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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

Page last updated: August 23, 2015

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