- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02521493
Response-Based Chemotherapy in Treating Newly Diagnosed Acute Myeloid Leukemia or Myelodysplastic Syndrome in Younger Patients With Down Syndrome
Risk-Stratified Therapy for Acute Myeloid Leukemia in Down Syndrome
Study Overview
Status
Conditions
Detailed Description
PRIMARY OBJECTIVES:
I. To determine the 2-year event-free-survival (EFS) for children with standard risk Down syndrome (DS) acute myeloid leukemia (AML) (minimal residual disease [MRD]-negative after one cycle of induction therapy) after elimination of high dose (HD) Ara-C (cytarabine) from the treatment regimen.
II. To determine the 2-year EFS for children with high risk DS AML (MRD-positive after one cycle of induction therapy) after intensification of treatment equivalent to that used for high risk AML in children without DS.
EXPLORATORY OBJECTIVES:
I. To compare the feasibility and analytical characteristics of flow cytometry, polymerase chain reaction (PCR) and targeted error-corrected sequencing of GATA binding protein 1 (globin transcription factor 1) (GATA1) mutations as methods to detect MRD in DS AML.
II. To establish a DS AML cell bank of viably frozen bone marrow samples collected at the end of induction and corresponding non-tumor deoxyribonucleic acid (DNA) samples collected at end of Induction 1.
OUTLINE:
INDUCTION I: Patients receive cytarabine intrathecally (IT) on day 1 and intravenously (IV) continuously over 96 hours, daunorubicin hydrochloride IV over 1-15 minutes, and thioguanine orally (PO) twice daily (BID) on days 1-4. Induction I continues for a minimum of 28 days.
Patients are assigned to 1 of 2 treatment arms based on their MRD status after completion of Induction I.
ARM A (STANDARD RISK) (Closed to accrual and treatment with amendment #4A 01/07/2019):
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.
ARM B (HIGH RISK):
INDUCTION II: Patients receive high dose cytarabine IV over 1-3 hours every 12 (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 (E. carotovora) intramuscularly (IM) or IV over 30 minutes on days 2 and 9. Intensification II continues for a minimum of 28 days.
After completion of study treatment, patients are followed up at 1 month, monthly for 12 months, every 3 months for 12 months, every 6 months for 3 years, annually for 10 years, and in case of relapse.
Study Type
Enrollment (Estimated)
Phase
- Phase 3
Contacts and Locations
Study Locations
-
-
New South Wales
-
Hunter Regional Mail Centre, New South Wales, Australia, 2310
- John Hunter Children's Hospital
-
Randwick, New South Wales, Australia, 2031
- Sydney Children's Hospital
-
Westmead, New South Wales, Australia, 2145
- The Children's Hospital at Westmead
-
-
Victoria
-
Parkville, Victoria, Australia, 3052
- Royal Children's Hospital
-
-
Western Australia
-
Perth, Western Australia, Australia, 6008
- Princess Margaret Hospital for Children
-
Perth, Western Australia, Australia, 6009
- Perth Children's Hospital
-
-
-
-
-
Quebec, Canada, G1V 4G2
- CHU de Quebec-Centre Hospitalier de l'Universite Laval (CHUL)
-
-
British Columbia
-
Vancouver, British Columbia, Canada, V6H 3V4
- British Columbia Children's Hospital
-
-
Manitoba
-
Winnipeg, Manitoba, Canada, R3E 0V9
- CancerCare Manitoba
-
-
Nova Scotia
-
Halifax, Nova Scotia, Canada, B3K 6R8
- IWK Health Centre
-
-
Ontario
-
Hamilton, Ontario, Canada, L8N 3Z5
- McMaster Children's Hospital at Hamilton Health Sciences
-
Kingston, Ontario, Canada, K7L 2V7
- Kingston Health Sciences Centre
-
London, Ontario, Canada, N6A 5W9
- Children's Hospital
-
Ottawa, Ontario, Canada, K1H 8L1
- Children's Hospital of Eastern Ontario
-
Toronto, Ontario, Canada, M5G 1X8
- Hospital for Sick Children
-
-
Quebec
-
Montreal, Quebec, Canada, H3H 1P3
- The Montreal Children's Hospital of the MUHC
-
Montreal, Quebec, Canada, H3T 1C5
- Centre Hospitalier Universitaire Sainte-Justine
-
-
-
-
-
Christchurch, New Zealand, 8011
- Christchurch Hospital
-
-
Auckland
-
Grafton, Auckland, New Zealand, 1145
