A Randomized Multicenter Study to Compare the Safety and Efficacy of 166Ho-DOTMP Plus Melphalan to Melphalan Alone as Conditioning for Autologous Peripheral Blood Stem Cell Transplant in Subjects With Primary Refractory 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.