Trial Information

IDA VS MTZ IN INDUCTION AND INTENSIFICATION TREATMENT OF AML OR MDS IN CHILDREN, A PHASE III RANDOMIZED STUDY

OBJECTIVES:

- Compare the efficacy of idarubicin vs mitoxantrone in induction and first
intensification in terms of achieving and maintaining complete remissions in children
with acute myeloid leukemia or myelodysplastic syndrome.

OUTLINE: This is a randomized, multicenter study. Patients are stratified according to
center and disease type (de novo acute myeloid leukemia (AML) vs AML secondary to
myelodysplastic syndrome (MDS) vs MDS).

- Induction: Patients are randomized to 1 of 2 treatment arms.

- Arm I: Patients receive cytarabine (ARA-C) IV continuously on days 1 and 2 and
then IV over 30 minutes every 12 hours on days 3-8, mitoxantrone IV on days 3-5,
etoposide (VP-16) IV over 1 hour on days 6-8, and ARA-C intrathecally (IT) on days
1 and 8.

- Arm II: Patients receive ARA-C and VP-16 as in arm I and idarubicin IV on days
3-5.

Patients on both arms with CNS disease at presentation receive ARA-C IT every 3 days until
the CSF clears and then weekly until the first intensification. After induction, patients on
both arms proceed to first intensification, regardless of response.

- First intensification: When blood counts recover and within 40 days after initiating
induction, patients are randomized to 1 of 2 treatment arms.

- Arm III: Patients receive high-dose ARA-C IV over 3 hours every 12 hours on days
1-3 (if allogeneic bone marrow transplantation (BMT) is planned) or days 1-4 (if
allogeneic BMT is not planned) and mitoxantrone IV on days 7-9.

- Arm IV: Patients receive high-dose ARA-C as in arm III and idarubicin IV on days
7-9.

- Patients who achieve complete remission (CR) after first intensification and have an
HLA-identical, chronic myelomonocytic leukemia-nonreactive, sibling donor undergo
allogeneic BMT. Patients who achieve CR after intensification and have no suitable
donor receive intensive chemotherapy as defined below. All patients with chloroma at
presentation undergo local radiotherapy beginning after final intensification.

- Second intensification: When blood counts recover, patients receive daunorubicin IV
continuously, ARA-C IV continuously, VP-16 IV continuously, oral thioguanine, and oral
dexamethasone on days 1-4 and 11-14 and ARA-C IT on days 1, 4, 11, and 14.

- Third intensification: When blood counts recover, patients receive high-dose ARA-C IV
over 3 hours every 12 hours on days 1-3 and VP-16 IV over 1 hour on days 2-5. When
blood counts recover, autologous bone marrow is harvested in the event of subsequent
relapse.

- Maintenance: When blood counts recover, patients receive oral thioguanine daily and
ARA-C subcutaneously 4 days a month for 1 year.

PROJECTED ACCRUAL: A total of 310 patients will be accrued for this study within 5 years.