Schéma : Experimental :
Total Bone Marrow Irradiation (TBMI) is delivered by the Tomotherapy HI-ART machine, in 2 fractions per day during 4 consecutive days from d -6 to d -3. The escalated dose levels are determined according to a "3x3" modified Fibonacci method and five dose levels will be explored. The doses per fraction are: 1gy, 1.25gy, 1.5gy, 1.75gy and 2gy, and consequently the cumulative TBMI doses are: 8gy, 10gy, 12gy, 14gy and 16gy.
Drug : Melphalan is infused intravenously in 30 minutes on day -2 after IV anti-emetics.
Autologous Peripheral Stem Cell Rescue : are re-infused in the central line on day "0" after adequate premedication.
Despite the recent finding of new drugs (proteasome inhibitors and IMIDs), Multiple Myeloma still remain uncurable, especially after the first relapse, even in responding disease under conventional chemotherapy. In the healthy youngest patients (<65 yo), when peripheral stem cells collection is available, a high-dose therapy is often proposed in consolidation of complete or very good partial remission: the conditioning regimen usually includes high dose alkylating agent (mostly Melphalan) and/or Total Body Irradiation. The new Tomotherapy HI-ART technology allows irradiating on a 1.6m length field all the bone marrow sites together with optimal respect of the Organ at Risk (lungs, oral cavity, heart, liver, kidneys…). The proposed phase-1 study will explore the safety and efficacy of escalated dose of Total Bone-Marrow Irradiation in combination with a fixed dose of Melphalan (140mg/m²), followed by autologous SCR. To determine the MTD is the main objective of the study, then the toxicity profile (DLTs) and the RP2D in an extended cohort at the MTD dose.
Current primary outcome:
Maximal Tolerated Dose, type of Dose-Limiting Toxicities [ Time Frame: 1 year ]
Current secondary outcomes:
- Safety profile Recommended Dose for Phase-2 (RDP2) [ Time Frame: 1 year ]
Safety profile: acute, short and middle term toxicities Recommended Dose for Phase-2 (RDP2) and Extended Cohort for 14 patients at this dose
- Efficacy [ Time Frame: 1 and 2 years ]
Bone-marrow control evaluation by FDG PET-Scan Disease-free survival at 1 year and Overall Survival
Phase : I/II
Stade : NA