An Open-Label, Non-Randomized, Phase I, Prospective, Dose- Finding Study to Evaluate the Safety and Clinical Activity of GF- CART01 (CD20/19 CAR T Cell) in Subjects With Relapsed or Refractory B-Cell Hematological Malignancies
This is a Phase I, prospective, dose-finding study to evaluate the safety, persistence, and clinical activity of GF-CART01 in subjects aged 18-70 with relapsed or refractory (R/R) B-cell hematological malignancies and failure of two-line or more standard chemotherapies or auto-hematopoietic stem cell transplantation (HSCT).This study is a traditional 3+3 dose-escalation design to observe dose-limiting toxicity (DLT), establish the maximum tolerated dose(MTD)/recommended phase 2 doses (RP2D), and preliminary efficacy of GF-CART01. RP2D may equal to or lower than MTD
• Subjects must be of age ≥ 18 years and ≤ 70 years
• Subjects or their legal guardians must volunteer to participate in the study and sign the informed consent
• Histologically confirmed diagnosis of Diffuse Large B-Cell Lymphoma - Not Otherwise Specified (DLBCL-NOS), follicular lymphoma (FL), Primary Mediastinal Large B-cell Lymphoma (PMBCL), or High-Grade B-Cell Lymphoma (HGBCL) per the world health organization (WHO) Classification Criteria for Lymphoma (2022)
• Tumor cell surface expression of CD19 (+) and/or CD20 (+) by flow cytometry or immunohistochemistry staining
• Relapsed, progressive or refractory disease (defined as have not achieved a complete response) after ≥ two lines of systemic therapy, including anti-CD20 antibody and anthracycline and/or Relapsed, progressive or refractory disease ( defined as have not achieved a complete response) after auto-HSCT
• Subjects have any accessible PET-positive lesion or measurable CT-positive lesion per Lugano 2014 criteria
• Adequate hematologic function: absolute neutrophil count (ANC) \> 1,000/μL, absolute lymphocyte count (ALC) \> 300/μL, platelet count ≥ 75,000/μL, hemoglobin ≥ 8.0 g/dL
• Adequate hepatic function: alanine aminotransferase (ALT) ≤ 5 times upper limit of normal (ULN), aspartate transaminase (AST) ≤ 5 times ULN, total bilirubin ≤ 1.5 times ULN
• Adequate renal function: blood estimated glomerular filtration rate (eGFR) ≥ 60 mL/min/1.73m2 (calculated by Modification of Diet in Renal Disease (MDRD) equation)
⁃ Adequate cardiac function: echocardiogram or multigated blood pool analysis (MUGA) shows left ventricular ejection fraction (LVEF) ≥ 50%; and no clinically significant electrocardiogram (ECG) findings
⁃ Adequate pulmonary function: no active infection in the lungs, blood oxygen saturation in indoor air ≥ 92%
⁃ No clinically significant pleural effusion determined by the investigators
⁃ Estimated survival time ≥ 3 months
⁃ Eastern Cooperative Oncology Group (ECOG) performance status 0 to 2
⁃ Willingness and ability to comply with protocol-stated requirements, instructions, and restrictions in the investigator's judgement