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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT00070174




Registration number
NCT00070174
Ethics application status
Date submitted
3/10/2003
Date registered
7/10/2003
Date last updated
20/02/2014

Titles & IDs
Public title
Gemtuzumab Ozogamicin in Treating Young Patients With Newly Diagnosed Acute Myeloid Leukemia Undergoing Remission Induction and Intensification Therapy
Scientific title
Treatment of Newly Diagnosed Childhood Acute Myeloid Leukemia (AML) Using Intensive MRC-Based Therapy and Gemtuzumab Ozogamicin (GMTZ): A COG Pilot Study
Secondary ID [1] 0 0
CDR0000330133
Secondary ID [2] 0 0
AAML03P1
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Leukemia 0 0
Condition category
Condition code
Cancer 0 0 0 0
Leukaemia - Acute leukaemia
Cancer 0 0 0 0
Leukaemia - Chronic leukaemia
Cancer 0 0 0 0
Children's - Leukaemia & Lymphoma

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - asparaginase
Treatment: Drugs - busulfan
Treatment: Drugs - cyclophosphamide
Treatment: Drugs - cyclosporine
Treatment: Drugs - cytarabine
Treatment: Drugs - daunorubicin hydrochloride
Treatment: Drugs - etoposide
Treatment: Drugs - gemtuzumab ozogamicin
Treatment: Drugs - methotrexate
Treatment: Drugs - mitoxantrone hydrochloride
Treatment: Surgery - allogeneic bone marrow transplantation

Treatment: Drugs: asparaginase


Treatment: Drugs: busulfan


Treatment: Drugs: cyclophosphamide


Treatment: Drugs: cyclosporine


Treatment: Drugs: cytarabine


Treatment: Drugs: daunorubicin hydrochloride


Treatment: Drugs: etoposide


Treatment: Drugs: gemtuzumab ozogamicin


Treatment: Drugs: methotrexate


Treatment: Drugs: mitoxantrone hydrochloride


Treatment: Surgery: allogeneic bone marrow transplantation
Intervention code [1] 0 0
Treatment: Drugs
Intervention code [2] 0 0
Treatment: Surgery
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Safety
Timepoint [1] 0 0
Primary outcome [2] 0 0
Complete remission rate
Timepoint [2] 0 0
Secondary outcome [1] 0 0
Feasibility
Timepoint [1] 0 0
Secondary outcome [2] 0 0
Effect of karyotypic abnormalities
Timepoint [2] 0 0

Eligibility
Key inclusion criteria
DISEASE CHARACTERISTICS:

- Newly diagnosed primary acute myeloid leukemia (AML)

- At least 20% bone marrow blasts

- Meets the customary FAB criteria for AML

- Patients with cytopenias and bone marrow blasts who do not meet the FAB
criteria are eligible provided they have a karyotypic abnormality
characteristic of de novo AML (e.g., t[8;21], inv16, or t[16;16]) OR they
have the unequivocal presence of megakaryoblasts

- Isolated granulocytic sarcoma (myeloblastoma) allowed regardless of the results
outlined above

- Previously untreated disease

- No promyelocytic leukemia (FAB M3)

- No documented myelodysplastic syndromes (preleukemia) (e.g., chronic myelomonocytic
leukemia, refractory anemia [RA], RA with excess blasts, or RA with ringed
sideroblasts)

- No juvenile myelomonocytic leukemia

- No Fanconi's anemia, Kostmann syndrome, Shwachman syndrome, or any other known bone
marrow failure syndrome

- No Down syndrome

PATIENT CHARACTERISTICS:

Age

- 1 month to 21 years* NOTE: *Children under 1 month of age who have progressive disease
are allowed

Performance status

- Karnofsky 50-100% (over 16 years of age) OR

- Lansky 50-100% (ages 1 to 16)* NOTE: Children under 1 year of age do not require a
performance status

Life expectancy

- Not specified

Hematopoietic

- Not specified

Hepatic

- No inadequate liver function

Renal

- No inadequate renal function

- No hyperuricemia (greater than 8.0 mg/dL)

