Phase 1-2 Study of the Combination of Escalated Total Bone Marrow Irradiation (TBMI) by Helicoidal Tomotherapy and a Fixed High-dose Melphalan (140 mg/m²) Followed by Peripheral Stem Cell Rescue (PSC) in First Relapsed Multiple Myeloma.
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
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.
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Maximal Tolerated Dose, type of DLTs
Maximal Tolerated Dose Type of Dose-limiting Toxicities 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.
Marc A MAHE, MD, PhD
Institut de Cancerologie de l'Ouest
France: Agence Nationale de Sécurité du Médicament et des produits de santé