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

Toulouse University Hospital

Status and phase

Completed

Phase 2

Conditions

Multiple Myeloma

Treatments

Drug: Bortezomib

Study type

Interventional

Funder types

Other

NETWORK

Identifiers

NCT00642395

0603603

Details and patient eligibility

About

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.

Enrollment

61 patients

Sex

All

Ages

18 to 65 years old

Volunteers

No Healthy Volunteers

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