NCT00002798

Brief Summary

Randomized phase III trial to compare the effectiveness of different chemotherapy regimens with or without bone marrow transplantation in treating children who have acute myelogenous leukemia or myelodysplastic syndrome. Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Combining chemotherapy with bone marrow transplantation may allow the doctor to give higher doses of chemotherapy drugs and kill more cancer cells. It is not yet known which treatment regimen is more effective for acute myelogenous leukemia or myelodysplastic syndrome

Trial Health

80
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
880

participants targeted

Target at P75+ for phase_3

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

August 1, 1996

Completed
4.3 years until next milestone

First Submitted

Initial submission to the registry

November 24, 2000

Completed
2.2 years until next milestone

First Posted

Study publicly available on registry

January 27, 2003

Completed
3.6 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

September 1, 2006

Completed
Last Updated

January 16, 2013

Status Verified

January 1, 2013

Enrollment Period

10.1 years

First QC Date

November 24, 2000

Last Update Submit

January 15, 2013

Conditions

Outcome Measures

Primary Outcomes (11)

  • Proportions of patients achieving remission rate during induction therapy

    Up to 42 days

  • Proportion of patients dying or with residual disease during induction therapy

    Up to 42 days

  • Time to marrow recovery (induction phase)

    Up to 42 days

  • Frequency of toxicities, including infectious complications (induction phase)

    Up to 42 days

  • Marrow status

    At 14 days

  • Percent of blasts

    At the end of induction therapy

  • Complete remission at the end of consolidation therapy

    Up to 5 years

  • Survival following consolidation

    Up to 5 years

  • Event-free survival following consolidation

    Up to 5 years

  • Overall survival (intensification)

    Up to 5 years

  • EFS (intensification)

    Up to 5 years

Study Arms (5)

Arm I (combination chemotherapy)

EXPERIMENTAL

Patients receive treatment as in induction therapy, plus G-CSF SC beginning on day 16 and continuing until blood counts recover. If CSF is clear by day 10 of induction, patients receive cytarabine IT on days 0, 10, and 35. If CSF is not clear, patients receive triple intrathecal therapy (TIT; cytarabine, hydrocortisone, methotrexate) on days 0 and 10. See Detailed Description

Drug: daunorubicin hydrochlorideDrug: therapeutic hydrocortisoneProcedure: allogeneic bone marrow transplantationBiological: filgrastimDrug: cytarabineDrug: idarubicinDrug: dexamethasoneDrug: thioguanineDrug: etoposideDrug: methotrexate

Arm II (combination chemotherapy)

EXPERIMENTAL

Patients receive fludarabine IV over 24 hours on days 0 and 1, cytarabine IV over 72 hours on days 2-4, and idarubicin IV over 15 minutes on days 0-2. G-CSF begins on day 6 and continues until blood counts recover. Patients also receive TIT on days -1 and 7, if CSF is not clear on day 10 of induction. Patients on both arms are reassessed on day 35. Those patients with M1 marrow proceed to intensification; all others are removed from the study. Intensification: See Detailed Description

Drug: asparaginaseDrug: fludarabine phosphateDrug: therapeutic hydrocortisoneProcedure: allogeneic bone marrow transplantationBiological: filgrastimDrug: cytarabineDrug: idarubicinDrug: thioguanineDrug: methotrexateDrug: cyclophosphamideDrug: busulfan

Arm III (combination chemotherapy, aldesleukin)

EXPERIMENTAL

Patients receive interleukin-2 IV continuously on days 1-4 and 9-18.

Drug: daunorubicin hydrochlorideBiological: filgrastimDrug: cytarabineDrug: idarubicinDrug: dexamethasoneDrug: thioguanineDrug: etoposideBiological: aldesleukin

Arm IV (combination chemotherapy)

ACTIVE COMPARATOR

No further treatment

Drug: daunorubicin hydrochlorideBiological: filgrastimDrug: cytarabineDrug: idarubicinDrug: dexamethasoneDrug: thioguanineDrug: etoposide

Arm V (combination chemotherapy, radiotherapy)

EXPERIMENTAL

Patients undergo radiotherapy to the chloroma 5 days a week for 2 weeks.

