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

Phase 1

Recruiting

• Conditions: Chronic Lymphocytic Leukemia (CLL); Central Nervous System Lymphoma; Non Hodgkin Lymphoma (NHL); Mantle Cell Lymphoma (MCL); Follicular Lymphoma; Marginal Zone Lymphoma; Diffuse Large B Cell Lymphoma; Primary Mediastinal Large B-cell Lymphoma (PMBCL)
• Interventions: Biological: 8/12-Day Production of Car-T Cells; Biological: 8/12-Day Production of Cryopreserved Car-T Cells; Biological: 12-Day Production of Car-T Cells

• Registration Number: NCT04186520
• Lead Sponsor: Medical College of Wisconsin

Brief Summary

This is a Phase I/II, interventional, single-arm, open-label, treatment study designed to evaluate the safety and efficacy of Interleukin-7 and Interleukin-15 (IL-7/IL-15) manufactured chimeric antigen receptor (CAR)-20/19-T cells as well as the feasibility of a flexible manufacturing schema in adult patients with B cell malignancies that have failed prior therapies.

Detailed Description

This is a Phase 1/Phase 2 study. The objectives are as follows:

1. Phase 1: Determine the safety of a fixed dose of 2.5x10\^6 CAR-20/19-T cells/kg expanded with IL-7/IL-15 in relapsed refractory B-cell NHL with flexible 8/12-day manufacturing and a fixed 12-day manufacturing process along with an evaluation in chronic lymphocytic leukemia (CLL) and central nervous system (CNS) lymphoma.

2. Phase 1b: Four arms:

Arm A: 8/12 flexible manufacturing arm. Determine safety, efficacy, and feasibility of flexible manufacturing.

Arm B: Fixed 12-day manufacturing arm. Determine safety and efficacy of fixed CAR manufacturing.

Arm C: 8/12 flexible manufacturing with mandated cryopreservation prior to infusion of LV20.19 CAR T-cells. Determine the impact of cryopreservation on safety or efficacy of LV20.19 CAR T-cells.

Arm D: 8/12 flexible manufacturing expansion cohort in CLL. Determine safety and efficacy in CLL.

Arm E: 8/12 flexible manufacturing cohort in central nervous system (CNS) lymphoma.

3. Phase 2

1. Determine the 3-month CR rate of CAR-20/19-T cells in MCL

2. Determine the feasibility of a flexible manufacturing process of CAR-20/19-T cells from patient apheresis products using the CliniMACS Prodigy Cell processing device

Study Timeline

• Study First Submitted: 2019-12-02
• Study First Submitted QC: 2019-12-02
• Study First Posted: 2019-12-04
• Study Start: 2020-05-18
• Status Verified: 2024-06
• Last Update Submitted: 2024-06-08
• Last Update Posted: 2024-06-11
• Primary Completion: 2025-01
• Study Completion: 2025-01

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 100

Inclusion Criteria

Not provided

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Exclusion Criteria

Not provided

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
8/12 Day Production of CAR-T for NHL	8/12-Day Production of Car-T Cells	Phase 1: Determine safety of 2.5x10\^6 cells/kg IL-7/IL-15 expanded CAR-20/19-T cells in patients with relapsed, refractory B-cell NHL. Patients will be enrolled in 3+3 fashion. Phase 1b: Six to nine patient expansion cohorts at eight or 12-day manufacturing. If six patients are enrolled in Phase 1 then only six additional patients will be added. If three patients are enrolled in Phase 1 then nine additional patients will be treated for a total of 12 in each group.
Phase 2 - Efficacy of CAR-20/19-T cells in MCL	8/12-Day Production of Car-T Cells	Single-stage Phase II design with three-month CR as the target endpoint.
8/12 Day Production of CAR-T for Relapsed/Refractory Primary or Secondary CNS Lymphoma	8/12-Day Production of Car-T Cells	Phase 1: Determine safety of 2.5x106 cells/kg IL-7/IL-15 expanded CAR-20/19-T cells in patients with primary/secondary central nervous system (CNS) lymphoma. Phase 1b: Safety and efficacy will be evaluated in this study that will enroll 12 to 24 patients.
8/12 Day Production of CAR-T for CLL	8/12-Day Production of Car-T Cells	Phase 1: Determine safety of 2.5x10\^6 cells/kg IL-7/IL-15 expanded CAR-20/19-T cells in patients with CLL. Patients will be enrolled in 3+3 fashion. Phase 1b: The enrollment will cap at 24 subjects.
8/12 Flexible Manufacturing with Mandated Cryopreservation	8/12-Day Production of Cryopreserved Car-T Cells	8/12 flexible manufacturing with mandated cryopreservation prior to infusion of LV20.19 CAR T-cells. The enrollment will cap at 24 subjects.
12-Day Production of Car-T Cells for NHL	12-Day Production of Car-T Cells	Phase 1: Determine safety of 2.5x10\^6 cells/kg IL-7/IL-15 expanded CAR-20/19-T cells in patients with relapsed, refractory B-cell NHL. Patients will be enrolled in 3+3 fashion. Phase 1b: Six to nine patient expansion cohorts at 12-day manufacturing. If six patients are enrolled in Phase 1 then only six additional patients will be added. If three patients are enrolled in Phase 1 then nine additional patients will be treated for a total of 12 in each group.

Primary Outcome Measures

Name	Time	Method
Number of Adverse Events after CAR 20/19-T cell infusion	Within the first 28 days after infusion	Incidence of adverse events using NCI CTCAE version 5.0.

Trial Locations

Locations (1)

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