- Starship Children's Hospital
-
-
-
-
-
San Juan, Puerto Rico, 00926
- University Pediatric Hospital
-
San Juan, Puerto Rico, 00912
- San Jorge Children's Hospital
-
-
-
-
-
Riyadh, Saudi Arabia, 11211
- King Faisal Specialist Hospital and Research Centre
-
-
-
-
Alabama
-
Birmingham, Alabama, United States, 35233
- Children's Hospital of Alabama
-
-
Alaska
-
Anchorage, Alaska, United States, 99508
- Providence Alaska Medical Center
-
-
Arizona
-
Mesa, Arizona, United States, 85202
- Banner Children's at Desert
-
Phoenix, Arizona, United States, 85016
- Phoenix Childrens Hospital
-
-
Arkansas
-
Little Rock, Arkansas, United States, 72202-3591
- Arkansas Children's Hospital
-
-
California
-
Downey, California, United States, 90242
- Kaiser Permanente Downey Medical Center
-
Loma Linda, California, United States, 92354
- Loma Linda University Medical Center
-
Long Beach, California, United States, 90806
- Miller Children's and Women's Hospital Long Beach
-
Los Angeles, California, United States, 90027
- Children's Hospital Los Angeles
-
Los Angeles, California, United States, 90048
- Cedars Sinai Medical Center
-
Madera, California, United States, 93636
- Valley Children's Hospital
-
Oakland, California, United States, 94609
- UCSF Benioff Children's Hospital Oakland
-
Oakland, California, United States, 94611
- Kaiser Permanente-Oakland
-
Orange, California, United States, 92868
- Children's Hospital of Orange County
-
Palo Alto, California, United States, 94304
- Lucile Packard Children's Hospital Stanford University
-
Sacramento, California, United States, 95816
- Sutter Medical Center Sacramento
-
Sacramento, California, United States, 95817
- University of California Davis Comprehensive Cancer Center
-
San Diego, California, United States, 92123
- Rady Children's Hospital - San Diego
-
San Diego, California, United States, 92134
- Naval Medical Center -San Diego
-
San Francisco, California, United States, 94158
- UCSF Medical Center-Mission Bay
-
Torrance, California, United States, 90502
- Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center
-
-
Colorado
-
Aurora, Colorado, United States, 80045
- Children's Hospital Colorado
-
Denver, Colorado, United States, 80218
- Rocky Mountain Hospital for Children-Presbyterian Saint Luke's Medical Center
-
-
Connecticut
-
Hartford, Connecticut, United States, 06106
- Connecticut Children's Medical Center
-
New Haven, Connecticut, United States, 06520
- Yale University
-
-
Delaware
-
Wilmington, Delaware, United States, 19803
- Alfred I duPont Hospital for Children
-
-
District of Columbia
-
Washington, District of Columbia, United States, 20010
- Children's National Medical Center
-
Washington, District of Columbia, United States, 20007
- MedStar Georgetown University Hospital
-
-
Florida
-
Fort Lauderdale, Florida, United States, 33316
- Broward Health Medical Center
-
Fort Myers, Florida, United States, 33908
- Golisano Children's Hospital of Southwest Florida
-
Gainesville, Florida, United States, 32610
- University of Florida Health Science Center - Gainesville
-
Hollywood, Florida, United States, 33021
- Memorial Regional Hospital/Joe DiMaggio Children's Hospital
-
Jacksonville, Florida, United States, 32207
- Nemours Children's Clinic-Jacksonville
-
Loxahatchee Groves, Florida, United States, 33470
- Palms West Radiation Therapy
-
Miami, Florida, United States, 33155
- Nicklaus Children's Hospital
-
Miami, Florida, United States, 33136
- University of Miami Miller School of Medicine-Sylvester Cancer Center
-
Orlando, Florida, United States, 32827
- Nemours Children's Hospital
-
Orlando, Florida, United States, 32803
- AdventHealth Orlando
-
Orlando, Florida, United States, 32806
- Arnold Palmer Hospital for Children
-
Pensacola, Florida, United States, 32504
- Sacred Heart Hospital
-
Pensacola, Florida, United States, 32504
- Nemours Children's Clinic - Pensacola
-
Saint Petersburg, Florida, United States, 33701
- Johns Hopkins All Children's Hospital
-
Tampa, Florida, United States, 33607
- Saint Joseph's Hospital/Children's Hospital-Tampa
-
West Palm Beach, Florida, United States, 33407
- Saint Mary's Hospital
-
-
Georgia
-
Atlanta, Georgia, United States, 30322
- Children's Healthcare of Atlanta - Egleston
-
Savannah, Georgia, United States, 31404
- Memorial Health University Medical Center
-
-
Hawaii
-
Honolulu, Hawaii, United States, 96826
- Kapiolani Medical Center for Women and Children
-
-
Idaho
-
Boise, Idaho, United States, 83712
- Saint Luke's Cancer Institute - Boise
-
-
Illinois
-
Chicago, Illinois, United States, 60637
- University of Chicago Comprehensive Cancer Center
-
Chicago, Illinois, United States, 60612
- University of Illinois
-
Chicago, Illinois, United States, 60611
- Lurie Children's Hospital-Chicago
-
Oak Lawn, Illinois, United States, 60453
- Advocate Children's Hospital-Oak Lawn
-
Park Ridge, Illinois, United States, 60068
- Advocate Children's Hospital-Park Ridge
-
Peoria, Illinois, United States, 61637
- Saint Jude Midwest Affiliate
-
Springfield, Illinois, United States, 62702
- Southern Illinois University School of Medicine
-
-
Indiana
-
Indianapolis, Indiana, United States, 46202
- Riley Hospital for Children
-
Indianapolis, Indiana, United States, 46260
- Ascension Saint Vincent Indianapolis Hospital
-
-
Iowa
-
Des Moines, Iowa, United States, 50309
- Blank Children's Hospital
-
Iowa City, Iowa, United States, 52242
- University of Iowa/Holden Comprehensive Cancer Center
-
-
Kentucky
-
Lexington, Kentucky, United States, 40536
- University of Kentucky/Markey Cancer Center
-
Louisville, Kentucky, United States, 40202
- Norton Children's Hospital
-
-
Louisiana
-
New Orleans, Louisiana, United States, 70121
- Ochsner Medical Center Jefferson
-
New Orleans, Louisiana, United States, 70118
- Children's Hospital New Orleans
-
-
Maine
-
Bangor, Maine, United States, 04401
- Eastern Maine Medical Center
-
-
Maryland
-
Baltimore, Maryland, United States, 21287
- Johns Hopkins University/Sidney Kimmel Cancer Center
-
Baltimore, Maryland, United States, 21215
- Sinai Hospital of Baltimore
-
Bethesda, Maryland, United States, 20889-5600
- Walter Reed National Military Medical Center
-
-
Massachusetts
-
Boston, Massachusetts, United States, 02215
- Dana-Farber Cancer Institute
-
Boston, Massachusetts, United States, 02111
- Tufts Children's Hospital
-
Springfield, Massachusetts, United States, 01199
- Baystate Medical Center
-
Worcester, Massachusetts, United States, 01655
- UMass Memorial Medical Center - University Campus
-
-
Michigan
-
Ann Arbor, Michigan, United States, 48109
- C S Mott Children's Hospital
-
Detroit, Michigan, United States, 48201
- Wayne State University/Karmanos Cancer Institute
-
Detroit, Michigan, United States, 48236
- Ascension Saint John Hospital
-
East Lansing, Michigan, United States, 48824
- Michigan State University Clinical Center
-
Flint, Michigan, United States, 48503
- Hurley Medical Center
-
Grand Rapids, Michigan, United States, 49503
- Helen DeVos Children's Hospital at Spectrum Health
-
Kalamazoo, Michigan, United States, 49007
- Bronson Methodist Hospital
-
Royal Oak, Michigan, United States, 48073
- Beaumont Children's Hospital-Royal Oak
-
-
Minnesota
-
Minneapolis, Minnesota, United States, 55404
- Children's Hospitals and Clinics of Minnesota - Minneapolis
-
Minneapolis, Minnesota, United States, 55455
- University of Minnesota/Masonic Cancer Center
-
Rochester, Minnesota, United States, 55905
- Mayo Clinic in Rochester
-
-
Mississippi
-
Jackson, Mississippi, United States, 39216
- University of Mississippi Medical Center
-
-
Missouri
-
Columbia, Missouri, United States, 65201
- Columbia Regional
-
Kansas City, Missouri, United States, 64108
- Children's Mercy Hospitals and Clinics
-
Saint Louis, Missouri, United States, 63110
- Washington University School of Medicine
-
Saint Louis, Missouri, United States, 63141
- Mercy Hospital Saint Louis
-
-
Nevada
-
Las Vegas, Nevada, United States, 89144
- Summerlin Hospital Medical Center
-
Las Vegas, Nevada, United States, 89109
