Clinical trial NCT00642395: Velcade®-Melphalan Association in Autologous Stem-Cell Transplantation (ASCT)
Official title: Velcade®-Melphalan Association as Conditioning Regimen Before Autologous Stem-cell Transplantation in Multiple Myeloma Patients Under 65 Years
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Multiple Myeloma
Keywords: Multiple Myeloma
Autologous Stem Cells Transplantation
High Dose Melphalan
Bortezomib
Lead sponsor: University Hospital, Toulouse
Sponsor class: OTHER
Collaborators: name: Intergroupe Francophone du Myelome
First posted: 2008-03-25
Enrollment: 61
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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

Primary outcomes:
measure: Evaluate the Complete Response and Very Good Partial Response (VGPR) rates 3 months after autologous blood stem cell transplantation conditioned by Velcade-Melphalan
timeFrame: 3 months after autologous stem cell transplantation
Secondary outcomes:
measure: 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
timeFrame: 3 months
Other outcomes:
Locations:
city: Amiens
country: France
facility: Service of Blood Deseases - South Hospital
city: Angers
country: France
facility: Service of Clinical Hematology - Bocage Hospital
city: Bayonne
country: France
facility: Service of Clinical Hematology - Cote Basque Hospital
city: Besançon
country: France
facility: Service of Clinical Hematology - Minjoz Hospital
city: Bobigny
country: France
facility: Service of Clinical Hematology - Avicenne Hospital
city: Brest
country: France
facility: Service of Clinical Hematology - A. Morvan Hospital
city: Caen
country: France
facility: Service of Clinical Hematology - F. Baclesse Center
city: Clamart
country: France
facility: Service of Clinical Hematology - Army Instruction Hospital of Percy
city: Clermont-Ferrand
country: France
facility: Service of Clinical Hematology - UH of Clermont-Ferrand
city: Colmar
country: France
facility: Service of Oncohematology - Louis Pasteur Hospital
city: Dijon
country: France
facility: Service of Hematology - Bocage Hospital
city: Dunkerque
country: France
facility: Service of Hematology - General Hospital
city: Grenoble
country: France
facility: Service of Hematology - A. Michallon Hospital
city: Lille
country: France
facility: Service of Hematology - Claude Hurriez Hospital
city: Lyon
country: France
facility: Service of Hematology - Léon Bérard Center
city: Lyon
country: France
facility: Service of Hematology - Edouard Herriot Hospital
city: Lyon
country: France
facility: Service of Hematology - Lyon Sud Hospital
city: Marseille
country: France
facility: Service of Hematology - Paoli Calmette Institute
city: Metz
country: France
facility: Service of Hematology - Notre Dame du Bon Secours Hospital
city: Nantes
country: France
facility: Service of Blood Deseases - UH of Nantes
city: Nice
country: France
facility: Service of Clinical Hematology - Archet 1 Hospital
city: Nice
country: France
facility: Service of Oncology - Archet 1 Hospital
city: Paris
country: France
facility: Service of Hematology - Hotel Dieu
city: Paris
country: France
facility: Service of Hematology - Cochin Hospital
city: Paris
country: France
facility: Service of Blood Deseases - Saint Antoine Hospital
city: Poitiers
country: France
facility: Service of Hematology - Jean Bernard Hospital
city: Reims
country: France
facility: Service of Hematology - R.Debré Hospital
city: Rennes
country: France
facility: Service of Hematology - Pontchaillou Hospital
city: Rouen
country: France
facility: Service of Hematology -Henri Becquerel Center
city: Strasbourg
country: France
facility: Service of Hematology - Hautepierre Hospital
city: Toulouse
country: France
facility: Service of Clinical Hematology - Purpan hospital TSA 40031
city: Tours
country: France
facility: Service of Onco-Hematology - Bretonneau Hospital
city: Vandoeuvre
country: France
facility: Service of Hematology - Brabois Hospital
city: Villejuif
country: France
facility: Service of Hematology -Gustave Roussy Institute
Study officials:
affiliation: Purpan Hospital - UH Toulouse
name: Murielle ROUSSEL, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Roussel M, Moreau P, Huynh A, Mary JY, Danho C, Caillot D, Hulin C, Fruchart C, Marit G, Pegourie B, Lenain P, Araujo C, Kolb B, Randriamalala E, Royer B, Stoppa AM, Dib M, Dorvaux V, Garderet L, Mathiot C, Avet-Loiseau H, Harousseau JL, Attal M; Intergroupe Francophone du Myelome (IFM). Bortezomib and high-dose melphalan as conditioning regimen before autologous stem cell transplantation in patients with de novo multiple myeloma: a phase 2 study of the Intergroupe Francophone du Myelome (IFM). Blood. 2010 Jan 7;115(1):32-7. doi: 10.1182/blood-2009-06-229658. Epub 2009 Nov 2.