Liposome-encapsulated Daunorubicin-Cytarabine, Fludarabine Phosphate, Cytarabine, and Filgrastim in Treating Younger Patients With Relapsed or Refractory Acute Myeloid Leukemia
Acute Myeloid Leukemia Post Cytotoxic Therapy, Recurrent Childhood Acute Myeloid Leukemia, Secondary Acute Myeloid Leukemia
About this trial
This is an interventional treatment trial for Acute Myeloid Leukemia Post Cytotoxic Therapy
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
Sites / Locations
- Children's Hospital of Alabama
- Phoenix Childrens Hospital
- Arkansas Children's Hospital
- Kaiser Permanente Downey Medical Center
- City of Hope Comprehensive Cancer Center
- Loma Linda University Medical Center
- Children's Hospital Los Angeles
- Valley Children's Hospital
- UCSF Benioff Children's Hospital Oakland
- Children's Hospital of Orange County
- University of California Davis Comprehensive Cancer Center
- UCSF Medical Center-Mission Bay
- Children's Hospital Colorado
- Connecticut Children's Medical Center
- Alfred I duPont Hospital for Children
- Children's National Medical Center
- University of Florida Health Science Center - Gainesville
- Nemours Children's Clinic-Jacksonville
- Nemours Children's Clinic - Pensacola
- Johns Hopkins All Children's Hospital
- Children's Healthcare of Atlanta - Egleston
- Lurie Children's Hospital-Chicago
- Riley Hospital for Children
- Ascension Saint Vincent Indianapolis Hospital
- University of Kentucky/Markey Cancer Center
- Eastern Maine Medical Center
- Maine Children's Cancer Program
- Johns Hopkins University/Sidney Kimmel Cancer Center
- Massachusetts General Hospital Cancer Center
- Dana-Farber Cancer Institute
- C S Mott Children's Hospital
- Ascension Saint John Hospital
- University of Minnesota/Masonic Cancer Center
- Mayo Clinic in Rochester
- University of Mississippi Medical Center
- Children's Mercy Hospitals and Clinics
- Washington University School of Medicine
- Mercy Hospital Saint Louis
- Children's Hospital and Medical Center of Omaha
- University of Nebraska Medical Center
- Roswell Park Cancer Institute
- NYU Winthrop Hospital
- Laura and Isaac Perlmutter Cancer Center at NYU Langone
- NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center
- University of Rochester
- State University of New York Upstate Medical University
- Mission Hospital
- Children's Hospital Medical Center of Akron
- Cincinnati Children's Hospital Medical Center
- Rainbow Babies and Childrens Hospital
- Nationwide Children's Hospital
- University of Oklahoma Health Sciences Center
- Oregon Health and Science University
- Children's Hospital of Philadelphia
- Children's Hospital of Pittsburgh of UPMC
- Saint Jude Children's Research Hospital
- The Children's Hospital at TriStar Centennial
- UT Southwestern/Simmons Cancer Center-Dallas
- Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center
- Children's Hospital of San Antonio
- Primary Children's Hospital
- University of Vermont and State Agricultural College
- Children's Hospital of The King's Daughters
- Seattle Children's Hospital
- Providence Sacred Heart Medical Center and Children's Hospital
- University of Wisconsin Carbone Cancer Center
- Children's Hospital of Wisconsin
- CancerCare Manitoba
- IWK Health Centre
- Kingston Health Sciences Centre
- The Montreal Children's Hospital of the MUHC
- Centre Hospitalier Universitaire Sainte-Justine
- Centre Hospitalier Universitaire de Quebec
Arms of the Study
Arm 1
Experimental
Treatment (CPX-351 and FLAG)
COURSE 1: Patients receive cytarabine 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 IV over 90 minutes on days 1, 3, and 5. Patients with CNS1 receive no further CNS-directed therapy in course 1. Patients with 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 QD on days 1-5.