NCT00136084

Brief Summary

The purpose of this study is to compare the effectiveness of two multi-agent chemotherapy regimens using different dosages of cytarabine to eliminate all detectable leukemia.

Trial Health

87
On Track

Trial Health Score

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

Enrollment
238

participants targeted

Target at P50-P75 for phase_3

Timeline
Completed

Started Aug 2002

Longer than P75 for phase_3

Geographic Reach
1 country

8 active sites

Status
completed

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

Trial Relationships

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Study Timeline

Key milestones and dates

Study Start

First participant enrolled

August 1, 2002

Completed
3.1 years until next milestone

First Submitted

Initial submission to the registry

August 24, 2005

Completed
2 days until next milestone

First Posted

Study publicly available on registry

August 26, 2005

Completed
2.8 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

July 1, 2008

Completed
1.7 years until next milestone

Results Posted

Study results publicly available

March 26, 2010

Completed
2.2 years until next milestone

Study Completion

Last participant's last visit for all outcomes

June 1, 2012

Completed
Last Updated

December 5, 2012

Status Verified

November 1, 2012

Enrollment Period

5.9 years

First QC Date

August 24, 2005

Results QC Date

March 5, 2010

Last Update Submit

November 2, 2012

Conditions

Keywords

Leukemia,Erythroblastic, AcuteErythroblastic Leukemia, AcuteLeukemia, Myeloid, AcuteMyeloid Leukemia, Acute

Outcome Measures

Primary Outcomes (1)

  • Minimal Residual Disease (MRD).

    Detection of Minimal Residual Disease following one course of chemotherapy where positive MRD was defined as one or more leukemic cell per 1000 mononuclear bone-marrow cells (\>=0.1%).

    Day 22 MRD measurement

Secondary Outcomes (6)

  • Proportion of Minimal Residual Disease (MRD)+ Patients Who Become MRD- After One Course of Gemtuzumab Ozogamicin (GO)

    Consolidation I

  • Proportion of MRD Reduction After One Course of Cytarabine + Daunomycin + Etoposide (ADE) + GO

    Induction II

  • Proportion of Patients Experienced Toxicity of Cytarabine + Daunomycin + Etoposide (ADE) + GO.

    Induction II

  • To Estimate the Overall Event-free Survival (EFS) of AML Patients Who Undergo Risk-adapted and Genotype-directed Therapy

    Five Year

  • To Assess Whether Inhibition of DNA Synthesis is Greater After High-dose Ara-C (HDAC) Than After Low-dose Ara-C (LDAC) Therapy

    Measurements were assessed in Induction I chemotherapy

  • +1 more secondary outcomes

Study Arms (2)

HDAC (High-Dose Cytarabine)

EXPERIMENTAL

Since limited characters are allowed in this passage, please see detailed Description for HDAC.

Drug: Cladribine, Cyclophosphamide, Cytarabine, Daunorubicin, Dexamethasone

LDAC (Low-Dose Cytarabine)

EXPERIMENTAL

Since limited characters are allowed in this passage, please see detailed Description for LDAC.

Drug: Etoposide, Cytarabine, Gemtuzumab, L-asparaginase, Mercaptopurine, methotrexate, Mitoxantrone, Prednisone, Vincristine

Interventions

Since limited characters are allowed in this passage, please see detailed Description to know the dosage, dosage form, frequency of administration for the above mentioned drugs

HDAC (High-Dose Cytarabine)

Since limited characters are allowed in this passage, please see detailed Description to know the dosage, dosage form, frequency of administration for the above mentioned drugs

LDAC (Low-Dose Cytarabine)

Eligibility Criteria

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

You may qualify if:

  • Diagnosis of acute myeloid leukemia by immunophenotyping, morphology, and cytochemical staining; myelodysplasia; or biphenotypic leukemia.
  • Age less than or equal to 21 years at time of study entry.
  • No prior therapy for this malignancy (patients with secondary AML following treatment of primary malignancy are eligible) except for one dose of intrathecal therapy.
  • Negative pregnancy test
  • Patient does not have Down syndrome, acute promyelocytic leukemia (APL), or juvenile myelomonocytic leukemia (JMML)

You may not qualify if:

  • Positive pregnancy test
  • Down syndrome, acute promyelocytic leukemia (APL), or juvenile myelomonocytic leukemia (JMML)

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (8)

Stanford University Medical Center

Palo Alto, California, 94304, United States

Location

Dana-Farber Cancer Institute

Boston, Massachusetts, 02115, United States

Location

Children's Hospital of Michigan (Wayne State University)

Detroit, Michigan, 48201, United States

Location

St. Jude Children's Research Hospital

Memphis, Tennessee, 38105, United States

Location

Cook Children's Medical Center

Fort Worth, Texas, 76104, United States

Location

MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Texas Children's Cancer Center

Houston, Texas, 77030, United States

Location

Seattle Children's Hospital

Seattle, Washington, 98105, United States

Location

Related Publications (3)

  • Elsayed AH, Rafiee R, Cao X, Raimondi S, Downing JR, Ribeiro R, Fan Y, Gruber TA, Baker S, Klco J, Rubnitz JE, Pounds S, Lamba JK. A six-gene leukemic stem cell score identifies high risk pediatric acute myeloid leukemia. Leukemia. 2020 Mar;34(3):735-745. doi: 10.1038/s41375-019-0604-8. Epub 2019 Oct 23.

