This study is testing Allo-QuadCAR01-T, a new off-the-shelf CAR-T therapy for people with hard-to-treat B-cell cancers. Unlike current CAR-T treatments that use a patient's own cells, this therapy uses donor cells that are ready to use, which can save time and reduce costs. It targets two proteins, CD19 and CD20, to lower the chance of relapse and uses gene editing to make it safer. The trial has three parts: first to find a safe dose, then to confirm it, and finally to test how well it works in patients with diffuse large B-cell lymphoma (DLBCL). Patients will get one infusion after chemotherapy to prepare their body. The main goal is to check safety and see how many patients have a complete response by Week 13. About 160 patients will take part, and researchers will follow them for up to 15 years.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
178
Intravenous infusion over 3 days (d-5 to d-3)
Intravenous infusion over 3 days (d-5 to d-3)
Single dose IV infusion on Day 1
University of Chicago
Chicago, Illinois, United States
NOT_YET_RECRUITINGNorthwestern University
Evanston, Illinois, United States
NOT_YET_RECRUITINGBrown University Health
Providence, Rhode Island, United States
NOT_YET_RECRUITINGSarah Cannon Research Institute
Nashville, Tennessee, United States
RECRUITINGMD Anderson Cancer Center
Houston, Texas, United States
NOT_YET_RECRUITINGUniversitätsklinikum Ulm
Ulm, Baden-Wurttemberg, Germany
RECRUITINGUniversitätsklinikum Erlangen
Erlangen, Bavaria, Germany
RECRUITINGKlinikum der Universität München
Munich, Bavaria, Germany
RECRUITINGUniversitätsklinikum Marburg
Marburg, Hesse, Germany
NOT_YET_RECRUITINGUniklinikum Erlangen
Essen, North Rhine-Westphalia, Germany
NOT_YET_RECRUITING...and 3 more locations
Incidence of AEs defined as DLTs
Incidence and intensity of adverse events (AEs) graded according to Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0, except for cytokine release syndrome (CRS), immune effector cell associated neurotoxicity syndrome (ICANS), tumor lysis syndrome, and graft versus host disease (GvHD), which will be graded according to widely accepted specialized criteria
Time frame: At the end of cycle 1 (in total 28 days, given no treatment interruptions)
To determine the maximum tolerated dose (MTD)
MTD
Time frame: At the End of Cycle 1 (in total 28 days, given no treatment interruptions)
To determine the incidence of dose-limiting toxicities (DLT)
Incidence of DLTs
Time frame: At the end of cycle 1 (in total 28 days, given no treatment interruptions)
Phase 2: Complete response rate (CRR)
Complete remission rate is defined as the proportion of participants with complete remission, per international working group (IWG) Lugano classification, as assessed by the investigator.
Time frame: Up to week 13
Pharmacokinetics of Allo-QuadCAR01-T in PB in patients after infusion of Allo-QuadCAR01-T
Detection of VCN in blood samples
Time frame: Up to 24 months
To investigate the impact of Allo-QuadCAR01-T on MRD
MRD levels in responding CLL patients
Time frame: Up to 24 months
To evaluate immunogenicity against Allo-QuadCAR01-T
Incidence of ADA1 formation against anti-CD19/CD20 ECD and ADA2 formation against the RevCAR ECD of Allo-QuadCAR01-T
Time frame: Up to 24 months
To evaluate host immune cell depletion and reconstitution resulting from LD
Enumeration of host PB B-cell, T cell, and NK cell numbers
Time frame: Up to 24 months
Overall Response Rate (ORR)
ORR is defined as the proportion of participants with best objective response of either a CR or a partial response (PR) during the trial prior to any new anti-lymphoma, anti-CLL therapy or local radiotherapy for lymphoma , per the Lugano Classification, as determined by the investigator.
Time frame: Up to 24 months
Progression-Free Survival (PFS)
PFS is defined as the time from Allo-QuadCAR01-T infusion to disease progression per the Lugano Classification, as determined by investigator review or death from any cause.
Time frame: Up to 24 months
Duration of Response (DOR)
DOR is defined as the time from first objective response to disease progression or death from any cause among participants who have achieved CR or PR per the Lugano Classification, as determined by the investigator.
Time frame: Up to 24 months
Overall Survival (OS)
OS is defined as the time from Allo-QuadCAR01-T infusion to death from any cause.
Time frame: Up to 24 months
Time to Next Treatment (TTNT)
TTNT is defined as time from Allo-QuadCAR01-T infusion to the start of subsequent new anti-lymphoma, anti-CLL therapy or local radiotherapy for lymphoma.
Time frame: Up to 24 months
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