TMI With HD Mel in ASCT for R/R Multiple Myeloma (BMT-03)
- Conditions
- Multiple Myeloma, RelapsedMultiple Myeloma, Refractory to Standard Treatment
- Interventions
- Radiation: Total Marrow IrradiationProcedure: Autologous transplant
- Registration Number
- NCT02043847
- Lead Sponsor
- University of Illinois at Chicago
- 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 12
- 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)
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Cohort 1Total Marrow Irradiation (TMI) 3Gy Autologous transplant 3Gy with standard high dose melphalan prior to autologous stem cell rescue Cohort 2 Total Marrow Irradiation (TMI) 6Gy Total Marrow Irradiation 6Gy with standard high dose melphalan prior to autologous stem cell rescue Cohort 2 Total Marrow Irradiation (TMI) 6Gy Melphalan 6Gy with standard high dose melphalan prior to autologous stem cell rescue Cohort 2 Total Marrow Irradiation (TMI) 6Gy Filgrastim (G-CSF) 6Gy with standard high dose melphalan prior to autologous stem cell rescue Cohort 2 Total Marrow Irradiation (TMI) 6Gy Autologous transplant 6Gy with standard high dose melphalan prior to autologous stem cell rescue Cohort 1Total Marrow Irradiation (TMI) 3Gy Total Marrow Irradiation 3Gy with standard high dose melphalan prior to autologous stem cell rescue Cohort 1Total Marrow Irradiation (TMI) 3Gy Melphalan 3Gy with standard high dose melphalan prior to autologous stem cell rescue Cohort 1Total Marrow Irradiation (TMI) 3Gy Filgrastim (G-CSF) 3Gy with standard high dose melphalan prior to autologous stem cell rescue Cohort 3 Total Marrow Irradiation (TMI) 9Gy Total Marrow Irradiation 9Gy with standard high dose melphalan prior to autologous stem cell rescue Cohort 3 Total Marrow Irradiation (TMI) 9Gy Melphalan 9Gy with standard high dose melphalan prior to autologous stem cell rescue Cohort 3 Total Marrow Irradiation (TMI) 9Gy Filgrastim (G-CSF) 9Gy with standard high dose melphalan prior to autologous stem cell rescue Cohort 3 Total Marrow Irradiation (TMI) 9Gy Autologous transplant 9Gy with standard high dose melphalan prior to autologous stem cell rescue
- Primary Outcome Measures
Name Time Method Maximum Tolerated Dose (MTD) of Gy Up to 60 days post-transplant. Assessing MTD of TMI of 3Gy, 6Gy and 9Gy
- Secondary Outcome Measures
Name Time Method 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. 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
Trial Locations
- Locations (1)
University of Illinois Cancer Center
🇺🇸Chicago, Illinois, United States