Conditions: Acute Lymphoblastic Leukemia Precursor B-Cell Lymphoblastic Leukemia Precursor T-Cell Lymphoblastic Leukemia
Keywords: Relapse Lymphoblastic Leukemia Decitabine Vorinostat Refractory Acute Childhood Pediatric ALL
Allocation: NON_RANDOMIZED | Intervention model: SINGLE_GROUP
Enrollment: 23
Healthy volunteers: no

Brief summary:
This is a pilot study using decitabine and vorinostat before and during chemotherapy with vincristine, dexamethasone, mitoxantrone, and peg-asparaginase in pediatric patients with acute lymphoblastic leukemia (ALL).

Detailed description:
Decitabine is a demethylating agent and vorinostat is a HDAC inhibitor. The use of demethylating agents and HDAC inhibitors in combination have been previously shown to have synergistic effects in altering neoplastic pathways of cancer cells and be well tolerated in human clinical studies. With the ability of decitabine and vorinostat to alter the abnormal cellular pathways of leukemic blasts and essentially turn off anti-apoptotic proteins, the leukemia cells have become primed for cytotoxic cell kill via chemotherapeutic agents. This study will ask the question as to whether or not the combination of decitabine and vorinostat followed by chemotherapy is feasible and whether it can positively impact outcome in patients with relapsed or refractory acute lymphoblastic leukemia.

Arms:
arm 1: Decitabine 15 mg/m2/day given IV over 1 hour on days 1 through 7 and days 15 through 21.

Vorinostat: 180 mg/m2/day (Max dose=400 mg daily) given orally on days 3 through 10 and days 17 through 24 arm 2: Decitabine 10 mg/m2/day given IV over 1 hour on days 1 through 5 and days 15 through 19.

Vorinostat: 180 mg/m2/day (Max dose=400 mg daily) given orally on days 2 through 7 and days 16 through 21

Interventions: intervention 1: Decitabine intervention 2: Vorinostat intervention 3: Vincristine intervention 4: Dexamethasone intervention 5: Mitoxantrone intervention 6: Pegaspargase intervention 7: Methotrexate
Intervention descriptions: intervention 1: 10 mg/m2/day given IV over 1 hour on days 1 through 5 and days 15 through 19. intervention 2: 180 mg/m2/day (Max dose=400mg daily) given orally on days 2 through 7 and days 16 through 21. intervention 3: 1.5 mg/m2/day (Max dose 2 mg) given IV push on days 10, 17, 24 and 31. intervention 4: 20 mg/m2/day divided BID given orally on days 8 through 12 and 22 through 26. intervention 5: 10 mg/m2/day given on days 8 and 9 as a short IV infusion over 5-15 minutes; do not infuse over less than 3 minutes intervention 6: 2500 international units/m2/day IM or IV on days 10 and 24. intervention 7: Given intrathecally to all patients the dose defined by age below.

* 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

CNS 1 or 2 patients get doses on day 8, 22 and 35 and CNS 3 patients should get doses on day 8, 15, 22, 29 and 35

Protocol document: