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

Phase 1

Terminated

Interventions: Radiation: Total Marrow Irradiation
Procedure: Autologous Transplant
Drug: Melphalan
Drug: Filgrastim (G-CSF)

Brief Summary: 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.

Detailed Description: 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.

Recruitment & Eligibility

Inclusion Criteria

Patients meeting criteria for symptomatic myeloma
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
Patients who have received at least 2 cycles of systemic treatment of any kind in the preceding 12 months
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)

Exclusion Criteria

Patients with diagnosis of plasma cell leukemia
Patients with myeloma who have had any disease progression prior to enrollment
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 allograft or autologous transplant
Prior solid organ transplant
Patients receiving prior radiation to more than 20% of bone marrow containing areas

Arm && Interventions

Group	Intervention	Description
Total Marrow Irradiation	Filgrastim (G-CSF)	Escalating doses of total marrow irradiation (3Gy, 6Gy, 9Gy, or 12Gy) with standard high dose melphalan prior to autologous stem cell rescue.
Total Marrow Irradiation	Autologous Transplant	Escalating doses of total marrow irradiation (3Gy, 6Gy, 9Gy, or 12Gy) with standard high dose melphalan prior to autologous stem cell rescue.
Total Marrow Irradiation	Total Marrow Irradiation	Escalating doses of total marrow irradiation (3Gy, 6Gy, 9Gy, or 12Gy) with standard high dose melphalan prior to autologous stem cell rescue.
Total Marrow Irradiation	Melphalan	Escalating doses of total marrow irradiation (3Gy, 6Gy, 9Gy, or 12Gy) with standard high dose melphalan prior to autologous stem cell rescue.

Primary Outcome Measures

Name	Time	Method
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	Up to 1 year post-transplant.	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.

Secondary Outcome Measures