CART-19 T Cells after Stem Cell Transplant in Treating Patients with High-Risk Multiple Myeloma

Inclusion Criteria

• Subjects must have Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
• Subjects must have a confirmed diagnosis of active multiple myeloma according to IMWG criteria; in addition, subjects must have “high-risk” multiple myeloma according to one of the following criteria: * Any of the following high-risk cytogenetic features, documented by fluorescence in situ hybridization (FISH) or metaphase karyotyping: deletion 17p, t(4;14), t(14;16), t(14;20) * Standard-risk cytogenetics but elevated lactate dehydrogenase (LDH) and beta-2-microglobulin > 5.5 mg/L (i.e., Revised International Staging System [R-ISS] stage III)
• Clonal bone marrow plasma cells >= 10% or biopsy-proven bony or extramedullary plasmacytoma and any one or more of the following myeloma defining events: Evidence of end organ damage that can be attributed to the underlying plasma cell proliferative disorder, specifically: * Serum calcium > 0.25 mmol/L (> 1 mg/dL) higher than the upper limit of normal or > 2.75 mmol/L (> 11 mg/dL) * Creatinine clearance < 40 mL per min (measured or estimated by validated equations) or serum creatinine > 177 umol/L (> 2 mg/dL) * Hemoglobin value of > 20 g/L below the lower limit of normal, or a hemoglobin value * One or more osteolytic lesions on skeletal radiography, computed tomography (CT), or positron emission tomography (PET)-CT; if bone marrow has less than 10% clonal plasma cells, more than one bone lesion is required to distinguish from solitary plasmacytoma with minimal marrow involvement * Any one or more of the following biomarkers of malignancy: ** Clonal bone marrow plasma cell percentage ≥60%; clonality should be established by showing kappa/lambda-light-chain restriction on flow cytometry, immunohistochemistry, or immunofluorescence; bone marrow plasma cell percentage should preferably be estimated from a core biopsy specimen; in case of a disparity between the aspirate and core biopsy, the highest value should be used ** Involved:uninvolved serum free light chain ratio >= 100 mg/L; these values are based on the serum Freelite assay (The Binding Site Group, Birmingham, UK); the involved free light chain must be >= 100 mg/L ** > 1 focal lesions on magnetic resonance imaging (MRI) studies; each focal lesion must be 5 mm or more in size
• At time of enrollment, subjects must be within 9 months of initiation of systemic therapy for multiple myeloma
• Subjects must have received or be receiving, at time of enrollment, “RVD” therapy (combination therapy with lenalidomide, bortezomib, and dexamethasone); patients must have received =< 6 cycles of RVD at time of enrollment and must not have progressed (by IMWG criteria) on RVD; patients may have received other regimens prior to RVD if such therapy was limited to =< 3 cycles; patients may have received radiation therapy prior to enrollment; patients must not have received infusional chemotherapy (e.g., bortezomib/thalidomide/dexamethasone-cisplatin/doxorubicin/cyclophosphamide/etoposide [VTD-PACE] or similar regimen) prior to enrollment
• Left ventricular ejection fraction >= 40%
• Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) =< 2.5 times the upper limit of normal
• Total bilirubin =< 1.5 mg/dL, unless hyperbilirubinemia is attributable solely to Gilbert’s syndrome
• Estimated (by Chronic Kidney Disease Epidemiology Collaboration [CKD-EPI] or Cockgroft-Gault equations) or calculated creatinine clearance (CrCl) >= 40 ml/min
• Diffusing capacity of the lungs for carbon monoxide (DLCO) >= 50% of predicted after correction for anemia
• Subjects must have measurable disease by standard serum and urine tests to enable post-transplant monitoring for progression-free survival; any of the following criteria are sufficient to define measurable disease: * Serum monoclonal protein spike (M-spike) >= 0.5 g/dL * 24 hour urine M-spike >= 200mg * Involved serum free light chain (FLC) >= 50 mg/L with abnormal ratio * For immunoglobulin A (IgA) multiple myeloma, total serum IgA level elevated above normal range Note: Measurable disease does not need to be documented at enrollment but can be based on historical lab results obtained at or since diagnosis with multiple myeloma; for example, a patient who does not have measurable disease at enrollment due to complete remission after induction therapy is eligible if the disease was previously measurable by one of the above criteria
• Subjects must have signed written, informed consent
• Subjects of reproductive potential must agree to use acceptable birth control methods

Exclusion Criteria

• Be pregnant or lactating
• Have inadequate venous access for or contraindications to leukapheresis
• Have any active and uncontrolled infection
• Any uncontrolled medical or psychiatric disorder that would preclude participation as outlined
• Have New York Heart Association (NYHA) Class III or IV heart failure, unstable angina, or a history of recent (within 6 months) myocardial infarction or sustained (> 30 seconds) ventricular tachyarrhythmias
• Have undergone allogeneic stem cell transplantation
• Have received prior gene therapy or gene-modified cellular immunotherapy
• Have active auto-immune disease, including connective tissue disease, uveitis, sarcoidosis, inflammatory bowel disease, or multiple sclerosis, or have a history of severe (as judged by the principal investigator) autoimmune disease requiring prolonged immunosuppressive therapy
• Have prior or active central nervous system (CNS) involvement (e.g. leptomeningeal disease, parenchymal masses) with myeloma; screening for this (e.g. with lumbar puncture) is not required unless suspicious symptoms are present
• Have a contraindication to post-ASCT maintenance lenalidomide
• Have active infection with human immunodeficiency virus (HIV) (negative HIV 1/2 antibody screen), hepatitis C (negative hepatitis C antibody screen), or hepatitis B (negative hepatitis B surface antigen); any positive serologies for HIV or viral hepatitis should be confirmed with appropriate confirmatory testing before concluding that an active infection is present; subjects with positive hepatitis core antibody are also excluded since the effect of long-term B cell depletion on the risk of hepatitis B reactivation is unknown
• Patients with a known history or prior diagnosis of optic neuritis or other immunologic or inflammatory disease affecting the central nervous system