NCT01483690

A Pilot Study of Decitabine and Vorinostat With Chemotherapy for Relapsed ALL

• Status: Terminated
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 23 (actual)
• Sponsor: Therapeutic Advances in Childhood Leukemia Consortium · Academic / Other
• Sex: All
• Age: 1 Year – 21 Years
• Healthy volunteers: Not accepted

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.

Conditions

• Acute Lymphoblastic Leukemia
• Precursor B-Cell Lymphoblastic Leukemia
• Precursor T-Cell Lymphoblastic Leukemia

Interventions

Type	Name	Description
DRUG	Decitabine	10 mg/m2/day given IV over 1 hour on days 1 through 5 and days 15 through 19.
DRUG	Vorinostat	180 mg/m2/day (Max dose=400mg daily) given orally on days 2 through 7 and days 16 through 21.
DRUG	Vincristine	1.5 mg/m2/day (Max dose 2 mg) given IV push on days 10, 17, 24 and 31.
DRUG	Dexamethasone	20 mg/m2/day divided BID given orally on days 8 through 12 and 22 through 26.
DRUG	Mitoxantrone	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
DRUG	Pegaspargase	2500 international units/m2/day IM or IV on days 10 and 24.
DRUG	Methotrexate	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

Timeline

• Start date: 2011-12-01
• Primary completion: 2015-07-31
• Completion: 2015-07-31
• First posted: 2011-12-01
• Last updated: 2020-10-27
• Results posted: 2020-10-27

Locations

28 sites across 2 countries: United States, Australia