TMI With HD Mel in ASCT for R/R Multiple Myeloma (BMT-03) (BMT-03)

October 23, 2024 updated by: Damiano Rondelli, MD, University of Illinois at Chicago

BMT-03: A Phase I Trial of Total Marrow Irradiation in Addition to High Dose Melphalan Conditioning Prior to Autologous Transplant for Patients With Relapsed or Refractory Multiple Myeloma

In this phase I trial, patients with relapsed or refractory multiple myeloma will receive standard autologous stem cell transplant conditioned with high dose melphalan. In addition to Melphalan, the conditioning will include targeted total marrow irradiation (TMI). This is a conventional 3+3 phase I trial with increasing doses of TMI from minimum 3Gy to Maximum 9Gy.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

In this phase I trial, patients with relapsed or refractory multiple myeloma will receive standard high dose melphalan with autologous stem cell rescue. In addition the pre-transplant conditioning will include targeted total marrow irradiation (TMI). This conventional 3+3 phase I trial will increase the dose of TMI until the maximum tolerated dose (MTD) is reached. Initial patients enrolled will receive the lowest possible dose of 3Gy. Maximum dose will be 9Gy.

Study Type

Interventional

Enrollment (Actual)

12

Phase

  • 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

  • United States
    • Illinois
      • Chicago, Illinois, United States, 60612
        • University of Illinois Cancer Center

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 75 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. Patients meeting criteria for symptomatic myeloma
  2. Patients who have progressive myeloma following initial induction (patients may have received any number of treatment regimens including prior autologous transplant)
  3. Patient age 18-75 years at time of enrollment
  4. Karnofsky performance status of ≥70
  5. Cardiac function: LVEF >40%
  6. Hepatic: Bilirubin <2x upper limit of normal and ALT and AST < 2.5x the upper limit of normal
  7. Renal: Creatinine clearance of >30mL/min, estimated or calculated
  8. Pulmonary: DLCO, FEV1, FVC >50% of predicted (after correction for hemoglobin)

Exclusion Criteria:

  1. Patients with diagnosis of plasma cell leukemia
  2. Patients with truly non secretory myeloma (patients with light chain disease are eligible)
  3. Pregnant or breast-feeding
  4. Uncontrolled viral, fungal or bacterial infection Note: Infection is permitted if there is evidence of response to medication. Eligibility of HIV infected patients will be determined on a case-by-case basis.
  5. Patients who have undergone prior allogeneic stem cell transplant
  6. Prior solid organ transplant
  7. Patients receiving prior radiation to more than 20% of bone marrow containing areas

