Microdose Study of Melphalan, Bortezomib and Dexamethasone

Study Overview
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Brief Summary
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The purpose of the study is to identify specific genes that are up- or downregulated in multiple myeloma patients who receive a microdose of either Melphalan (Alkeran®), Bortezomib (Velcade®) or Dexamethasone (Dexaven®). The study treatment constitutes 1% of the planned standard myeloma treatment and will be given two hours prior to standard treatment. Blood samples are taken at baseline, 15, 30, 60 and 120 minutes for microarray analysis.

Official Title
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Phase 0 Microdose Study to Evaluate the Effect of Melphalan, Bortezomib and Dexamethasone on Cellular Gene-expression in Patients With Multiple Myeloma

Conditions
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Multiple Myeloma

Intervention / Treatment
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* Drug: Melphalan
* Drug: Bortezomib
* Drug: Dexamethasone


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Planned treatment for Multiple Myeloma (newly diagnosed as well as relapse and refractory disease) with one of the following chemotherapy regimens: 1) Highdose melphalan, 2) Bortezomib or 3) Dexamethasone 18 years or older. Understand and have the will to sign the informed consent. Exclusion Criteria: Prior treatment with the study drug Received treatment with biphosphonates in the week prior to study treatment

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Melphalan<br>A microdose of 2 mg/m2 iv Melphalan (1% of standard dose) is given two hours prior to planned standard dose Melphalan | Drug: Melphalan<br>* A microdose of 2 mg/m2 iv Melphalan (1% of standard dose) is given two hours prior to planned standard dose Melphalan<br>* Other names: Alkeran®;|
| Experimental: Bortezomib<br>A microdose of 0.013 mg/m2 iv Bortezomib (1% of standard dose) is given two hours prior to planned standard dose Bortezomib | Drug: Bortezomib<br>* A microdose of 0.013 mg/m2 iv Bortezomib (1% of standard dose) is given two hours prior to planned standard dose Bortezomib<br>* Other names: Velcade®;|
| Experimental: Dexamethasone<br>A microdose of 0.4 mg iv Dexamethasone (1% of standard dose) is given two hours prior to planned standard dose of Dexamethasone | Drug: Dexamethasone<br>* A microdose of 0.4 mg iv Dexamethasone (1% of standard dose) is given two hours prior to planned standard dose of Dexamethasone<br>* Other names: Dexaven®);|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline in gene expression at 15, 30, 60, 120 minutes upon microdose drug exposure. | The primary outcome measure is determination of differential and significantly expressed genes across time successive samples from each individual patient. The analysis will be based on global gene expression profiling and differentially expressed genes will be identified using pairwise comparisons of samples means by two sample t-tests and corrections for multiple testing. | Prior to microdose and 15, 30, 60 and 120 minutes post-microdose | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Multiple Myeloma, Phase 0 study, Microdose study, Micro array, Gene expression profiling