Eligibility Criteria:

• Written informed consent and HIPAA authorization for release of personal health information. Patients must sign a consent to undergo cell procurement. Written informed consent to enroll in the CAR T-cell therapy trial must be obtained prior to lymphodepletion.
• Age ≥ 18 years at the time of consent.
• Karnofsky score of ≥ 60%.
• Diagnosis of relapsed or refractory multiple myeloma (as defined by the Revised Uniform Response Criteria outlined by the IMWG
• Measurable disease as defined by one or more of the following: 1) serum M-protein ≥1.0 g/dL (≥0.5 g/dL for immunoglobulin A myeloma); 2) urine M-protein ≥200 mg/24 hours; 3) involved serum free light chain level ≥10 mg/dL AND an abnormal serum free light chain ratio. Patients with non-secretory disease and a baseline marrow burden of myeloma of at least 30% will also be eligible to participate.
  • Two lines of therapy will be allowed if the patient has disease that is refractory to both an immunomodulatory agent (lenalidomide or pomalidomide) and a proteasome inhibitor.
• Received high dose melphalan followed by autologous stem-cell transplant or is not eligible for or has declined the procedure.
• Allogeneic stem cell transplantation is allowed provided the patient is ≥ 1 year from transplant, not on immunosuppressive therapy to treat/prevent graft-versus-host disease, has no evidence of active graft-versus-host disease, and has no evidence of active graft-versus-host disease or infection.
• Demonstrate adequate organ function prior to cell procurement as defined below:
  • Creatinine Clearance using the Cockcroft-Gault formula: ≥ 50 mL/min
  • Bilirubin: ≤ 1.5 × upper limit of normal (ULN)
  • Aspartate aminotransferase (AST): ≤ 2.5 × ULN
  • Alanine aminotransferase (ALT): ≤ 2.5 × ULN
  • Oxygen saturation: ≥ 92% on room air
  • Forced expiratory volume at 1 second (FEV1), forced vital capacity (FVC), total lung capacity (TLC), diffusion capacity of lung for carbon monoxide (DLCO): ≥ 50% of predicted values
  • Ejection fraction: ≥ 50%
  • Hemoglobin: ≥ 8.0 g/dL; transfusion of red blood cells within 1 weeks will be permitted
  • Platelets: ≥ 50,000 /mm^3; Patients should not have received platelet transfusions within 1 week of screening
  • ANC: ≥ 1000 /mm^3; Patients should not have received Granulocyte-colony stimulating factor (G-CSF) or Granulocyte macrophage colony-stimulating factor (GM-CSF) within 1 week or pegylated G-CSF (Neulasta) within 2 weeks of screening
• Negative serum pregnancy test within 72 hours prior to procurement and again 72 hours prior to lymphodepleting therapy for female participants of child bearing potential. NOTE: Females are considered of child bearing potential unless they are surgically sterile (have undergone a hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or they are naturally postmenopausal for at least 12 consecutive months.
• Women of childbearing potential (WOCBP) should be willing to use 2 methods of birth control or be surgically sterile, or abstain from heterosexual activity for the course of the study, and for 6 months after the study is concluded. WOCBP are those who have not been surgically sterilized or have not been free from menses for > 1 year. The two birth control methods can be composed of: two barrier methods or a barrier method plus a hormonal method to prevent pregnancy. The male partner of WOCBP patients enrolled into the trial should use a condom and female participants must take the responsibility to inform their partners of the need to use a condom. As determined by the enrolling physician or protocol designee, ability of the patient to understand and comply with study procedures for the entire length of the study.
• Male patients with female partners must have had a prior vasectomy or agree to use an adequate method of contraception (i.e., double barrier method: condom plus spermicidal agent) prior to lymphodepletion through 3 months after the last dose of study therapy.
• No active infection (fungal, bacterial or viral) including Human Immunodeficiency Virus (HIV), Human T-lymhotropic virus (HTLV), Hepatits B virus (HBV), Hepatitis C virus (HCV) (tests can be pending at the time of cell procurement; only those samples confirming lack of active infection will be used to generate transduced cells). Note: To meet eligibility, patients are required to be negative for HIV antibody or HIV viral load, negative for HTLV1 and 2 antibody or PCR negative for HTLV1 and 2, negative for Hepatitis B surface antigen, and negative for HCV antibody or HCV viral load.