- Creatinine clearance or radioisotope glomerular filtration rate (GFR) at least 70
mL/min OR an equivalent normal GFR OR

- Creatinine no greater than 1.5 times normal

Cardiovascular

- Shortening fraction at least 27% by echocardiogram OR

- Ejection fraction at least 50% by MUGA

Pulmonary

- No proven or suspected pneumonia

Other

- Not pregnant or nursing

- No proven or suspected sepsis or meningitis

PRIOR CONCURRENT THERAPY:

Biologic therapy

- Not specified

Chemotherapy

- No prior chemotherapy except intrathecal cytarabine administered that was administered
at diagnosis

Endocrine therapy

- Prior topical and inhalation steroids allowed

- No concurrent steroids as antiemetics

Radiotherapy

- No prior radiotherapy

Surgery

- Not specified

Other

- No prior antileukemic therapy

- No concurrent pressor agent or ventilatory support unless approved by the study chair

- No concurrent participation in another COG therapeutic study
Minimum age
No limit
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria

Study design
Purpose of the study
Treatment
Allocation to intervention
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
1/12/2003
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
1/12/2013
Sample size
Target
Accrual to date
Final
350
Recruitment in Australia
Recruitment state(s)
NSW,QLD,WA
Recruitment hospital [1] 0 0
Westmead Hospital - Westmead
Recruitment hospital [2] 0 0
Office of S. David Lang - Herston, Brisbane
Recruitment hospital [3] 0 0
Princess Margaret Hospital for Children - Perth
Recruitment postcode(s) [1] 0 0
2145 - Westmead
Recruitment postcode(s) [2] 0 0
4029 - Herston, Brisbane
Recruitment postcode(s) [3] 0 0
6001 - Perth
Recruitment outside Australia
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United States of America
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Alabama
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Arizona
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Arkansas
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California
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Colorado
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Connecticut
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Delaware
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District of Columbia
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Florida
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Georgia
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Hawaii
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Idaho
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Illinois
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Indiana
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Iowa
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Kansas
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Kentucky
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Maine
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Maryland
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Massachusetts
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Michigan
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Minnesota
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Mississippi
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Missouri
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Nebraska
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Nevada
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New Jersey
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New Mexico
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New York
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North Carolina
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North Dakota
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Ohio
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Oklahoma
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Oregon
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Pennsylvania
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South Carolina
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South Dakota
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Tennessee
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Texas
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Utah
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Vermont
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Washington
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West Virginia
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Wisconsin
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Alberta
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British Columbia
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Manitoba
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Newfoundland and Labrador
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Nova Scotia
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Ontario
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Quebec
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Puerto Rico
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Santurce
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Switzerland
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Chihuahua

Funding & Sponsors
Primary sponsor type
Other
Name
Children's Oncology Group
Address
Country
Other collaborator category [1] 0 0
Government body
Name [1] 0 0
National Cancer Institute (NCI)
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
RATIONALE: Giving chemotherapy before a donor bone marrow transplant helps stop the growth of
cancer cells. It also helps stop the patient's immune system from rejecting the donor's stem
cells. Also, monoclonal antibodies, such as gemtuzumab ozogamicin, can find cancer cells and
either kill them or deliver cancer-killing substances to them without harming normal cells.
When the healthy stem cells from a donor are infused into the patient they may help the
patient's bone marrow make stem cells, red blood cells, white blood cells, and platelets.

