Combination Chemotherapy in Treating Young Patients With Newly Diagnosed Acute Promyelocytic Leukemia

October 3, 2022 updated by: Children's Oncology Group

Risk Adapted Treatment of Newly Diagnosed Childhood Acute Promyelocytic Leukemia (APL) Using Arsenic Trioxide (Trisenox® ) During Consolidation

This phase III trial is studying combination chemotherapy to see how well it works in treating young patients with newly diagnosed acute promyelocytic leukemia. 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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

PRIMARY OBJECTIVES:

I. To decrease the total anthracycline dose from the best current published results in standard risk childhood acute promyelocytic leukemia (APL) while still maintaining a comparable event-free survival (EFS).

SECONDARY OBJECTIVES:

I. To assign treatment based on risk stratification by white blood cell count (WBC) at diagnosis.

II. To estimate the induction failure rate, toxic death rate, disease-free survival rate and overall survival rate in both standard and high risk APL patients.

III. To monitor for cardiotoxicity in an idarubicin/mitoxantrone based regimen. IV. To document the toxicity of a traditional chemotherapy/all-trans retinoic acid (ATRA) (tretinoin) based regimen combined with arsenic trioxide therapy.

V. To study the relationship of Fms-like tyrosine kinase 3 (FLT3) mutations to clinical features and outcome in APL.

VI. To study risk factors for pseudotumor cerebri in APL. VII. To study the relationship of early progenitor cell involvement to treatment failure in FLT3 positive APL.

VIII. To compare the EFS of children enrolled on AAML0631 with the EFS of children enrolled on C9710 who were between the ages of 2 and 21 and did not receive arsenic trioxide.

IX. To estimate the proportion of patients who carry a cryptic t(15;17), i.e., those who are positive for a promyelocytes.(PML)-retinoic acid receptor alpha (RARA) fusion transcript by polymerase chain reaction (PCR) analysis but have normal chromosomes.

X. To estimate the proportion of patients with variant RARA partners. XI. To compare the outcome of patients with only a t(15;17) with that of patients who carry a t(15;17) and other chromosomal abnormalities.

OUTLINE: This is a multicenter study. Patients are assigned to 1 of 2 arms based on risk factor (standard-risk [WBC less than 10,000/mm^3] or high-risk [WBC 10,000/mm^3 or higher]).

ARM I (STANDARD-RISK):

INDUCTION THERAPY: Patients receive tretinoin orally (PO) twice daily (BID) on days 1-30 and idarubicin intravenously (IV) over 15 minutes once on days 3, 5, and 7.

CONSOLIDATION THERAPY:

CONSOLIDATION 1: Patients receive arsenic trioxide IV over 2 hours on days 1-5, 8-12, 15-19, 22-26, and 29-33 and tretinoin PO BID on days 1-14. Treatment repeats every 5 weeks for 2 courses, followed by a 2-week break, and then treatment repeats for 2 more courses. Beginning 1 week later or when blood counts recover, patients proceed to consolidation 2.

CONSOLIDATION 2: Patients receive cytarabine intrathecally (IT) on day 1, tretinoin PO BID on days 1-14, high-dose cytarabine IV over 3 hours every 12 hours on days 1-3, and mitoxantrone hydrochloride IV over 15-30 minutes once on days 3 and 4. Patients proceed to consolidation 3 1 week later or when blood counts recover.

CONSOLIDATION 3: Patients receive cytarabine IT on day 1, tretinoin PO BID on days 1-14, and idarubicin IV over 15 minutes once daily on days 1, 3, and 5. High-risk patients and those standard-risk patients who are positive for minimal residual disease by real-time quantitative (RQ)-PCR receive consolidation 4 one week later or when blood counts recover. All other standard-risk patients proceed to maintenance therapy.

MAINTENANCE THERAPY: Patients receive cytarabine IT on day 1 (course 1 only), tretinoin PO BID on days 1-14, mercaptopurine PO once daily (QD) on days 1-84, methotrexate PO once on days 1, 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, and 78. Treatment repeats every 12 weeks for 9 courses.

ARM II (HIGH-RISK):

INDUCTION THERAPY: Patients receive tretinoin PO BID on days 1-30 and idarubicin IV over 15 minutes once on days 1, 3, and 5. Patients proceed to consolidation therapy one week later or when blood counts recover.

CONSOLIDATION THERAPY: Patients receive consolidation 1, 2, and 3 as in Arm I.

