Velcade®-Melphalan Association in Autologous Stem-Cell Transplantation (ASCT)

Study Overview
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Brief Summary
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Intensification with autologous stem cell (ASCT) is currently the most effective treatment for subjects under 65 and the essential goal is to achieve complete response (CR) or very good partial response (VGPR= greater than 90% reduction of monoclonal component). However, only 50% of patients achieve this CR/VGPR even with tandem ASCT early in the course of disease. Optimization of the conditioning regimen could improve this CR/VGPR rate. The combinaison of Velcade and HD Melphalan has never been evaluated. However, at conventional doses, Velcade potentiates the antimyeloma effect of Melphalan without inducing any common toxicity. This study will be conducted in patients under the age of 65 with de novo multiple myeloma or in first relapse, with Salmon and Durie stage of III, II, I with one symptomatic bone lesion (radiological)and no contraindication to intensification. The primary objective will be to increase the CR/VGPR rate 3 months after autologous peripheral blood stem cell transplantation conditioned by Velcade-Melphalan from 40% to 70%. With alpha=5% and bêta=10%, 61 patients will be included. Secondary objectives will be to assess the toxicity of the Velcade-Melphalan conditioning regimen, the progression-free survival and the overall survival after intensification. Response rates will be evaluated according to the response criteria defined by. Analysis will be performed on an intention-to-treat basis. After conventional induction therapy and PBSC collection, patients will be offered this new conditioning regimen. they will be free to refuse this regimen, in which case they will receive standard intensification therapy by Melphalan 200 mg/m² followed by autologous stem cell transplantation. Evaluation will occur at 3 months post intensification.

Official Title
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Velcade®-Melphalan Association as Conditioning Regimen Before Autologous Stem-cell Transplantation in Multiple Myeloma Patients Under 65 Years

Conditions
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Multiple Myeloma

Intervention / Treatment
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* Drug: Bortezomib


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: At time of diagnosis De novo multiple myeloma patients under 65 or in first relapse, in whom screening for chromosome 13 deletion and beta2microglobulin assay have been performed. Salmon and Durie Stage: III, II, I with symptomatic bone lesion (radiological) Patient's written informed consent No clinical signs of heart failure or coronary insufficiency with LVEF>50% No hepatic in insufficiency: bilirubin<35μmol/l and SGOT, SGPT, alkaline phosphatase less than 2.5 N No respiratory insufficiency: normal pulmonary function tests and DLCO>50% No pre-existing renal impairment not related to the disease No history of any other malignant disease with the exception of basal cell carcinoma and stage I cervical cancer Negative HIV serology Effective contraception when justified At the time of transplantation Good performance status (WHO score≤2) Creatinine≤170μmol/l and no ineligibility criteria for intensification Stem cells harvest ≥ 5x10E6 CD34/kg for 2 ASCT Absence of progressive disease before transplantation Exclusion Criteria: Known refusal of the subject to participate to the study Female subject who is pregnant or breast-feeding History of allergy to any of the study medications, their analogues, or excipients in the various formulations Main liver insufficiency ≥ Grade 3 peripheral neuropathy on clinical examination within 14 days before enrollment

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 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: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>bortézomib | Drug: Bortezomib<br>* bortezomib-Melphalan<br>* Other names: Velcade;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluate the Complete Response and Very Good Partial Response (VGPR) rates 3 months after autologous blood stem cell transplantation conditioned by Velcade-Melphalan |  | 3 months after autologous stem cell transplantation | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Assess the toxicity of this Velcade-Melphalan conditioning regimen (hematological and visceral toxicity-NCI criteria) - To assess the progression-free survival after transplantation - To assess the overall survival after tran |  | 3 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Multiple Myeloma, Autologous Stem Cells Transplantation, High Dose Melphalan, Bortezomib