Study of CAR-20/19-T Cells in Patients With Relapsed Refractory B Cell

Phase 1

Completed

• Conditions: Lymphoma, B-Cell; Chronic Lymphocytic Leukemia; Small Lymphocytic Lymphoma; Lymphoma, Non-Hodgkin
• Interventions: Biological: CAR-20/19-T cells (2.5 x10^6 CAR-20/19-T cells/kg); Biological: CAR-20/19-T cells (1.0 x10^5 CAR-20/19-T cells/kg); Biological: CAR-20/19-T cells (2.5 x10^5 CAR-20/19-T cells/kg); Biological: CAR-20/19-T cells (7.5 x10^5 CAR-20/19-T cells/kg)

• Registration Number: NCT03019055
• Lead Sponsor: Medical College of Wisconsin

Brief Summary

This is a phase 1/1b, interventional single arm, open label, treatment study designed to evaluate the safety and feasibility of infusion of autologous T cells engineered to contain an anti-cluster of differentiation 19 (CD19) and anti-cluster of differentiation 20 (CD20) single chain variable fragment (scFv) coupled to cluster of differentiation CD3ζ (CD3ζ) and co-stimulatory domain 4-1BB (4-1BB) signaling domains in patients with relapsed and/or refractory CD19 or CD20 positive B cell malignancies

Detailed Description

This is a single center, single arm, open label phase I/1b study to demonstrate the feasibility of manufacturing CAR-T cells expressing tandem receptors against both CD20 and CD19 (CAR-20/19-T) in a completely closed system using the CliniMACS Prodigy device and then determine the safety of this dual targeted CAR in a first-in-human study of patients with relapsed and refractory B cell malignancies. Secondary outcomes will include response rates, and observed toxicities of the treatment, specifically the development of cytokine release syndrome (CRS), an inflammatory storm that has been seen with previous CAR-T therapies.

Study Timeline

• Study First Submitted: 2017-01-05
• Study First Submitted QC: 2017-01-10
• Study First Posted: 2017-01-12
• Study Start: 2017-10-16
• Primary Completion: 2019-10-01
• Results First Submitted: 2021-04-12
• Results First Submitted QC: 2021-05-06
• Results First Posted: 2021-05-07
• Study Completion: 2021-08-24
• Status Verified: 2023-07
• Last Update Submitted: 2023-07-24
• Last Update Posted: 2023-07-27

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 26

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
CAR-20/19-T cells (2.5 x10^6 CAR-20/19-T cells/kg)	CAR-20/19-T cells (2.5 x10^6 CAR-20/19-T cells/kg)	Dose Escalation Phase: CAR-20/19-T transduced with a lentiviral vector to express an anti CD19 and anti CD20 tandem receptor coupled to CD3ζ and 4-1BB signaling domains will be administered by IV injection. Patients will receive one of four dose levels based the study protocol. Cells will be given over 2 days, 30% of cells infused on Day 0 and 70% of cells infused on Day 1 in the Phase 1 portion and as a single infusion in the Phase 1b portion.
CAR-20/19-T cells (1.0 x10^5 CAR-20/19-T cells/kg)	CAR-20/19-T cells (1.0 x10^5 CAR-20/19-T cells/kg)	Dose Escalation Phase: CAR-20/19-T transduced with a lentiviral vector to express an anti CD19 and anti CD20 tandem receptor coupled to CD3ζ and 4-1BB signaling domains will be administered by IV injection. Patients will receive one of four dose levels based the study protocol. Cells will be given over 2 days, 30% of cells infused on Day 0 and 70% of cells infused on Day 1 in the Phase 1 portion and as a single infusion in the Phase 1b portion.
CAR-20/19-T cells (2.5 x10^5 CAR-20/19-T cells/kg)	CAR-20/19-T cells (2.5 x10^5 CAR-20/19-T cells/kg)	Dose Escalation Phase: CAR-20/19-T transduced with a lentiviral vector to express an anti CD19 and anti CD20 tandem receptor coupled to CD3ζ and 4-1BB signaling domains will be administered by IV injection. Patients will receive one of four dose levels based the study protocol. Cells will be given over 2 days, 30% of cells infused on Day 0 and 70% of cells infused on Day 1 in the Phase 1 portion and as a single infusion in the Phase 1b portion.
CAR-20/19-T cells (7.5 x10^5 CAR-20/19-T cells/kg)	CAR-20/19-T cells (7.5 x10^5 CAR-20/19-T cells/kg)	Dose Escalation Phase: CAR-20/19-T transduced with a lentiviral vector to express an anti CD19 and anti CD20 tandem receptor coupled to CD3ζ and 4-1BB signaling domains will be administered by IV injection. Patients will receive one of four dose levels based the study protocol. Cells will be given over 2 days, 30% of cells infused on Day 0 and 70% of cells infused on Day 1 in the Phase 1 portion and as a single infusion in the Phase 1b portion.

Primary Outcome Measures

Name	Time	Method
Number of Adverse Events After CAR 20/19-T Cell Infusion	28 days after infusion	This measure is the number of adverse events with grade 3 to 5 severity per Common Terminology Criteria for Adverse Events (ver. 4.03) occurring within the first 28 days following infusion.

Trial Locations

Locations (1)

Froedtert Hospital & Medical College of Wisconsin; 🇺🇸 Milwaukee, Wisconsin, United States