Trials / Completed

CompletedNCT00666588

Bortezomib and Combination Chemotherapy in Treating Younger Patients With Recurrent, Refractory, or Secondary Acute Myeloid Leukemia

A Phase II Pilot Study of Bortezomib (PS-341, Velcade) Combined With Reinduction Chemotherapy in Children and Young Adults With Recurrent, Refractory or Secondary Acute Myeloid Leukemia

Status: Completed
Phase: Phase 2
Study type: Interventional
Enrollment: 52 (actual)

Sponsor: National Cancer Institute (NCI) · NIH
Sex: All
Age: 1 Year – 21 Years
Healthy volunteers: Not accepted

Summary

This phase II trial is studying the side effects and best dose of bortezomib and to see how well it works when given together with combination chemotherapy in treating younger patients with recurrent, refractory, or secondary acute myeloid leukemia (AML). Bortezomib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as idarubicin, cytarabine, and etoposide, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) together with bortezomib may kill more cancer cells

Detailed description

PRIMARY OBJECTIVES: I. To determine the toxicities and tolerability of bortezomib in combination with standard-relapse AML therapy (idarubicin/cytarabine or etoposide/high-dose cytarabine) in pediatric and young adult patients with relapsed or primary-refractory or secondary AML. II. To estimate the complete response rate to the Arm A and Arm B regimens. SECONDARY OBJECTIVES: I. To determine whether bortezomib inhibits proteasome activity, NF-kB activity and induces apoptosis pathway proteins in leukemia myeloblasts. II. To determine the feasibility of measuring AML stem cells in relapsed and recovering bone marrow. OUTLINE: This is a multicenter, dose-escalation study of bortezomib. Patients are stratified according to anthracycline\*-equivalent cumulative exposure (≤ 400 mg/m² vs \> 400 mg/m²). Patients are assigned to 1 of 2 groups. GROUP I (efficacy phase, patients with ≤ 400 mg/m² anthracycline-equivalent cumulative exposure - Closed as of 08/01/10): Patients receive idarubicin IV over 15 minutes on days 1-3, low-dose cytarabine IV continuously over days 1-7, and bortezomib IV on days 1, 4, and 8. GROUP II (dose-finding phase (closed as of 10/10) and efficacy phase, patients with \> 400 mg/m² anthracycline\*-equivalent cumulative exposure): Patients receive etoposide IV over 1 hour on days 1-5, high-dose cytarabine IV over 1 hour twice daily on days 1-5, and bortezomib IV on days 1, 4, and 8. NOTE: \* Anthracycline restriction no longer required for group 2 as of 10/02/10. All patients receive intrathecal cytarabine prior to courses 1 and 2. In both arms, treatment repeats every 28 days for up to 2 courses in the absence of disease progression or unacceptable toxicity. After completion of study therapy, patients are followed periodically for at least 5 years.

Conditions

Interventions

Type	Name	Description
DRUG	idarubicin	Given IV
DRUG	cytarabine	Given IV or IT
DRUG	bortezomib	Given IV
DRUG	etoposide	Given IV
OTHER	laboratory biomarker analysis	Correlative studies

Timeline

Start date: 2008-04-01
Primary completion: 2012-12-01
Completion: 2012-12-01
First posted: 2008-04-25
Last updated: 2018-05-22
Results posted: 2014-02-06

Locations

82 sites across 3 countries: United States, Australia, Canada

Source: ClinicalTrials.gov record NCT00666588. Inclusion in this directory is not an endorsement.