Protocol Summary

Protocol No.: OCR14773

Sponsor Protocol No.: AAML1531

Study Title
Risk-stratified Therapy for Acute Myeloid Leukemia in Down Syndrome

Principal Investigator(s)
Slayton, William

Objective
This phase III trial studies response-based chemotherapy in treating newly diagnosed acute myeloid leukemia or myelodysplastic syndrome in younger patients with Down syndrome. Drugs used in chemotherapy work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Response-based chemotherapy separates patients into different risk groups and treats them according to how they respond to the first course of treatment (Induction I). Response-based treatment may be effective in treating acute myeloid leukemia or myelodysplastic syndrome in younger patients with Down syndrome while reducing the side effects.

Phase: Phase III (Cancer Control)

Age Group: Children

Scope: National

Treatment
Arm A: Standard risk
INDUCTION II: Patients receive cytarabine, daunorubicin, and thioguanine. 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 and etoposide. 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 and mitoxantrone. Induction II continues for a minimum of 28 days.
INTENSIFICATION I: Patients receive high dose cytarabine and etoposide. Intensification I continues for a minimum of 28 days.
INTENSIFICATION II: Patients receive high dose cytarabine. Patients also receive asparaginase or asparaginase Erwinia chrysanthemi. Intensification II continues for a minimum of 28 days.

Detailed Eligibility
INCLUSION CRITERIA:
1. Ages 91 days to 3 years-old
2. Patients must have constitutional trisomy 21 (Down syndrome) or trisomy 21 mosaicism (by karyotype or fluorescence in situ hybridization [FISH])
3. Patients with previously untreated de novo AML who meet the criteria for AML with >= 20% bone marrow blasts as set out in the World Health Organization (WHO) Myeloid Neoplasm classification
4. Patients with cytopenias and/or bone marrow blasts who do not meet the criteria for the diagnosis of AML (WHO Myeloid Neoplasm classification) because of 5. Patients with a history of transient myeloproliferative disorder (which may or may not have required chemotherapy intervention), who:
- Are > 8 weeks since resolution of transient myeloproliferative disease (TMD) with >= 5% blasts, OR
- Patients sho have an increasing blast count (>= 5%) in serial bone marrow aspirates performed at least 4 weeks apart
6. Children who have previously received chemotherapy, radiation therapy or any anti-leukemic therapy are not eligible for this protocol, with the exception of cytarabine for the treatment of TMD
7. There are no minimal organ function requirements for enrollment on this study
- Note: Previous cardiac repair with sufficient cardiac function is not an exclusion criteria
8. Each patient's parents or legal guardians must sign a written informed consent
9. All institutional, Food and Drug Administration (FDA), and National Cancer Institute (NCI) requirements for human subjects research must be met

EXCLUSION CRITERIA:
1. Patients with promyelocytic leukemia (French-American-British [FAB] M3)
2. Prior therapy
- Patients =

Applicable Disease Sites
Pediatric (Childhood) Cancer

Participating Institutions
UF Gainesville

More Information:
View study listing on ClinicialTrials.gov
http://www.clinicaltrials.gov/ct2/show/
NCT02521493