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

NCT ID: NCT01794572

Last Updated: 2025-12-12

Study Results

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Basic Information

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Recruitment Status

TERMINATED

Clinical Phase

NA

Total Enrollment

13 participants

Study Classification

INTERVENTIONAL

Study Start Date

2013-04-09

Study Completion Date

2020-10-06

Brief Summary

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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

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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.

Conditions

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Multiple Myeloma in Relapse

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

SINGLE_GROUP

Total Bone Marrow Irradiation (TBMI) dose escalation
Primary Study Purpose

OTHER

Blinding Strategy

NONE

Study Groups

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Total Bone Marrow Irradiation (TBMI): 8 Gy

Cohort 1: Total Bone Marrow Irradiation (TBMI): 8 Gy delivered by the Tomotherapy HI-ART machine, in 2 fractions per day during 4 consecutive days from d -6 to d -3.

Melphalan 140 mg/m² infused intravenously during 30 minutes on day -2 after IV anti-emetics.

Autologous Peripheral Stem Cell Rescue : re-infused in the central line on day "0" after adequate premedication.

Group Type EXPERIMENTAL

Total Bone Marrow Irradiation (TBMI) 8 Gy

Intervention Type RADIATION

Total Bone Marrow Irradiation (TBMI): 8 Gy

Total Bone Marrow Irradiation (TBMI): 10 Gy

Cohort 2: Total Bone Marrow Irradiation (TBMI): 10 Gy delivered by the Tomotherapy HI-ART machine, in 2 fractions per day during 4 consecutive days from d -6 to d -3.

Melphalan 140 mg/m² infused intravenously during 30 minutes on day -2 after IV anti-emetics.

Autologous Peripheral Stem Cell Rescue : re-infused in the central line on day "0" after adequate premedication.

Group Type EXPERIMENTAL

Total Bone Marrow Irradiation (TBMI) 10 Gy

Intervention Type RADIATION

Total Bone Marrow Irradiation (TBMI): 10 Gy

Total Bone Marrow Irradiation (TBMI): 12 Gy

Cohort 3: Total Bone Marrow Irradiation (TBMI): 12 Gy delivered by the Tomotherapy HI-ART machine, in 2 fractions per day during 4 consecutive days from d -6 to d -3.

Melphalan 140 mg/m² infused intravenously during 30 minutes on day -2 after IV anti-emetics.

Autologous Peripheral Stem Cell Rescue : re-infused in the central line on day "0" after adequate premedication.

Group Type EXPERIMENTAL

Total Bone Marrow Irradiation (TBMI): 12 Gy

Intervention Type RADIATION

Total Bone Marrow Irradiation (TBMI): 12 Gy

Cohort 4: Total Bone Marrow Irradiation (TBMI): 14 Gy

Cohort 4: Total Bone Marrow Irradiation (TBMI): 14 Gy delivered by the Tomotherapy HI-ART machine, in 2 fractions per day during 4 consecutive days from d -6 to d -3.

Melphalan 140 mg/m² infused intravenously during 30 minutes on day -2 after IV anti-emetics.

Autologous Peripheral Stem Cell Rescue : re-infused in the central line on day "0" after adequate premedication.

Group Type EXPERIMENTAL

Total Bone Marrow Irradiation (TBMI): 14 Gy

Intervention Type RADIATION

Total Bone Marrow Irradiation (TBMI): 14 Gy

Total Bone Marrow Irradiation (TBMI): 16 Gy

Cohort 5: Total Bone Marrow Irradiation (TBMI): 16 Gy delivered by the Tomotherapy HI-ART machine, in 2 fractions per day during 4 consecutive days from d -6 to d -3.

Melphalan 140 mg/m² infused intravenously during 30 minutes on day -2 after IV anti-emetics.

Autologous Peripheral Stem Cell Rescue : re-infused in the central line on day "0" after adequate premedication.

Group Type EXPERIMENTAL

Total Bone Marrow Irradiation (TBMI): 16 Gy

Intervention Type RADIATION

Total Bone Marrow Irradiation (TBMI): 16 Gy

Interventions

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Total Bone Marrow Irradiation (TBMI) 8 Gy

Total Bone Marrow Irradiation (TBMI): 8 Gy

Intervention Type RADIATION

Total Bone Marrow Irradiation (TBMI) 10 Gy

Total Bone Marrow Irradiation (TBMI): 10 Gy

Intervention Type RADIATION

Total Bone Marrow Irradiation (TBMI): 12 Gy

Total Bone Marrow Irradiation (TBMI): 12 Gy

Intervention Type RADIATION

Total Bone Marrow Irradiation (TBMI): 14 Gy

Total Bone Marrow Irradiation (TBMI): 14 Gy

Intervention Type RADIATION

Total Bone Marrow Irradiation (TBMI): 16 Gy

Total Bone Marrow Irradiation (TBMI): 16 Gy

Intervention Type RADIATION

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Maximum Eligible Age

65 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Institut Cancerologie de l'Ouest

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Stéphane A SUPIOT, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Institut de Cancerologie de l'Ouest

Philippe MOREAU, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

University Hospital, CHU de NANTES

Locations

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CLCC Bergonie, service de radiotherapie

Bordeaux, , France

Site Status

CHU Haut-Leveque, service d'Hématologie

Bordeaux, , France

Site Status

CLCC Oscar Lambret, service de radiothérapie

Lille, , France

Site Status

CHU Claude Huriez, service d'hématologie

Lille, , France

Site Status

CHU Hotel-Dieu, service d'hématologie

Nantes, , France

Site Status

CLCC ICO, service de radiothérapie

Saint-Herblain, , France

Site Status

CLCC Paul Strauss, service de radiothérapie

Strasbourg, , France

Site Status

CHU Hautepierre, service d'hématologie

Strasbourg, , France

Site Status

Countries

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France

References

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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.

Reference Type BACKGROUND
PMID: 18786784 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 21047977 (View on PubMed)

Provided Documents

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Document Type: Study Protocol and Statistical Analysis Plan

View Document

Related Links

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https://doi.org/10.1016/j.ijrobp.2022.09.069

Publication in International journal of radiation oncology . biology . physics

Other Identifiers

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2012-001473-91

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

ICO-2012-04

Identifier Type: -

Identifier Source: org_study_id

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