- Sunrise Hospital and Medical Center
-
Las Vegas, Nevada, United States, 89135
- Alliance for Childhood Diseases/Cure 4 the Kids Foundation
-
Las Vegas, Nevada, United States, 89102
- University Medical Center of Southern Nevada
-
Reno, Nevada, United States, 89502
- Renown Regional Medical Center
-
-
New Hampshire
-
Lebanon, New Hampshire, United States, 03756
- Dartmouth Hitchcock Medical Center/Dartmouth Cancer Center
-
-
New Jersey
-
Hackensack, New Jersey, United States, 07601
- Hackensack University Medical Center
-
Morristown, New Jersey, United States, 07960
- Morristown Medical Center
-
New Brunswick, New Jersey, United States, 08903
- Rutgers Cancer Institute of New Jersey-Robert Wood Johnson University Hospital
-
Paterson, New Jersey, United States, 07503
- Saint Joseph's Regional Medical Center
-
-
New Mexico
-
Albuquerque, New Mexico, United States, 87102
- University of New Mexico Cancer Center
-
Albuquerque, New Mexico, United States, 87106
- Presbyterian Hospital
-
-
New York
-
Albany, New York, United States, 12208
- Albany Medical Center
-
Bronx, New York, United States, 10467
- Montefiore Medical Center - Moses Campus
-
Buffalo, New York, United States, 14263
- Roswell Park Cancer Institute
-
Mineola, New York, United States, 11501
- NYU Winthrop Hospital
-
New York, New York, United States, 10029
- Mount Sinai Hospital
-
New York, New York, United States, 10032
- NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center
-
New York, New York, United States, 10065
- NYP/Weill Cornell Medical Center
-
New York, New York, United States, 10016
- Laura and Isaac Perlmutter Cancer Center at NYU Langone
-
Rochester, New York, United States, 14642
- University of Rochester
-
Stony Brook, New York, United States, 11794
- Stony Brook University Medical Center
-
Syracuse, New York, United States, 13210
- State University of New York Upstate Medical University
-
Valhalla, New York, United States, 10595
- New York Medical College
-
-
North Carolina
-
Asheville, North Carolina, United States, 28801
- Mission Hospital
-
Chapel Hill, North Carolina, United States, 27599
- UNC Lineberger Comprehensive Cancer Center
-
Charlotte, North Carolina, United States, 28203
- Carolinas Medical Center/Levine Cancer Institute
-
Charlotte, North Carolina, United States, 28204
- Novant Health Presbyterian Medical Center
-
Durham, North Carolina, United States, 27710
- Duke University Medical Center
-
Greenville, North Carolina, United States, 27834
- East Carolina University
-
Winston-Salem, North Carolina, United States, 27157
- Wake Forest University Health Sciences
-
-
North Dakota
-
Fargo, North Dakota, United States, 58122
- Sanford Broadway Medical Center
-
-
Ohio
-
Akron, Ohio, United States, 44308
- Children's Hospital Medical Center of Akron
-
Cincinnati, Ohio, United States, 45229
- Cincinnati Children's Hospital Medical Center
-
Cleveland, Ohio, United States, 44195
- Cleveland Clinic Foundation
-
Cleveland, Ohio, United States, 44106
- Rainbow Babies and Childrens Hospital
-
Columbus, Ohio, United States, 43205
- Nationwide Children's Hospital
-
Dayton, Ohio, United States, 45404
- Dayton Children's Hospital
-
Toledo, Ohio, United States, 43606
- ProMedica Toledo Hospital/Russell J Ebeid Children's Hospital
-
-
Oklahoma
-
Oklahoma City, Oklahoma, United States, 73104
- University of Oklahoma Health Sciences Center
-
-
Oregon
-
Portland, Oregon, United States, 97239
- Oregon Health and Science University
-
Portland, Oregon, United States, 97227
- Legacy Emanuel Children's Hospital
-
-
Pennsylvania
-
Danville, Pennsylvania, United States, 17822
- Geisinger Medical Center
-
Hershey, Pennsylvania, United States, 17033
- Penn State Children's Hospital
-
Philadelphia, Pennsylvania, United States, 19104
- Children's Hospital of Philadelphia
-
Philadelphia, Pennsylvania, United States, 19134
- Saint Christopher's Hospital for Children
-
Pittsburgh, Pennsylvania, United States, 15224
- Children's Hospital of Pittsburgh of UPMC
-
-
Rhode Island
-
Providence, Rhode Island, United States, 02903