CONSOLIDATION 4: Patients receive cytarabine IT on day 1, tretinoin PO BID on days 1-14, high-dose cytarabine IV over 3 hours every 12 hours on days 1-3, and idarubicin IV over 15 minutes once on day 4. Patients who demonstrate molecular complete remission (CR) and remain in hematological CR proceed to maintenance therapy 1 week later or when blood counts recover.

MAINTENANCE THERAPY: Patients receive maintenance therapy as in Arm I.

After completion of study treatment, patients are followed every month for 1 year, every 3 months for 2 years, every 6 months for 2 years, and then annually for 5 years.

Study Type

Interventional

Enrollment (Actual)

106

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Canada
      • Quebec, Canada, G1V 4G2
        • Centre Hospitalier Universitaire de Quebec
    • 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
      • Ottawa, Ontario, Canada, K1H 8L1
        • Children's Hospital of Eastern Ontario
      • Toronto, Ontario, Canada, M5G 1X8
        • Hospital for Sick Children
    • Quebec
      • Montreal, Quebec, Canada, H3T 1C5
        • Centre Hospitalier Universitaire Sainte-Justine
  • Puerto Rico
      • San Juan, Puerto Rico, 00912
        • San Jorge Children's Hospital
  • United States
    • Alabama
      • Birmingham, Alabama, United States, 35233
        • University of Alabama at Birmingham Cancer Center
      • Birmingham, Alabama, United States, 35233
        • Children's Hospital of Alabama
    • Arizona
      • Phoenix, Arizona, United States, 85016
        • Phoenix Childrens Hospital
    • Arkansas
      • Little Rock, Arkansas, United States, 72205
        • University of Arkansas for Medical Sciences
      • 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, 90095
        • UCLA / Jonsson Comprehensive Cancer Center
      • Madera, California, United States, 93636
        • Valley Children's Hospital
      • Oakland, California, United States, 94609
        • UCSF Benioff Children's Hospital 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
      • San Diego, California, United States, 92123
        • Rady Children's Hospital - San Diego
      • San Francisco, California, United States, 94115
        • UCSF Medical Center-Mount Zion
      • San Francisco, California, United States, 94143
        • UCSF Medical Center-Parnassus
      • Torrance, California, United States, 90502
        • Harbor-University of California at Los Angeles Medical Center
    • Colorado
      • Aurora, Colorado, United States, 80045
        • Children's Hospital Colorado
    • Connecticut
      • Farmington, Connecticut, United States, 06030
        • University of Connecticut
      • Hartford, Connecticut, United States, 06106
        • Connecticut Children's Medical Center
    • 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 Myers, Florida, United States, 33908
        • Golisano Children's Hospital of Southwest Florida
      • Fort Myers, Florida, United States, 33901
        • Lee Memorial Health System
      • Jacksonville, Florida, United States, 32207
        • Nemours Children's Clinic-Jacksonville
      • Orlando, Florida, United States, 32806
        • Orlando Health Cancer Institute
      • Orlando, Florida, United States, 32806
        • Nemours Children's Clinic - Orlando
      • Orlando, Florida, United States, 32803
        • AdventHealth Orlando
      • 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
        • Emory University Hospital/Winship Cancer Institute
      • 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, 96813
        • University of Hawaii Cancer Center
    • Illinois
      • Chicago, Illinois, United States, 60611
        • Lurie Children's Hospital-Chicago
      • Maywood, Illinois, United States, 60153
        • Loyola University Medical Center
      • Oak Lawn, Illinois, United States, 60453
        • Advocate Children's Hospital-Oak Lawn
      • 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
        • Indiana University/Melvin and Bren Simon Cancer Center
      • Indianapolis, Indiana, United States, 46202
        • Riley Hospital for Children
      • Indianapolis, Indiana, United States, 46260
        • Ascension Saint Vincent Indianapolis Hospital
    • 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, 70112
        • Tulane University Health Sciences Center
    • 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
    • Massachusetts
      • Boston, Massachusetts, United States, 02215
        • Dana-Farber Cancer Institute
      • 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, 48824-7016
        • Michigan State University Clinical Center
      • Grand Rapids, Michigan, United States, 49503
        • Spectrum Health at Butterworth Campus
      • Grand Rapids, Michigan, United States, 49503
        • Helen DeVos Children's Hospital at Spectrum Health
    • Minnesota
      • Minneapolis, Minnesota, United States, 55404
        • Children's Hospitals and Clinics of Minnesota - Minneapolis
      • Rochester, Minnesota, United States, 55905
        • Mayo Clinic in Rochester
    • Mississippi
      • Jackson, Mississippi, United States, 39216
        • University of Mississippi Medical Center
    • Missouri
      • 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, 63104
        • Cardinal Glennon Children's Medical Center
    • Nevada
      • Las Vegas, Nevada, United States, 89169
        • Nevada Cancer Research Foundation NCORP
    • 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
      • Summit, New Jersey, United States, 07902
        • Overlook Hospital
    • New Mexico
      • Albuquerque, New Mexico, United States, 87102
        • University of New Mexico Cancer Center
    • New York
      • Bronx, New York, United States, 10467
        • Montefiore Medical Center - Moses Campus
      • Buffalo, New York, United States, 14263
        • Roswell Park Cancer Institute
      • New York, New York, United States, 10032
        • NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center
      • Syracuse, New York, United States, 13210
        • State University of New York Upstate Medical University
    • North Carolina
      • 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
      • 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
      • 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
    • Pennsylvania
      • Hershey, Pennsylvania, United States, 17033-0850
        • Penn State Milton S Hershey 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, 19104
        • Children's Oncology Group
      • Pittsburgh, Pennsylvania, United States, 15224
        • Children's Hospital of Pittsburgh of UPMC
    • South Carolina
      • Columbia, South Carolina, United States, 29203
        • Prisma Health Richland Hospital
      • Greenville, South Carolina, United States, 29605
        • BI-LO Charities Children's Cancer Center
      • Greenville, South Carolina, United States, 29605
        • Greenville Cancer Treatment Center
    • Tennessee
      • Chattanooga, Tennessee, United States, 37403
        • T C Thompson Children's Hospital
      • Memphis, Tennessee, United States, 38105
        • Saint Jude Children's Research Hospital
    • Texas
      • Corpus Christi, Texas, United States, 78411
        • Driscoll Children's Hospital
      • Fort Worth, Texas, United States, 76104
        • Cook Children's Medical Center
      • San Antonio, Texas, United States, 78229
        • University of Texas Health Science Center at 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
    • Washington
      • Seattle, Washington, United States, 98105
        • Seattle Children's Hospital
    • Wisconsin
      • Green Bay, Wisconsin, United States, 54301
        • Saint Vincent Hospital Cancer Center Green Bay
      • Marshfield, Wisconsin, United States, 54449
        • Marshfield Medical Center-Marshfield
      • Milwaukee, Wisconsin, United States, 53226
        • Children's Hospital of Wisconsin