PURPOSE: This phase II trial is studying how well gemtuzumab ozogamicin works in treating
young patients who are undergoing remission induction, intensification therapy, and
allogeneic bone marrow transplant for newly diagnosed acute myeloid leukemia.
Trial website
https://clinicaltrials.gov/ct2/show/NCT00070174
Trial related presentations / publications
Pollard JA, Alonzo TA, Loken M, Gerbing RB, Ho PA, Bernstein ID, Raimondi SC, Hirsch B, Franklin J, Walter RB, Gamis A, Meshinchi S. Correlation of CD33 expression level with disease characteristics and response to gemtuzumab ozogamicin containing chemotherapy in childhood AML. Blood. 2012 Apr 19;119(16):3705-11. doi: 10.1182/blood-2011-12-398370. Epub 2012 Feb 29.
Ho PA, Kopecky KJ, Alonzo TA, Gerbing RB, Miller KL, Kuhn J, Zeng R, Ries RE, Raimondi SC, Hirsch BA, Oehler V, Hurwitz CA, Franklin JL, Gamis AS, Petersdorf SH, Anderson JE, Godwin JE, Reaman GH, Willman CL, Bernstein ID, Radich JP, Appelbaum FR, Stirewalt DL, Meshinchi S. Prognostic implications of the IDH1 synonymous SNP rs11554137 in pediatric and adult AML: a report from the Children's Oncology Group and SWOG. Blood. 2011 Oct 27;118(17):4561-6. doi: 10.1182/blood-2011-04-348888. Epub 2011 Aug 26.
Ho PA, Kuhn J, Gerbing RB, Pollard JA, Zeng R, Miller KL, Heerema NA, Raimondi SC, Hirsch BA, Franklin JL, Lange B, Gamis AS, Alonzo TA, Meshinchi S. WT1 synonymous single nucleotide polymorphism rs16754 correlates with higher mRNA expression and predicts significantly improved outcome in favorable-risk pediatric acute myeloid leukemia: a report from the children's oncology group. J Clin Oncol. 2011 Feb 20;29(6):704-11. doi: 10.1200/JCO.2010.31.9327. Epub 2010 Dec 28.
Ho PA, Alonzo TA, Kopecky KJ, Miller KL, Kuhn J, Zeng R, Gerbing RB, Raimondi SC, Hirsch BA, Oehler V, Hurwitz CA, Franklin JL, Gamis AS, Petersdorf SH, Anderson JE, Reaman GH, Baker LH, Willman CL, Bernstein ID, Radich JP, Appelbaum FR, Stirewalt DL, Meshinchi S. Molecular alterations of the IDH1 gene in AML: a Children's Oncology Group and Southwest Oncology Group study. Leukemia. 2010 May;24(5):909-13. doi: 10.1038/leu.2010.56. Epub 2010 Apr 8.
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.
Phillips CL, Gerbing R, Alonzo T, Perentesis JP, Harley IT, Meshinchi S, Bhatla D, Radloff G, Davies SM. MDM2 polymorphism increases susceptibility to childhood acute myeloid leukemia: a report from the Children's Oncology Group. Pediatr Blood Cancer. 2010 Aug;55(2):248-53. doi: 10.1002/pbc.22519.
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.
Berman JN, Gerbing RB, Alonzo TA, Ho PA, Miller K, Hurwitz C, Heerema NA, Hirsch B, Raimondi SC, Lange B, Franklin JL, Gamis A, Meshinchi S. Prevalence and clinical implications of NRAS mutations in childhood AML: a report from the Children's Oncology Group. Leukemia. 2011 Jun;25(6):1039-42. doi: 10.1038/leu.2011.31. Epub 2011 Mar 1. No abstract available.
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.
Sung L, Alonzo TA, Gerbing RB, Aplenc R, Lange BJ, Woods WG, Feusner J, Franklin J, Patterson MJ, Gamis AS; Children's Oncology Group. Respiratory syncytial virus infections in children with acute myeloid leukemia: a report from the Children's Oncology Group. Pediatr Blood Cancer. 2008 Dec;51(6):784-6. doi: 10.1002/pbc.21710.
Pollard J, Alonzo T, Gerbing R, et al.: Prevalence and prognostic significance of c-KIT mutations in pediatric CBF AML patients enrolled on serial CCG/COG protocols. [Abstract] Blood 110 (11): A-1442, 2007.
Public notes

Contacts
Principal investigator
Name 0 0
Janet Franklin, MD, MPH
Address 0 0
Children's Hospital Los Angeles
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT00070174