Status:
RECRUITING
Phase 1/2 Study of CD19 Chimeric Antigen Receptor T-cell (CD19 CAR-T; PL001) for Relapsed or Refractory B-cell Lymphoma
Lead Sponsor:
Pell Bio-Med Technology Co., Ltd.
Conditions:
Diffuse Large B Cell Lymphoma
Primary Mediastinal Large B Cell Lymphoma
Eligibility:
All Genders
14+ years
Phase:
PHASE1
PHASE2
Brief Summary
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 ...
Detailed 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 ...
Eligibility Criteria
Inclusion
- 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.
Exclusion
- 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:
- Nasal, ophthalmic, inhaled, intra-articular, and topical steroid preparation.
- Short term systemic steroid for drug, contrast, or blood transfusion allergic reaction management.
- Low dose maintenance steroid therapy for other conditions (e.g., asthma).
- 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:
- absolute neutrophil count (ANC) \<500/µL
- Absolute lymphocyte count (ALC) \<300/µL, excluding leukemic cells.
- Hemoglobin (Hb) \<8.0 g/dL
- Platelet count \<75,000/µL without transfusion support within 3 days
- e. Baseline O2 saturation \<92% by pulse oximetry at room air
- Significant CNS diseases such as dementia, major stroke, seizure while under antiepileptic drug
- Aspartate aminotransferase (AST) \>5 × upper limit of normal (ULN) and alanine aminotransferase (ALT) \>5 × ULN, or total bilirubin \>2 × ULN (except for constitutional jaundice)
- Serum creatinine \> 1.5 × ULN and estimated glomerular filtration rate (eGFR) \< 60 mL/min/1.73 m², as calculated by the Cockcroft-Gault formula.
- Significant cardiac disease including but not limited to: left ventricular ejection fraction (LVEF) \<50%, QTc(the corrected QT interval) \> 480 msec based on Fredericia's formula, clinically significant arrhythmias, history of myocardial infarction or unstable angina within 3 months prior to consent.
- 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).
- 21\. 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.
- Patients with insufficient leukapheresis cells.
- Screening 2:
- Inadequate major organ functions at Screening which were defined as any of below:
- ANC \<500/µL
- Hb \<8.0 g/dL
- Platelet count \<50,000/µL, without transfusion support within 3 days
- Baseline O2 saturation \<92% by pulse oximetry on room air
- AST \>5 × ULN and ALT\>5 × ULN, or total bilirubin \>2 × ULN (except for constitutional jaundice)
- Significant CNS diseases such as dementia, major stroke, seizure while under antiepileptic drug
- Serum creatinine \> 1.5 × ULN and estimated glomerular filtration rate (eGFR) \< 60 mL/min/1.73 m², as calculated by the Cockcroft-Gault formula.
- Long-term use of systemic corticosteroids, defined as daily use \>10 mg of prednisolone or equivalent.
- Exception examples:
- Nasal, ophthalmic, inhaled, intra-articular, and topical steroid preparation.
- Short term systemic steroid for drug, contrast, or blood transfusion allergic reaction management.
- Low dose maintenance steroid therapy for other conditions (e.g., asthma).
- 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.
Key Trial Info
Start Date :
May 31 2022
Trial Type :
INTERVENTIONAL
Allocation :
ESTIMATED
End Date :
March 31 2027
Estimated Enrollment :
49 Patients enrolled
Trial Details
Trial ID
NCT05326243
Start Date
May 31 2022
End Date
March 31 2027
Last Update
May 13 2025
Active Locations (5)
Enter a location and click search to find clinical trials sorted by distance.
1
National Taiwan University Hospital
Taipei, Taiwan, Taiwan, 100225
2
Kaohsiung Medical University Chung-Ho Memorial Hospital
Kaohsiung City, Taiwan, 807377
3
Chi Mei Medical Center
Tainan, Taiwan, 710
4
Taipei Medical University - Taipei Medical University Hospital
Taipei, Taiwan, 11031