Radioimmunotherapy (211At-OKT10-B10) and Chemotherapy (Melphalan) Before Stem Cell Transplantation for the Treatment of Multiple Myeloma

Inclusion Criteria:

• Patients with a diagnosis of multiple myeloma
• Patients must have autologous hematopoietic stem cells collected with a minimum CD34+stem cell yield of >= 4 x 10^6 CD34+ cells/kg of body weight
• Subjects must have disease meeting criteria for clinical relapse or progressivedisease (International Myeloma Working Group [IMWG] consensus criteria) and a historyof >= 1 prior autologous stem cell transplant(s)
• Subjects must have received at least 3 prior lines of therapy: an immunomodulatorydrug, a proteasome inhibitor, and a CD38-targeting antibody

• Aline of therapy is defined as one or more cycles of a planned treatment program.This may consist of one or more planned cycles of a single-agent therapy orcombination therapy, as well as a sequence of treatments administered in a plannedmanner. For example, a planned treatment approach of induction therapy followed byautologous stem cell transplantation, followed by maintenance is considered one lineof therapy. A new line of therapy starts when a planned course of therapy is modifiedto include other treatment agents (alone or in combination) as a results of diseaseprogression, relapse, or toxicity. A new line of therapy also starts when a plannedperiod of observation off therapy is interrupted by a need for additional treatmentfor the disease

• Subjects must have an estimated creatinine clearance greater than 60 ml per minute bythe following formula (Cockcroft-Gault). Serum creatinine value must be within 28 +/-days prior to registration
• Subjects must have an Eastern Cooperative Oncology Group (ECOG) score =< 2 orKarnofsky score >= 70%
• Ability to provide informed consent
• Subjects 18 years of age

Exclusion Criteria:

• Subjects with a history of plasma cell leukemia
• History of central nervous system involvement by multiple myeloma
• Prior radioimmunotherapy or radiation of > 20 Gy to pelvis or at maximally toleratedlevels to any critical normal organ
• Prior allogeneic hematopoietic cell transplant
• More than 2 prior autologous hematopoietic cell transplants
• Subjects with medullary or extramedullary plasmacytoma/s measuring > 3 cm by magneticresonance imaging (MRI) or positron emission tomography (PET)-computed tomography (CT) (radiated lesions are exempt from this criterion)
• Subjects with a history of any one of the following cardiovascular conditions withinthe past 6 months: Class III or IV heart failure as defined by the New York HeartAssociation (NYHA), cardiac angioplasty or stenting, myocardial infarction, unstableangina, or other clinically significant cardiac disease as determined by the principalinvestigator (PI) or designee
• Subjects with corrected QT (QTc) prolongation at baseline
• Subjects with a history of cardiac arrhythmia and a heart rate > 100 beats per minute (BPM) (oral beta-blocker [excluding sotalol] and/or calcium channel blocker therapyare acceptable to achieve rate control)
• History of reactive airway disease and clinically significant asthma requiring anyform of medical treatment in the prior three months
• Left ventricular ejection fraction < 40%
• Corrected diffusing capacity of the lungs for carbon monoxide (DLCO) < 50% orreceiving supplemental continuous oxygen
• Liver abnormalities: fulminant liver failure, cirrhosis of the liver with evidence ofportal hypertension, alcoholic hepatitis, esophageal varices, hepatic encephalopathy,uncorrectable hepatic synthetic dysfunction as evidenced by prolongation of theprothrombin time, ascites related to portal hypertension, bacterial or fungal liverabscess, biliary obstruction, chronic viral hepatitis, or symptomatic biliary disease.
• Bilirubin > 2 times the upper limit of normal
• Aspartate aminotransferase [AST] and alanine aminotransferase [ALT] > 2 times theupper limit of normal
• Subjects who are known to be seropositive for human immunodeficiency virus (HIV)
• Women of childbearing potential who are pregnant (beta-human chorionic gonadotropin [HCG]+) or breast feeding
• Fertile subjects unwilling to use contraceptives during and for 12 monthspost-transplant
• Subjects with untreated and uncontrolled infection at time of enrollment
• Subjects with known amyloid light-chain (AL) subtype amyloidosis
• Known allergy to murine-based monoclonal antibodies
• Known contraindications to radiotherapy
• History of another primary malignancy that has not been in remission for at least 2years (the following are exempt from the 2-year limit: non-melanoma skin cancer,curatively treated localized prostate cancer, and cervical carcinoma in situ on biopsyor a squamous intraepithelial lesion on Papanicolaou [PAP] smear)
• Any anti-CD38 monoclonal antibody within 30 days of anticipated date of infusion of 211At-OKT10-B10
• Individuals with a history of CTCAE grade 4 gastrointestinal toxicity associated withprior high-dose melphalan conditioning therapy (previous autologous stem celltransplant)