- Rhode Island Hospital
-
-
South Carolina
-
Charleston, South Carolina, United States, 29425
- Medical University of South Carolina
-
Greenville, South Carolina, United States, 29605
- BI-LO Charities Children's Cancer Center
-
-
South Dakota
-
Sioux Falls, South Dakota, United States, 57117-5134
- Sanford USD Medical Center - Sioux Falls
-
-
Tennessee
-
Chattanooga, Tennessee, United States, 37403
- T C Thompson Children's Hospital
-
Knoxville, Tennessee, United States, 37916
- East Tennessee Childrens Hospital
-
Memphis, Tennessee, United States, 38105
- Saint Jude Children's Research Hospital
-
Nashville, Tennessee, United States, 37232
- Vanderbilt University/Ingram Cancer Center
-
Nashville, Tennessee, United States, 37203
- The Children's Hospital at TriStar Centennial
-
-
Texas
-
Amarillo, Texas, United States, 79106
- Texas Tech University Health Sciences Center-Amarillo
-
Austin, Texas, United States, 78723
- Dell Children's Medical Center of Central Texas
-
Corpus Christi, Texas, United States, 78411
- Driscoll Children's Hospital
-
Dallas, Texas, United States, 75390
- UT Southwestern/Simmons Cancer Center-Dallas
-
Dallas, Texas, United States, 75230
- Medical City Dallas Hospital
-
El Paso, Texas, United States, 79905
- El Paso Children's Hospital
-
Fort Worth, Texas, United States, 76104
- Cook Children's Medical Center
-
Houston, Texas, United States, 77030
- Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center
-
Lubbock, Texas, United States, 79410
- Covenant Children's Hospital
-
Lubbock, Texas, United States, 79415
- UMC Cancer Center / UMC Health System
-
San Antonio, Texas, United States, 78229
- University of Texas Health Science Center at San Antonio
-
San Antonio, Texas, United States, 78207
- Children's Hospital of San Antonio
-
San Antonio, Texas, United States, 78229
- Methodist Children's Hospital of South Texas
-
-
Utah
-
Salt Lake City, Utah, United States, 84113
- Primary Children's Hospital
-
-
Vermont
-
Burlington, Vermont, United States, 05405
- University of Vermont and State Agricultural College
-
-
Virginia
-
Falls Church, Virginia, United States, 22042
- Inova Fairfax Hospital
-
Norfolk, Virginia, United States, 23507
- Children's Hospital of The King's Daughters
-
Richmond, Virginia, United States, 23298
- Virginia Commonwealth University/Massey Cancer Center
-
-
Washington
-
Seattle, Washington, United States, 98105
- Seattle Children's Hospital
-
Spokane, Washington, United States, 99204
- Providence Sacred Heart Medical Center and Children's Hospital
-
Tacoma, Washington, United States, 98405
- Mary Bridge Children's Hospital and Health Center
-
Tacoma, Washington, United States, 98431
- Madigan Army Medical Center
-
-
West Virginia
-
Charleston, West Virginia, United States, 25304
- West Virginia University Charleston Division
-
-
Wisconsin
-
Green Bay, Wisconsin, United States, 54301
- Saint Vincent Hospital Cancer Center Green Bay
-
Madison, Wisconsin, United States, 53792
- University of Wisconsin Carbone Cancer Center
-
Milwaukee, Wisconsin, United States, 53226
- Children's Hospital of Wisconsin
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
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
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Non-Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Arm A (standard 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) |
Correlative studies
Given IV
Other Names:
Given IV
Other Names:
Given PO
Other Names:
Given IT and IV
Other Names:
|
Experimental: Arm B (high risk)
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. |
Correlative studies
Given IM or IV
Other Names:
Given IV
Other Names:
Given IT and IV
Other Names:
Given IM or IV
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Event-free survival probability at 2 years
Time Frame: At 2 years
|
The Kaplan-Meier method will be used to estimate 2-year event-free survival (EFS) from the end of Induction I along with 95% log-minus-log transformed confidence limits.
