Response-Based Chemotherapy in Treating Newly Diagnosed Acute Myeloid Leukemia or Myelodysplastic Syndrome in Younger Patients With Down Syndrome
Acute Myeloid Leukemia, Down Syndrome, Myelodysplastic Syndrome
About this trial
This is an interventional treatment trial for Acute Myeloid Leukemia
Eligibility Criteria
Inclusion Criteria:
- Patients must have constitutional trisomy 21 (Down syndrome) or trisomy 21 mosaicism (by karyotype or fluorescence in situ hybridization [FISH])
Patient has one of the following:
Patient has previously untreated de novo AML and meets the criteria for AML with >= 20% bone marrow blasts as set out in the World Health Organization (WHO) Myeloid Neoplasm classification
- Attempts to obtain bone marrow either by aspirate or biopsy must be made unless clinically prohibitive; in cases where it is clinically prohibitive, peripheral blood with an excess of 20% blasts and in which adequate flow cytometric and cytogenetics/FISH testing is feasible can be substituted for the marrow exam at diagnosis
- Patient has cytopenias and/or bone marrow blasts but does not meet the criteria for the diagnosis of AML (WHO Myeloid Neoplasm classification) because of < 20% marrow blasts and meets the criteria for a diagnosis of myelodysplastic syndrome (MDS)
For patients who do not meet criteria for AML or MDS as outlined above; patient has a history of transient myeloproliferative disorder (which may or may not have required chemotherapy intervention and:
- Is > 8 weeks since resolution of transient myeloproliferative disease (TMD) with >= 5% blasts, OR
- Has an increasing blast count (>= 5%) in serial bone marrow aspirates performed at least 4 weeks apart
- Children who have previously received chemotherapy, radiation therapy or any anti-leukemic therapy are not eligible for this protocol, with the exception of cytarabine for the treatment of TMD
There are no minimal organ function requirements for enrollment on this study
- Note: Previous cardiac repair with sufficient cardiac function is not an exclusion criteria
- Each patient's 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 subjects research must be met
Exclusion Criteria:
- Patients with promyelocytic leukemia (French-American-British [FAB] M3)
Prior therapy
- Patients =< 30 days from the last dose of cytarabine used for treatment of TMD
Sites / Locations
- Children's Hospital of Alabama
- Providence Alaska Medical Center
- Banner Children's at Desert
- Phoenix Childrens Hospital
- Arkansas Children's Hospital
- Kaiser Permanente Downey Medical Center
- Loma Linda University Medical Center
- Miller Children's and Women's Hospital Long Beach
- Children's Hospital Los Angeles
- Cedars Sinai Medical Center
- Valley Children's Hospital
- UCSF Benioff Children's Hospital Oakland
- Kaiser Permanente-Oakland
- Children's Hospital of Orange County
- Lucile Packard Children's Hospital Stanford University
- Sutter Medical Center Sacramento
- University of California Davis Comprehensive Cancer Center
- Rady Children's Hospital - San Diego
- Naval Medical Center -San Diego
- UCSF Medical Center-Mission Bay
- Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center
- Children's Hospital Colorado
- Rocky Mountain Hospital for Children-Presbyterian Saint Luke's Medical Center
- Connecticut Children's Medical Center
- Yale University
- Alfred I duPont Hospital for Children
- MedStar Georgetown University Hospital
- Children's National Medical Center
- Broward Health Medical Center
- Golisano Children's Hospital of Southwest Florida
- University of Florida Health Science Center - Gainesville
- Memorial Regional Hospital/Joe DiMaggio Children's Hospital
- Nemours Children's Clinic-Jacksonville
- Palms West Radiation Therapy
- University of Miami Miller School of Medicine-Sylvester Cancer Center
- Nicklaus Children's Hospital
- AdventHealth Orlando
- Arnold Palmer Hospital for Children
- Nemours Children's Hospital
- Nemours Children's Clinic - Pensacola
- Sacred Heart Hospital
- Johns Hopkins All Children's Hospital
- Saint Joseph's Hospital/Children's Hospital-Tampa
- Saint Mary's Hospital
- Children's Healthcare of Atlanta - Egleston
- Memorial Health University Medical Center
- Kapiolani Medical Center for Women and Children
- Saint Luke's Cancer Institute - Boise
- Lurie Children's Hospital-Chicago
- University of Illinois
- University of Chicago Comprehensive Cancer Center
- Advocate Children's Hospital-Oak Lawn
- Advocate Children's Hospital-Park Ridge
- Saint Jude Midwest Affiliate
- Southern Illinois University School of Medicine
- Riley Hospital for Children
- Ascension Saint Vincent Indianapolis Hospital
- Blank Children's Hospital
- University of Iowa/Holden Comprehensive Cancer Center
- University of Kentucky/Markey Cancer Center
- Norton Children's Hospital
- Children's Hospital New Orleans
- Ochsner Medical Center Jefferson
- Eastern Maine Medical Center
- Sinai Hospital of Baltimore
- Johns Hopkins University/Sidney Kimmel Cancer Center
- Walter Reed National Military Medical Center
- Tufts Children's Hospital
- Dana-Farber Cancer Institute
- Baystate Medical Center
- UMass Memorial Medical Center - University Campus
- C S Mott Children's Hospital
- Wayne State University/Karmanos Cancer Institute
- Ascension Saint John Hospital
- Michigan State University Clinical Center
- Hurley Medical Center
- Helen DeVos Children's Hospital at Spectrum Health
- Bronson Methodist Hospital
- Beaumont Children's Hospital-Royal Oak
- Children's Hospitals and Clinics of Minnesota - Minneapolis
- University of Minnesota/Masonic Cancer Center
- Mayo Clinic in Rochester
- University of Mississippi Medical Center
- Columbia Regional
- Children's Mercy Hospitals and Clinics
- Washington University School of Medicine
- Mercy Hospital Saint Louis
- University Medical Center of Southern Nevada
- Sunrise Hospital and Medical Center
- Alliance for Childhood Diseases/Cure 4 the Kids Foundation
- Summerlin Hospital Medical Center
- Renown Regional Medical Center
- Dartmouth Hitchcock Medical Center/Dartmouth Cancer Center
- Hackensack University Medical Center
- Morristown Medical Center
- Rutgers Cancer Institute of New Jersey-Robert Wood Johnson University Hospital
- Saint Joseph's Regional Medical Center
- University of New Mexico Cancer Center
- Presbyterian Hospital
- Albany Medical Center
- Montefiore Medical Center - Moses Campus
- Roswell Park Cancer Institute
- NYU Winthrop Hospital
- Laura and Isaac Perlmutter Cancer Center at NYU Langone
- Mount Sinai Hospital
- NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center
- NYP/Weill Cornell Medical Center
- University of Rochester
- Stony Brook University Medical Center
- State University of New York Upstate Medical University
- New York Medical College
- Mission Hospital
- UNC Lineberger Comprehensive Cancer Center
- Carolinas Medical Center/Levine Cancer Institute
- Novant Health Presbyterian Medical Center
- Duke University Medical Center
- East Carolina University
- Wake Forest University Health Sciences
- Sanford Broadway Medical Center
- Children's Hospital Medical Center of Akron
- Cincinnati Children's Hospital Medical Center
- Rainbow Babies and Childrens Hospital
- Cleveland Clinic Foundation
- Nationwide Children's Hospital
- Dayton Children's Hospital
- ProMedica Toledo Hospital/Russell J Ebeid Children's Hospital
- University of Oklahoma Health Sciences Center
- Legacy Emanuel Children's Hospital
- Oregon Health and Science University
- Geisinger Medical Center
- Penn State Children's Hospital
- Children's Hospital of Philadelphia
- Saint Christopher's Hospital for Children