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

2 years to 21 years (ADULT, CHILD)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Patients must be newly diagnosed with a clinical diagnosis of acute promyelocytic leukemia initially by morphology (bone marrow or peripheral blood); bone marrow is highly preferred but in cases where marrow cannot be obtained at diagnosis, peripheral blood will be accepted; APL is considered a hematological emergency and treatment should be initiated as quickly as possible without waiting for molecular or cytogenetic/fluorescence in situ hybridization (FISH) confirmation; for patients who are unable to begin receiving ATRA in a timely manner following a presumed diagnosis of APL, consideration should be given to initiating ATRA and proceeding with treatment outside of the AAML0631 protocol; if the RQ-PCR results are known at the time of study enrollment, the patient must demonstrate PML-RARA and/or RARA-PML transcripts by RQ-PCR to be eligible; patients without evidence of APL by bone marrow or peripheral blood morphology but with isolated myeloid sarcoma (myeloblastoma; chloroma, including leukemia cutis) are eligible provided that the t(15;17) translocation is documented on either marrow or tumor tissue by cytogenetics, FISH, or PCR prior to study enrollment; in this situation, touch preps from the tumor site can be evaluated by FISH with PML-RARA probes; NOTE: A lumbar puncture is not required to be enrolled on study; if the diagnosis of APL is known or suspected, extreme caution must be exercised in performing a lumbar puncture during active coagulopathy; in addition a computed tomography (CT) or magnetic resonance imaging (MRI) should be considered to rule out the possibility of an associated chloroma if central nervous system (CNS) disease is suspected or proven; if CNS disease is documented, patients are still eligible
  • No minimal performance status criteria
  • The patient must not have received systemic definitive treatment for APL or other suspected leukemia, including cytotoxic chemotherapy, retinoids, or arsenic; prior therapy with corticosteroids, hydroxyurea, or leukopheresis will not exclude the patient; if a patient received intrathecal cytarabine prior to the diagnosis of APL being known, the patient will still be eligible as long as they meet all other eligibility requirements

Exclusion Criteria:

  • Pregnant women or nursing mothers are excluded; treatment under this protocol would expose an unborn child to significant risks; patients should not be pregnant or plan to become pregnant while on treatment; women and men of reproductive potential should agree to use an effective means of birth control; there is an extremely high risk of fetal malformation if pregnancy occurs while on ATRA in any amount even for short periods
  • Patients with a pre-existing prolonged QT Syndrome will not be eligible for this protocol due to the use of arsenic trioxide which can prolong the QT interval

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: NON_RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: NONE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
EXPERIMENTAL: Arm I (standard risk, combination chemotherapy)
See Detailed Description
Drug: Mitoxantrone Hydrochloride
Given IV
Other Names:
  • CL 232315
  • DHAD
  • DHAQ
  • Dihydroxyanthracenedione Dihydrochloride
  • Mitoxantrone Dihydrochloride
  • Mitoxantroni Hydrochloridum
  • Mitozantrone Hydrochloride
  • Mitroxone
  • Neotalem
  • Novantrone
  • Onkotrone
  • Pralifan
Other: Diagnostic Laboratory Biomarker Analysis
Correlative studies
Drug: Cytarabine
Given IT or IV
Other Names:
  • .beta.-Cytosine arabinoside
  • 1-.beta.-D-Arabinofuranosyl-4-amino-2(1H)pyrimidinone
  • 1-.beta.-D-Arabinofuranosylcytosine
  • 1-Beta-D-arabinofuranosyl-4-amino-2(1H)pyrimidinone
  • 1-Beta-D-arabinofuranosylcytosine
  • 1.beta.-D-Arabinofuranosylcytosine
  • 2(1H)-Pyrimidinone, 4-Amino-1-beta-D-arabinofuranosyl-
  • 2(1H)-Pyrimidinone, 4-amino-1.beta.-D-arabinofuranosyl-
  • Alexan
  • Ara-C
  • ARA-cell
  • Arabine
  • Arabinofuranosylcytosine
  • Arabinosylcytosine
  • Aracytidine
  • Aracytin
  • Aracytine
  • Beta-Cytosine Arabinoside
  • CHX-3311
  • Cytarabinum
  • Cytarbel
  • Cytosar
  • Cytosine Arabinoside
  • Cytosine-.beta.-arabinoside
  • Cytosine-beta-arabinoside
  • Erpalfa
  • Starasid
  • Tarabine PFS
  • U 19920
  • U-19920
  • Udicil
  • WR-28453
Drug: Arsenic Trioxide
Given IV
Other Names:
  • ATO
  • Arsenic (III) Oxide
  • Arsenic Sesquioxide
  • Arsenous Acid Anhydride
  • Trisenox
  • Arsenous Acid
  • Arsenous Oxide
  • White Arsenic
Drug: Idarubicin
Given IV
Other Names:
  • 4-Demethoxydaunomycin
  • 4-DMDR
  • 4-Demethoxydaunorubicin
Drug: Mercaptopurine
Given orally
Other Names:
  • 6-MP
  • Purinethol
  • 3H-Purine-6-thiol
  • 6 MP
  • 6 Thiohypoxanthine
  • 6 Thiopurine
  • 6-Mercaptopurine
  • 6-Mercaptopurine Monohydrate
  • 6-Purinethiol
  • 6-Thiopurine
  • 6-Thioxopurine
  • 6H-Purine-6-thione, 1,7-dihydro- (9CI)
  • 7-Mercapto-1,3,4,6-tetrazaindene
  • Alti-Mercaptopurine
  • Azathiopurine
  • Bw 57-323H
  • Flocofil
  • Ismipur
  • Leukerin
  • Leupurin
  • Mercaleukim
  • Mercaleukin
  • Mercaptina
  • Mercaptopurinum
  • Mercapurin
  • Mern
  • NCI-C04886
  • Puri-Nethol
  • Purimethol
  • Purine, 6-mercapto-
  • Purine-6-thiol (8CI)
  • Purine-6-thiol, monohydrate
  • Purinethiol
  • U-4748
  • WR-2785
Drug: Methotrexate
Given orally
Other Names:
  • Abitrexate
  • Folex
  • Mexate
  • MTX
  • Alpha-Methopterin
  • Amethopterin
  • Brimexate
  • CL 14377
  • CL-14377
  • Emtexate
  • Emthexat
  • Emthexate
  • Farmitrexat
  • Fauldexato
  • Folex PFS
  • Lantarel
  • Ledertrexate
  • Lumexon
  • Maxtrex
  • Medsatrexate
  • Metex
  • Methoblastin
  • Methotrexate LPF
  • Methotrexate Methylaminopterin
  • Methotrexatum
  • Metotrexato
  • Metrotex
  • Mexate-AQ
  • Novatrex
  • Rheumatrex
  • Texate
  • Tremetex
  • Trexeron
  • Trixilem
  • WR-19039
Drug: Tretinoin
Given orally
Other Names:
  • Vesanoid
  • ATRA
  • Renova
  • Retin-A
  • Airol
  • Avita
  • Stieva-A
  • 2,4,6,8-Nonatetraenoic acid, 3, 7-dimethyl-9-(2,6,6-trimethyl-1-cyclohexen-1-yl)-, (all-E)-
  • Aberel
  • Aknoten
  • all trans-Retinoic acid
  • All-trans Retinoic Acid
  • All-trans Vitamin A Acid
