Neoplasms

Heart and Blood Diseases

Blood and Lymph Conditions

Immune System Diseases

All Conditions

Symptoms and General Pathology

Rare Diseases

Multiple Myeloma

Neoplasms, Plasma Cell

Recurrence

Neoplasms by Histologic Type

Hemostatic Disorders

Blood Coagulation Disorders

Vascular Diseases

Paraproteinemias

Blood Protein Disorders

Hematologic Diseases

Hemorrhagic Disorders

Lymphoproliferative Disorders

Immunoproliferative Disorders

Disease Attributes

Antineoplastic Agents

All Drugs and Chemicals

Antiemetics

Gastrointestinal Agents

Emetics

Melphalan

Mechlorethamine

Serotonin

Serotonin 5-HT3 Receptor Antagonists

Antineoplastic Agents, Alkylating

Alkylating Agents

Immunosuppressive Agents

Immunologic Factors

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.

For Every patients:

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.

Melphalan: 140 mg/m²is infused intravenously in 30 minutes on day -2 after IV anti-emetics (5-HT3 antagonists).

Autologous Peripheral Stem Cell Rescue : 2.5 10\^6 CD-34/Kg are re-infused in the central line on day "0" after adequate premedication.

Autologous Hematopoietic Stem cell

Stéphane A SUPIOT, MD, PhD

Philippe MOREAU, MD, PhD

In Multiple Myeloma, an adult hematological malignancy, mainly located in the Bone Marrow (BM), dramatic recent progresses have been observed, thanks to new agents (proteasome inhibitors and IMIDs). However, at time of first relapse, high-dose therapy followed by Stem Cell Rescue (SCR) is frequently mandatory as a consolidation in minimal residual disease, to healthy patients under 65 yo, combining Melphalan (MPH) and/or Total Body Irradiation. Modern irradiation modalities are now available by the use of HI-ART Tomotherapy system to realize a Total Bone Marrow Irradiation (TBMI), in order both to limit the dose administered to Organ at Risk (lungs, oral cavity) and to focus efficacy on BM. In this phase-1 study, the conditioning regimen before SCR will combine a fixed high-dose MPH (140 mg/m²) and a dose escalated TBMI, so as to define its Maximal Tolerated Dose (MTD) and the Dose Limiting Toxicities (DLT). An extended cohort will further in a phase-2 setting.

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.

Phase 1-2 Study of Total Bone Marrow Irradiation With Helicoidal Tomotherapy in 1st Myeloma Relapse

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.

osteo-medullary PET fixations evaluation by FDG PET-Scan Disease-free survival at 1 year and Overall Survival

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.

Safety profile: acute, short and middle term toxicities Recommended Dose for Phase-2 (RDP2) and Extended Cohort for 14 patients at this dose

Institut Cancerologie de l'Ouest

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Phase 1-2 Study of Total Bone Marrow Irradiation With Helicoidal Tomotherapy in 1st Myeloma Relapse	NCT01794572	Multiple Myelom...	Melphalan Autologous Hema...	18 Years - 65 Years	Institut Cancerologie de l'Ouest
Phase 1-2 Study of Total Bone Marrow Irradiation With Helicoidal Tomotherapy in 1st Myeloma Relapse	NCT01794572	Multiple Myelom...	Melphalan Autologous Hema...	18 Years - 65 Years	Institut Cancerologie de l'Ouest
Phase 1-2 Study of Total Bone Marrow Irradiation With Helicoidal Tomotherapy in 1st Myeloma Relapse	NCT01794572	Multiple Myelom...	Melphalan Autologous Hema...	18 Years - 65 Years	Institut Cancerologie de l'Ouest

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