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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).
Full description
Cluster of differentiation (CD) 19 chimeric antigen receptor T-cell (CAR-T) has been a very promising treatment option for multiple types of B-cell lymphoma. Kymriah® (tisagenlecleucel, Novartis) and Yescarta® (axicabtagene ciloleucel, Gilead) were licensed by the United States Food and Drug Administration (US FDA) and European Medicines Agency (EMA) in 2017 to treat relapsed or refractory B-cell acute lymphoblastic leukemia (B-ALL), diffuse large B-cell lymphoma (DLBCL), and High-grade B-cell lymphoma (HGBCL). A third anti-CD19 CAR-T product, Tecartus (brexucabtagene autoleucel, Gilead) was approved by the US FDA for relapsed and refractory mantle cell lymphoma (MCL) in July 2020. In February 2021, another product, Breyanzi® (lisocabtagene maraleucel, Juno Therapeutics, Inc.), was approved by the US FDA for relapsed or refractory large B-cell lymphoma after two or more lines of systemic therapy, including DLBCL not otherwise specified (including DLBCL arising from indolent lymphoma), high-grade B-cell lymphoma, Primary mediastinal large B cell lymphoma (PMLBCL), and Gr. 3b FL.
Currently, in Taiwan, no CD19 CAR-T therapies are available commercially.This Phase 1/Phase 2 study will test PL001, a CD19 CAR-T therapy manufactured by Pell Bio-Med Technology Co., Ltd., as a monotherapy for relapsed or refractory B-cell lymphoma. The Phase 1 of the study will be conducted to establish a dose range that is well tolerated by the majority of patients and to provide a safety profile of PL001 in the target patient population. The results of the Phase 1 of the study will recommend the dose selection for the Phase 2 of the study. Phase 2 of the study will assess the efficacy and safety of PL001 in patients with relapsed or refractory B cell lymphoma.
Enrollment
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Ages
Volunteers
Inclusion criteria
Screening 1:
Patient is 14 to 70 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:
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:
Exclusion criteria
Screening 1:
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.
History of cancers (includes myelodysplastic syndrome) other than non-melanoma skin cancer or carcinoma in situ (e.g., cervix, bladder, breast) unless disease-free without active treatment for at least 3 years.
History of allogeneic HSCT.
History of autologous HSCT within 3 months prior to consent.
Received any investigational product within 4 weeks prior to consent.
Systemic anticancer therapy within 3 weeks prior to apheresis.
Long-term use of systemic corticosteroids, defined as daily use >10 mg of prednisolone or equivalent, within 2 weeks prior to leukapheresis.
Exception examples:
Use of long-acting and short-acting myeloid growth factor within 2 weeks, 5 days prior to leukapheresis, respectively.
Received anti-thymocyte globulin within 4 weeks prior to consent.
Intrathecal chemotherapy within 1 week prior to leukapheresis.
Inadequate major organ functions at Screening, which were defined as any of below:
Active hepatitis B virus (HBV) infection defined as detectable HBV DNA (Patients with positive anti-hepatitis B core antibody [HBcAb] must consent to regular monitoring of HBV DNA, and anti-HBV prophylaxis with oral anti-viral agent (such as entecavir) is mandatory until End-of-Study visit [Visit 15].)
Active hepatitis C virus (HCV) infection defined as positive anti- HCV antibody plus detectable HCV RNA.
Positive for human immunodeficiency virus (HIV) or human T-cell lymphotropic virus (HTLV) infection.
Uncontrolled acute life-threatening bacterial, viral, or fungal infection (e.g., the need for intravenous therapeutic antibiotics, blood culture positive ≤72 hours prior to apheresis).
Any medical conditions which might compromise the patient's safety from leukapheresis, lymphodepletion chemotherapy, or CAR-T therapy and anticipated AEs, according to the Investigator's evaluation.
22.Patients with insufficient leukapheresis cells.
Screening 2:
Inadequate major organ functions at Screening which were defined as any of below:
Long-term use of systemic corticosteroids, defined as daily use >10 mg of prednisolone or equivalent.
Exception examples:
Use of long-acting and short-acting myeloid growth factor within 12 days, 2 days prior to lymphodepletion therapy, respectively.
Uncontrolled acute life-threatening bacterial, viral, or fungal infection (e.g. the need for intravenous therapeutic antibiotics, blood culture positive ≤72 hours prior to lymphodepletion).
Any medical condition which might compromise the patient's safety because of lymphodepletion chemotherapy or CAR-T therapy and anticipated AEs, according to the Investigator's opinion.
Primary purpose
Allocation
Interventional model
Masking
49 participants in 1 patient group
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Central trial contact
Cherry Lo, MSC
Data sourced from clinicaltrials.gov
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