Bispecific CAR T Cells for B-cell Malignancies (BaseCAR-01 Trial)

A vizsgálat adatai

Ki végzi

University Hospital, Basel, Switzerland

Azonosító

NCT07166549

A regiszteradat frissítve

2025. december 24.

Eredeti leírás

This study is to provide locally produced, bispecific CD19 CD20 CAR T cells to patients with B-cell lymphoma/leukemia who have no access to commercial CAR T cells or who have relapsed thereafter. The primary objective is to assess the safety of bispecific anti-CD19, anti- CD20 CAR T cell-therapies after lymphodepleting chemotherapy in patients with B cell malignancies with exhausted standard treatment options.A teljes eredeti leírásKevesebb

A Phase I Trial of Bispecific Anti-CD19, Anti-CD20 CAR T Cells for B Cell Malignancies

This study is to provide locally produced, bispecific CD19 CD20 CAR T cells to patients with B-cell lymphoma/leukemia who have no access to commercial CAR T cells or who have relapsed thereafter. The primary objective is to assess the safety of bispecific anti-CD19, anti- CD20 CAR T cell-therapies after lymphodepleting chemotherapy in patients with B cell malignancies with exhausted standard treatment options.

Bevonási feltételek: Age ≥ 18 years; Diagnosis of B-cell NHL or B-ALL with relapsed, refractory disease and no available standard therapeutic options (including commercially accessible CAR T products), including:; Acute B-lymphoblastic leukaemia; Burkitt lymphoma; Primary CNS lymphoma; DLBCL or high-grade lymphoma of any subtype; Primary mediastinal B cell lymphoma (including grey zone lymphoma); Mantle Cell lymphoma; Low-grade B-cell NHLs: Follicular lymphoma, chronic lymphocytic leukaemia (CLL)/ small lymphocytic lymphoma (SLL), marginal zone lymphoma, hairy cell leukaemia, splenic B-cell lymphoma/leukaemia with prominent nucleoli, and lymphoplasmacytic lymphoma; CD19 and/or CD20 positive disease on most recent evaluation (by immunohistochemistry or flow cytometry); ECOG clinical performance status ≤2; Able to provide written informed consent; Adequate organ function and bone marrow reserve, unless clearly caused by lymphoma and considered reversible, defined as:; Adequate hepatic function: Aspartate Aminotransferase (AST) and Alanine Aminotransferase (ALT) ≤3.0 × (ULN) and serum bilirubin ≤2.0 × ULN (except in congenital hyperbilirubinemia, such as Gilbert syndrome, where direct bilirubin ≤3.0 × ULN is allowed); Adequate renal function: creatinine clearance ≥30 mL/min/1.73 m2; Adequate pulmonary function: Forced Expiratory Volume in 1 second (FEV1) ≥50% (with adequate compliance) and pulse oxygenation > 91% with room air; Adequate cardiac function: Left Ventricular Ejection Fraction (LVEF) ≥ 40%, and no clinically significant arrhythmia; Adequate bone marrow reserve (Hemoglobin ≥80 g/L (with or without recombinant erythropoietin or red blood cell transfusions), Platelets ≥ 50×10\^9/L (with or without platelet transfusions), Absolute Neutrophil Count (ANC) 1.0 ×10\^9/L (prior growth factor support is permitted but must be without support in the 7 days before the laboratory test), Absolute Lymphocyte Count ≥0.3 ×10\^9/L); Willingness to practice highly effective methods of birth control, and, in females of childbearing potential, negative urine or serum pregnancy test before study inclusion, lymphapheresis, and lymphodepleting chemotherapy.

Kizáró feltételek: Requirement for systemic corticosteroids, i.e. ≥20 mg of prednisone or equivalent daily. Other immunosuppressive drugs; Stroke within the previous 6 months, a history of neurodegenerative disorder or overt clinical evidence of dementia or altered mental status; Contraindications, known life-threatening allergies, hypersensitivity, or intolerance to any of the study treatments, including previous severe reactions to dimethyl-sulfoxide; Cytotoxic chemotherapy within 14 days before apheresis collection for CAR-T cells, respectively 12 weeks for Bendamustin and Fludarabine, and 6 months for Alemtuzumab and ATG; Cytotoxic chemotherapy (except for lymphodepletion) within 14 days of CAR-T cell infusion; Patients who have undergone allogeneic hematopoietic stem cell transplantation less than 12 weeks ago, have evidence of active graft-versus-host-disease (GVHD) of any grade, or are currently on immunosuppression; Previous CAR-T cell therapy within 12 weeks of planned CAR-T cell infusion; Investigational treatments within other trials ≤ 4 weeks before enrollment; Lack of safe contraception; Women who are pregnant or breastfeeding; and men who plan to father a child while enrolled in this study within 1 year of receiving bispecific anti-CD20, anti-CD19 CAR T cells; Any organ failure, respectively not meeting the inclusion criteria of adequate organ function, or active, BKuncontrolled autoimmune disease; Uncontrolled coronary artery disease or uncontrolled arrhythmias; Seizure within 6 months of signing the ICF unless related to the primary disease (e.g. CNS lymphoma); Active secondary malignancy that progressed or required treatment in the last 24 months, other than basal or squamous cell carcinomas of the skin. Further allowed exceptions are: Non-muscle-invasive bladder cancer, non-invasive cervical cancer, or other malignancy that is considered cured or to have a minimal risk of recurrence (e.g. a history of localized prostate or localized and treated breast cancer); Uncontrolled active bacterial, fungal, or viral infections, particularly active hepatitis B, hepatitis C, or HIV infection.

ClinicalTrials.gov NCT07166549