• Not pregnant or breastfeeding (NOTE: breast milk cannot be stored for future use while the mother is being treated on study).
• No tumor in a location where enlargement could cause airway obstruction.
• No history of hypersensitivity reactions to murine protein-containing products.
• No known sensitivity to mouse monoclonal antibodies.
• Has not received treatment with any investigational drug within 21 days or any tumor vaccines within the previous six weeks prior to lymphodepletion.
• No major surgery within 28 days prior to lymphodepletion.
• No diagnosis of any of the following conditions: amyloidosis, POEMS syndrome or multiple myeloma with central nervous system involvement.
  • Patients with plasma cell leukemia are allowed to participate.
• No active inflammatory or infectious gastrointestinal disorder (e.g. infectious colitis, diverticulitis or inflammatory bowel disease).
• No psychiatric illness which would prevent the patient from giving informed consent.
• No medical condition which, in the opinion of the treating physician, would make this protocol unreasonably hazardous for the patient.
• No other prior or concomitant malignancies with the exception of:
  • Non-melanoma skin cancer
  • In-situ malignancy
  • Low-risk prostate cancer after curative therapy
  • Other cancer for which the patient has been disease free for ≥ 3 years.
• Adequate cardiac function, defined as:
  • No EKG evidence of acute ischemia
  • No EKG evidence of active, clinically significant conduction system abnormalities
  • Prior to study entry, any EKG abnormality at screening not felt to put the patient at risk has to be documented by the investigator as not medically significant
  • No uncontrolled angina or severe ventricular arrhythmias
  • No clinically significant pericardial disease
  • No history of myocardial infarction within the last 6 months prior to registration
  • No Class 3 or higher New York Heart Association Congestive Heart Failure
• To qualify for lymphodepletion and CAR138 T-cell infusion, patients must meet all of the above eligibility criteria. A repeat EKG, echocardiogram or multigated acquisition scan, pulmonary function tests and viral serologies do not need to be repeated unless clinically indicated. In addition:
  • Patients must have autologous transduced activated CAR 138 T-cells with appropriate transduction efficiency (as discussed with FDA)
  • Patients must have autologous transduced activated CAR138 T-cells with ≥15% expression of CAR138
• Patients must have stopped taking corticosteroids for at least 48 hours prior to lymphodepleting chemotherapy; (those receiving <10mg/day prednisone equivalent may be enrolled at discretion of investigator)
• Patients must have stopped systemic chemotherapy for at least 14 days prior to lymphodepletion
• Patients must have stopped radiation therapy for at least 7 days prior to lymphodepletion
• Patients should have repeat multiple myeloma serologies performed within 7 days of lymphodepletion. If markers of measurable disease no longer fall within the guidelines outlined above (eligibility criterion #5), the Principal Investigator should be contacted. In such an event, the patient may be allowed to receive lymphodepletion and CAR138 T-cell infusion if it is felt to be in the patient's best interests. The patient would not be evaluable for response (disease not measurable) but would be evaluable for all other safety and efficacy measures.
• Patients must demonstrate adequate organ function prior to lymphodepletion as defined in the table below; all tests must be obtained within 48 hours prior to lymphodepletion.
  • Hemoglobin: ≥ 8 g/dL
  • Absolute Neutrophil Count (ANC): ≥ 1000 cells/mm^3; patients should not have received G-CSF or GM-CSF within 1 week or pegylated G-CSF (Neulasta) within 2 weeks of screening for lymphodepletion
  • Platelets: ≥ 50,000 cells/mm^3; patients should not have received platelet transfusion within 1 week of screening for lymphodepletion
  • Calculated creatinine clearance: ≥ 50 mL/min using the Cockcroft-Gault formula
  • Bilirubin: ≤ 1.5 × upper limit of normal (ULN)
  • Aspartate aminotransferase (AST): ≤ AST ≤ 2.5 × ULN
  • Alanine aminotransferase (ALT): ≤ AST ≤ 2.5 × ULN
  • Pulse oximetry: ≥92% on room air