PRIMARY OBJECTIVES:
I. To determine the 2-year event-free-survival (EFS) for children with standard risk Down
syndrome (DS) acute myeloid leukemia (AML) (minimal residual disease [MRD]-negative after one
cycle of induction therapy) after elimination of high dose (HD) Ara-C (cytarabine) from the
treatment regimen.
II. To determine the 2-year EFS for children with high risk DS AML (MRD-positive after one
cycle of induction therapy) after intensification of treatment equivalent to that used for
high risk AML in children without DS.
EXPLORATORY OBJECTIVES:
I. To compare the feasibility and analytical characteristics of flow cytometry, polymerase
chain reaction (PCR) and targeted error-corrected sequencing of GATA binding protein 1
(globin transcription factor 1) (GATA1) mutations as methods to detect MRD in DS AML.
II. To establish a DS AML cell bank of viably frozen bone marrow samples collected at the end
of induction and corresponding non-tumor deoxyribonucleic acid (DNA) samples collected at end
of Induction 1.
OUTLINE:
INDUCTION I: Patients receive cytarabine intrathecally (IT) on day 1 and intravenously (IV)
continuously over 96 hours, daunorubicin hydrochloride IV over 1-15 minutes, and thioguanine
orally (PO) twice daily (BID) on days 1-4. Induction I continues for a minimum of 28 days.
Patients are assigned to 1 of 2 treatment arms based on their MRD status after completion of
Induction I.
ARM A (STANDARD RISK) (Closed to accrual and treatment with amendment #4A 01/07/2019):
INDUCTION II: Patients receive cytarabine IV continuously over 96 hours, daunorubicin
hydrochloride IV over 1-15 minutes, and thioguanine PO BID on days 1-4. Induction II
continues for a minimum of 28 days.
INDUCTION III: Patients receive cytarabine, daunorubicin hydrochloride, and thioguanine as in
Induction II. Induction III continues for a minimum of 28 days.
INTENSIFICATION I: Patients receive cytarabine IV continuously over 168 hours on days 1-7 and
etoposide IV over 60-120 minutes on days 1-3. Intensification I continues for a minimum of 28
days.
INTENSIFICATION II: Patients receive cytarabine and etoposide as in Intensification I.
Intensification II continues for a minimum of 28 days.
ARM B (HIGH RISK):
INDUCTION II: Patients receive high dose cytarabine IV over 1-3 hours every 12 (Q12) hours on
days 1-4 and mitoxantrone hydrochloride IV over 15-30 minutes on days 3-6. Induction II
continues for a minimum of 28 days.
INTENSIFICATION I: Patients receive high dose cytarabine IV over 1-3 hours Q12 hours and
etoposide IV over 90-120 minutes on days 1-5. Intensification I continues for a minimum of 28
days.
INTENSIFICATION II: Patients receive high dose cytarabine IV over 3 hours Q12 hours on days
1, 2, 8, and 9. Patients also receive asparaginase or asparaginase Erwinia chrysanthemi (E.
carotovora) intramuscularly (IM) or IV over 30 minutes on days 2 and 9. Intensification II
continues for a minimum of 28 days.
After completion of study treatment, patients are followed up at 1 month, monthly for 12
months, every 3 months for 12 months, every 6 months for 3 years, annually for 10 years, and
in case of relapse.