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

January 18, 2021 updated by: Institut Cancerologie de l'Ouest

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.

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.

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

13

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • France
      • Bordeaux, France, 33076
        • CLCC Bergonie, service de radiotherapie
      • Bordeaux, France, 33604
        • CHU Haut-Leveque, service d'Hématologie
      • Lille, France, 59020
        • CLCC Oscar Lambret, service de radiothérapie
      • Lille, France, 59037
        • CHU Claude Huriez, service d'hématologie
      • Nantes, France, 44093
        • CHU Hotel-Dieu, service d'hématologie
      • Saint-Herblain, France, 44805
        • CLCC ICO, service de radiothérapie
      • Strasbourg, France, 67091
        • CLCC Paul Strauss, service de radiothérapie
      • Strasbourg, France, 67098
        • CHU Hautepierre, service d'hématologie

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 65 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / 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 Names:
  • 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 Names:
  • Hematopoietic stem cell

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
1 year

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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
1 year

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
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
1 and 2 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Institut Cancerologie de l'Ouest

Investigators

  • Principal Investigator: Stéphane A SUPIOT, MD, PhD, Institut de Cancérologie de l'Ouest
  • Principal Investigator: Philippe MOREAU, MD, PhD, University Hospital, CHU de NANTES

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

April 24, 2013

Primary Completion (Actual)

January 7, 2020

Study Completion (Actual)

January 7, 2020

Study Registration Dates

First Submitted

February 15, 2013

First Submitted That Met QC Criteria

February 19, 2013

First Posted (Estimate)

February 20, 2013

Study Record Updates

Last Update Posted (Actual)

January 22, 2021

Last Update Submitted That Met QC Criteria

January 18, 2021

Last Verified

January 1, 2021

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • ICO-2012-04
  • 2012-001473-91 (EudraCT Number)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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