Current treatments for relapsed/refractory hematopoietic malignancies such as B-cell lymphomas (BCLs) and peripheral T-cell lymphomas (PTCLs) are far from satisfactory. CD5 is widely expressed in multiple subtypes of BCLs and PTCLs but rarely found in normal tissues except certain types of lymphocytes. Chimeric antigen receptor (CAR) T cells against CD5 offer another potential therapeutic option for patients with relapsed/refractory CD5 positive hematopoietic malignancies. In the current study, the safety and efficacy of a novel CAR T cell therapy, termed CT125A cells, are evaluated in patients with relapsed/refractory CD5+ hematopoietic malignancies. The endogenous CD5 in CT125A cells is knocked out via CRISPR/Cas9 genome editing technology to prevent fratricide during CAR T cells manufacturing.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
18
Subjects will undergo leukapheresis to isolate peripheral blood mononuclear cells (PBMCs) to manufacture CT125A cells, during which cyclophosphamide and fludarabine will be administered for the purpose of lymphocytes depletion. After lymphodepletion, subjects will receive one dose treatment with CT125A cells by intravenous (IV) infusion. The initial dose of 1×10\^6 CAR+ T cells/kg will be infused on day 0.
Subjects will be given IV infusion of cyclophosphamide 500 mg/m2/day and fludarabine 30 mg/m2/day on days -4, -3 and -2
Incidence and types of dose limited toxicities (DLTs) following infusion of CT125A chimeric antigen receptor (CAR) T cells
Incidence and types of dose limited toxicities (DLTs) after administration of CT125A cells in patients with relapsed/refractory CD5+ hematopoietic malignancies will be recorded at 3 dose levels to investigate the maximum tolerated dose of CT125A. DLT is defined as the following adverse events that occur during the first 28 days after CT125A infusion and are definitely or probably related to CT125A cells: 1) Cytokine release syndrome equal or greater than grade 4 lasting longer than 3 days graded by ASTCT 2019 consensus; 2) Grade 4 immune effector cell-associated neurotoxicity syndrome graded by ASTCT 2019 consensus; 3) Grade 4 hematological toxicity lasting longer than 28 days except for T cell aplasia; 4) Non-hematological toxicity equal or greater than grade 3 lasting longer than 7 days or Grade 4 non-hematological toxicity lasting longer than 3 days.
Time frame: 28 days after CAR T cell infusion
Incidence and severity of adverse events (AEs) following infusion of CT125A chimeric antigen receptor (CAR) T cells
Incidence of adverse events (AEs) after administration of each dose of CT125A cells in patients with relapsed/refractory CD5+ hematopoietic malignancies will be recorded and the severity of AEs will be graded according to the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 except that cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome will be graded according to the consensus by ASTCT in 2019. AE is defined as any untoward medical occurrence in a patient after CAR T cell infusion and which does not necessarily have a causal relationship with this treatment.
Time frame: 2 years after CAR T cell infusion
Overall response rate (ORR) at 4th week and 12th week
At 4 weeks and 12 weeks after CT125A infusion, the response rate of subjects that are evaluated as complete response (CR) and partial response (PR) according to Lugano 2014 criteria will be measured
Time frame: 12 weeks after CAR T cell infusion
Time to first response after CT125A cells infusion
The number of days elapsed between the time when subjects receive CT125A infusion and the time when the response is first evaluated as partial response (PR) or complete response (CR) will be measured
Time frame: 2 years after CAR T cell infusion
Time to complete response (CR) after CT125A infusion
The number of days elapsed between the time when subjects receive CT125A infusion and the time when the response is first evaluated as complete response (CR) will be measured
Time frame: 2 years after CAR T cell infusion
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