Phase 1-2 Study of Total Bone Marrow Irradiation With Helicoidal Tomotherapy in 1st Myeloma Relapse
Conditions
Multiple Myeloma in Relapse
Conditions: official terms
Multiple Myeloma - Neoplasms, Plasma Cell
Conditions: Keywords
Multiple Myeloma, Relapse, Complete Remission, Very Good Partial Remission
Study Type
Interventional
Study Phase
Phase 1/Phase 2
Study Design
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Intervention
Name: Melphalan Type: Drug
Name: Autologous Hematopoietic Stem cell Type: Biological
Overall Status
Recruiting
Summary
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.
Detailed Description
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.
Criteria for eligibility
Healthy Volunteers: No
Maximum Age: 65 Years
Minimum Age: 18 Years
Gender: Both
Criteria: Inclusion Criteria:

- Multiple Myeloma in first relapse.

- In Complete or very good partial remission

- Available Collected Autologous Peripheral Stem cells: 2.5x106 CD34+/Kg

Exclusion Criteria:

- Uncontrolled visceral disease: kidney, heart, lung, diabetes mellitus

- Previous Total body irradiation

- Any previous radiation dose to the spinal cord which could reach to 45gy equivalent, including the proposed TBMI

- Amyloidosis

- Brain localizations
Locations
CHU Haut-Leveque, service d'Hématologie
Bordeaux, France
Status: Not yet recruiting
Contact: Gerald Marit, MD, PhD - +33 556795679 - gerald.marit@chu-bordeaux.fr
CLCC Bergonie, service de radiotherapie
Bordeaux, France
Status: Not yet recruiting
Contact: Benedicte Henriques de Figueiredo, MD - +33 556333366 - b.henriques@bordeaux.unicancer.fr
CHU Claude Huriez, service d'hématologie
Lille, France
Status: Recruiting
Contact: Thierry Facon, MD, PhD - +33 320445962 - thierry.facon@chru.lille.fr
CLCC Oscar Lambret, service de radiothérapie
Lille, France
Status: Recruiting
Contact: Eric Lartigau, MD, PhD - +33 320295911 - e-lartigau@o-lambret.fr
CLCC ICO, service de radiothérapie
Nantes, St Herblain, France
Status: Recruiting
Contact: Marc A Mahé, MD, PhD - +33 240679900 - marc-andre.mahe@ico.unicancer.fr
CHU Hotel-Dieu, service d'hématologie
Nantes, France
Status: Recruiting
Contact: Philippe Moreau, MD, PhD - +33 240083260 - philippe.moreau@chu-nantes.fr
CHU Hautepierre, service d'hématologie
Strasbourg, France
Status: Recruiting
Contact: Bruno Lioure, MD, PhD - +33 88 127676 - bruno.lioure@chru-strasbourg.fr
CLCC Paul Strauss, service de radiothérapie
Strasbourg, France
Status: Recruiting
Contact: Georges Noel, MD, PhD - +33 88252478 - gnoel@strasbourg.fr
Start Date
January 2013
Completion Date
January 2017
Sponsors
Institut Cancerologie de l'Ouest
Source
Institut Cancerologie de l'Ouest
Record processing date
ClinicalTrials.gov processed this data on July 28, 2015
ClinicalTrials.gov page