Combination Chemotherapy in Treating Young Patients With Down Syndrome and Acute Myeloid Leukemia or Myelodysplastic Syndromes

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Children's Oncology Group
ClinicalTrials.gov Identifier:
NCT00369317
First received: August 24, 2006
Last updated: April 29, 2014
Last verified: April 2014
  Purpose

This phase III trial is studying how well combination chemotherapy works in treating young patients with Down syndrome and acute myeloid leukemia or myelodysplastic syndromes. Drugs used in chemotherapy work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) may kill more cancer cells.


Condition Intervention Phase
Childhood Acute Basophilic Leukemia
Childhood Acute Eosinophilic Leukemia
Childhood Acute Erythroleukemia (M6)
Childhood Acute Megakaryocytic Leukemia (M7)
Childhood Acute Minimally Differentiated Myeloid Leukemia (M0)
Childhood Acute Monoblastic Leukemia (M5a)
Childhood Acute Monocytic Leukemia (M5b)
Childhood Acute Myeloblastic Leukemia With Maturation (M2)
Childhood Acute Myeloblastic Leukemia Without Maturation (M1)
Childhood Acute Myelomonocytic Leukemia (M4)
Childhood Myelodysplastic Syndromes
de Novo Myelodysplastic Syndromes
Secondary Acute Myeloid Leukemia
Secondary Myelodysplastic Syndromes
Untreated Childhood Acute Myeloid Leukemia and Other Myeloid Malignancies
Drug: asparaginase
Drug: daunorubicin hydrochloride
Drug: cytarabine
Drug: thioguanine
Drug: etoposide
Other: laboratory biomarker analysis
Phase 3

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: The Treatment of Down Syndrome Children With Acute Myeloid Leukemia (AML) and Myelodysplastic Syndromes (MDS) Under the Age of 4 Years

Resource links provided by NLM:


Further study details as provided by Children's Oncology Group:

Primary Outcome Measures:
  • Event-free survival (EFS) [ Time Frame: Time from study entry to induction failure, relapse, or death ] [ Designated as safety issue: No ]
  • Overall survival (OS) [ Time Frame: Up to 10 years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Induction remission rate [ Time Frame: End of induction therapy ] [ Designated as safety issue: No ]
  • Percentage of patients experiencing grade 3 or 4 toxicity assessed by the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 [ Time Frame: From the beginning of induction therapy to the end of intensification therapy ] [ Designated as safety issue: Yes ]
  • Prevalence of leukemia phenotype of DS patients < 4 years of age at diagnosis by flow cytometry [ Time Frame: At baseline and at the end of therapy (intensification) or disease relapse ] [ Designated as safety issue: No ]
    The prevalence of AMkL phenotype will be estimated as the proportion of patients with phenotype data available determined to have the AMkL phenotype. EFS will be estimated for those with and without AMkL using the approach of Kaplan and Meier. Differences in these estimates will be tested for significance using the log-rank statistic test.

  • Prevalence of of GATA1 mutations of DS patients < 4 years of age at diagnosis [ Time Frame: At baseline and at the end of therapy (intensification) or disease relapse ] [ Designated as safety issue: No ]
    The prevalence of GATA1 mutations will be estimated as the proportion of patients with phenotype data available determined to have the GATA1 mutations.

  • Proportions of patients in morphologic remission with positive MRD by flow cytometry [ Time Frame: After completion of induction therapy (I, IV) and after completion of intensification therapy ] [ Designated as safety issue: No ]
    Differences in the cumulative incidence of relapse for those with and without MRD will be tested using Gray's test.

  • Cytarabine drug sensitivity by R-Strip (MicroMath) curve fitting program. [ Time Frame: Days 1, 2, 8, and 9 of induction II ] [ Designated as safety issue: No ]
    Descriptive statistics will be used to summarize pharmacokinetic parameters, such as peak plasma concentration, area under the concentration time curve, and half-life of elimination

  • Gene expression profiles by microarrays [ Time Frame: At baseline and at the time of relapse (if available) ] [ Designated as safety issue: No ]
    A hierarchical clustering algorithm is used to assemble the genes into a dendrogram or tree structure with branches containing genes with similar patterns of expression. This ordered representation can be graphically displayed with colors that reflect the qualitative and quantitative relationships of the expressed genes.


