NCT00510939

Study to Assess the Safety, Tolerability, and Efficacy of Tipifarnib Plus Bortezomib in the Treatment of Acute Myeloid Leukemia

Phase II, Open-Label, Multi-centre, 2-part Study to Assess the Safety, Tolerability, and Efficacy of Tipifarnib Plus Bortezomib in the Treatment of Newly Diagnosed Acute Myeloid Leukemia (AML) Unfit for Conventional Chemotherapy ( >18 Years) or in Patients With Acute Myeloid Leukemia in First Relapse ( >60 Years)

• Status: Unknown
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 72 (estimated)
• Sponsor: University of Bologna · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This is one of the first studies of combination of Zarnestra plus Velcade in man. A primary objective of the study is therefore to assess the safety and tolerability of multiple doses of Zarnestra plus Velcade in patients with AML. New treatments for patients that are untreatable with intensive chemotherapy aged de novo AML patients or post-relapse AML are urgently required since, at present, many of the drugs used for second line therapy are the same as those used for first induction and response rates are much lower. * The following evidence suggests that Velcade plus Zarnestra can be an attractive therapeutic combination for: AML patients. * Affymetrix gene profiling data showed expression of NFkB1 in all of 5 myeloid cell lines cell lines tested and 35% of over 250 patient samples ( data generated in collaboration with Sergio Ferrari and Pier Paolo Piccaluga unpublished results, our Institute and University of Modena,Italy) * Preclinical evidence showed that AML cells in suspension culture were prevented to develop de novo drug resistance and mediated drug resistance. In Part B additional patients with AML will be treated to further characterize the tolerability,biological effects, and clinical efficacy of the combination Velcade plus Zarnestra. Patients on treatment for AML will undergo regular bone marrow aspirates and biopsies to assess responses to treatment. This will facilitate frequent assessment of biological endpoints (reduction in expression and phosphorylation of IKKb kinase, and downstream markers of signalling along with apoptosis, survival, proliferation and cellular size and ploidy) will be made in an attempt to confirm that the desired biological activity has been achieved at the maximum tolerated dose.

Conditions

• Acute Myeloid Leukemia

Interventions

Type	Name	Description
DRUG	Tipifarnib plus Bortezomib

Timeline

• Start date: 2007-03-01
• First posted: 2007-08-03
• Last updated: 2009-08-14

Locations

1 site across 1 country: Italy