- Children's Hospital of Pittsburgh of UPMC
- Rhode Island Hospital
- Medical University of South Carolina
- BI-LO Charities Children's Cancer Center
- Sanford USD Medical Center - Sioux Falls
- T C Thompson Children's Hospital
- East Tennessee Childrens Hospital
- Saint Jude Children's Research Hospital
- The Children's Hospital at TriStar Centennial
- Vanderbilt University/Ingram Cancer Center
- Texas Tech University Health Sciences Center-Amarillo
- Dell Children's Medical Center of Central Texas
- Driscoll Children's Hospital
- Medical City Dallas Hospital
- UT Southwestern/Simmons Cancer Center-Dallas
- El Paso Children's Hospital
- Cook Children's Medical Center
- Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center
- Covenant Children's Hospital
- UMC Cancer Center / UMC Health System
- Children's Hospital of San Antonio
- Methodist Children's Hospital of South Texas
- University of Texas Health Science Center at San Antonio
- Primary Children's Hospital
- University of Vermont and State Agricultural College
- Inova Fairfax Hospital
- Children's Hospital of The King's Daughters
- Virginia Commonwealth University/Massey Cancer Center
- Seattle Children's Hospital
- Providence Sacred Heart Medical Center and Children's Hospital
- Mary Bridge Children's Hospital and Health Center
- Madigan Army Medical Center
- West Virginia University Charleston Division
- Saint Vincent Hospital Cancer Center Green Bay
- University of Wisconsin Carbone Cancer Center
- Children's Hospital of Wisconsin
- John Hunter Children's Hospital
- Sydney Children's Hospital
- The Children's Hospital at Westmead
- Royal Children's Hospital
- Princess Margaret Hospital for Children
- Perth Children's Hospital
- British Columbia Children's Hospital
- CancerCare Manitoba
- IWK Health Centre
- McMaster Children's Hospital at Hamilton Health Sciences
- Kingston Health Sciences Centre
- Children's Hospital
- Children's Hospital of Eastern Ontario
- Hospital for Sick Children
- The Montreal Children's Hospital of the MUHC
- Centre Hospitalier Universitaire Sainte-Justine
- Centre Hospitalier Universitaire de Quebec
- Starship Children's Hospital
- Christchurch Hospital
- San Jorge Children's Hospital
- University Pediatric Hospital
- King Faisal Specialist Hospital and Research Centre
Arms of the Study
Arm 1
Arm 2
Experimental
Experimental
Arm A (standard risk)
Arm B (high risk)
INDUCTION II: Patients receive cytarabine IV continuously over 96 hours, daunorubicin hydrochloride IV over 1-15 minutes, and thioguanine PO BID on days 1-4. Induction II continues for a minimum of 28 days. INDUCTION III: Patients receive cytarabine, daunorubicin hydrochloride, and thioguanine as in Induction II. Induction III continues for a minimum of 28 days. INTENSIFICATION I: Patients receive cytarabine IV continuously over 168 hours on days 1-7 and etoposide IV over 60-120 minutes on days 1-3. Intensification I continues for a minimum of 28 days. INTENSIFICATION II: Patients receive cytarabine and etoposide as in Intensification I. Intensification II continues for a minimum of 28 days. (This arm is closed to accrual and treatment with amendment #4A 01/07/2019)
INDUCTION II: Patients receive high dose cytarabine IV over 1-3 hours Q12 hours on days 1-4 and mitoxantrone hydrochloride IV over 15-30 minutes on days 3-6. Induction II continues for a minimum of 28 days. INTENSIFICATION I: Patients receive high dose cytarabine IV over 1-3 hours Q12 hours and etoposide IV over 90-120 minutes on days 1-5. Intensification I continues for a minimum of 28 days. INTENSIFICATION II: Patients receive high dose cytarabine IV over 3 hours Q12 hours on days 1, 2, 8, and 9. Patients also receive asparaginase or asparaginase Erwinia chrysanthemi IM or IV over 30 minutes on days 2 and 9. Intensification II continues for a minimum of 28 days.