EFS is defined as the time from the end of Induction I to failure to achieve remission at the end of Induction II, relapse, occurrence of a second malignancy, or death.
|
At 2 years
|
Other Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Mean length on protocol therapy
Time Frame: 6 months
|
The mean number of days patients spent on protocol therapy.
|
6 months
|
Proportion of patients with an early death
Time Frame: 1 month
|
The proportion of patients experiencing an early death in the first month.
|
1 month
|
Overall survival probability at 2 years.
Time Frame: 2 years
|
The Kaplan-Meier method will be used to estimate 2-year Overall Survival (OS) from the end of Induction I along with 95% log-minus-log transformed confidence limits.
OS is defined as the time from the end of Induction I to death.
|
2 years
|
Proportion with treatment related mortality
Time Frame: 6 months
|
The proportion of patients experiencing a treatment related death will be reported along with a corresponding confidence interval.
|
6 months
|
Proportion of patients experiencing a relapse risk
Time Frame: 2 years
|
The proportion of patients experiencing a relapse after achieving remission will be reported along with a corresponding confidence interval.
|
2 years
|
Percentage of patients experiencing grade 3 or adverse events
Time Frame: 6 months
|
The percentage of patients experiencing grade 3 or higher toxicity will be reported, where adverse events are graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0.
|
6 months
|
Mean time to absolute neutrophil count (ANC) recovery
Time Frame: 6 months
|
The mean time to recovery of ANC to at least 1000/uL will be reported.
|
6 months
|
Mean duration of hospitalization
Time Frame: 6 months
|
Mean number of days patients are hospitalized.
|
6 months
|
Proportion of patients with at least 1 infection
Time Frame: 6 months
|
The proportion of patients having at least one infection will be reported.
|
6 months
|
Collaborators and Investigators
Sponsor
Collaborators
Investigators
- Principal Investigator: Jason N Berman, Children's Oncology Group
Publications and helpful links
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimated)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Pathologic Processes
- Nervous System Diseases
- Neoplasms by Histologic Type
- Neoplasms
- Neurologic Manifestations
- Neurobehavioral Manifestations
- Disease
- Congenital Abnormalities
- Bone Marrow Diseases
- Hematologic Diseases
- Genetic Diseases, Inborn
- Intellectual Disability
- Precancerous Conditions
- Abnormalities, Multiple
- Chromosome Disorders
- Syndrome
- Myelodysplastic Syndromes
- Leukemia
- Leukemia, Myeloid
- Leukemia, Myeloid, Acute
- Preleukemia
- Down Syndrome
- Myeloproliferative Disorders
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Anti-Infective Agents
- Peripheral Nervous System Agents
- Antiviral Agents
- Nucleic Acid Synthesis Inhibitors
- Enzyme Inhibitors
- Analgesics
- Sensory System Agents
- Antimetabolites, Antineoplastic
- Antimetabolites
- Antineoplastic Agents
- Immunosuppressive Agents
- Immunologic Factors
- Tubulin Modulators
- Antimitotic Agents
- Mitosis Modulators
- Antineoplastic Agents, Phytogenic
- Topoisomerase II Inhibitors
- Topoisomerase Inhibitors
- Dermatologic Agents
- Antibiotics, Antineoplastic
- Keratolytic Agents
- Etoposide
- Etoposide phosphate
- Podophyllotoxin
- Cytarabine
- Daunorubicin
- Asparaginase
- Mitoxantrone
- Mercaptopurine
- Thioguanine
- 2-Aminopurine
Other Study ID Numbers
- AAML1531 (Other Identifier: CTEP)
