Study Comparing STR (Skeletal Targeted Radiotherapy) Plus Melphalan to Melphalan Alone, With Stem Cell Transplant in Multiple Myeloma

Inclusion Criteria: A subject must meet all of the following criteria to be eligible for the study. These will be evaluated within four weeks prior to enrollment. Subject must have primary refractory multiple myeloma defined as having failed to achieve an objective response (CR or PR using EBMT/IBMTR/ABMTR criteria) to any therapy since the initiation of induction therapy. At least one previous therapy must be a qualifying therapy that includes high dose pulsed steroids. There must be < 18 months from the beginning of induction therapy to time of enrollment on study. Subject must meet institutional guidelines for autologous PBSCT. Subject must have a minimum of 2 x 106 unmanipulated CD34+ cells/kg cryopreserved and available for transplant. Age 18 and 70 years. Adequate pulmonary function defined by FEV1, FVC and DLCO > or = 50% of predicted. Adequate cardiac function, defined as left ventricular ejection fraction (LVEF) of > or = 45%, with no evidence of cardiac amyloidosis. Adequate liver function, defined as serum total bilirubin < or = 2x institutional laboratory upper limit of normal and ALT/SGPT < or = 3x institutional laboratory upper limit of normal. Adequate renal function, defined as 24 hour measured creatinine clearance of > or = 50 mL/min/1.73 m2 BSA and serum creatinine < or = 1.8 mg/dL. ECOG performance score (PS) of 0, 1, or 2. Women of childbearing potential must have a negative pregnancy test (serum or urine beta HCG) and be using appropriate birth control methods. Ability to understand the study and provide informed consent. Exclusion Criteria: A subject meeting any of the following criteria is not eligible for participation in the study: Non-secretory multiple myeloma. Asymptomatic MGUS, smoldering multiple myeloma, or indolent multiple myeloma. Solitary bone or extramedullary plasmacytoma. Waldenstrom's macroglobulinemia (IgM myeloma). Evidence of disease progression (such as new bone lesions) in the setting of a greater than 50% reduction in M-protein. Absence of previous therapy with pulsed corticosteroids for multiple myeloma. Previous high-dose therapy with stem cell or bone marrow transplant, including autologous, allogeneic, and reduced-intensity or non-myeloablative allogeneic transplants. Life expectancy severely limited by concomitant illness (less than 6 months). Evidence of symptomatic spinal cord compression or pathological fracture within 3 months. Cumulative external beam radiation to > 20% of marrow volume or > 40 Gy to any single region of the spinal cord. Prior radiation to the bladder or kidney, defined as radiation portals that directly include any volume of either kidney or the bladder. Uncontrolled arrhythmia or symptomatic cardiac disease. Clinical evidence of amyloidosis involving the heart, lungs, liver, kidney, autonomic nervous system, or GI tract. History of hemorrhagic cystitis. Current microscopic or gross hematuria in the absence of vaginal bleeding. Obstructive uropathy. Inability to have bladder catheter placed. Evidence of HIV-seropositivity. Recent history of alcohol or drug abuse. History of non-compliance in other studies. Use of bisphosphonates within 14 days preceding enrollment. Use of any other therapy for multiple myeloma (including standard, induction, investigational, and alternative therapies) within 4 weeks prior to enrollment. Experimental therapies for any other conditions in the four weeks prior to enrollment. Pregnant or lactating women. Known allergy to vitamin C or bisphosphonates. Other prior malignancy except for: adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, or any other cancer from which the subject has been disease-free for 5 years.