Anti-BCMA or/and Anti-CD19 CART Cells Treatment of Relapsed Multiple Myeloma

Inclusion Criteria:

• Have the capacity to give informed consent

• Have measurable disease by International Myeloma Working Group (IMWG) criteria basedon one or more of the following findings:

• Serum M-protein >= 1 g/dL

• Urine M-protein >= 200 mg/24 hour

• Involved serum free light chain (sFLC) level >= 10 mg/dL with abnormal κ/λ ratio

• Measurable biopsy-proven plasmacytomas (>= 1 lesion that has a single diameter >= 2cm)

• Bone marrow plasma cells >= 30%

• Have a diagnosis of BCMA+ multiple myeloma (MM) (>= 5% BCMA+ by flow cytometry onCD138 co-expressing plasma cells obtained within 45 days of study enrollment); the MMdiagnosis must be confirmed by internal pathology review of a fresh biopsy specimen atthe Fred Hutchinson Cancer Research Center (FHCRC)/Seattle Cancer Care Alliance (SCCA)

• Have relapsed or treatment refractory disease with >= 10% CD138+ malignant plasmacells (IHC) on bone marrow (BM) core biopsy, either:

• Following autologous stem cell transplant (ASCT)

• Or, if a patient has not yet undergone ASCT, the individual must:

• Be transplant ineligible, due to age, comorbidity, patient choice, insurance reasons,concerns of rapidly progressive disease, and/or discretion of attending physician,and,

• Demonstrate disease that persists after > 4 cycles of induction therapy and that isdouble refractory (persistence/progression) after therapy with both a proteasomeinhibitor and immunomodulatory drug (IMiD) administered either in tandem, or insequence.

Exclusion Criteria:

• Active hepatitis B, hepatitis C at the time of screening

• Patients who are (human immunodeficiency virus [HIV]) seropositive

• Subjects with uncontrolled systemic fungal, bacterial, viral or other infectiondespite appropriate antibiotics or other treatment at the time of leukapheresis

• > 1 hospital admission for infection in prior 3 months

• Presence of acute or chronic graft-versus-host disease (GVHD) unless limited to skininvolvement and managed with topical steroid therapy alone

• History of any one of the following cardiovascular conditions within the past 6months: class III or IV heart failure as defined by the New York Heart Association (NYHA), cardiac angioplasty or stenting, myocardial infarction, unstable angina, orother clinically significant cardiac disease

• History or presence of clinically relevant central nervous system (CNS) pathology suchas epilepsy, seizure, paresis, aphasia, stroke, severe brain injuries, dementia,Parkinson's disease, cerebellar disease, organic brain syndrome, psychosis, activecentral nervous system MM involvement and/or carcinomatous meningitis; subjects withpreviously treated central nervous systems involvement may participate, provided theyare free of disease in the CNS (documented by flow cytometry performed on thecerebrospinal fluid (CSF) within one week of enrollment) and have no evidence of newsites of CNS activity

• Pregnant or nursing women; NOTE: Women of reproductive potential must have a negativeserum pregnancy test performed within 48 hours of starting conditioning chemotherapy

• Use of any of the following:

• Therapeutic doses of corticosteroids (defined as > 20 mg/day prednisone or equivalent)within 7 days prior to leukapheresis; physiologic replacement, topical, and inhaledsteroids are permitted

• Allogeneic hematopoietic stem cell transplant (allo-HSCT) within 90 days ofleukapheresis

• Cytotoxic chemotherapeutic agents within 1 week of leukapheresis; oralchemotherapeutic agents are allowed if at least 3 half-lives have elapsed prior toleukapheresis

• Low dose chemotherapy (e.g., bortezomib, lenalidomide, cyclophosphamide =< 300 mg/m^2)given after leukapheresis to maintain disease control must be stopped >= 7 days priorto initiation of lymphodepleting chemotherapy

• Lymphotoxic chemotherapeutic agents within 2 weeks of leukapheresis

• Experimental agents within 4 weeks of leukapheresis unless progression is documentedon therapy and at least 3 half-lives have elapsed prior to leukapheresis

• Uncontrolled medical, psychological, familial, sociological, or geographicalconditions that do not permit compliance with the protocol, as judged by theinvestigator; or unwillingness or inability to follow the procedures required in theprotocol

• Absolute neutrophil count (ANC) < 1.0×10E9/L, Hemoglobin (Hgb) < 80 g/L, Plateletcount < 50×10E9/L

• Active autoimmune disease requiring immunosuppressive therapy

• Major organ dysfunction defined as:

• Creatinine clearance < 20 ml/min

• Significant hepatic dysfunction (serum glutamic-oxaloacetic transaminase [SGOT] orserum glutamic-oxaloacetic transaminase (SGOT) or serum alanine aminotransferase (SALT) > 5×upper limit of normal; bilirubin > 3.0 mg/dL)

• Forced expiratory volume in 1 second (FEV1) of < 50% predicted or diffusion capacityof the lung for carbon monoxide (DLCO) (corrected) < 40% (patients with clinicallysignificant pulmonary dysfunction, as determined by medical history and physical examshould undergo pulmonary function testing)

• Anticipated survival of < 3 months

• Contraindication to cyclophosphamide or fludarabine chemotherapy

• Patients with known AL subtype amyloidosis