CRISPR Delivered Anti-BCMA Chimeric Antigen Receptor T Cells (1XX BCMA CAR-T cells) for the Treatment of Relapsed or Refractory Multiple Myeloma

Inclusion Criteria

• Voluntarily sign informed consent form
• ≥ 18 years of age at the time of signing informed consent
• Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
• Diagnosis of MM (per IMWG criteria) with relapsed or refractory disease and has received at least 3 prior lines of therapy including proteasome inhibitor (PI; e.g., bortezomib or carfilzomib) immunomodulatory therapy (IMiD; e.g., lenalidomide or pomalidomide), and anti-CD38 antibody therapy
• Patients may have received BCMA targeted therapy but must be at least 6 months from last BCMA therapy
• Participants must have documented evidence of progressive disease within 12 months of the last line of therapy or be refractory/nonresponsive to their most recent line
• Participants must have measurable disease, defined as at least one of the criteria below: * Serum monoclonal (M)-protein greater or equal to 0.5 g/dL * Urine M-protein greater or equal to 200 mg/24 h * Serum free light chain (FLC) assay: Involved FLC level of ≥ 100 mg/L
• Adequate bone marrow function for apheresis and lymphodepleting chemotherapy
• Hemoglobin (Hgb) > 8 gm/dl (transfusions allowed)
• Platelets > 50,000/uL (in the absence of platelet transfusion within 7 days of apheresis, but transfusion permitted prior to lymphodepleting chemotherapy)
• Absolute neutrophil count (ANC) > 1000/uL in the absence of growth factor support (filgrastim within 7 days or pegfilgrastim within 14 days of apheresis, but growth factor permitted prior to lymphodepleting chemotherapy). For those patients who have evidence of duffy null, ANC > 750/uL is allowed
• Absolute lymphocyte count (ALC) > 300/uL
• Alanine aminotransferase (ALT)/aspartate aminotransferase (AST) ≤ 3 x institutional upper limit of normal (ULN)
• Total bilirubin ≤ 1.5 mg/dl x institutional ULN, except with Gilbert’s syndrome
• Serum creatinine clearance (CrCl) ≥ 30 mL/min using Cockcroft-Gault formula or as measured with a 24 hour urine collection
• Adequate cardiac function, defined as left ventricular ejection fraction (LVEF) ≥ 40% as assessed by echocardiogram or multiple uptake gated acquisition (MUGA)
• Adequate pulmonary function (measured by room air pulse oximetry ≥ 92%)
• Women of childbearing potential (defined as all women physiologically capable of becoming pregnant) must have a negative serum or urine pregnancy test AND agree to use highly effective methods of contraception for 1 year after the last dose of anti-BCMA CAR-T cells
• Males who have partners of childbearing potential must agree to use an effective barrier contraceptive method for 6 months after CAR-T therapy

Exclusion Criteria

• Autologous transplant within 12 weeks of planned CAR-T cell infusion
• Prior antitumor therapy as follows, prior to apheresis: * Investigational therapy within 14 days, or at least 5 half-lives * Monoclonal antibody therapy within 21 days * Cytotoxic therapy within 14 days * Proteasome inhibitor therapy within 14 days * Immunomodulatory therapy within 14 days * Radiotherapy within 14 days-with the exception that if external radiation therapy (XRT) covers < 5% of marrow reserve-no rest window needed
• Toxicity from previous anticancer therapy must resolve to baseline levels or to grade 1 or less except for alopecia, peripheral neuropathy and baseline hematologic toxicity that otherwise meets inclusion
• Active central nervous system (CNS) multiple myeloma, plasma cell leukemia, primary AL amyloidosis or polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes (POEMS) syndrome
• Active other malignancy, other than non-melanoma skin cancer, carcinoma in situ (e.g., cervix, bladder, or breast). Any fully treated malignancies or indolent, clinically insignificant malignancies can be discussed among the study team to determine eligibility
• HIV seropositivity
• Serologic status reflects active hepatitis B or C infection. Patients that are positive for hepatitis B core antibody, hepatitis B surface antigen (HBsAg), or hepatitis C antibody must have a negative polymerase chain reaction (PCR) prior to enrollment. (PCR positive patients will be excluded)
• Participants with uncontrolled intercurrent illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, uncontrolled cardiac arrhythmia, pulmonary abnormalities, or psychiatric illness/social situations that would limit compliance with study requirements
• Pregnant or breastfeeding women are excluded from this study because CAR-T cell therapy may be associated with the potential for teratogenic or abortifacient effects. Because there is an unknown, but potential risk for adverse events in nursing infants secondary to treatment of the mother with CAR-T cells, breastfeeding should be discontinued. These potential risks may also apply to other agents used in this study * NOTE: Women of childbearing potential must have a negative serum or urine pregnancy test
• Patients with currently symptomatic central nervous system (CNS) pathology such as epilepsy, seizure disorders, paresis, aphasia, uncontrolled cerebrovascular disease, severe brain injuries, dementia, and Parkinson’s disease OR seizure or stroke within 6 months
• History of autoimmune disease (e.g., rheumatoid arthritis, systemic lupus erythematosus) with requirement of immunosuppressive medication within 6 months