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Cohort 1: Must meet all the following 3 criteria |
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Histologically confirmed newly diagnosed or recurrent solitary plasmacytoma/lytic lesion (recurrent solitary plasmacytomas will be considered based on treating physician discretion for cases where they clinically plan to treat with RT alone) - Minimal marrow involvement (Detectable clonal bone marrow plasma cells by multicolor flow cytometry and </= 10% clonal plasma cells in a bone marrow biopsy by immunohistochemistry, morphology, or flow cytometry) |
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Secretory M protein < 3 g/dL |
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Cohort 2: Must meet all the following criteria |
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Relapsed multiple myeloma with plasmacytomas/lytic lesion appropriate for RT on imaging |
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Relapsed (reappearance of M-spike/serum FLC) or progressive myeloma defined by a 25% increase from nadir in M-spike or involved serum FLB on 2 separate measurements; or with bone marrow involvement by clonal plasma cells detectable by IHC or flow cytometry |
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Any prior number of therapies is permitted, including prior radiation therapy |
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Allogeneic transplant patients are permitted |
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All Cohorts |
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Age >/= 18 years |
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Surgical resection of plasmacytoma or stabilization surgery is permitted if necessary based on physician judgement |
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ECOG performance status of 0-1 |
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Anticipated lifespan greater than 3 months |
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Able and willing to give valid written informed consent |
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Creatinine clearance >/=30ml/min by Cockroft-Gault method. See section below, "Dosing Regimen", regarding lenalidomide dose adjustment for calculated creatinine clearance >/= 30ml/min and <60ml/min |
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Serum bilirubin levels </= 1.5 times the upper limit of the normal range for the laboratory (ULN). Higher levels are acceptable if these can be attributed to active hemolysis or ineffective erythropoiesis of Gilbert's syndrome |
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Recommendation is for 2 effective contraceptive methods during the study and for at least 6 |
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Women of childbearing potential should be advised to avoid becoming pregnant and must adhere to the scheduled pregnancy testing a required in the Revlimid REMS program. They must be agreeable to use acceptable methods of birth control throughout the study and for at least 6 months after the last dose |
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AST (SGOT) and ALT (SGPT) </= 2.5 x ULN |
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months after the last dose. Adequate forms of contraception are double-barrier methods |
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(condoms with spermicidal jelly or foam and diaphragm with spermicidal jelly or foam) |
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oral, depo provera, or injectable contraceptive, intrauterine devices, and tubal ligation |
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Agree to abstain from breastfeeding during study participation and for at least 90 |
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days after the last dose of investigational product (IP). Men should be advised to not |
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father a child while receiving treatment with azacitidine. Male patients with female |
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partners who are of childbearing potential: Recommendation is for the patient and |
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partner use at least 2 effective contraceptive methods, as described above, during the |
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study and for 3 months following the last dose of study drug |
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Refrain from semen or sperm donation while taking IP and for at least 90 days after the |
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last dose of IP |
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Willing to be registered into the mandatory Revlimid REMS program, and be willing and |
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able to comply with the requirements of the REMS program |
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Able to swallow oral medication |
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Able to take aspirin (81 or 325 mg) daily as prophylactic anticoagulation (patients |
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Hematologic criteria: Hemoglobin >/= 9 g/dL, platelets >/= 50,000 and ANC >/= 1 |
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intolerant to ASA may use physician's choice of anticoagulation) |
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fulfilled
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Subjects should not enter the study if any of the following exclusion criteria are
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Pregnant or breast feeding females. (Lactating females must agree not to breast feed
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while taking azacitidine)
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Significant active cardiac disease within the previous 6 months including
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Uncontrolled systemic fungal, bacterial or viral infection (defined as ongoing
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NYHA class 4 CHF Unstable angina Myocardial infarction
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signs/symptoms related the infection without improvement despite appropriate
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known or suspected hypersensitivity to azacitidine or mannitol
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antibiotics, antiviral therapy and/or other treatment)
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History of inflammatory bowel disease (eg, Crohn's disease, ulcerative colitis)
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Known hypersensitivity to thalidomide or lenalidomide
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celiac disease (ie, sprue), prior gastrectomy or upper bowel removal, or any other
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Patients on tacrolimus therapy
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gastrointestinal disorder or defect that would interfere with the absorption
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Concurrent systemic chemotherapy with drugs other than CC-486 and lenalidomide
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distribution, metabolism or excretion of the study drug and/or predispose the subject
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to an increased risk of gastrointestinal toxicity
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Abnormal coagulation parameters without any known etiology (PTT > 45 seconds, and/or
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INR > 1.5). Patients currently on therapeutic anti-coagulation treatment are exempt
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from these parameters
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The development of erythema nodosum if characterized by a desquamating rash while
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taking thalidomide or similar drugs
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Active viral infection with human immunodeficiency virus (HIV), hepatitis B virus
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(HBV), or hepatitis C virus (HCV) as determined by a positive Polymerase Chain
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Reaction (PCR) will be excluded. Patients who are seropositive because of HBV vaccine
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are eligible. Seropositive status-antibody positive patients with negative PCR on two
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occasions will be eligible
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