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

Fecha de inicio: 1 de marzo de 2004

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.