A Phase 1/2 Multicenter, Open-label, Single-arm Study to Evaluate the Safety and Efficacy of CD19-targeted Chimeric Antigen Receptor T-cell (CD19 CAR-T; PL001) Therapy in Patients With Relapsed or Refractory B-cell Lymphoma
This is a multiple center, non-randomized, open-label, phase 1/2 study. The primary objective of Phase 1 is to evaluate the safety of PL001 and find the recommended Phase 2 dose (RP2D). The objective of Phase 2 is to evaluate the safety and efficacy of CD19 CAR-T(known as PL001).
• Screening 1:
• Patient is ≥14 years of age, inclusive, at the time of signing the informed consent.
• Histologically confirmed diagnosis of diffuse large B-cell lymphoma (DLBCL), primary mediastinal large B-cell lymphoma (PMLBCL), large B-cell lymphoma transformed from follicular lymphoma (FL), or grade 3a or 3b FL.
• On-site documentation of CD19 on the dominant population of cancer cells.
• Disease status should meet any one of the below:
∙ Patients with previous autologous-hematopoietic stem cell transplantation (auto HSCT) have relapsed, progressive, or refractory disease (defined as having not achieved a CR) after transplantation regardless of lines of systemic therapy.
‣ Patients without previous HSCT have relapsed, progressive, or refractory disease (defined as having not achieved a CR) after at least 2 lines of systemic therapy, including anti-CD20 antibody and anthracycline.
• Have no available effective systemic therapy as judged by the Investigator.
• At least one measurable non-CNS (central nervous system) lesion based on Lugano classification for lymphoma.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2.
• Life expectancy of at least 3 months.
• Patient is male or female.
⁃ A male patient must agree to use a highly effective contraception as detailed in Section 10.4 (Appendix 4) during the treatment period and for at least 2 years after the dose of PL001 and refrain from donating sperm during this period.
⁃ Female Patients:
⁃ A female patient is eligible to participate if she is not pregnant (Section 10.4; Appendix 4), not breastfeeding, and at least one of the following conditions applies:
⁃ • Not a woman of childbearing potential (WOCBP) as defined in Section 10.4 (Appendix 4).
⁃ OR
⁃ • A WOCBP who agrees to follow the contraceptive guidance in Section 10.4 (Appendix 4) during the treatment period and for at least 2 years after the dose of PL001 and refrain from donating ova during this period.
⁃ Patient/patient's parent/legal guardian is capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol.
• Screening 2:
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2.
• CAR-T is successfully manufactured and ready for use, from cells harvested by non mobilized leukapheresis.
• WOCBP who have a negative serum pregnancy test at Screening 2.