AAML1531

Principal Investigator: Phillip Barnette
Keywords: Pediatric , Oncology , Acute Myeloid Leukemia , Down Syndrome AML , TMD , Transient Myeloproliferative Disease Department: Pediatric Administration
IRB Number: 00088475 Co Investigator:  
Specialty: Oncology
Sub Specialties:
Recruitment Status: Recruiting

Contact Information

Jennifer Craig
jennifer.craig@imail.org
8016624715

Brief Summary

1. Primary Aims

1.1 To determine the 2-year event-free-survival (EFS) for children with standard risk DS AML (MRD-negative after one cycle of induction therapy) after elimination of HD Ara-C from the treatment regimen.

1.2 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.

2. Exploratory Aims

2.1 To determine the extent to which elimination of HD Ara-C from the treatment of standard risk DS AML decreases adverse events and resource utilization. Specifically, to determine if elimination of HD Ara-C from treatment of standard risk DS AML results in:
         2.1.1 A significant decrease in the number of days per patient spent on protocol therapy compared to predecessor study AAML0431.
         2.1.2 A significant decrease in the average number of days of hospitalization per patient compared to predecessor studies AAML0431 and A2971.
         2.1.3 A significant decrease in the number (per patient) and rate (per duration of treatment) of sterile site infections compared to the predecessor study AAML0431.
         2.1.4 A significant decrease of resource utilization by AML treatment compared to the predecessor study AAML0431.

2.2 To compare the feasibility and analytical characteristics of flow cytometry, PCR and targeted error-corrected sequencing of GATA1 mutations as methods to detect MRD in DS AML.

2.3 To establish a DS AML cell bank of viably frozen bone marrow samples collected at the end of induction and corresponding non-tumor DNA samples collected at end of Induction 1.

Inclusion Criteria

Patients must be greater than 90 days but less than 4 years of age at time of diagnosis.

• Patients must have constitutional trisomy 21 (Down syndrome) or trisomy 21 mosaicism (by karyotype or FISH).

• Patients with previously untreated de novo AML who meet the criteria for AML with ≥ 20% bone marrow blasts as set out in the WHO Myeloid Neoplasm classification OR

• 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 < 20% marrow blasts) are eligible if they meet the criteria for a diagnosis of MDS OR

• Patients with a history of Transient Myeloproliferative Disorder (which may or may not have required chemotherapy intervention), who:

i) are > 8 weeks since resolution of TMD with 5% blasts, OR

ii) Patients who have an increasing blast count (5%) in serial bone marrow aspirates performed at least 4 weeks apart.

• 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.

 

Exclusion Criteria

Patients with promyelocytic leukemia (FAB M3).

Patients ≤ 30 days from the last dose of cytarabine used for treatment of TMD.