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Treatment of Newly Diagnosed Childhood Acute Myeloid Leukemia (AML) Using Intensive MRC-Based Therapy and Gemtuzumab Ozogamicin (GMTZ): A COG Pilot Study

Phase 2
Not Enrolling

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Trial Information

Treatment of Newly Diagnosed Childhood Acute Myeloid Leukemia (AML) Using Intensive MRC-Based Therapy and Gemtuzumab Ozogamicin (GMTZ): A COG Pilot Study



- Determine the safety of gemtuzumab ozogamicin in children with newly diagnosed acute
myeloid leukemia undergoing intensive remission induction and intensification therapy.

- Determine the complete remission rate of patients treated with this regimen.


- Determine the feasibility of performing biological studies (e.g., FLT3-ITD and MRD) for
risk group stratification in these patients.

- Determine the effect of karyotypic abnormalities on survival in patients treated with
this regimen.

OUTLINE: This is a multicenter study.

- Induction I: Patients receive high-dose cytarabine (ARA-C) IV twice daily on days 1-10;
daunorubicin IV over 6 hours on days 1, 3, and 5; etoposide IV over 4 hours on days
1-5; and gemtuzumab ozogamicin IV over 2 hours on day 6. Patients with CNS-negative
disease receive ARA-C intrathecally (IT) on day 1. Patients with CNS-positive disease
receive ARA-C IT twice weekly for 2-3 weeks. Between days 28-35, patients are
evaluated. Patients achieving remission or who have no more than 20% blasts proceed to
induction II.

- Induction II: Patients receive ARA-C IV twice daily on days 1-8; ARA-C IT on day 1; and
daunorubicin IV and etoposide IV as in induction I. Between days 28-35 patients are
evaluated. Patients achieving complete remission proceed to intensification course I.

- Intensification course I: Patients receive ARA-C IV over 1 hour twice daily on days
1-5; ARA-C IT as in induction II; and etoposide IV over 1 hour on days 1-5. Patients
are evaluated at day 28. Patients with a 5/6 or 6/6 matched family donor proceed to
allogeneic bone marrow transplantation. All other patients in complete remission
proceed to intensification course II.

- Intensification course II: Patients receive ARA-C IV over 2 hours twice daily on days
1-4; ARA-C IT as in induction II; mitoxantrone IV over 1 hour on days 3-6; and
gemtuzumab ozogamicin IV over 2 hours on day 7. Patients are evaluated on day 28 and
then proceed to intensification course III.

- Intensification course III: Patients receive ARA-C IV over 3 hours twice daily on days
1, 2, 8, and 9 and asparaginase intramuscularly on days 2 and 9.

- Allogeneic bone marrow transplantation: Patients receive a preparative regimen
comprising busulfan IV over 2 hours 4 times daily on days -9 to -6 and cyclophosphamide
IV over 1 hour once daily on days -5 to -2. Allogeneic stem cells are infused on day 0.

- Graft-versus-host disease prophylaxis: Patients receive oral or IV cyclosporine twice
daily on days -1 to 50 and methotrexate IV once daily on days 1, 3, 6, and 11.

In all courses, treatment continues in the absence of disease progression or unacceptable

Patients are followed monthly for 6 months, every 2 months for 6 months, every 4 months for
1 year, every 6 months for 1 year, and then annually thereafter.

PROJECTED ACCRUAL: A total of 330 patients will be accrued for this study.

Inclusion Criteria


- 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

- No juvenile myelomonocytic leukemia

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

- No Down syndrome



- 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


- Not specified


- No inadequate liver function


- 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


- Shortening fraction at least 27% by echocardiogram OR

- Ejection fraction at least 50% by MUGA


- No proven or suspected pneumonia


- Not pregnant or nursing

- No proven or suspected sepsis or meningitis


Biologic therapy

- Not specified


- 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


- No prior radiotherapy


- Not specified


- 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

Type of Study:


Study Design:

Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:


Safety Issue:


Principal Investigator

Janet Franklin, MD, MPH

Investigator Role:

Study Chair

Investigator Affiliation:

Children's Hospital Los Angeles


United States: Federal Government

Study ID:




Start Date:

December 2003

Completion Date:

Related Keywords:

  • Leukemia
  • untreated childhood acute myeloid leukemia and other myeloid malignancies
  • childhood acute monocytic leukemia (M5b)
  • childhood acute megakaryocytic leukemia (M7)
  • childhood acute minimally differentiated myeloid leukemia (M0)
  • childhood acute myeloblastic leukemia with maturation (M2)
  • childhood acute myeloblastic leukemia without maturation (M1)
  • childhood acute myelomonocytic leukemia (M4)
  • childhood acute monoblastic leukemia (M5a)
  • childhood acute erythroleukemia (M6)
  • Leukemia
  • Leukemia, Myeloid, Acute
  • Leukemia, Myeloid



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