Phase 1-2 Study of Total Bone Marrow Irradiation With Helicoidal Tomotherapy in 1st Myeloma Relapse
Information source: Institut Cancerologie de l'Ouest
ClinicalTrials.gov processed this data on August 23, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Multiple Myeloma in Relapse
Intervention: Melphalan (Drug); Autologous Hematopoietic Stem cell (Biological)
Phase: Phase 1/Phase 2
Status: Recruiting
Sponsored by: Institut Cancerologie de l'Ouest Official(s) and/or principal investigator(s): Marc A MAHE, MD, PhD, Principal Investigator, Affiliation: Institut de Cancerologie de l'Ouest Philippe MOREAU, MD, PhD, Principal Investigator, Affiliation: University Hospital, CHU de NANTES
Overall contact: Marc A MAHE, MD, PhD, Phone: +33 240679900, Email: marc-andre.mahe@ico.unicancer.fr
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.
Clinical Details
Official title: 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/m˛) Followed by Peripheral Stem Cell Rescue (PSC) in First Relapsed Multiple Myeloma.
Study design: Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Primary outcome: Maximal Tolerated Dose, type of DLTs
Secondary outcome: Safety profile Recommended Dose for Phase-2 (RDP2)
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.
Eligibility
Minimum age: 18 Years.
Maximum age: 65 Years.
Gender(s): 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 and Contacts
Marc A MAHE, MD, PhD, Phone: +33 240679900, Email: marc-andre.mahe@ico.unicancer.fr
CHU Haut-Leveque, service d'HĂ©matologie, Bordeaux 33604, France; Not yet recruiting Gerald Marit, MD, PhD, Phone: +33 556795679, Email: gerald.marit@chu-bordeaux.fr Gerald Marit, MD, PhD, Principal Investigator
CLCC Bergonie, service de radiotherapie, Bordeaux 33076, France; Not yet recruiting Benedicte Henriques de Figueiredo, MD, Phone: +33 556333366, Email: b.henriques@bordeaux.unicancer.fr Benedicte Henriques de Figueriredo, MD, Principal Investigator
CHU Claude Huriez, service d'hématologie, Lille 59037, France; Recruiting Thierry Facon, MD, PhD, Phone: +33 320445962, Email: thierry.facon@chru.lille.fr Thierry Facon, MD, PhD, Principal Investigator
CLCC Oscar Lambret, service de radiothérapie, Lille 59020, France; Recruiting Eric Lartigau, MD, PhD, Phone: +33 320295911, Email: e-lartigau@o-lambret.fr Eric Lartigau, MD, PhD, Principal Investigator
CLCC ICO, service de radiothérapie, Nantes, St Herblain 44805, France; Recruiting Marc A Mahé, MD, PhD, Phone: +33 240679900, Email: marc-andre.mahe@ico.unicancer.fr Marc A Mahé, MD, PhD, Principal Investigator
CHU Hotel-Dieu, service d'hématologie, Nantes 44093, France; Recruiting Philippe Moreau, MD, PhD, Phone: +33 240083260, Email: philippe.moreau@chu-nantes.fr Philippe Moreau, MD, PhD, Principal Investigator
CHU Hautepierre, service d'hématologie, Strasbourg 67098, France; Recruiting Bruno Lioure, MD, PhD, Phone: +33 88 127676, Email: bruno.lioure@chru-strasbourg.fr Bruno Lioure, MD, PhD, Principal Investigator
CLCC Paul Strauss, service de radiothérapie, Strasbourg 67091, France; Recruiting Georges Noel, MD, PhD, Phone: +33 88252478, Email: gnoel@strasbourg.fr Gerard Noel, MD, PhD, Principal Investigator
Additional Information
Related publications: Wong JY, Rosenthal J, Liu A, Schultheiss T, Forman S, Somlo G. Image-guided total-marrow irradiation using helical tomotherapy in patients with multiple myeloma and acute leukemia undergoing hematopoietic cell transplantation. Int J Radiat Oncol Biol Phys. 2009 Jan 1;73(1):273-9. doi: 10.1016/j.ijrobp.2008.04.071. Epub 2008 Sep 9. Somlo G, Spielberger R, Frankel P, Karanes C, Krishnan A, Parker P, Popplewell L, Sahebi F, Kogut N, Snyder D, Liu A, Schultheiss T, Forman S, Wong JY. Total marrow irradiation: a new ablative regimen as part of tandem autologous stem cell transplantation for patients with multiple myeloma. Clin Cancer Res. 2011 Jan 1;17(1):174-82. doi: 10.1158/1078-0432.CCR-10-1912. Epub 2010 Nov 3.
Starting date: January 2013
Last updated: February 19, 2013
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