Drug: daunorubicin hydrochlorideRadiation: 3-dimensional conformal radiation therapyBiological: filgrastimDrug: cytarabineDrug: idarubicinDrug: dexamethasoneDrug: thioguanineDrug: etoposide

Interventions

Also known as: ASNase, Colaspase, Crasnitin, Elspar, L-ASP
Arm II (combination chemotherapy)
Also known as: Cerubidin, Cerubidine, daunomycin hydrochloride, daunorubicin, RP-13057
Arm I (combination chemotherapy)Arm III (combination chemotherapy, aldesleukin)Arm IV (combination chemotherapy)Arm V (combination chemotherapy, radiotherapy)
Also known as: 2-F-ara-AMP, Beneflur, Fludara
Arm II (combination chemotherapy)
Also known as: Aeroseb-HC, Barseb HC, Cetacort, Cort-Dome, Cortef
Arm I (combination chemotherapy)Arm II (combination chemotherapy)
Also known as: bone marrow therapy, allogeneic, bone marrow therapy, allogenic, transplantation, allogeneic bone marrow, transplantation, allogenic bone marrow
Arm I (combination chemotherapy)Arm II (combination chemotherapy)
Also known as: 3D conformal radiation therapy, 3D-CRT
Arm V (combination chemotherapy, radiotherapy)
filgrastimBIOLOGICAL

Given SC

Also known as: G-CSF, Neupogen
Arm I (combination chemotherapy)Arm II (combination chemotherapy)Arm III (combination chemotherapy, aldesleukin)Arm IV (combination chemotherapy)Arm V (combination chemotherapy, radiotherapy)

Given IV or IT

Also known as: ARA-C, arabinofuranosylcytosine, arabinosylcytosine, Cytosar-U, cytosine arabinoside
Arm I (combination chemotherapy)Arm II (combination chemotherapy)Arm III (combination chemotherapy, aldesleukin)Arm IV (combination chemotherapy)Arm V (combination chemotherapy, radiotherapy)

Given IV

Also known as: 4-demethoxydaunorubicin, 4-DMDR, DMDR, IDA
Arm I (combination chemotherapy)Arm II (combination chemotherapy)Arm III (combination chemotherapy, aldesleukin)Arm IV (combination chemotherapy)Arm V (combination chemotherapy, radiotherapy)

Given PO

Also known as: Aeroseb-Dex, Decaderm, Decadron, DM, DXM
Arm I (combination chemotherapy)Arm III (combination chemotherapy, aldesleukin)Arm IV (combination chemotherapy)Arm V (combination chemotherapy, radiotherapy)

Given PO

Also known as: 6-TG
Arm I (combination chemotherapy)Arm II (combination chemotherapy)Arm III (combination chemotherapy, aldesleukin)Arm IV (combination chemotherapy)Arm V (combination chemotherapy, radiotherapy)

Given IV

Also known as: EPEG, VP-16, VP-16-213
Arm I (combination chemotherapy)Arm III (combination chemotherapy, aldesleukin)Arm IV (combination chemotherapy)Arm V (combination chemotherapy, radiotherapy)

Given IT

Also known as: amethopterin, Folex, methylaminopterin, Mexate, MTX
Arm I (combination chemotherapy)Arm II (combination chemotherapy)

Given IV

Also known as: CPM, CTX, Cytoxan, Endoxan, Endoxana
Arm II (combination chemotherapy)
aldesleukinBIOLOGICAL
Also known as: IL-2, Proleukin, recombinant human interleukin-2, recombinant interleukin-2
Arm III (combination chemotherapy, aldesleukin)
Also known as: BSF, BU, Misulfan, Mitosan, Myeloleukon
Arm II (combination chemotherapy)

