A Phase I Study of 5-Azacytidine in Combination With Chemotherapy for Children With Relapsed or Refractory ALL or AML

Dose assigned at study entry (75 mg/m2/day). Given subcutaneously, once daily on days 1 to 5, for a total of 5 doses.

30 mg/m2/dose, intravenous infusion over 30 minutes, once daily, on days 6 to 10, total 5 doses

2000 mg/m2/dose intravenous infusion over 3 hours, starting 4 hours after the beginning of fludarabine, once daily, on days 6 to 10, total 5 doses.

"Intrathecally to AML patients on day 1 of course 1 and 2.~* Omit on day 1 of course 1 if patient received IT therapy within 7 days prior to study enrollment~* IT therapy may be given during the end of course 1 disease evaluation and repeated every 7 days~* For patients with CNS disease, IT cytarabine can be given weekly until the CSF is clear. Two additional doses of IT cytarabine should be given weekly after the initial CSF clearing. It is permitted to change to intrathecal triple therapy (ITT) if persistent blasts are present in the CSF based on the treating physician's clinical judgment. Cytarabine dose defined by age:~* 30 mg for patients age 1-1.99~* 50 mg for patients age 2-2.99~* 70 mg for patients \>3 years of age~ITT Dosing:~Age (yrs) - Dose Methotrexate (MTX), Hydrocortisone (HC), Cytarabine (ARAC):~1. \- 1.99 MTX: 8 mg, HC: 15 mg, ARAC: 30 mg~2. \- 2.99 MTX: 10 mg, HC: 25 mg, ARAC: 50 mg~ * 3 - MTX: 12 mg, HC: 35 mg, ARAC: 70 mg"

"* Intrathecally to patients with ALL on day 1 of course 1 and 2.~* Omit IT MTX on Day 1 of course 1 if patient received IT therapy within 7 days prior to study enrollment~* IT therapy may be given during the end of course 1 disease evaluation and repeated every 7 days~* For patients with CNS 2 or 3 disease, IT MTX can be given weekly until the CSF is clear. Two additional doses of IT MTX should be given weekly after the initial clearing of the CSF. It is permitted to change to ITT if persistent blasts are present in the CSF. Methotrexate dose defined by age~* 8 mg for patients age 1-1.99~* 10 mg for patients age 2-2.99~* 12 mg for patients 3-8.99 years of age~* 15 mg for patients \>9 years of age~Triple IT Therapy Dosing:~Age (yrs): Dose Methotrexate (MTX), Hydrocortisone (HC), Cytarabine (ARAC):~1. \- 1.99 MTX: 8 mg, HC: 8 mg, ARAC: 16 mg~2. \- 2.99 MTX: 10 mg, HC: 10 mg, ARAC: 20 mg~3. \- 8.99 MTX: 12 mg, HC: 12 mg, ARAC: 24 mg~ * 9 MTX: 15 mg, HC: 15 mg, ARAC: 30 mg"