Genomic-Based Diagnosis, Classification and Targeted Treatment of Multiple Myeloma

Multiple Myeloma Clinical Trial

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT01619358
• Other study ID #: 2012/00058
• Status: Recruiting
• Phase: N/A
• First received: April 2, 2012
• Last updated: December 10, 2013
• Start date: March 2012

Study information

• Verified date: December 2013
• Source: National University Hospital, Singapore
• Contact: Wee Joo Chng, PhD
• Phone: +65 6779 5555
• Email: Wee_Joo_Chng[@]nuhs.edu.sg
• Is FDA regulated: No
• Health authority: Singapore: Domain Specific Review Boards
• Study type: Observational

Clinical Trial Summary

Multiple myeloma is an incurable bone marrow cancer characterized by an abnormal expansion of plasma cells that secretes monoclonal immunoglobulin. Over the years, the molecular and genetic heterogeneity of the disease have been dissected. With the maturation of technologies, the time is ripe now to apply genomics to diagnose, classify, risk-stratify and prognosticate myeloma in the clinical setting and use this information to guide current treatment. The investigators hypothesize that the use of gene expression profiling as a single test will be more economical, efficient and accurate compared to the current standard panel of tests done at diagnosis. The investigators also hypothesize that the investigator can use predictive markers to identify prospectively patients who will respond to Velcade and that with more effective trebasedonatment, ability to measure depth of response beyond conventional complete response become important since more patients are achieving conventionally determined complete response. Using a cohort of patients treated on a standard treatment protocol based on Velcade-based induction treatment followed by consolidation and maintenance treatment, the investigators will study specifically the feasibility and accuracy of gene expression diagnostics, the predictive power of the investigators predefined predictive markers and the clinical utility of minimal residual disease measurement in myeloma. The results of the investigators study will allow us to improve the diagnosis, and prognostication of MM patients

1. The investigators hypothesized that this will speed up diagnosis, provide comprehensive information for the classification and risk stratification of MM patients and can completely replace the current FISH assay and may be cheaper.

2. The investigators hypothesized that TRAF3 deletion or mutation and MYC activation will identify patients that will have a significantly better response to Velcade.

3. Modern treatment induced deeper response. More sensitive method of disease detection will allow us to know the fully extent of response to these treatment

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 150
• Est. primary completion date: February 2017
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 21 Years and older

Eligibility

Inclusion Criteria:

• All Patients fulfilling IMWG diagnostic criteria for myeloma

Exclusion Criteria:

• Unable to take consent

Study Design

Observational Model: Cohort, Time Perspective: Prospective

Related Conditions & MeSH terms

• Multiple Myeloma
• Neoplasms, Plasma Cell

Locations

Country	Name	City	State
Singapore	Nationa University Hospital	Singapore

Sponsors (1)

Lead Sponsor	Collaborator
National University Hospital, Singapore

Country where clinical trial is conducted

Singapore, 

References & Publications (2)

Bergsagel PL, Kuehl WM, Zhan F, Sawyer J, Barlogie B, Shaughnessy J Jr. Cyclin D dysregulation: an early and unifying pathogenic event in multiple myeloma. Blood. 2005 Jul 1;106(1):296-303. Epub 2005 Mar 8. — View Citation

Chng WJ, Braggio E, Mulligan G, Bryant B, Remstein E, Valdez R, Dogan A, Fonseca R. The centrosome index is a powerful prognostic marker in myeloma and identifies a cohort of patients that might benefit from aurora kinase inhibition. Blood. 2008 Feb 1;111(3):1603-9. Epub 2007 Nov 15. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Prospectively validate the use of gene expression profiling (GEP) for the risk-stratification and classification of MM	All patients will have additional bone marrow taken for GEP studies after informed consent at entry into the treatment protocol. CD138 positive cells will be selected using magnetic beads and RNA extracted. The quality of RNA will be checked using the Agilent Bioanalyzer. GEP will be performed using Affymetrix U133plus2.0 chip.
Secondary	Prospectively validate predictive biomarkers in MM	We will prospectively validate 4 predictive makers we have previously identified for Velcade. Using diagnostic samples from patients entered into the above treatment protocol, we will assay for MYC activationusing IHC, TRAF3 inactivation using FISH for TRAF3 deletion and sequencing to check for TRAF3 mutations, NKFB index by GEP, and MYC activation index (MAI) by GEP.
Secondary	Study the impact of different treatment phases on minimal residual disease (MRD) and their impaction outcome.	We will be assessing MRD using 4 methods: ASO-PCR; FCM; sFLC; Serum Heavylite