Enrollment: 205
Study Start Date: March 2007
Primary Completion Date: December 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 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.

Drug: asparaginase
Given IM
Other Names:
  • ASNase
  • Colaspase
  • Crasnitin
  • Elspar
  • L-ASP
Drug: daunorubicin hydrochloride
Given IV
Other Names:
  • Cerubidin
  • Cerubidine
  • daunomycin hydrochloride
  • daunorubicin
  • RP-13057
Drug: cytarabine
Given IV or IT
Other Names:
  • ARA-C
  • arabinofuranosylcytosine
  • arabinosylcytosine
  • Cytosar-U
  • cytosine arabinoside
Drug: thioguanine
Given orally
Other Name: 6-TG
Drug: etoposide
Given IV
Other Names:
  • EPEG
  • VP-16
  • VP-16-213
Other: laboratory biomarker analysis
Correlative studies

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   up to 4 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Diagnosis DS or DS mosaicism by karyotype or chromosomal analysis
  • 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00369317

  Hide Study Locations
Locations
United States, Arizona
Phoenix Childrens Hospital
Phoenix, Arizona, United States, 85016
United States, California
Southern California Permanente Medical Group
Downey, California, United States, 90242
Miller Children's Hospital
Long Beach, California, United States, 90806
Children's Hospital Los Angeles
Los Angeles, California, United States, 90027
Children's Hospital Central California
Madera, California, United States, 93636-8762
Kaiser Permanente-Oakland
Oakland, California, United States, 94611
Children's Hospital and Research Center at Oakland
Oakland, California, United States, 94609-1809
Childrens Hospital of Orange County
Orange, California, United States, 92868-3874
Lucile Packard Children's Hospital Stanford University
Palo Alto, California, United States, 94304
Rady Children's Hospital - San Diego
San Diego, California, United States, 92123
University of California San Francisco Medical Center-Parnassus
San Francisco, California, United States, 94143
United States, Colorado
Children's Hospital Colorado
Aurora, Colorado, United States, 80045
United States, Delaware
Alfred I duPont Hospital for Children
Wilmington, Delaware, United States, 19803
United States, District of Columbia
Children's National Medical Center
Washington, District of Columbia, United States, 20010
Lombardi Comprehensive Cancer Center at Georgetown University
Washington, District of Columbia, United States, 20057
United States, Florida
Broward Health Medical Center
Fort Lauderdale, Florida, United States, 33316
Memorial Healthcare System - Joe DiMaggio Children's Hospital
Hollywood, Florida, United States, 33021
Nemours Children's Clinic - Jacksonville
Jacksonville, Florida, United States, 32207-8426
Florida Hospital
Orlando, Florida, United States, 32803
All Children's Hospital
Saint Petersburg, Florida, United States, 33701
United States, Georgia
Children's Healthcare of Atlanta - Egleston
Atlanta, Georgia, United States, 30322
United States, Hawaii
University of Hawaii
Honolulu, Hawaii, United States, 96813
United States, Idaho
Saint Luke's Mountain States Tumor Institute
Boise, Idaho, United States, 83712
United States, Illinois
Lurie Children's Hospital-Chicago
Chicago, Illinois, United States, 60614
Loyola University Medical Center
Maywood, Illinois, United States, 60153
Advocate Lutheran General Hospital.
Park Ridge, Illinois, United States, 60068
Saint Jude Midwest Affiliate
Peoria, Illinois, United States, 61602
Southern Illinois University
Springfield, Illinois, United States, 62702
United States, Indiana
Indiana University Medical Center
Indianapolis, Indiana, United States, 46202
Riley Hospital for Children
Indianapolis, Indiana, United States, 46202
Saint Vincent Hospital and Health Services
Indianapolis, Indiana, United States, 46260
United States, Kentucky
Kosair Children's Hospital
Louisville, Kentucky, United States, 40202
United States, Louisiana
Tulane University Health Sciences Center
New Orleans, Louisiana, United States, 70112
United States, Maine
Eastern Maine Medical Center
Bangor, Maine, United States, 04401
United States, Maryland
Johns Hopkins University-Sidney Kimmel Cancer Center
Baltimore, Maryland, United States, 21287
Sinai Hospital of Baltimore
Baltimore, Maryland, United States, 21215
Walter Reed National Military Medical Center
Bethesda, Maryland, United States, 20889-5600
United States, Michigan
C S Mott Children's Hospital
Ann Arbor, Michigan, United States, 48109
Saint John Hospital and Medical Center
Detroit, Michigan, United States, 48236
Wayne State University-Karmanos Cancer Institute
Detroit, Michigan, United States, 48201
Hurley Medical Center
Flint, Michigan, United States, 48502
Helen DeVos Children's Hospital at Spectrum Health
Grand Rapids, Michigan, United States, 49503
United States, Minnesota
Children's Hospitals and Clinics of Minnesota - Minneapolis
Minneapolis, Minnesota, United States, 55404
