CS1-CAR T Therapy Following Chemotherapy in Treating Patients With Relapsed or Refractory CS1 Positive Multiple Myeloma

Recurrent Plasma Cell Myeloma Clinical Trial

Official title: Phase I Study to Evaluate Cellular Immunotherapy Using Memory-Enriched T Cells Lentivirally Transduced to Express a CS1-Targeting, Hinge-Optimized, 41BB-Costimulatory Chimeric Antigen Receptor and a Truncated EGFR Following Lymphodepleting Chemotherapy in Adult Patients With CS1+ Multiple Myeloma

Status Recruiting

Clinical Trial Summary

This phase I trial studies the side effects and best dose of CS1-chimeric antigen receptor (CAR) T therapy after chemotherapy in treating patients who have CS1 positive multiple myeloma that has come back (relapsed) or does not respond to treatment (refractory). Immune cells can be engineered to kill multiple myeloma cells by inserting a piece of deoxyribonucleic acid (DNA) into the immune cells using a lentiviral vector such as CS1, that allows them to recognize multiple myeloma cells. These engineered immune cells, CS1-CAR T cells, may kill multiple myeloma cells.

Clinical Trial Description

PRIMARY OBJECTIVE:

I. To evaluate the safety and tolerability of intravenous (i.v.) delivered autologous CS1-CAR T cells for research participants with CS1+ recurrent/refractory multiple myeloma (MM).

SECONDARY OBJECTIVES:

I. Evaluate the response rates at days 28, 100, and 180 post CAR T cell infusion.

II. Measure the persistence of CS1-CAR T cells in blood and marrow. III. Measure phenotype and anti-tumor functionality of CS1-CAR T cells in marrow and blood.

IV. Measure the levels of cytokines in blood and marrow, and soluble CS-1 in blood post infusion as a surrogate indicator of CAR T cell activity.

V. Evaluate CS-1 expression on MM cancer cells before, during and at progressive disease (PD) to determine antigenic loss.

EXPLORATORY OBJECTIVE:

I. Describe the percentage of MM cells that express CS-1 surface marker before, during and at PD.

OUTLINE: This is a dose-escalation study of CS1-CAR T cells.

Patients undergo leukapheresis over 2-4 hours. Beginning 3-4 weeks, patients receive cyclophosphamide intravenously (IV) on days -4 and/or -3 or fludarabine IV and cyclophosphamide IV on days -5 to -3. Patients then undergo CS1-CAR T therapy over 10-15 minutes on day 0.

After completion of study treatment, patients are followed up at 1 day, at least every 2 days for up to a minimum of 14 days, weekly for 1 month, monthly for 1 year, then periodically for up to 15 years. ;

Related Conditions & MeSH terms

• Multiple Myeloma
• Neoplasms, Plasma Cell
• Recurrent Plasma Cell Myeloma
• Refractory Plasma Cell Myeloma

• NCT number: NCT03710421
• Study type: Interventional
• Source: City of Hope Medical Center
• Status: Recruiting
• Phase: Phase 1
• Start date: April 23, 2019
• Completion date: February 13, 2025