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

NCT02043847 | Completed Phase 1 Results DMC FDA Drug

• 1 other identifier: 2013-0201
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Multiple Myeloma, Relapsed; Multiple Myeloma, Refractory to Standard Treatment

Keywords

Multiple Myeloma; Relapsed; Refractory; Progressive Disease; Symptomatic

Outcome Measures

Primary Outcomes (1)

• Maximum Tolerated Dose (MTD) of Gy

  Assessing MTD of TMI of 3Gy, 6Gy and 9Gy

  Up to 60 days post-transplant.

Secondary Outcomes (1)

• 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

  Up to 1 year post-transplant.

Study Arms (3)

Cohort 1Total Marrow Irradiation (TMI) 3Gy

EXPERIMENTAL

3Gy with standard high dose melphalan prior to autologous stem cell rescue

Radiation: Total Marrow Irradiation; Drug: Melphalan; Drug: Filgrastim (G-CSF); Procedure: Autologous transplant

Cohort 2 Total Marrow Irradiation (TMI) 6Gy

EXPERIMENTAL

6Gy with standard high dose melphalan prior to autologous stem cell rescue

Radiation: Total Marrow Irradiation; Drug: Melphalan; Drug: Filgrastim (G-CSF); Procedure: Autologous transplant

Cohort 3 Total Marrow Irradiation (TMI) 9Gy

EXPERIMENTAL

9Gy with standard high dose melphalan prior to autologous stem cell rescue

Radiation: Total Marrow Irradiation; Drug: Melphalan; Drug: Filgrastim (G-CSF); Procedure: Autologous transplant

Interventions

Total Marrow Irradiation RADIATION

Subjects in this trial will receive total marrow irradiation 3Gy per day for up to four days and as little as one day

Cohort 1Total Marrow Irradiation (TMI) 3Gy

Melphalan DRUG

Subjects will receive standard melphalan 200mg/m\^2 (100mg/m\^2 day-2 and day-1) conditioning therapy prior to transplant

Also known as: Alkeran ®

Cohort 1Total Marrow Irradiation (TMI) 3Gy

Filgrastim (G-CSF) DRUG

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.

Also known as: Neupogen®

Cohort 1Total Marrow Irradiation (TMI) 3Gy

Autologous transplant PROCEDURE

Subjects will receive standard melphalan 200mg/m\^2 (100mg/m\^2 day-2 and day-1) conditioning with autologous stem cell rescue

Cohort 1Total Marrow Irradiation (TMI) 3Gy

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• Patients with diagnosis of plasma cell leukemia
• Patients with truly non secretory myeloma (patients with light chain disease are eligible)
• Pregnant or breast-feeding
• 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.
• Patients who have undergone prior allogeneic stem cell transplant
• Prior solid organ transplant
• Patients receiving prior radiation to more than 20% of bone marrow containing areas

Sponsors & Collaborators

• University of Illinois at Chicago: lead

Study Sites (1)

University of Illinois Cancer Center

Chicago, Illinois, 60612, United States

Location

Related Publications (1)

• Patel P, Oh AL, Koshy M, Sweiss K, Saraf SL, Quigley JG, Khan I, Mahmud N, Hacker E, Ozer H, Peace DJ, Weichselbaum RR, Aydogan B, Rondelli D. A phase 1 trial of autologous stem cell transplantation conditioned with melphalan 200 mg/m2 and total marrow irradiation (TMI) in patients with relapsed/refractory multiple myeloma. Leuk Lymphoma. 2018 Jul;59(7):1666-1671. doi: 10.1080/10428194.2017.1390231. Epub 2017 Oct 25.

  PMID: 29065747 DERIVED

MeSH Terms

Conditions

Multiple Myeloma; Recurrence; Disease Progression

Interventions

Melphalan; Filgrastim; Granulocyte Colony-Stimulating Factor; Transplantation, Autologous

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phenylalanine; Amino Acids, Aromatic; Amino Acids, Cyclic; Amino Acids; Amino Acids, Peptides, and Proteins; Colony-Stimulating Factors; Glycoproteins; Glycoconjugates; Carbohydrates; Hematopoietic Cell Growth Factors; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Proteins; Biological Factors; Transplantation; Surgical Procedures, Operative

Results Point of Contact

• Title: Dr. Rondelli
• Organization: University of Illinois at Chicago

drond@uic.edu

312-996-6179

Study Officials

• Damiano Rondelli, MD

  University of Illinois at Chicago

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Model Details: Increasing doses of Total Marrow Irradiation (TMI), 3 Gy, 6 Gy, and 9 Gy.

Study Record Dates

• First Submitted: January 21, 2014
• First Posted: January 23, 2014
• Study Start: January 14, 2014
• Primary Completion: September 14, 2016
• Study Completion: September 14, 2016
• Last Updated: November 13, 2024
• Results First Posted: October 21, 2024

Record last verified: 2024-10

Locations

US (1)