University of Minnesota Medical Center-Fairview
Minneapolis, Minnesota, United States, 55455
United States, Mississippi
University of Mississippi Medical Center
Jackson, Mississippi, United States, 39216
United States, Missouri
The Childrens Mercy Hospital
Kansas City, Missouri, United States, 64108
United States, Nebraska
Children's Hospital and Medical Center of Omaha
Omaha, Nebraska, United States, 68114
University of Nebraska Medical Center
Omaha, Nebraska, United States, 68198
United States, Nevada
Nevada Cancer Research Foundation CCOP
Las Vegas, Nevada, United States, 89106
United States, New Jersey
Hackensack University Medical Center
Hackensack, New Jersey, United States, 07601
Saint Peter's University Hospital
New Brunswick, New Jersey, United States, 08901
UMDNJ - Robert Wood Johnson University Hospital
New Brunswick, New Jersey, United States, 08903
Newark Beth Israel Medical Center
Newark, New Jersey, United States, 07112
United States, New York
Roswell Park Cancer Institute
Buffalo, New York, United States, 14263
Memorial Sloan-Kettering Cancer Center
New York, New York, United States, 10065
Columbia University Medical Center
New York, New York, United States, 10032
University of Rochester
Rochester, New York, United States, 14642
State University of New York Upstate Medical University
Syracuse, New York, United States, 13210
Ny Cancer%
Valhalla, New York, United States, 10595
United States, North Carolina
University of North Carolina
Chapel Hill, North Carolina, United States, 27599
Carolinas Medical Center
Charlotte, North Carolina, United States, 28203
Duke University Medical Center
Durham, North Carolina, United States, 27710
United States, North Dakota
Sanford Medical Center-Fargo
Fargo, North Dakota, United States, 58122
United States, Ohio
Children's Hospital Medical Center of Akron
Akron, Ohio, United States, 44308
Cleveland Clinic Foundation
Cleveland, Ohio, United States, 44195
Nationwide Children's Hospital
Columbus, Ohio, United States, 43205
United States, Oklahoma
University of Oklahoma Health Sciences Center
Oklahoma City, Oklahoma, United States, 73104
United States, Oregon
Legacy Emanuel Hospital and Health Center
Portland, Oregon, United States, 97227
Oregon Health and Science University
Portland, Oregon, United States, 97239
United States, Pennsylvania
Penn State Hershey Children's Hospital
Hershey, Pennsylvania, United States, 17033
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, United States, 19104
Saint Christopher's Hospital for Children
Philadelphia, Pennsylvania, United States, 19134
Children's Hospital of Pittsburgh of UPMC
Pittsburgh, Pennsylvania, United States, 15224
United States, Rhode Island
Rhode Island Hospital
Providence, Rhode Island, United States, 02903
United States, South Carolina
Palmetto Health Richland
Columbia, South Carolina, United States, 29203
United States, Tennessee
St. Jude Children's Research Hospital
Memphis, Tennessee, United States, 38105
Vanderbilt-Ingram Cancer Center
Nashville, Tennessee, United States, 37232
United States, Texas
University of Texas Southwestern Medical Center
Dallas, Texas, United States, 75390
Cook Children's Medical Center
Fort Worth, Texas, United States, 76104
Baylor College of Medicine
Houston, Texas, United States, 77030
Covenant Children's Hospital
Lubbock, Texas, United States, 79410
University of Texas Health Science Center at San Antonio
San Antonio, Texas, United States, 78229-3900
United States, Utah
Primary Children's Hospital
Salt Lake City, Utah, United States, 84113
United States, Vermont
University of Vermont
Burlington, Vermont, United States, 05401
United States, Virginia
Childrens Hospital-King's Daughters
Norfolk, Virginia, United States, 23507
United States, Washington
Seattle Children's Hospital
Seattle, Washington, United States, 98105
Mary Bridge Children's Hospital and Health Center
Tacoma, Washington, United States, 98405
United States, Wisconsin
Midwest Children's Cancer Center
Milwaukee, Wisconsin, United States, 53226
Australia, Western Australia
Princess Margaret Hospital for Children
Perth, Western Australia, Australia, 6008
Canada, British Columbia
British Columbia Children's Hospital
Vancouver, British Columbia, Canada, V6H 3V4
Canada, Manitoba
CancerCare Manitoba
Winnipeg, Manitoba, Canada, R3E 0V9
Canada, Newfoundland and Labrador
Janeway Child Health Centre
Saint John's, Newfoundland and Labrador, Canada, A1B 3V6
Canada, Ontario
Cancer Centre of Southeastern Ontario at Kingston General Hospital
Kingston, Ontario, Canada, K7L 5P9
Children's Hospital
London, Ontario, Canada, N6A 5W9
Children's Hospital of Eastern Ontario
Ottawa, Ontario, Canada, K1H 8L1
Hospital for Sick Children
Toronto, Ontario, Canada, M5G 1X8
Puerto Rico
San Jorge Children's Hospital
Santurce, Puerto Rico, 00912
Sponsors and Collaborators
Children's Oncology Group
Investigators
Principal Investigator: Jeffrey Taub, MD Children's Oncology Group
  More Information