  • Gamazon ER, Lamba JK, Pounds S, Stark AL, Wheeler HE, Cao X, Im HK, Mitra AK, Rubnitz JE, Ribeiro RC, Raimondi S, Campana D, Crews KR, Wong SS, Welsh M, Hulur I, Gorsic L, Hartford CM, Zhang W, Cox NJ, Dolan ME. Comprehensive genetic analysis of cytarabine sensitivity in a cell-based model identifies polymorphisms associated with outcome in AML patients. Blood. 2013 May 23;121(21):4366-76. doi: 10.1182/blood-2012-10-464149. Epub 2013 Mar 28.

  • Rubnitz JE, Inaba H, Dahl G, Ribeiro RC, Bowman WP, Taub J, Pounds S, Razzouk BI, Lacayo NJ, Cao X, Meshinchi S, Degar B, Airewele G, Raimondi SC, Onciu M, Coustan-Smith E, Downing JR, Leung W, Pui CH, Campana D. Minimal residual disease-directed therapy for childhood acute myeloid leukaemia: results of the AML02 multicentre trial. Lancet Oncol. 2010 Jun;11(6):543-52. doi: 10.1016/S1470-2045(10)70090-5. Epub 2010 May 5.

Related Links

MeSH Terms

Conditions

Leukemia, Myeloid, AcuteLeukemia, Erythroblastic, Acute

Interventions

CladribineCyclophosphamideCytarabineDaunorubicinDexamethasoneEtoposideGemtuzumabAsparaginaseMercaptopurineMethotrexateMitoxantronePrednisoneVincristine

Condition Hierarchy (Ancestors)

Leukemia, MyeloidLeukemiaNeoplasms by Histologic TypeNeoplasmsHematologic DiseasesHemic and Lymphatic DiseasesMyeloproliferative DisordersBone Marrow Diseases

Intervention Hierarchy (Ancestors)

2-ChloroadenosineAdenosinePurine NucleosidesPurinesHeterocyclic Compounds, 2-RingHeterocyclic Compounds, Fused-RingHeterocyclic CompoundsDeoxyadenosinesDeoxyribonucleosidesNucleosidesNucleic Acids, Nucleotides, and NucleosidesRibonucleosidesPhosphoramide MustardsNitrogen Mustard CompoundsMustard CompoundsHydrocarbons, HalogenatedHydrocarbonsOrganic ChemicalsPhosphoramidesOrganophosphorus CompoundsCytidinePyrimidine NucleosidesPyrimidinesHeterocyclic Compounds, 1-RingArabinonucleosidesAnthracyclinesNaphthacenesPolycyclic Aromatic HydrocarbonsHydrocarbons, AromaticHydrocarbons, CyclicPolycyclic CompoundsAminoglycosidesGlycosidesCarbohydratesPregnadienetriolsPregnadienesPregnanesSteroidsFused-Ring CompoundsSteroids, FluorinatedPodophyllotoxinTetrahydronaphthalenesNaphthalenesGlucosidesCalicheamicinsAntibodies, Monoclonal, HumanizedAntibodies, MonoclonalAntibodiesImmunoglobulinsImmunoproteinsBlood ProteinsProteinsAmino Acids, Peptides, and ProteinsSerum GlobulinsGlobulinsAmidohydrolasesHydrolasesEnzymesEnzymes and CoenzymesSulfhydryl CompoundsSulfur CompoundsAminopterinPterinsPteridinesAnthraquinonesAnthronesAnthracenesQuinonesPregnadienediolsVinca AlkaloidsSecologanin Tryptamine AlkaloidsIndole AlkaloidsAlkaloidsIndolesIndolizidinesIndolizines

Results Point of Contact

Title
Jeffrey Rubnitz, M.D
Organization
St. Jude Children's Research Hospital

Study Officials

  • Jeffrey Rubnitz, M.D., PhD

    St. Jude Children's Research Hospital

    PRINCIPAL INVESTIGATOR

Publication Agreements

PI is Sponsor Employee
Yes

Study Design

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

Study Record Dates

First Submitted

August 24, 2005

First Posted

August 26, 2005

Study Start

August 1, 2002

Primary Completion

July 1, 2008

Study Completion

June 1, 2012

Last Updated

December 5, 2012

Results First Posted

March 26, 2010

Record last verified: 2012-11

Locations