A Phase 1b Clinical Trial of CRISPR Delivered Anti-BCMA Chimeric Antigen Receptor T Cells for Treatment of Relapsed or Refractory Multiple Myeloma
Thomas Martin, MD
Summary
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).
Description
PRIMARY OBJECTIVES: Dose Escalation: I. To evaluate the safety and toxicity of administering Chimeric Antigen Receptor T Cells (CAR-T) cells targeting BCMA to participants with Relapsed or Refractory Multiple Myeloma (RRMM). II. To determine the maximum tolerated dose (MTD) for anti-BCMA CAR-T cells. Dose Expansion: III. Determine whether administering conforming CAR T-cell product targeting BCMA to participants with RRMM increases the overall response rate (ORR) compared with historical data for non-CAR agents per International Myeloma Working Group (IMWG) response criteria. IV. Determi…
Eligibility
- Age range
- 18+ years
- Sex
- All
- Healthy volunteers
- No
Inclusion Criteria: 1. Voluntarily sign informed consent form. 2. Age ≥18 years. 3. Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1. 4. 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. 5. Participants may have received BCMA targeted therapy and must be at least 6 months from last BCMA therapy. 6. Participants must have documented evidence of progressive disease within…
Interventions
- ProcedureLeukapheresis
Undergo Leukapheresis
- DrugCyclophosphamide
Given Intravenously (IV)
- BiologicalChimeric Antigen Receptor T cells (CAR-T) Targeting BCMA
Given Intravenously (IV)
- BehavioralQuality of Life (QoL) Questionnaires
Ancillary studies
- ProcedureBone Marrow Biopsy
Undergo biopsy
- BiologicalBiospecimen Collection
Undergo Blood, serum and urine collection
- DrugFludarabine
Location
- University of California, San FranciscoSan Francisco, California