  • all-trans-Retinoic acid
  • all-trans-Vitamin A acid
  • beta-Retinoic Acid
  • Cordes Vas
  • Dermairol
  • Epi-Aberel
  • Eudyna
  • Retin-A MICRO
  • Retin-A-Micro
  • Retinoic Acid
  • Retisol-A
  • Ro 5488
  • Stieva-A Forte
  • Trans Retinoic Acid
  • Trans Vitamin A Acid
  • trans-Retinoic Acid
  • Tretinoinum
  • Vitamin A Acid
  • Vitamin A acid, all-trans-
  • Vitinoin
EXPERIMENTAL: Arm II (high risk, combination chemotherapy)
See Detailed Description.
Drug: Mitoxantrone Hydrochloride
Given IV
Other Names:
  • CL 232315
  • DHAD
  • DHAQ
  • Dihydroxyanthracenedione Dihydrochloride
  • Mitoxantrone Dihydrochloride
  • Mitoxantroni Hydrochloridum
  • Mitozantrone Hydrochloride
  • Mitroxone
  • Neotalem
  • Novantrone
  • Onkotrone
  • Pralifan
Other: Diagnostic Laboratory Biomarker Analysis
Correlative studies
Drug: Cytarabine
Given IT or IV
Other Names:
  • .beta.-Cytosine arabinoside
  • 1-.beta.-D-Arabinofuranosyl-4-amino-2(1H)pyrimidinone
  • 1-.beta.-D-Arabinofuranosylcytosine
  • 1-Beta-D-arabinofuranosyl-4-amino-2(1H)pyrimidinone
  • 1-Beta-D-arabinofuranosylcytosine
  • 1.beta.-D-Arabinofuranosylcytosine
  • 2(1H)-Pyrimidinone, 4-Amino-1-beta-D-arabinofuranosyl-
  • 2(1H)-Pyrimidinone, 4-amino-1.beta.-D-arabinofuranosyl-
  • Alexan
  • Ara-C
  • ARA-cell
  • Arabine
  • Arabinofuranosylcytosine
  • Arabinosylcytosine
  • Aracytidine
  • Aracytin
  • Aracytine
  • Beta-Cytosine Arabinoside
  • CHX-3311
  • Cytarabinum
  • Cytarbel
  • Cytosar
  • Cytosine Arabinoside
  • Cytosine-.beta.-arabinoside
  • Cytosine-beta-arabinoside
  • Erpalfa
  • Starasid
  • Tarabine PFS
  • U 19920
  • U-19920
  • Udicil
  • WR-28453
Drug: Arsenic Trioxide
Given IV
Other Names:
  • ATO
  • Arsenic (III) Oxide
  • Arsenic Sesquioxide
  • Arsenous Acid Anhydride
  • Trisenox
  • Arsenous Acid
  • Arsenous Oxide
  • White Arsenic
Drug: Idarubicin
Given IV
Other Names:
  • 4-Demethoxydaunomycin
  • 4-DMDR
  • 4-Demethoxydaunorubicin
Drug: Mercaptopurine
Given orally
Other Names:
  • 6-MP
  • Purinethol
  • 3H-Purine-6-thiol
  • 6 MP
  • 6 Thiohypoxanthine
  • 6 Thiopurine
  • 6-Mercaptopurine
  • 6-Mercaptopurine Monohydrate
  • 6-Purinethiol
  • 6-Thiopurine
  • 6-Thioxopurine
  • 6H-Purine-6-thione, 1,7-dihydro- (9CI)
  • 7-Mercapto-1,3,4,6-tetrazaindene
  • Alti-Mercaptopurine
  • Azathiopurine
  • Bw 57-323H
  • Flocofil
  • Ismipur
  • Leukerin
  • Leupurin
  • Mercaleukim
  • Mercaleukin
  • Mercaptina
  • Mercaptopurinum
  • Mercapurin
  • Mern
  • NCI-C04886
  • Puri-Nethol
  • Purimethol
  • Purine, 6-mercapto-
  • Purine-6-thiol (8CI)
  • Purine-6-thiol, monohydrate
  • Purinethiol
  • U-4748
  • WR-2785
Drug: Methotrexate
Given orally
Other Names:
  • Abitrexate
  • Folex
  • Mexate
  • MTX
  • Alpha-Methopterin
  • Amethopterin
  • Brimexate
  • CL 14377
  • CL-14377
  • Emtexate
  • Emthexat
  • Emthexate
  • Farmitrexat
  • Fauldexato
  • Folex PFS
  • Lantarel
  • Ledertrexate
  • Lumexon
  • Maxtrex
  • Medsatrexate
  • Metex
  • Methoblastin
  • Methotrexate LPF
  • Methotrexate Methylaminopterin
  • Methotrexatum
  • Metotrexato
  • Metrotex
  • Mexate-AQ
  • Novatrex
  • Rheumatrex
  • Texate
  • Tremetex
  • Trexeron
  • Trixilem
  • WR-19039
Drug: Tretinoin
Given orally
Other Names:
  • Vesanoid
  • ATRA
  • Renova
  • Retin-A
  • Airol
  • Avita
  • Stieva-A
  • 2,4,6,8-Nonatetraenoic acid, 3, 7-dimethyl-9-(2,6,6-trimethyl-1-cyclohexen-1-yl)-, (all-E)-
  • Aberel
  • Aknoten
  • all trans-Retinoic acid
  • All-trans Retinoic Acid
  • All-trans Vitamin A Acid
  • all-trans-Retinoic acid
  • all-trans-Vitamin A acid
  • beta-Retinoic Acid
  • Cordes Vas
  • Dermairol
  • Epi-Aberel
  • Eudyna
  • Retin-A MICRO
  • Retin-A-Micro
  • Retinoic Acid
  • Retisol-A
  • Ro 5488
  • Stieva-A Forte
  • Trans Retinoic Acid
  • Trans Vitamin A Acid
  • trans-Retinoic Acid
  • Tretinoinum
  • Vitamin A Acid
  • Vitamin A acid, all-trans-
  • Vitinoin

