A Phase 1b Clinical Trial of CRISPR Delivered Anti-BCMA Chimeric Antigen Receptor T Cells for Treatment of Relapsed or Refractory Multiple Myeloma
This phase Ib trial tests the safety, side effects and best dose of clustered regularly interspaced short palindromic repeats (CRISPR) delivered anti-B-cell maturation antigen (BCMA) chimeric antigen receptor (CAR)-T cells (1XX BCMA CAR-T cells) in treating patients with multiple myeloma that has come back after a period of improvement (relapsed) or that has not responded to previous treatment (refractory). Anti-BCMA CAR-T cell therapy is a type of treatment in which a person's T cells (a type of immune system cell) are changed in the laboratory so they will attack cancer cells. T cells are taken from a patient's blood. Then the gene for a special receptor that binds to a certain protein, such as BCMA, on the patient's cancer cells is added to the T cells in the laboratory by a tool called clustered regularly interspaced short palindromic repeats (CRISPR)-Cas9. The special receptor is called a CAR. Large numbers of the CAR-T cells are grown in the laboratory and given to the patient by infusion for treatment of certain cancers. Giving chemotherapy before CAR-T cells may decrease the number of lymphocytes (a type of white blood cells) in the blood and may help the 1XX BCMA CAR-T cells fight the cancer cells. Treatment with 1XX BCMA CAR-T cells may be safe, tolerable, and/or effective in treating patients with relapsed or refractory multiple myeloma (RRMM).
• Voluntarily sign informed consent form.
• Age ≥18 years.
• Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1.
• Diagnosis of multiple myeloma (per IMWG criteria) with relapsed or refractory disease and has received at least 3 prior lines of therapy including proteasome inhibitor immunomodulatory therapy, and anti-Cluster of differentiation 38 (CD38) antibody therapy.
• Participants may have received BCMA targeted therapy and 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 M-protein greater or equal to 0.5 grams per deciliter (g/dL).
⁃ Urine M-protein greater or equal to 200 milligrams, over a 24-hour period (mg/24 h).
⁃ Serum free light chain (FLC) assay: involved FLC level of ≥ 100 milligrams per liter (mg/L).
• Adequate organ function, defined as:
‣ Adequate bone marrow function for apheresis and lymphodepleting chemotherapy.
⁃ Hgb \>8 gm/dl (transfusions allowed).
⁃ Platelets \>50,000/microliter (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/aspartate aminotransferase (ALT/AST) \< 3 x institutional upper limit of normal (ULN) and Total bilirubin \< 1.5 milligrams per deciliter (mg/dl) x institutional ULN, except with Gilbert's syndrome.
⁃ Serum creatinine clearance (CrCl) ≥ 30 milliliter per minute (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) and adequate pulmonary function (measured by room air pulse oximetry ≥ 92%).
• Women of childbearing potential 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.