Combination Chemotherapy in Treating Young Patients With Down Syndrome and Acute Myeloid Leukemia or Myelodysplastic Syndromes
NCT ID: NCT00369317
Last Updated: 2022-01-28
Study Results
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View full resultsBasic Information
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COMPLETED
PHASE3
205 participants
INTERVENTIONAL
2007-03-31
2021-12-31
Brief Summary
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Detailed Description
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I. Determine the event-free survival (EFS) and overall survival rates in pediatric patients with Down syndrome (DS) and acute myeloid leukemia AML or myelodysplastic syndromes MDS treated with induction therapy comprising cytarabine, daunorubicin hydrochloride, thioguanine, and asparaginase followed by intensification therapy comprising cytarabine and etoposide.
II. Determine if the EFS rate in these patients can be increased with an intensified course of cytarabine therapy during induction therapy, compared to the EFS rate of patients in protocol COG-A2971.
III. Determine if the number of intrathecal chemotherapy treatments can be reduced in these patients.
IV. Determine if the total cumulative anthracycline dose can be reduced in these patients.
SECONDARY OBJECTIVES:
I. Determine the type and degree of treatment-related toxicity in these patients.
II. Determine the prevalence of leukemia phenotype and globin transcription factor 1 (GATA1) mutations of DS patients \< 4 years of age at diagnosis.
III. Determine the relationship of GATA1 mutations with leukemia phenotype and EFS rates of DS patients \< 4 years of age at diagnosis.
IV. Determine the relationship of minimal residual disease monitored by flow cytometry and remission status during and after completion of therapy based on bone marrow morphology.
V. Examine parameters of in vitro drug sensitivity and in vivo Ara-C pharmacokinetics.
VI. Examine gene expression profiles by microarrays and the relationship to leukemia phenotype and outcome.
VII. Examine the relationship of functional polymorphisms in phase I and phase II detoxification genes and DNA repair pathways that may modify susceptibility to leukemia and outcome of therapy in DS children.
VIII. Assess the effect of karyotypic abnormalities on survival. IX. Establish a DS leukemia cell bank for future biological studies.
OUTLINE: This is a nonrandomized, multicenter study.
INDUCTION THERAPY: Patients undergo 4 courses of induction therapy. Each course is 28 days.
COURSE I: Patients receive intrathecal (IT) cytarabine on day 1\* and cytarabine IV continuously over 96 hours, daunorubicin hydrochloride IV continuously over 96 hours, and oral thioguanine twice daily on days 1-4.
NOTE: \*Patients with Central Nervous System (CNS) disease receive cytarabine IT twice weekly for up to 6 doses; patients with persistent CNS leukemia after 6 doses of IT cytarabine are removed from the study.
COURSE II: Patients receive high-dose cytarabine IV over 3 hours twice daily on days 1, 2, 8, and 9 and asparaginase intramuscularly (IM) on days 2 and 9.
COURSE III: Patients receive treatment as in course 1.
COURSE IV: Patients receive cytarabine IV, daunorubicin hydrochloride IV, and oral thioguanine as in course 1.
Induction therapy continues in the absence of disease progression or unacceptable toxicity. Patients with partial response, relapsed, or refractory disease after completion of course 4 are taken off study. Patients achieving complete response proceed to intensification therapy.
INTENSIFICATION THERAPY: Patients receive cytarabine IV continuously over 168 hours on days 1-7 and etoposide IV over 1 hour on days 1-3. Treatment repeats every 28 days for 2 courses in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up periodically for 5 years and then annually thereafter.
Conditions
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Study Design
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NA
SINGLE_GROUP
TREATMENT
NONE
Study Groups
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Treatment (combination chemotherapy)
INDUCTION THERAPY COURSE I: Patients receive cytarabine IT on day 1 and cytarabine IV continuously over 96 hours, daunorubicin hydrochloride IV continuously, and oral thioguanine BID on days 1-4. COURSE II: Patients receive high-dose cytarabine IV over 3 hours BID on days 1, 2, 8, and 9 and asparaginase (IM) on days 2 and 9.
COURSE III: Patients receive treatment as in course I. COURSE IV: Patients receive cytarabine IV, daunorubicin hydrochloride IV, and oral thioguanine as in course I
INTENSIFICATION THERAPY: Patients receive cytarabine IV continuously over 168 hours on days 1-7 and etoposide IV over 1 hour on days 1-3. Treatment repeats every 28 days for 2 courses in the absence of disease progression or unacceptable toxicity.
asparaginase
Given IM
daunorubicin hydrochloride
Given IV
cytarabine
Given IV or IT
thioguanine
Given orally
etoposide
Given IV
laboratory biomarker analysis
Correlative studies
Interventions
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asparaginase
Given IM
daunorubicin hydrochloride
Given IV
cytarabine
Given IV or IT
thioguanine
Given orally
etoposide
Given IV
laboratory biomarker analysis
Correlative studies
Other Intervention Names
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Eligibility Criteria
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Inclusion Criteria
* Diagnosis of myelodysplastic syndromes (MDS) with \< 30% blasts or acute myeloid leukemia (AML)
* Newly diagnosed disease
* Patients with a history of transient myeloproliferative disorder (TMD) are eligible provided the patient is diagnosed with AML or MDS at \> 90 days of age AND meets either of the following criteria:
* At least 30% blasts in the bone marrow regardless of time since resolution of TMD
* More than 8 weeks since resolution of TMD with ≥ 5% blasts in the bone marrow
* Immunophenotype required for study entry
* No promyelocytic leukemia
* Shortening fraction ≥ 27% by echocardiogram OR ejection fraction ≥ 50% by radionuclide angiogram
* Bilirubin ≤ 1.5 times upper limit of normal (ULN)
* AST or ALT \< 2.5 times ULN
* Creatinine adjusted according to age as follows:
* No greater than 0.4 mg/dL (≤ 5 months)
* No greater than 0.5 mg/dL (6 months -11 months)
* No greater than 0.6 mg/dL (1 year-23 months)
* No greater than 0.8 mg/dL (2 years-5 years)
* No greater than 1.0 mg/dL (6 years-9 years)
* No greater than 1.2 mg/dL (10 years-12 years)
* No greater than 1.4 mg/dL (13 years and over \[female\])
* No greater than 1.5 mg/dL (13 years to 15 years \[male\])
* No greater than 1.7 mg/dL (16 years and over \[male\])
* Creatinine clearance or radioisotope glomerular filtration rate at least 70 mL/min
* No evidence of dyspnea at rest
* No exercise intolerance
* Pulse oximetry \> 94%
* No prior chemotherapy, radiotherapy, or any antileukemic therapy
* Intrathecal cytarabine therapy given at diagnosis allowed
* Prior therapy for TMD allowed
4 Years
ALL
No
Sponsors
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National Cancer Institute (NCI)
NIH
Children's Oncology Group
NETWORK
Responsible Party
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Principal Investigators
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Jeffrey Taub, MD
Role: PRINCIPAL_INVESTIGATOR
Children's Oncology Group
Locations
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Phoenix Childrens Hospital
Phoenix, Arizona, United States
Southern California Permanente Medical Group
Downey, California, United States
Miller Children's Hospital
Long Beach, California, United States
Children's Hospital Los Angeles
Los Angeles, California, United States
Children's Hospital Central California
Madera, California, United States
Children's Hospital and Research Center at Oakland
Oakland, California, United States
Kaiser Permanente-Oakland
Oakland, California, United States
Childrens Hospital of Orange County
Orange, California, United States
Lucile Packard Children's Hospital Stanford University
Palo Alto, California, United States
Rady Children's Hospital - San Diego
San Diego, California, United States
University of California San Francisco Medical Center-Parnassus
San Francisco, California, United States
Children's Hospital Colorado
Aurora, Colorado, United States
Alfred I duPont Hospital for Children
Wilmington, Delaware, United States
Children's National Medical Center
Washington D.C., District of Columbia, United States
Lombardi Comprehensive Cancer Center at Georgetown University
Washington D.C., District of Columbia, United States
Broward Health Medical Center
Fort Lauderdale, Florida, United States
Memorial Healthcare System - Joe DiMaggio Children's Hospital
Hollywood, Florida, United States
Nemours Children's Clinic - Jacksonville
Jacksonville, Florida, United States
Florida Hospital
Orlando, Florida, United States
All Children's Hospital
St. Petersburg, Florida, United States
Children's Healthcare of Atlanta - Egleston
Atlanta, Georgia, United States
University of Hawaii
Honolulu, Hawaii, United States
Saint Luke's Mountain States Tumor Institute
Boise, Idaho, United States
Lurie Children's Hospital-Chicago
Chicago, Illinois, United States
Loyola University Medical Center
Maywood, Illinois, United States
Advocate Lutheran General Hospital.