- U10CA180886 (U.S. NIH Grant/Contract)
- NCI-2015-00324 (Registry Identifier: CTRP (Clinical Trial Reporting Program))
- s16-01673
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Acute Myeloid Leukemia
-
University of PennsylvaniaActive, not recruitingAcute Myeloid Leukemia, in Relapse | Acute Myeloid Leukemia, Refractory | Acute Myeloid Leukemia, PediatricUnited States
-
Terrence J Bradley, MDImago BioSciences, Inc., a subsidiary of Merck & Co., Inc., (Rahway, New...RecruitingAcute Myeloid Leukemia | Refractory Acute Myeloid Leukemia | Acute Myeloid Leukemia, in RelapseUnited States
-
National Cancer Institute (NCI)RecruitingAcute Myeloid Leukemia | Secondary Acute Myeloid Leukemia | Recurrent Acute Myeloid Leukemia | Refractory Acute Myeloid LeukemiaUnited States
-
Bhavana BhatnagarCTI BioPharmaCompletedRecurrent Adult Acute Myeloid Leukemia | Secondary Acute Myeloid Leukemia | Untreated Adult Acute Myeloid Leukemia | Therapy-Related Acute Myeloid LeukemiaUnited States
-
Washington University School of MedicineWithdrawnRefractory Acute Myeloid Leukemia | Relapsed Acute Myeloid LeukemiaUnited States
-
C. Babis AndreadisGateway for Cancer Research; AVEO Pharmaceuticals, Inc.TerminatedAcute Myeloid Leukemia | Refractory Acute Myeloid Leukemia | Relapsed Acute Myeloid LeukemiaUnited States
-
Jacqueline Garcia, MDEli Lilly and CompanyCompletedCombination Merestinib and LY2874455 for Patients With Relapsed or Refractory Acute Myeloid LeukemiaRelapsed Adult Acute Myeloid Leukemia | Refractory Adult Acute Myeloid LeukemiaUnited States
-
Massachusetts General HospitalExelixisCompletedRefractory Acute Myeloid Leukemia | Relapsed Acute Myeloid LeukemiaUnited States
-
University of NebraskaNational Cancer Institute (NCI)Active, not recruitingSecondary Acute Myeloid Leukemia | Therapy-Related Acute Myeloid Leukemia | Adult Acute Myeloid LeukemiaUnited States
-
City of Hope Medical CenterNational Cancer Institute (NCI)RecruitingAcute Myeloid Leukemia | Recurrent Adult Acute Myeloid Leukemia | Secondary Acute Myeloid Leukemia | Refractory Acute Myeloid LeukemiaUnited States
Clinical Trials on Laboratory Biomarker Analysis
-
Children's Oncology GroupNational Cancer Institute (NCI)Completed
-
ECOG-ACRIN Cancer Research GroupNational Cancer Institute (NCI)CompletedProstate Cancer
-
Alliance for Clinical Trials in OncologyNational Cancer Institute (NCI)Active, not recruitingLeukemia | Acute Lymphoblastic Leukemia | Acute Promyelocytic LeukemiaUnited States
-
Children's Oncology GroupNational Cancer Institute (NCI)CompletedUntreated Adult Acute Lymphoblastic Leukemia | Untreated Childhood Acute Lymphoblastic LeukemiaUnited States, Canada, Australia, New Zealand, Puerto Rico, Switzerland
-
Children's Oncology GroupNational Cancer Institute (NCI)CompletedChildhood Acute Lymphoblastic Leukemia in Remission | Recurrent Childhood Acute Lymphoblastic LeukemiaUnited States
-
Alliance for Clinical Trials in OncologyNational Cancer Institute (NCI)CompletedLung CancerUnited States
-
Alliance for Clinical Trials in OncologyNational Cancer Institute (NCI)Completed
-
Children's Oncology GroupNational Cancer Institute (NCI)WithdrawnClear Cell Renal Cell Carcinoma | Rhabdoid Tumor of the Kidney | Congenital Mesoblastic Nephroma | Childhood Kidney NeoplasmUnited States
-
Gynecologic Oncology GroupNational Cancer Institute (NCI)WithdrawnBreast Carcinoma | BRCA1 Mutation Carrier | BRCA2 Mutation CarrierUnited States
-
Children's Oncology GroupNational Cancer Institute (NCI)CompletedWilms Tumor and Other Childhood Kidney TumorsUnited States