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Event-free Survival (EFS)
Time Frame: At 3 years from study entry
EFS - time from study entry until failure to achieve complete remission during consolidation, relapse, or death. For further clarification see definitions provided in the protocol.
At 3 years from study entry

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Hematologic Remission Rate
Time Frame: End of consolidation, course 1: up to 5 months
Proportion of patients in hematologic remission at end of consolidation, course 1 are reported.
End of consolidation, course 1: up to 5 months
Hematologic, Molecular, and Cytogenetic Remission Rate
Time Frame: End of consolidation, course 3; up to 7 months (for Standard Risk) or end of consolidation, course 4; up to 9 months (for High Risk)
Proportion of patients in hematologic, molecular, and cytogenetic remission at end of consolidation, course 3 and 4 are reported. Patients were determined to be in remission by all three criteria.
End of consolidation, course 3; up to 7 months (for Standard Risk) or end of consolidation, course 4; up to 9 months (for High Risk)
Overall Survival (OS)
Time Frame: At 3 years from study entry
OS - time from study entry to death.
At 3 years from study entry

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Children's Oncology Group

Collaborators

National Cancer Institute (NCI)

Investigators

  • Principal Investigator: John J Gregory, Children's Oncology Group

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ACTUAL)

March 9, 2009

Primary Completion (ACTUAL)

June 30, 2015

Study Completion (ACTUAL)

September 30, 2022

Study Registration Dates

First Submitted

March 20, 2009

First Submitted That Met QC Criteria

March 20, 2009

First Posted (ESTIMATE)

March 23, 2009

Study Record Updates

Last Update Posted (ACTUAL)

October 25, 2022

Last Update Submitted That Met QC Criteria

October 3, 2022

Last Verified

October 1, 2022

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • AAML0631 (OTHER: CTEP)
  • U10CA098543 (U.S. NIH Grant/Contract)
  • NCI-2011-01904 (REGISTRY: CTRP (Clinical Trial Reporting Program))
  • CDR0000637184

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.

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