AID is a phase I multi-cohort study to assess the safety and tolerability of zamtocabtagene autoleucel (zamto-cel) in patients with refractory autoimmune diseases (SLE-Non renal, SLE-LN, SSc/dcSSc) after receiving standard therapy.
This is a Phase 1, multicohort, dose-finding study evaluating autologous T cells engineered to target dual CD19 and CD20 antigens in subjects with refractory autoimmune diseases following standard therapy. The investigational product, Zamto-cel, is a chimeric antigen receptor T-cell (CAR-T) therapy genetically engineered to enable subjects' T cells to express CARs on their surfaces. Eligible subjects will undergo leukapheresis for the collection of cells required for manufacturing. Prior to infusion of the fresh CAR-T product, subjects will receive a lymphodepleting regimen consisting of cyclophosphamide and fludarabine. The CAR-T cell infusion will be administered intravenously at a dose of 2.5 x 10\^6 or 1.0 x 10\^6 CAR+ cells/kg body weight, based on the dose level assigned to the cohort. The study will initially enroll 3 subjects per cohort in a staggered manner to evaluate safety. Upon confirmation of safety, the study will proceed to cohort-specific recommended Phase 2 dose (RP2D) and dose expansion phases. Subjects will be monitored for up to 1 year to assess safety, preliminary efficacy, and health-related quality of life (HRQoL). Additional long-term follow-up will be conducted under a separate long-term follow-up protocol.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
48
chimeric antigen receptor T-cell (CAR-T) therapy
Lymphodepleting chemotherapy
Lymphodepleting chemotherapy
Froedtert Hospital and the Medical College of Wisconsin
Milwaukee, Wisconsin, United States
RECRUITINGThe incidence and severity of adverse events (AEs), adverse events of special interest (AESIs), and serious adverse events (SAEs)
Time frame: From enrollment through study completion 12 months post zamto-cel infusion
The proportion of subjects with dose-limiting toxicities (DLTs) up to Day 28 and determination of recommended Phase 2 dose (RP2D)
Time frame: From enrollment through Day 28 post zamto-cel infusion
The incidence and severity of cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS)
Time frame: From enrollment through study completion 12 months post zamto-cel infusion
Clinical response at Week 4, 12, 24, and 52 evaluated by defined disease-specific activity measures in SLE-Non renal, SLE-LN, and SSc/dcSSc
Time frame: From enrollment through study completion 12 months post zamto-cel infusion
The duration of remission or low disease activity status in respective diseases under the study
Time frame: From enrollment through study completion 12 months post zamto-cel infusion
Persistence, maximal drug concentration (Cmax), time to reach Cmax, area under the concentration curve, and phenotype of zamto-cel
Time frame: From enrollment through study completion 12 months post zamto-cel infusion
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