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.