Treatment of Myeloma in Patients <= 65 Years Old With Response >= 50% After HSC Autotransplant by Allogenic Transplant Genoidentical or Phenoidentical After Reduced Intensity Conditioning

Study Overview
=================
Brief Summary
-----------------
Donor mobilization : Donor will be mobilized with G-CSF (Granocyte) sub-cutaneous 10 µg/kg/day during 5 to 6 days. Hematopoïetic Stem Cell Harvest: By 1, 2, or 3 aphaeresis, a number of 4 x 106 cellules CD34+ /kg is required. If the CD34+ >= 2 and <= 4x106/kg: the center must decide on the strategy Decision. In case of insufficient graft : a Bone Marrow Harvest is recommended Conditioning : Fludarabine - Busulfan - ATG D-5 : Fludarabine (30 mg/m²) D-4 : Fludarabine (30 mg/m²)+ Busilvex (0,8 mg/kg every 6 h) D-3 : Fludarabine (30 mg/m²)+ Busilvex (0,8 mg/kg every 6 h) D-2 : Fludarabine (30 mg/m²) + ATG (Genzyme) (2.5 mg/Kg) D-1 : Fludarabine (30 mg/m²) + ATG (Genzyme) (2.5 mg/Kg) GVHD Prophylaxis: CsA alone at 3 mg/ kg + Methotrexate D1, D3 and D6 only in case of minor ABO incompatibility and with an anti A/B antibodies titer> 1/32. Transplant : HSC at D0 • 3 months after Transplantation : Disease Evaluation : If CR : Supervision. Then if progression: 4 cycles of Bortezomib. If no CR : Bortezomib (4 cycles) • Evaluation after Bortezomib cycles If CR : Supervision. Then, if progression and no GvHD : DLI If no RC and no GVHD : DLI

Official Title
-----------------
Treatment of Myeloma in Patients <= 65 Years Old With Response >= 50% After HSC Autotransplant by Allogenic Transplant Genoidentical or Phenoidentical After Reduced Intensity Conditioning (IFM 2005-03)

Conditions
-----------------
Myeloma

Intervention / Treatment
-----------------
* Drug: reduced intensity conditioning


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Major patients not under guardianship Myeloma with high b2 microglobulin level (> 3 mg/l) and/or chromosome 13 deletion, and/or translocation t(4;14) stage I DS with high evolutive potential or stage II, III DS. AND With response >= 50% and <= 90% after the first AutoHSCT (IFM 2005 01). The evaluation must be performed within 2 months after the first AutoHSCT. with an HLA identical related or unrelated donor ( match 10/10). Donor and recipient must have signed a written informed consent.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Allogenic Transplant<br> | Drug: reduced intensity conditioning<br>* reduced intensity conditioning for allogenic transplant<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Improvement of 15% of Event-free survival (EFS) at 3 years after allo HSCT (decrease of the number of deaths and progressions). |  | 3 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Haematological recovery |  | 3 years | 
| Engraftment rate and graft failure rate |  | 3 years | 
| The tolerance of Bortezomib after AlloHCST |  | 5 years | 
| CR (Complete Response) length rate defined by Bladé criteria. |  | 5 years | 
| Incidence and severity of acute and chronic GVHD |  | 5 years | 
| Outcome of GVHD under treatment by Bortezomib |  | 5 years | 
| Chimerism study by competitive PRC |  | 5 years | 
| Immunological study of the graft (ancillary study) |  | 5 years | 
| Study of immunological recovery by the recipient |  | 5 years | 
| TRM = Transplant- Related Mortality at 3 months |  | 3 months | 
| TRM = Transplant- Related Mortality at 1 year |  | 1 year | 
| Study of quality of life |  | 5 years | 
| Global survival at 3 years and 5 years |  | 3 and 5 years | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Myeloma, RICT, conditioning, allograft