NCT05950113

CART-BCMA/CS1 in Treating Patients With Relapsed or Refractory Multiple Myeloma

Phase I Dose-Escalation Study of BCMA/CS1 Bispecific Chimeric Antigen Receptor (CAR)-T Cells for Relapsed/Refractory Multiple Myeloma

• Status: Withdrawn
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 0 (actual)
• Sponsor: Jonsson Comprehensive Cancer Center · Academic / Other
• Sex: All
• Age: 18 Years – 74 Years
• Healthy volunteers: Not accepted

Summary

This phase I trial studies the side effects and how well CART-BCMA/CS1 works in treating patients with multiple myeloma (MM) that has come back (relapsed) or that does not respond to treatment (refractory). Chimeric antigen receptor (CAR) T-cell therapy is a type of treatment in which a patient'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 on the patient's cancer cells is added to the T cells in the laboratory. The special receptor is called a chimeric antigen receptor (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, including MM. Immune cells can be engineered to kill MM cells by inserting a piece of deoxyribonucleic acid (DNA) into the immune cells using a lentiviral vector, that allows them to recognize MM cells. CART-BCMA cells are such modified T cells that target markers called CS1 or B-cell maturation antigen (BCMA), which is expressed by a type of white blood cell called a "B-cell", which are cells that may help the MM cells grow. These engineered CART-BCMA/CS1 cells may kill MM cells.

Detailed description

PRIMARY OBJECTIVE: I. To evaluate the safety of CART-BCMA/CS1 cells in patients with R/R MM for determination of a recommended phase 2 dose (RP2D). SECONDARY OBJECTIVES: I. To describe the overall adverse event profile of CART-BCMA/CS1 cells. II. To investigate the efficacy of CART-BCMA/CS1 cells. III. To evaluate the persistence of CART-BCMA/CS1 cells. EXPLORATORY OBJECTIVES: I. To characterize the cytokine environment following CART-BCMA/CS1 cell infusion and to evaluate changes in the setting of CRS. II. To evaluate changes in T-cell subsets and function following CART-BCMA/CS1 cell infusion. III. To examine the change in expression of BCMA and CS1 on clonal plasma cells in the bone marrow and/or extramedullary disease after CART-BCMA/CS1 cell treatment. IV. To evaluate for plasma-cell aplasia. OUTLINE: This is a first-in-human, phase I, single-arm, open-label, dose-escalation study. Patients undergo leukapheresis 35 to 21 days before Infusion Day (I-Day -35 to I-Day -21) and receive cyclophosphamide intravenously (IV) over 60 minutes and fludarabine IV over 30 minutes on I-Days -5, -4, and -3. Patients then receive the CART-BCMA/CS1 infusion IV on I-Day -0 on study. Patients undergo echocardiography (ECHO), electrocardiogram (ECG), and magnetic resonance imaging (MRI) during screening. Patients undergo bone marrow biopsy and/or bone marrow aspirate screening, between I-Day -28 to I-Day -5, I-Day 30, and at 1 year post CART-BCMA/CS1 infusion. Patients also undergo fluorodeoxyglucose F-18 (FDG) positron emission tomography/computed tomography (PET/CT) during screening, between I-Day -28 to I-Day -5, I-Day 90 and I-Day 180 and every 3 months thereafter. After completion of study treatment, patients are followed up every 3 months for 2 years, every 6 months until 5 years, then annually for 15 years.

Conditions

• Recurrent Multiple Myeloma
• Refractory Multiple Myeloma

Interventions

Type	Name	Description
PROCEDURE	Bone Marrow Aspiration	Undergo bone marrow biopsy and aspiration
PROCEDURE	Bone Marrow Biopsy	Undergo bone marrow biopsy and aspiration
PROCEDURE	Computed Tomography	Undergo PET/CT
DRUG	Cyclophosphamide	Receive IV
PROCEDURE	Echocardiography	Undergo ECHO
DRUG	Fludarabine	Receive IV
OTHER	Fludeoxyglucose F-18	Receive IV
OTHER	Immunotherapy	Receive CART-BCMA/CS1 cells IV
PROCEDURE	Leukapheresis	Undergo leukapheresis
PROCEDURE	Magnetic Resonance Imaging	Undergo MRI
PROCEDURE	Positron Emission Tomography	Undergo PET/CT

Timeline

• Start date: 2024-03-28
• Primary completion: 2027-03-28
• Completion: 2028-03-28
• First posted: 2023-07-18
• Last updated: 2024-05-01

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study