Eligibility Criteria

AgeUp to 21 Years
Sexall
Healthy VolunteersNo
Age GroupsChild (0-17), Adult (18-64)

You may qualify if:

  • Histologically confirmed previously untreated acute myeloid leukemia (AML) in patients 1 month to 21 years of age
  • Infants under 1 month with progressive disease eligible
  • Supportive care may be given to confirm that the leukemia is not regressing prior to entry
  • No acute promyelocytic leukemia (FAB M3)
  • No acute undifferentiated leukemia (FAB M0)
  • Histochemical verification of AML required by the following stains:
  • Wright or Giemsa
  • Peroxidase
  • PAS
  • Chloroacetate esterase
  • Sudan black
  • Nonspecific esterase (NSE) with and without fluoride (NaF) inhibition
  • Combined NSE/NaF and butyrate inhibition or diagnosis of megakaryoblasticleukemia (FAB M7) should be supported by one of the following:
  • CD41 reactivity
  • Glycoprotein 1b reactivity
  • +21 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Children's Oncology Group

Arcadia, California, 91006-3776, United States

Location

Related Publications (5)

  • Tarlock K, Gerbing RB, Ries RE, Smith JL, Leonti A, Huang BJ, Kirkey D, Robinson L, Peplinski JH, Lange B, Cooper TM, Gamis AS, Kolb EA, Aplenc R, Pollard JA, Alonzo TA, Meshinchi S. Prognostic impact of cooccurring mutations in FLT3-ITD pediatric acute myeloid leukemia. Blood Adv. 2024 May 14;8(9):2094-2103. doi: 10.1182/bloodadvances.2023011980.

  • Bertrums EJM, Smith JL, Harmon L, Ries RE, Wang YJ, Alonzo TA, Menssen AJ, Chisholm KM, Leonti AR, Tarlock K, Ostronoff F, Pogosova-Agadjanyan EL, Kaspers GJL, Hasle H, Dworzak M, Walter C, Muhlegger N, Morerio C, Pardo L, Hirsch B, Raimondi S, Cooper TM, Aplenc R, Gamis AS, Kolb EA, Farrar JE, Stirewalt D, Ma X, Shaw TI, Furlan SN, Brodersen LE, Loken MR, Van den Heuvel-Eibrink MM, Zwaan CM, Triche TJ, Goemans BF, Meshinchi S. Comprehensive molecular and clinical characterization of NUP98 fusions in pediatric acute myeloid leukemia. Haematologica. 2023 Aug 1;108(8):2044-2058. doi: 10.3324/haematol.2022.281653.

  • Ho PA, Zeng R, Alonzo TA, Gerbing RB, Miller KL, Pollard JA, Stirewalt DL, Heerema NA, Raimondi SC, Hirsch B, Franklin JL, Lange B, Meshinchi S. Prevalence and prognostic implications of WT1 mutations in pediatric acute myeloid leukemia (AML): a report from the Children's Oncology Group. Blood. 2010 Aug 5;116(5):702-10. doi: 10.1182/blood-2010-02-268953. Epub 2010 Apr 22.

  • Pollard JA, Alonzo TA, Gerbing RB, Ho PA, Zeng R, Ravindranath Y, Dahl G, Lacayo NJ, Becton D, Chang M, Weinstein HJ, Hirsch B, Raimondi SC, Heerema NA, Woods WG, Lange BJ, Hurwitz C, Arceci RJ, Radich JP, Bernstein ID, Heinrich MC, Meshinchi S. Prevalence and prognostic significance of KIT mutations in pediatric patients with core binding factor AML enrolled on serial pediatric cooperative trials for de novo AML. Blood. 2010 Mar 25;115(12):2372-9. doi: 10.1182/blood-2009-09-241075. Epub 2010 Jan 7.

