity =< grade 2

Patients with a known history of human immunodeficiency virus (HIV) are eligible, if they meet all of the following conditions:

No history of HIV complications with the exception of cluster of differentiation (CD)4 count < 200 cells/mm^3
No antiretroviral therapy with overlapping toxicity such as myelosuppression
HIV viral loads below the limit of detection
No history of highly active antiretroviral therapy (HAART)-resistant HIV
All patients and/or their parents or legal guardians must sign a written informed consent
All institutional, Food and Drug Administration (FDA), and National Cancer Institute (NCI) requirements for human studies must be met

Exclusion Criteria:

Patients who have received > 450 mg/m^2 daunorubicin equivalents; patients who relapse after receiving AAML0531/AAML1031 therapy will be eligible for this study, provided they have not received any additional anthracyclines; NOTE: for the purposes of determining eligibility for this protocol, the following cardiotoxicity multipliers will be used to determine daunorubicin equivalents:

Doxorubicin (doxorubicin hydrochloride): 1
Mitoxantrone: 3
Idarubicin: 3
Epirubicin: 0.5
Patients who are currently receiving another investigational drug
Patients receiving medications for treatment of left ventricular systolic dysfunction

Patients with any of the following diagnoses:

Acute promyelocytic leukemia (APL)
Down syndrome
Fanconi anemia, Kostmann syndrome, Shwachman syndrome or any other known bone marrow failure syndrome
Wilson's disease and any other disorder of copper metabolism
Juvenile myelomonocytic leukemia (JMML)
Patients with documented active, uncontrolled infection at the time of study entry
Patients with known active hepatitis B virus (HBV) and hepatitis C virus (HCV) infections
Patients with prior allergy to daunorubicin and/or cytarabine
Female patients who are pregnant are ineligible
Lactating females are not eligible
Female patients of childbearing potential are not eligible unless a negative pregnancy test result has been obtained
Sexually active patients of reproductive potential are not eligible unless they have agreed to use an effective contraceptive method for the duration of their study participation and for 6 months after the last dose of chemotherapy

Study is for people with:

Acute Myeloid Leukemia


Phase 1

Estimated Enrollment:


Study ID:


Recruitment Status:



Children's Oncology Group

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There are 73 Locations for this study

