A Phase I Study of Lintuzumab-Ac225 in Patients With Refractory Multiple Myeloma

Inclusion Criteria- * Confirmed diagnosis of multiple myeloma with measurable disease, as defined by the presence of M immunoglobulin protein in serum electrophoresis of at least 0.5 g/dL for IgG or 0.5 g/dL for IgA or urinary excretion of at least 200 mg monoclonal light chain per 24 hours. * Clinical diagnosis of multiple myeloma requiring treatment that has relapsed after or proven refractory to at least three prior treatment regimens, and in the opinion of the investigator must not be candidates for any FDA approved drug known to provide clinical benefit. * All acute toxicities from any prior therapy (radiotherapy, chemotherapy, or surgical procedures) resolved to Grade ≤ 2, NCI CTCAE. * Serum potassium and magnesium levels within institutional normal limits. Total serum calcium or ionized calcium level must be greater than or equal to the lower limit of normal. * Greater than 25% of myeloma plasmocytes from bone marrow must be CD33 positive. * Required baseline laboratory data including: White blood cell count, Absolute neutrophil count (ANC), Platelets, Hemoglobin, Serum creatinine, AST, Creatinine clearance, Bilirubin , AST and ALT , FEV1/FVC * Eastern Cooperative Oncology Group (ECOG) Performance Status ≤ 2 Exclusion Criteria- * Sex and Reproductive Status * Women of child bearing potential (WOCBP) who are unwilling or unable to use an acceptable method to avoid pregnancy for the entire study period and for at least one month (4 weeks) before and for at least six months (6 months) after the last dose of study medication. * Women who are pregnant or breastfeeding * Women with a positive pregnancy test on enrollment or prior to investigational product administration. * Men whose sexual partners are WOCBP, who are unwilling or unable to use an acceptable method to avoid pregnancy for the entire study period and for at least six months (6 months) after completion of study medication. * Target Disease Exceptions * Concurrent therapy with any other investigational agent. * Concomitant therapy with bisphosphonates. * Pathological fracture within 3 months prior to treatment; * Symptomatic spinal cord compression; . * Medical History and Concurrent Diseases * Treatment with chemotherapy or biological therapy 3 weeks prior to enrollment; * Presence of HAHA on screening * No bone marrow transplant within 3 months prior to treatment initiation * Prior treatment with radiation to cumulative maximum tolerated dose * Clinically significant cardiac disease (NYHA Class III or IV) including preexisting arrhythmia (such as ventricular tachycardia, ventricular fibrillation, or "Torsade de Pointes") * Myocardial infarction, uncontrolled angina within 6 months, congestive heart failure, or cardiomyopathy. * Abnormal QTc interval prolonged (\> 450 msec) after electrolytes have been corrected on baseline ECG. * Clinically significant pleural effusion in the previous 12 months or current ascites. * Clinically-significant coagulation or platelet function disorder (eg, known von Willebrand's disease). * Prior or concurrent malignancy, except for the following: i) Adequately treated basal cell or squamous cell skin cancer ii) Cervical carcinoma in situ iii) Adequately treated Stage I or II cancer from which the subject is currently in complete remission iv) Or any other cancer from which the subject has been disease-free for 3 years. * Physical and Laboratory Test Findings o Other severe, acute, or chronic medical or psychiatric condition or laboratory abnormality, serious uncontrolled medical disorder or active infection that may increase the risk associated with study participation or study drug administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the subject inappropriate for this study. * Allergies and Adverse Drug Reactions o Intolerance to humanized monoclonal antibodies * Other Exclusion Criteria * Prisoners or subjects who are involuntarily incarcerated. * Subjects who are compulsorily detained for treatment of either a psychiatric or physical (eg, infectious disease) illness. * Treatment with radiation within 6 weeks * Active serious infections uncontrolled by antibiotics * Clinically significant pulmonary disease