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: Non-Randomized
  • Interventional Model: Sequential Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Cohort 1Total Marrow Irradiation (TMI) 3Gy
3Gy with standard high dose melphalan prior to autologous stem cell rescue
Radiation: Total Marrow Irradiation
Subjects in this trial will receive total marrow irradiation 3Gy per day for up to four days and as little as one day
Drug: Melphalan
Subjects will receive standard melphalan 200mg/m^2 (100mg/m^2 day-2 and day-1) conditioning therapy prior to transplant
Other Names:
  • Alkeran ®
Drug: Filgrastim (G-CSF)
Subjects to begin GCSF 5 μg/kg/d SC or IV on Day 5 and continue until ANC > 1000/mm^3 over period of 3 days.
Other Names:
  • Neupogen®
Procedure: Autologous transplant
Subjects will receive standard melphalan 200mg/m^2 (100mg/m^2 day-2 and day-1) conditioning with autologous stem cell rescue
Radiation: Total Marrow Irradiation
Subjects in this trial will receive total marrow irradiation 6Gy per day for up to four days and as little as one day
Drug: Filgrastim (G-CSF)
Subjects to begin GCSF 5 μg/kg/d SC or IV on Day 5 and continue until ANC > 1000/mm^3 over period of 3 days
Other Names:
  • Neupogen®
Radiation: Total Marrow Irradiation
Subjects in this trial will receive total marrow irradiation 9Gy per day for up to four days and as little as one day
Experimental: Cohort 2 Total Marrow Irradiation (TMI) 6Gy
6Gy with standard high dose melphalan prior to autologous stem cell rescue
Radiation: Total Marrow Irradiation
Subjects in this trial will receive total marrow irradiation 3Gy per day for up to four days and as little as one day
Drug: Melphalan
Subjects will receive standard melphalan 200mg/m^2 (100mg/m^2 day-2 and day-1) conditioning therapy prior to transplant
Other Names:
  • Alkeran ®
Drug: Filgrastim (G-CSF)
Subjects to begin GCSF 5 μg/kg/d SC or IV on Day 5 and continue until ANC > 1000/mm^3 over period of 3 days.
Other Names:
  • Neupogen®
Procedure: Autologous transplant
Subjects will receive standard melphalan 200mg/m^2 (100mg/m^2 day-2 and day-1) conditioning with autologous stem cell rescue
Radiation: Total Marrow Irradiation
Subjects in this trial will receive total marrow irradiation 6Gy per day for up to four days and as little as one day
Drug: Filgrastim (G-CSF)
Subjects to begin GCSF 5 μg/kg/d SC or IV on Day 5 and continue until ANC > 1000/mm^3 over period of 3 days
Other Names:
  • Neupogen®
Radiation: Total Marrow Irradiation
Subjects in this trial will receive total marrow irradiation 9Gy per day for up to four days and as little as one day
Experimental: Cohort 3 Total Marrow Irradiation (TMI) 9Gy
9Gy with standard high dose melphalan prior to autologous stem cell rescue
Radiation: Total Marrow Irradiation
Subjects in this trial will receive total marrow irradiation 3Gy per day for up to four days and as little as one day
Drug: Melphalan
Subjects will receive standard melphalan 200mg/m^2 (100mg/m^2 day-2 and day-1) conditioning therapy prior to transplant
Other Names:
  • Alkeran ®
Drug: Filgrastim (G-CSF)
Subjects to begin GCSF 5 μg/kg/d SC or IV on Day 5 and continue until ANC > 1000/mm^3 over period of 3 days.
Other Names:
  • Neupogen®
Procedure: Autologous transplant
Subjects will receive standard melphalan 200mg/m^2 (100mg/m^2 day-2 and day-1) conditioning with autologous stem cell rescue
Radiation: Total Marrow Irradiation
Subjects in this trial will receive total marrow irradiation 6Gy per day for up to four days and as little as one day
Drug: Filgrastim (G-CSF)
Subjects to begin GCSF 5 μg/kg/d SC or IV on Day 5 and continue until ANC > 1000/mm^3 over period of 3 days
Other Names:
  • Neupogen®
Radiation: Total Marrow Irradiation
Subjects in this trial will receive total marrow irradiation 9Gy per day for up to four days and as little as one day

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Maximum Tolerated Dose (MTD) of Gy
Time Frame: Up to 60 days post-transplant.
Assessing MTD of TMI of 3Gy, 6Gy and 9Gy
Up to 60 days post-transplant.

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Progression Free Survival (PFS) and in Patients With Multiple Myeloma (Relapsed or Refractory) Undergoing Autologous Stem Cell Transplant Using the Combination of High Dose Melphalan and Total Marrow Irradiation
Time Frame: Up to 1 year post-transplant.

The disease status of enrolled patients will be evaluated based on the International Myeloma Working Group Criteria.

Response Criteria

Stringent Complete Response (sCR) in addition to CR all of the following:

  1. Normal free light chain ratio (FLC)
  2. Absence of clonal cells in the bone marrow by immunohistochemistry if this is performed

Complete Response (CR) requires all of the following:

  1. Absence of the original monoclonal paraprotein in the serum or the urine by routine electrophoresis and by immunofixation. The presence of new monoclonal bands consistent with oligoclonal immune reconstitution does not exclude CR.
  2. Less than 5% plasma cells in a bone marrow aspirate and bone marrow biopsy if this is performed.
  3. No increase in size or number of lytic bone lesions on radiologic investigation (development of compression fracture does not exclude CR and radiographs are not required to document CR if not clinically indicated)
  4. Disappearance of soft tissue plasmacytoma
Up to 1 year post-transplant.

Collaborators and Investigators

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

Sponsor

University of Illinois at Chicago

Investigators

  • Principal Investigator: Damiano Rondelli, MD, University of Illinois at Chicago

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)

January 14, 2014

Primary Completion (Actual)

September 14, 2016

Study Completion (Actual)

September 14, 2016

Study Registration Dates

First Submitted

January 21, 2014

First Submitted That Met QC Criteria

January 22, 2014

First Posted (Estimated)

January 23, 2014

Study Record Updates

Last Update Posted (Actual)

November 13, 2024

Last Update Submitted That Met QC Criteria

October 23, 2024

Last Verified

October 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2013-0201 (Other Identifier: UIC Office for the Protection of Research Subjects (OPRS))

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

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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