Total Marrow Irradiation With High Dose Melphalan Prior to Autologous Transplant for Multiple Myeloma

BMT-02: A Phase I Trial of Total Marrow Irradiation in Addition to High Dose Melphalan Conditioning Prior to Autologous Transplant for Multiple Myeloma Following Initial Induction Therapy

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.

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.

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