Clinical trial NCT02043847: TMI With HD Mel in ASCT for R/R Multiple Myeloma (BMT-03)
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Multiple Myeloma, Relapsed
Multiple Myeloma, Refractory to Standard Treatment
Keywords: Multiple Myeloma
Relapsed
Refractory
Progressive Disease
Symptomatic
Lead sponsor: University of Illinois at Chicago
Sponsor class: OTHER
First posted: 2014-01-23
Enrollment: 12
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Intervention model description: Increasing doses of Total Marrow Irradiation (TMI), 3 Gy, 6 Gy, and 9 Gy.
Primary purpose: TREATMENT

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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Maximum Tolerated Dose (MTD) of Gy
timeFrame: Up to 60 days post-transplant.
Secondary outcomes:
measure: 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
timeFrame: Up to 1 year post-transplant.
Other outcomes:
Locations:
city: Chicago
country: United States
facility: University of Illinois Cancer Center
state: Illinois
Study officials:
affiliation: University of Illinois at Chicago
name: Damiano Rondelli, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.