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.