response-based chemotherapy in treating newly diagnosed acute myeloid leukemia or myelodysplastic syndrome in younger patients with down syndrome

Conditions: Acute Myeloid Leukemia; Down Syndrome; Myelodysplastic Syndrome; Myeloid Leukemia Associated With Down Syndrome; Myeloproliferative Neoplasm

Summary: 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.

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.

Eligibility criteria:
inclusion criteria: * patients must have constitutional trisomy 21 (down syndrome) or trisomy 21 mosaicism (by karyotype or fluorescence in situ hybridization \[fish\]) * patient has one of the following: * patient has previously untreated de novo aml and meets the criteria for aml with \>= 20% bone marrow blasts as set out in the world health organization (who) myeloid neoplasm classification * attempts to obtain bone marrow either by aspirate or biopsy must be made unless clinically prohibitive; in cases where it is clinically prohibitive, peripheral blood with an excess of 20% blasts and in which adequate flow cytometric and cytogenetics/fish testing is feasible can be substituted for the marrow exam at diagnosis * patient has cytopenias and/or bone marrow blasts but does not meet the criteria for the diagnosis of aml (who myeloid neoplasm classification) because of \< 20% marrow blasts and meets the criteria for a diagnosis of myelodysplastic syndrome (mds) * for patients who do not meet criteria for aml or mds as outlined above; patient has a history of transient myeloproliferative disorder (which may or may not have required chemotherapy intervention and: * is \> 8 weeks since resolution of transient myeloproliferative disease (tmd) with \>= 5% blasts, or * has 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 * 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 * each patient's parents or legal guardians must sign a written informed consent * all institutional, food and drug administration (fda), and national cancer institute (nci) requirements for human subjects research must be met exclusion criteria: * patients with promyelocytic leukemia (french-american-british \[fab\] m3) * prior therapy * patients =\< 30 days from the last dose of cytarabine used for treatment of tmd