Park Ridge, Illinois, United States
Saint Jude Midwest Affiliate
Peoria, Illinois, United States
Southern Illinois University
Springfield, Illinois, United States
Indiana University Medical Center
Indianapolis, Indiana, United States
Riley Hospital for Children
Indianapolis, Indiana, United States
Saint Vincent Hospital and Health Services
Indianapolis, Indiana, United States
Kosair Children's Hospital
Louisville, Kentucky, United States
Tulane University Health Sciences Center
New Orleans, Louisiana, United States
Eastern Maine Medical Center
Bangor, Maine, United States
Sinai Hospital of Baltimore
Baltimore, Maryland, United States
Johns Hopkins University-Sidney Kimmel Cancer Center
Baltimore, Maryland, United States
Walter Reed National Military Medical Center
Bethesda, Maryland, United States
C S Mott Children's Hospital
Ann Arbor, Michigan, United States
Wayne State University-Karmanos Cancer Institute
Detroit, Michigan, United States
Saint John Hospital and Medical Center
Detroit, Michigan, United States
Hurley Medical Center
Flint, Michigan, United States
Helen DeVos Children's Hospital at Spectrum Health
Grand Rapids, Michigan, United States
Children's Hospitals and Clinics of Minnesota - Minneapolis
Minneapolis, Minnesota, United States
University of Minnesota Medical Center-Fairview
Minneapolis, Minnesota, United States
University of Mississippi Medical Center
Jackson, Mississippi, United States
The Childrens Mercy Hospital
Kansas City, Missouri, United States
Children's Hospital and Medical Center of Omaha
Omaha, Nebraska, United States
University of Nebraska Medical Center
Omaha, Nebraska, United States
Nevada Cancer Research Foundation CCOP
Las Vegas, Nevada, United States
Hackensack University Medical Center
Hackensack, New Jersey, United States
Saint Peter's University Hospital
New Brunswick, New Jersey, United States
UMDNJ - Robert Wood Johnson University Hospital
New Brunswick, New Jersey, United States
Newark Beth Israel Medical Center
Newark, New Jersey, United States
Roswell Park Cancer Institute
Buffalo, New York, United States
Columbia University Medical Center
New York, New York, United States
Memorial Sloan-Kettering Cancer Center
New York, New York, United States
University of Rochester
Rochester, New York, United States
State University of New York Upstate Medical University
Syracuse, New York, United States
Ny Cancer%
Valhalla, New York, United States
University of North Carolina
Chapel Hill, North Carolina, United States
Carolinas Medical Center
Charlotte, North Carolina, United States
Duke University Medical Center
Durham, North Carolina, United States
Sanford Medical Center-Fargo
Fargo, North Dakota, United States
Children's Hospital Medical Center of Akron
Akron, Ohio, United States
Cleveland Clinic Foundation
Cleveland, Ohio, United States
Nationwide Children's Hospital
Columbus, Ohio, United States
University of Oklahoma Health Sciences Center
Oklahoma City, Oklahoma, United States
Legacy Emanuel Hospital and Health Center
Portland, Oregon, United States
Oregon Health and Science University
Portland, Oregon, United States
Penn State Hershey Children's Hospital
Hershey, Pennsylvania, United States
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, United States
Saint Christopher's Hospital for Children
Philadelphia, Pennsylvania, United States
Children's Hospital of Pittsburgh of UPMC
Pittsburgh, Pennsylvania, United States
Rhode Island Hospital
Providence, Rhode Island, United States
Palmetto Health Richland
Columbia, South Carolina, United States
St. Jude Children's Research Hospital
Memphis, Tennessee, United States
Vanderbilt-Ingram Cancer Center
Nashville, Tennessee, United States
University of Texas Southwestern Medical Center
Dallas, Texas, United States
Cook Children's Medical Center
Fort Worth, Texas, United States
Baylor College of Medicine
Houston, Texas, United States
Covenant Children's Hospital
Lubbock, Texas, United States
University of Texas Health Science Center at San Antonio
San Antonio, Texas, United States
Primary Children's Hospital
Salt Lake City, Utah, United States
University of Vermont
Burlington, Vermont, United States
Childrens Hospital-King's Daughters
Norfolk, Virginia, United States
Seattle Children's Hospital
Seattle, Washington, United States
Mary Bridge Children's Hospital and Health Center
Tacoma, Washington, United States
Midwest Children's Cancer Center
Milwaukee, Wisconsin, United States
Princess Margaret Hospital for Children
Perth, Western Australia, Australia
British Columbia Children's Hospital
Vancouver, British Columbia, Canada
CancerCare Manitoba
Winnipeg, Manitoba, Canada
Janeway Child Health Centre
St. John's, Newfoundland and Labrador, Canada
Cancer Centre of Southeastern Ontario at Kingston General Hospital
Kingston, Ontario, Canada
Children's Hospital
London, Ontario, Canada
Children's Hospital of Eastern Ontario
Ottawa, Ontario, Canada
Hospital for Sick Children
Toronto, Ontario, Canada
San Jorge Children's Hospital
Santurce, , Puerto Rico
Countries
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References
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Taub JW, Berman JN, Hitzler JK, Sorrell AD, Lacayo NJ, Mast K, Head D, Raimondi S, Hirsch B, Ge Y, Gerbing RB, Wang YC, Alonzo TA, Campana D, Coustan-Smith E, Mathew P, Gamis AS. Improved outcomes for myeloid leukemia of Down syndrome: a report from the Children's Oncology Group AAML0431 trial. Blood. 2017 Jun 22;129(25):3304-3313. doi: 10.1182/blood-2017-01-764324. Epub 2017 Apr 7.
Related Links
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Data Available: Select individual patient-level data from this trial can be requested from the NCTN/NCORP Data Archive
Other Identifiers
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NCI-2009-00318
Identifier Type: REGISTRY
Identifier Source: secondary_id
CDR0000492776
Identifier Type: OTHER
Identifier Source: secondary_id
COG-AAML0431
Identifier Type: OTHER
Identifier Source: secondary_id
AAML0431
Identifier Type: OTHER
Identifier Source: secondary_id
AAML0431
Identifier Type: -
Identifier Source: org_study_id
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