The Pathophysiology of Bortezomib Induced Peripheral Neuropathy

Multiple Myeloma Clinical Trial

— BIPN  

Official title:

Is There a Role of Oxidative Stress in the Pathophysiology of Bortezomib Induced Peripheral Neuropathy (BIPN) in Multiple Myeloma Patients?

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT01171443
• Other study ID #: 0102-10CTIL
• Status: Not yet recruiting
• Phase: N/A
• First received: July 27, 2010
• Last updated: July 27, 2010
• Start date: August 2010
• Est. completion date: August 2011

Study information

• Verified date: July 2010
• Source: Wolfson Medical Center
• Contact: Ghoti Hossam
• Phone: 035028110
• Email: drghoti123[@]yahoo.com
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Observational

Clinical Trial Summary

Since the pathophysiology of BIPN still remains unclear, in the present study we are going to assess the development of BIPN in newly diagnosed myeloma patients, based on clinical neurological examination and electrophysiological study (EMG) and trying to find out if there is any relationship between oxidative stress generation measured by serum malonyldialdehyde - (MDA) and urinary isoprostane, and the development of BIPN, which can explain important part of the BIPN pathophysiology and can suggest new ideas of treatment and prophylactic strategies of peripheral neuropathy.

Description:

The proteasome inhibitor bortezomib has shown impressive clinical activity alone and in combination with other novel agents for the treatment of multiple myeloma (MM).

Peripheral neuropathy is a significant dose limiting toxicity of bortezomib, which typically occurs within the first treatment cycles with bortezomib, reaching plateau around cycle 5, and does not appear to increase thereafter.

Although bortezomib is known to be selective proteasome inhibitor, the mechanisms of cytotoxicity are poorly understood.

It has been theoretically hypothesized that bortezomib abrogates the degradation of I-kB, which blocks the transcriptional activity of NF-kB, however, recent studies demonstrated that bortezomib elicits activation of multiple pathways in cancer cells, such as reactive oxygen species (ROS) pathway.

The involvement of oxidative stress is supported by emerging studies showing that ROS generation plays a critical role in the initiation of the bortezomib induced apoptotic cascade.

Oxidative stress is a complex and dynamic situation characterized by an imbalance between the productions of ROS and the availability and action of antioxidants.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 30
• Est. completion date: August 2011
• Est. primary completion date: August 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. A total of 30 newly diagnosed patients (age > 18 years) with multiple myeloma (stage3 Durie and Salmon, ECOG-performance status <2), who are candidates for bortezomib therapy will be enrolled in the study (duration of the study 6 months).

Exclusion Criteria:

1. Patients with relapsed or progressive multiple myeloma.

2. Performance status > 2.

3. Prior treatment with neuropathic agents such as Oncovin and thalidomide.

Study Design

Observational Model: Case-Only, Time Perspective: Prospective

Related Conditions & MeSH terms

• Multiple Myeloma
• Neoplasms, Plasma Cell
• Peripheral Nervous System Diseases

Locations

Country	Name	City	State
Israel	Wolfsson Medical Center	Holon

Sponsors (1)

Lead Sponsor	Collaborator
Wolfson Medical Center

Country where clinical trial is conducted

Israel,