Trial Information

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

OBJECTIVES:

Primary

- 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.

Secondary

- 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
toxicity.

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.