  • Ho PA, Alonzo TA, Gerbing RB, Pollard J, Stirewalt DL, Hurwitz C, Heerema NA, Hirsch B, Raimondi SC, Lange B, Franklin JL, Radich JP, Meshinchi S. Prevalence and prognostic implications of CEBPA mutations in pediatric acute myeloid leukemia (AML): a report from the Children's Oncology Group. Blood. 2009 Jun 25;113(26):6558-66. doi: 10.1182/blood-2008-10-184747. Epub 2009 Mar 20.

MeSH Terms

Conditions

Leukemia, Myelomonocytic, ChronicAnemia, RefractoryAnemia, Refractory, with Excess of Blasts

Interventions

Asparaginasepalmitoyl-L-asparaginaseDaunorubicinfludarabine phosphateHydrocortisoneTransplantationRadiotherapy, ConformalFilgrastimGranulocyte Colony-Stimulating FactorCytarabineIdarubicinDexamethasoneCalcium DobesilateThioguanineEtoposideMethotrexatemerphosCyclophosphamidealdesleukinInterleukin-2Busulfan

Condition Hierarchy (Ancestors)

Leukemia, MyeloidLeukemiaNeoplasms by Histologic TypeNeoplasmsMyelodysplastic-Myeloproliferative DiseasesBone Marrow DiseasesHematologic DiseasesHemic and Lymphatic DiseasesChronic DiseaseDisease AttributesPathologic ProcessesPathological Conditions, Signs and SymptomsAnemiaMyelodysplastic Syndromes

Intervention Hierarchy (Ancestors)

AmidohydrolasesHydrolasesEnzymesEnzymes and CoenzymesAnthracyclinesNaphthacenesPolycyclic Aromatic HydrocarbonsHydrocarbons, AromaticHydrocarbons, CyclicHydrocarbonsOrganic ChemicalsPolycyclic CompoundsAminoglycosidesGlycosidesCarbohydratesPregnenedionesPregnenesPregnanesSteroidsFused-Ring Compounds11-HydroxycorticosteroidsHydroxycorticosteroidsAdrenal Cortex HormonesHormonesHormones, Hormone Substitutes, and Hormone Antagonists17-HydroxycorticosteroidsSurgical Procedures, OperativeRadiotherapy, Computer-AssistedRadiotherapyTherapeuticsColony-Stimulating FactorsGlycoproteinsGlycoconjugatesHematopoietic Cell Growth FactorsCytokinesIntercellular Signaling Peptides and ProteinsPeptidesAmino Acids, Peptides, and ProteinsProteinsBiological FactorsCytidinePyrimidine NucleosidesPyrimidinesHeterocyclic Compounds, 1-RingHeterocyclic CompoundsArabinonucleosidesNucleosidesNucleic Acids, Nucleotides, and NucleosidesPregnadienetriolsPregnadienesSteroids, FluorinatedBenzenesulfonatesBenzene DerivativesArylsulfonatesArylsulfonic AcidsSulfonic AcidsSulfur AcidsSulfur CompoundsPurinesHeterocyclic Compounds, 2-RingHeterocyclic Compounds, Fused-RingPodophyllotoxinTetrahydronaphthalenesNaphthalenesGlucosidesAminopterinPterinsPteridinesPhosphoramide MustardsNitrogen Mustard CompoundsMustard CompoundsHydrocarbons, HalogenatedPhosphoramidesOrganophosphorus CompoundsInterleukinsLymphokinesButylene GlycolsGlycolsAlcoholsMesylatesAlkanesulfonatesAlkanesulfonic AcidsAlkanesHydrocarbons, Acyclic

Study Officials

  • Beverly Lange

    Children's Oncology Group

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 3
Allocation
RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
NIH
Responsible Party
SPONSOR

Study Record Dates

First Submitted

November 24, 2000

First Posted

January 27, 2003

Study Start

August 1, 1996

Primary Completion

September 1, 2006

Last Updated

January 16, 2013

Record last verified: 2013-01

Locations