No publications provided

Responsible Party: Children's Oncology Group
ClinicalTrials.gov Identifier: NCT00369317     History of Changes
Other Study ID Numbers: AAML0431, NCI-2009-00318, CDR0000492776, COG-AAML0431, AAML0431, AAML0431, U10CA098543
Study First Received: August 24, 2006
Last Updated: April 29, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Neoplasms
Down Syndrome
Leukemia
Leukemia, Basophilic, Acute
Leukemia, Eosinophilic, Acute
Leukemia, Erythroblastic, Acute
Leukemia, Megakaryoblastic, Acute
Leukemia, Monocytic, Acute
Leukemia, Myeloid, Acute
Leukemia, Myeloid
Leukemia, Myelomonocytic, Acute
Myelodysplastic Syndromes
Preleukemia
Leukemia, Myelomonocytic, Chronic
Hypereosinophilic Syndrome
Intellectual Disability
Neurobehavioral Manifestations
Neurologic Manifestations
Nervous System Diseases
Abnormalities, Multiple
Congenital Abnormalities
Chromosome Disorders
Genetic Diseases, Inborn
Neoplasms by Histologic Type
Myeloproliferative Disorders
Bone Marrow Diseases
Hematologic Diseases
Precancerous Conditions
Myelodysplastic-Myeloproliferative Diseases
Eosinophilia

ClinicalTrials.gov processed this record on July 31, 2014