See Locations Near You

Children's Hospital of Alabama
Birmingham Alabama, 35233, United States
Phoenix Childrens Hospital
Phoenix Arizona, 85016, United States
Arkansas Children's Hospital
Little Rock Arkansas, 72202, United States
Kaiser Permanente Downey Medical Center
Downey California, 90242, United States
City of Hope Comprehensive Cancer Center
Duarte California, 91010, United States
Loma Linda University Medical Center
Loma Linda California, 92354, United States
Children's Hospital Los Angeles
Los Angeles California, 90027, United States
Valley Children's Hospital
Madera California, 93636, United States
UCSF Benioff Children's Hospital Oakland
Oakland California, 94609, United States
Children's Hospital of Orange County
Orange California, 92868, United States
University of California Davis Comprehensive Cancer Center
Sacramento California, 95817, United States
UCSF Medical Center-Mission Bay
San Francisco California, 94158, United States
Children's Hospital Colorado
Aurora Colorado, 80045, United States
Connecticut Children's Medical Center
Hartford Connecticut, 06106, United States
Alfred I duPont Hospital for Children
Wilmington Delaware, 19803, United States
Children's National Medical Center
Washington District of Columbia, 20010, United States
University of Florida Health Science Center - Gainesville
Gainesville Florida, 32610, United States
Nemours Children's Clinic-Jacksonville
Jacksonville Florida, 32207, United States
Nemours Children's Clinic - Pensacola
Pensacola Florida, 32504, United States
Johns Hopkins All Children's Hospital
Saint Petersburg Florida, 33701, United States
Children's Healthcare of Atlanta - Egleston
Atlanta Georgia, 30322, United States
Lurie Children's Hospital-Chicago
Chicago Illinois, 60611, United States
Riley Hospital for Children
Indianapolis Indiana, 46202, United States
Ascension Saint Vincent Indianapolis Hospital
Indianapolis Indiana, 46260, United States
University of Kentucky/Markey Cancer Center
Lexington Kentucky, 40536, United States
Eastern Maine Medical Center
Bangor Maine, 04401, United States
Maine Children's Cancer Program
Scarborough Maine, 04074, United States
Johns Hopkins University/Sidney Kimmel Cancer Center
Baltimore Maryland, 21287, United States
Massachusetts General Hospital Cancer Center
Boston Massachusetts, 02114, United States
Dana-Farber Cancer Institute
Boston Massachusetts, 02215, United States
C S Mott Children's Hospital
Ann Arbor Michigan, 48109, United States
Ascension Saint John Hospital
Detroit Michigan, 48236, United States
University of Minnesota/Masonic Cancer Center
Minneapolis Minnesota, 55455, United States
Mayo Clinic in Rochester
Rochester Minnesota, 55905, United States
University of Mississippi Medical Center
Jackson Mississippi, 39216, United States
Children's Mercy Hospitals and Clinics
Kansas City Missouri, 64108, United States
Washington University School of Medicine
Saint Louis Missouri, 63110, United States
Mercy Hospital Saint Louis
Saint Louis Missouri, 63141, United States
Children's Hospital and Medical Center of Omaha
Omaha Nebraska, 68114, United States
University of Nebraska Medical Center
Omaha Nebraska, 68198, United States
Roswell Park Cancer Institute
Buffalo New York, 14263, United States
NYU Winthrop Hospital
Mineola New York, 11501, United States
Laura and Isaac Perlmutter Cancer Center at NYU Langone
New York New York, 10016, United States
NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center
New York New York, 10032, United States
University of Rochester
Rochester New York, 14642, United States
State University of New York Upstate Medical University
Syracuse New York, 13210, United States
Mission Hospital
Asheville North Carolina, 28801, United States
Children's Hospital Medical Center of Akron
Akron Ohio, 44308, United States
Cincinnati Children's Hospital Medical Center
Cincinnati Ohio, 45229, United States
Rainbow Babies and Childrens Hospital
Cleveland Ohio, 44106, United States
Nationwide Children's Hospital
Columbus Ohio, 43205, United States
University of Oklahoma Health Sciences Center
Oklahoma City Oklahoma, 73104, United States
Oregon Health and Science University
Portland Oregon, 97239, United States
Children's Hospital of Philadelphia
Philadelphia Pennsylvania, 19104, United States
Children's Hospital of Pittsburgh of UPMC
Pittsburgh Pennsylvania, 15224, United States
Saint Jude Children's Research Hospital
Memphis Tennessee, 38105, United States
The Children's Hospital at TriStar Centennial
Nashville Tennessee, 37203, United States
UT Southwestern/Simmons Cancer Center-Dallas
Dallas Texas, 75390, United States
Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center
Houston Texas, 77030, United States
Children's Hospital of San Antonio
San Antonio Texas, 78207, United States
Primary Children's Hospital
Salt Lake City Utah, 84113, United States
University of Vermont and State Agricultural College
Burlington Vermont, 05405, United States
Children's Hospital of The King's Daughters
Norfolk Virginia, 23507, United States
Seattle Children's Hospital
Seattle Washington, 98105, United States
Providence Sacred Heart Medical Center and Children's Hospital
Spokane Washington, 99204, United States
University of Wisconsin Carbone Cancer Center
Madison Wisconsin, 53792, United States
Children's Hospital of Wisconsin
Milwaukee Wisconsin, 53226, United States
CancerCare Manitoba
Winnipeg Manitoba, R3E 0, Canada
IWK Health Centre
Halifax Nova Scotia, B3K 6, Canada
Kingston Health Sciences Centre
Kingston Ontario, K7L 2, Canada
The Montreal Children's Hospital of the MUHC
Montreal Quebec, H3H 1, Canada
Centre Hospitalier Universitaire Sainte-Justine
Montreal Quebec, H3T 1, Canada
Centre Hospitalier Universitaire de Quebec
Quebec , G1V 4, Canada

How clear is this clinincal trial information?

Study is for people with:

Acute Myeloid Leukemia


Phase 1

Estimated Enrollment:


Study ID:


Recruitment Status:



Children's Oncology Group

How clear is this clinincal trial information?


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