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).
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.
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.
Chronic lymphocytic leukemia with Richter's transformation.
Primary CNS lymphoma. (Non-primary CNS lymphoma with CNS involvement is eligible).
Primary intra-ocular lymphoma.
Prior CD19 targeted therapy, such as CAR-T, Bi-specific T-cell engagers (BiTE), or monoclonal antibody.
Single group
CD19-targeted chimeric antigen receptor T-cell
Biological/VaccineDrug: Fludarabine patients will receive a lymphodepletion chemotherapy with Fludarabine 25 mg/m2/day IV for 3 days on Day-5 to Day-3(a safe window for a small subset of patients will be D -7 to D -3). Drug: Cyclophosphamide patients will receive a lymphodepletion chemotherapy with cyclophosphamide 300 mg/m2/day IV for 3 dys Day-5 to Day-3(a safe window for a small subset of patients will be D -7 to D -3). Biological: CD19 CAR-T CD19 CAR-T cells will be administered using as a single dose at 0.1-9\*10\^6 cells/kg on Day 0 after completion of the lymphodepletion chemotherapy. The body weight calculated for PL001 dose is the actual body weight on the day of leukapheresis.
Phase 1: Dose-limiting toxicities
Dose-limiting toxicities through 30 days after PL001 infusion
Phase 2: best overall response (BOR)
The best overall response (BOR) comprising patients with partial and complete responses according to Lugano criteria assessed based on the image review result provided by the Independent Central Review from the start of infusion of PL001 until next subsequent cancer-specific therapy, disease progression, death, or end of study, whichever comes first
Phase 1 and Phase 2: Treatment-related adverse events
Treatment-related adverse events assessed by CTCAE v 5.0. Overall grading of Cytokine Release Syndrome, immune effector cell associated neurotoxicity syndrome, based on the American Society for Transplantation and Cellular Therapy (ASTCT) criteria.
Phase 1 and Phase 2: Best overall response (BOR)
The BOR of patients with partial and complete responses according to Lugano criteria assessed by the Investigator.
Phase 1 and Phase 2: Median duration of response (mDOR)
Median duration of response (mDOR) measured from the time of initial documented response (complete response or partial response) until documented disease progression or death.
Phase 1 and Phase 2: Progression-free survival (PFS)
Progression-free survival (PFS) defined as the time from the infusion of PL001 until objective disease progression or death, whichever occurs first.
Phase 1 and Phase 2: Pharmacokinetic (PK) profile of PL001-Persistence of PL001 by flow cytometry
Persistence of PL001 in peripheral blood using flow cytometry
Phase 1 and Phase 2: Pharmacokinetic (PK) profile of PL001-Persistence of PL001 by qPCR
PL001 transgene levels by qPCR (quantitative polymerase chain reaction) in peripheral blood
Phase 1 and Phase 2: Quality assurance of the product
Rates for successful production and infused patients
Phase 1 and Phase 2: To assess the cytokine biomarkers
Cytokine concentrations in peripheral blood
Click on the lead sponsor to view all of their trials.
