NCT00440726

Bortezomib With Chemotherapy for Relapsed Pediatric Acute Lymphoblastic Leukemia (ALL)

A Study of Bortezomib With Chemotherapy for Relapsed/Refractory Acute Lymphoblastic Leukemia

• Status: Completed
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 31 (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 Phase I/II study of a drug called bortezomib given in combination with chemotherapy drugs used to treat acute lymphoblastic leukemia (ALL) that has come back (recurred). Bortezomib is a drug that has been approved by the Food and Drug Administration (FDA) for treating adults with multiple myeloma which is a type of blood cancer. Bortezomib has been shown to cause cancer cells to die in studies done on animals (mice). Studies have been done that have shown that some adults and children with cancer have shown a response to bortezomib when it is used alone. Studies have also been done in adults to evaluate the dose of bortezomib that can be safely given in combination with other chemotherapy drugs.

Detailed description

All patients will receive 1 course of chemotherapy unless medical complications prevent the administration of some of the drugs. Treatment will last about 1 month. Treatment on this study will consist of a combination of 7 anti-cancer medications. The 7 anti-cancer medicines are bortezomib, vincristine, dexamethasone, PEG-asparaginase, doxorubicin, cytarabine (Ara-C), and methotrexate (MTX). If you are in the Phase I portion of this study, you will be given an assigned dose of bortezomib. The dose of bortezomib will be based on doses given in previous studies done with adults and children. At each dose level of bortezomib, between 3 and 6 children will receive bortezomib in combination with chemotherapy. If the side effects are not too severe, the next group of children will receive a higher dose. The dose will continue to be increased until we find the dose that causes serious side effects. Your dose of bortezomib will not be increased. If you have bad side effects, your dose may be decreased. The dose used during the Phase 2 part of this study will be determined by the outcome of the Phase I study. The highest dose used in Phase I that was tolerated without serious side effects will be the one used in Phase 2.

Conditions

• Acute Lymphoblastic Leukemia

Interventions

Type	Name	Description
DRUG	Bortezomib	Intravenous on days 1, 4, 8 and 11. Dose assigned at study entry.
DRUG	Dexamethasone	10 mg/m2/day divided BID, oral administration for 14 days.
DRUG	PEG-asparaginase	2500 IU/m2/day, intramuscular injection on Days 2, 8, 15 and 22
DRUG	Doxorubicin	60 mg/m2/day IV over 15 minutes on Day 1
DRUG	Cytarabine	Given intrathecally on Day 1 of course 1 at the dose defined by age below. * 30 mg for patients age 1-1.99 * 50 mg for patients age 2-2.99 * 70 mg for patients \>3 years of age
DRUG	Methotrexate	Given intrathecally to all patients who are CNS 1 at study entry on Day 15 at 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
DRUG	Vincristine	1.5 mg/m2/dose IV push (maximum single dose 2 mg) on Days 1, 8, 15 and 22.
DRUG	Triple IT Therapy	Triple IT therapy will be given intrathecally on Day 8, 15, and 22 for patients who are CNS 2 and CNS 3 at study entry. Regimen/dosing as follows: Methotrexate- * \<2 years: 8 mg * 2 - \<3 y: 10 mg * 3 - \<9 y: 12 mg * \>=9 y: 15 mg Cytarabine: * \<2 years: 16 mg * 2 - \<3 y: 20 mg * 3 - \<9 y: 24 mg * \>=9 y: 30 mg Hydrocortisone: * \<2 years: 8 mg * 2 - \<3 y: 10 mg * 3 - \<9 y: 12 mg * \>=9 y: 15 mg

Timeline

• Start date: 2006-08-04
• Primary completion: 2011-02-26
• Completion: 2011-02-26
• First posted: 2007-02-27
• Last updated: 2020-02-19
• Results posted: 2020-02-19

Locations

24 sites across 4 countries: United States, Australia, Brazil, Canada

Regulatory

• FDA-regulated drug study