In this phase I trial, patients with 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 12Gy.
Terminated
Phase 1
| Drug | Synonyms | Arms |
|---|---|---|
| Melphalan | Alkeran ® | Total Marrow Irradiation |
| Filgrastim (G-CSF) | Neupogen® | Total Marrow Irradiation |
To establish the maximal tolerated dose of total marrow irradiation which can be added to
high dose melphalan conditioning in patients with multiple myeloma undergoing autologous stem
cell transplant.
| Name | Type | Description | Interventions |
|---|---|---|---|
| Total Marrow Irradiation | Experimental | Escalating doses of total marrow irradiation (3Gy, 6Gy, 9Gy, or 12Gy) with standard high dose melphalan prior to autologous stem cell rescue. |
|
Inclusion Criteria:
1. Patients meeting criteria for symptomatic myeloma
2. Patients must be high or intermediate risk of disease progression as defined by having
one of the following criteria: 2.1 ISS stage 2 or 3 disease 2.2 Abnormal metaphase
cytogenetics 2.3 Presence of FISH abnormalities aside from hyperdiploidy
3. Patients who have received at least 2 cycles of systemic treatment of any kind in the
preceding 12 months
4. Patient age 18-75 years at time of enrollment
5. Karnofsky performance status of ≥70
6. Cardiac function: LVEF >40%
7. Hepatic: Bilirubin <2x upper limit of normal and ALT and AST < 2.5x the upper limit of
normal
8. Renal: Creatinine clearance of ≥30mL/min, estimated or calculated
9. Pulmonary: DLCO, FEV1, FVC >50% of predicted (after correction for hemoglobin)
Exclusion Criteria:
1. Patients with diagnosis of plasma cell leukemia
2. Patients with myeloma who have had any disease progression prior to enrollment
3. Patients with truly non secretory myeloma (patients with light chain disease are
eligible)
4. Pregnant or breast-feeding
5. 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.
6. Patients who have undergone prior allograft or autologous transplant
7. Prior solid organ transplant
8. Patients receiving prior radiation to more than 20% of bone marrow containing areas
| Maximum Eligible Age: | 75 Years |
| Minimum Eligible Age: | 18 Years |
| Eligible Gender: | All |
| Healthy Volunteers: | No |
| Measure: | Progression Free Survival No Results Due to 1 Subject Came Off Treatment Within 7 Days and 1 Subject Came Off Treatment Within 5 Days. Not Enough Data to Analyze |
| Time Frame: | Up to 1 year post-transplant. |
| Safety Issue: | |
| Description: | To evaluate progression free survival (PFS) and in patients with multiple myeloma undergoing autologous stem cell transplant using the combination of high dose melphalan and total marrow irradiation. |
| Phase: | Phase 1 |
| Primary Purpose: | Interventional |
| Overall Status: | Terminated |
| Lead Sponsor: | University of Illinois at Chicago |
October 14, 2019
