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

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ClinicalTrials.gov Identifier: NCT01794572
Recruitment Status : Terminated (Low patient recruitement rate and modification of the therapeutic standard)
First Posted : February 20, 2013
Last Update Posted : January 22, 2021
Sponsor:
Information provided by (Responsible Party):
Institut Cancerologie de l'Ouest

Brief 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.

Condition or disease Intervention/treatment Phase
Multiple Myeloma in Relapse Drug: Melphalan Biological: Autologous Hematopoietic Stem cell Phase 1 Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 13 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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/m²) Followed by Peripheral Stem Cell Rescue (PSC) in First Relapsed Multiple Myeloma.
Actual Study Start Date : April 24, 2013
Actual Primary Completion Date : January 7, 2020
Actual Study Completion Date : January 7, 2020

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Multiple Myeloma

Arm Intervention/treatment
Experimental: Total BM irradiation dose

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.

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

Biological: Autologous Hematopoietic Stem cell
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.
Other Name: Hematopoietic stem cell




Primary Outcome Measures :
  1. Maximal Tolerated Dose, type of DLTs [ Time Frame: 1 year ]
    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.


Secondary Outcome Measures :
  1. Safety profile Recommended Dose for Phase-2 (RDP2) [ Time Frame: 1 year ]
    Safety profile: acute, short and middle term toxicities Recommended Dose for Phase-2 (RDP2) and Extended Cohort for 14 patients at this dose


Other Outcome Measures:
  1. Efficacy expressed as the rate (%) of Complete Response and Very Good Partial Response [ Time Frame: 1 and 2 years ]
    osteo-medullary PET fixations evaluation by FDG PET-Scan Disease-free survival at 1 year and Overall Survival



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01794572


Locations
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France
CLCC Bergonie, service de radiotherapie
Bordeaux, France, 33076
CHU Haut-Leveque, service d'Hématologie
Bordeaux, France, 33604
CLCC Oscar Lambret, service de radiothérapie
Lille, France, 59020
CHU Claude Huriez, service d'hématologie
Lille, France, 59037
CHU Hotel-Dieu, service d'hématologie
Nantes, France, 44093
CLCC ICO, service de radiothérapie
Saint-Herblain, France, 44805
CLCC Paul Strauss, service de radiothérapie
Strasbourg, France, 67091
CHU Hautepierre, service d'hématologie
Strasbourg, France, 67098
Sponsors and Collaborators
Institut Cancerologie de l'Ouest
Investigators
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Principal Investigator: Stéphane A SUPIOT, MD, PhD Institut de Cancerologie de l'Ouest
Principal Investigator: Philippe MOREAU, MD, PhD University Hospital, CHU de NANTES
Publications:
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Responsible Party: Institut Cancerologie de l'Ouest
ClinicalTrials.gov Identifier: NCT01794572    
Other Study ID Numbers: ICO-2012-04
2012-001473-91 ( EudraCT Number )
First Posted: February 20, 2013    Key Record Dates
Last Update Posted: January 22, 2021
Last Verified: January 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Keywords provided by Institut Cancerologie de l'Ouest:
Multiple Myeloma
Relapse
Complete Remission
Very Good Partial Remission
Additional relevant MeSH terms:
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Multiple Myeloma
Neoplasms, Plasma Cell
Recurrence
Neoplasms by Histologic Type
Neoplasms
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Lymphoproliferative Disorders
Immunoproliferative Disorders
Immune System Diseases
Disease Attributes
Pathologic Processes
Melphalan
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs