B-Cell Non-Hodgkin Lymphoma, Follicular Lymphoma, Large B Cell Diffuse Lymphoma, Mantle Cell Lymphoma (MCL), Marginal Zone B Cell Lymphoma
Conditions
Keywords
CAR-T, dual target, B-NHL
Brief summary
JWCAR239 is a CD19/CD20 CAR-T product. This trial is intended to evaluate the safety, PK/PD and efficacy of JWCAR239 in patients with B Cell Non-Hodgkin Lymphoma (B-NHL)
Detailed description
JWCAR239 is a CD19/CD20 CAR-T product. By targeting both CD19 and CD20, it is expected to overcome some limitations with CD19 or CD20 single target products. In this study, patients with B B-NHL will be enrolled to receive JWCAR239. PK/PD properties and preliminary efficacy and safety will be evaluated. Each subject will receive JWCAR239 once and is followed up for up to 2 years.
Interventions
BIOLOGICALJWCAR239
A single infusion of chimeric antigen receptor (CAR)-transduced autologous T cells targeting CD19/CD20
DRUGFludarabine
Administered according to package insert
DRUGCyclophosphamide
Administered according to package insert
Sponsors
Shanghai JW Therapeutics Co., Ltd.
Peking University Cancer Hospital & Institute
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Histologically confirmed B-NHL with immunohistochemical positivity for CD20 and/or CD19 (accepting previous pathological reports and/or pathological review results of previous or fresh tumor tissues). According to the 2022 World Health Organization (WHO) classification, the pathological types include:Diffuse large B-cell lymphoma, Follicular large B-cell lymphoma (FL3B),Large B-cell lymphoma transformed from indolent B-NHL, Follicular lymphoma (excluding in situ follicular lymphoma, pediatric-type follicular lymphoma, and duodenal-type follicular lymphoma),Marginal zone lymphoma Mantle cell lymphoma (excluding in situ mantle cell neoplasms and leukemic non-nodal mantle cell lymphoma) 2. Relapsed or refractory disease after receiving two or more lines of adequate treatment, or failure after autologous hematopoietic stem cell transplantation (ASCT). 3. CT-measurable lesions and PET-evaluable positive lesions as defined by the 2014 Lugano criteria (lymph node or extranodal lesions must have two measurable diameters; lymph node lesions must have a long diameter \>1.5 cm, and extranodal lesions must have a long diameter \>1 cm). 4. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. 5. Adequate organ function: Sufficient bone marrow function as assessed by the investigator (absolute neutrophil count ≥1,000/μL after at least 72 hours off growth factors; platelet count ≥50,000/μL without blood transfusion within 7 days; absolute lymphocyte count ≥100/μL). Serum creatinine ≤1.5× upper limit of normal (ULN) or creatinine clearance ≥50 mL/min (calculated by the Cockcroft-Gault formula). Alanine aminotransferase (ALT) ≤5×ULN and total bilirubin \<2×ULN (or \<3×ULN for subjects with Gilbert syndrome or hepatic involvement by lymphoma). Pulmonary function: ≤ CTCAE Grade 1 dyspnea and SpO2 ≥92% in room air. Cardiac function: Left ventricular ejection fraction (LVEF) ≥50% as assessed by echocardiography. 6. Adequate vascular access for leukapheresis. 7. Expected survival \>12 weeks. 8. Non-abstinent female subjects of childbearing potential must agree to use a highly effective contraceptive method plus an additional barrier method from at least 28 days before lymphodepletion until 2 years after JWCAR239 infusion. Male subjects with fertile partners must agree to use effective contraception from at least 28 days before lymphodepletion until 2 years after JWCAR239 infusion and must not donate semen or sperm throughout the study.
Exclusion criteria
1. Lymphoma involving the central nervous system (CNS). 2. EBV-positive DLBCL or Richter transformation of chronic lymphocytic leukemia. 3. History of other malignant tumors with complete remission for less than 2 years, or current presence of other malignant tumors (exceptions to the 2-year restriction include: basal cell carcinoma of the skin, squamous cell carcinoma of the skin, treated localized prostate cancer, biopsy-confirmed cervical in situ carcinoma, or cervical smears showing squamous intraepithelial lesions, or completely resected tumors with low recurrence potential as assessed by the investigator). 4. At screening, the subject has: Active hepatitis B or C (subjects with HBV DNA or HCV RNA below the lower limit of the central reference value by PCR may be enrolled). For occult or prior HBV-infected subjects, prophylactic antiviral therapy and regular monitoring of HBV-DNA are required. Human immunodeficiency virus (HIV) infection or syphilis infection. 5. Acute deep vein thrombosis (DVT) (tumor thrombus or thrombus) or pulmonary embolism (PE) within 3 months prior to informed consent signing. 6. Receiving anticoagulant therapy for acute DVT or PE within 3 months prior to informed consent signing (prophylactic treatment ). 7. Uncontrolled systemic fungal, bacterial, viral, or other infections. 8. Acute or chronic graft-versus-host disease (GvHD). 9. History of any of the following cardiovascular diseases within the past 6 months: New York Heart Association (NYHA) Class III or IV heart failure, coronary angioplasty or stenting, myocardial infarction, unstable angina, or other clinically significant heart diseases. 10. Clinically significant CNS disease or symptoms at screening or within the past 6 months, such as epilepsy, seizures, paralysis, aphasia, stroke, severe brain injury, dementia, Parkinson's disease, cerebellar disease, organic brain syndrome, or psychiatric disorders. 11. Pregnant or lactating women. Females of childbearing potential must have a negative serum pregnancy test within 48 hours before starting lymphodepletion chemotherapy. 12. Use of any of the following drugs or treatments within the specified time before leukapheresis: Alemtuzumab within 6 months before leukapheresis. Bendamustine within 6 months before leukapheresis. Cladribine within 3 months before leukapheresis. Fludarabine within 3 months before leukapheresis. Anti-CD20 monoclonal antibodies within 7 days before leukapheresis. Venetoclax within 4 days before leukapheresis. Idelalisib within 2 days before leukapheresis. Lenalidomide within 1 day before leukapheresis. Pharmacological doses of corticosteroids (defined as prednisone \>5 mg/day or equivalent) within 7 days before leukapheresis or within 72 hours before JWCAR239 injection. Physiological replacement, topical, and inhaled steroids are permitted. Chemotherapy (e.g., vincristine, rituximab, cyclophosphamide) required to control the disease after leukapheresis must have been discontinued ≥7 days before lymphodepletion chemotherapy. Administration of non-lymphocyte-toxic cytotoxic chemotherapy within 1 week before leukapheresis. Enrollment is permitted if the oral chemotherapy has undergone at least 3 half-lives before leukapheresis. Receipt of lymphocyte-toxic chemotherapy (e.g., cyclophosphamide, ifosfamide, chlorambucil, or melphalan) within 2 weeks before leukapheresis. Use of investigational drugs within 4 weeks before leukapheresis. However, enrollment is permitted if the investigational treatment was ineffective or caused disease progression, and at least 3 half-lives have elapsed before leukapheresis. Treatment with immunosuppressive agents (e.g., calcineurin inhibitors, methotrexate or other chemotherapeutic drugs, mycophenolate, rapamycin, thalidomide, immunosuppressive antibodies such as anti-TNF, anti-IL-6, or anti-IL-6R) within 4 weeks before leukapheresis and JWCAR239 injection. Receipt of donor lymphocyte infusion (DLI) within 6 weeks before JWCAR239 injection. Radiation therapy involving large bone marrow areas (e.g., sternum or pelvis) within 6 weeks before leukapheresis. Subjects are eligible only if the disease progresses at the radiation site or PET-positive lesions exist in non-irradiated areas. If PET-positive lesions exist in non-irradiated areas, radiation therapy to a single lesion is permitted within 2 weeks before leukapheresis. 13. Any other significant disease, abnormality, or condition that, in the investigator's judgment, renders the subject unsuitable for participation in the study or places the subject at risk. Any factors affecting compliance with the protocol, including uncontrollable medical, psychological, family, sociological, or geographical factors; or unwillingness or inability to adhere to the procedures required by the study protocol. 14. Prior allogeneic hematopoietic stem cell transplantation. 15. Prior treatment with CAR+ T cells or other genetically modified T cells.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| AE and SAE rate | up to 2 years | ny adverse event (AE) or serious adverse event (SAE) occurring after JWCAR239 administration |
| The rate of Dose Limiting Toxicity events | 28 days | Dose-Limiting Toxicity (DLT) refers to a specific type of adverse effect or toxic reaction caused by a drug or treatment that is severe enough to prevent an increase in dose or continuation of treatment. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| PD | from baseline up to 2 years | Peripheral blood levels of CD19+ and/or CD20+ B cells |
| overall response rate (ORR) | from baseline up to 2 years | ORR is the proportion of subjects who achieve positive response to the treatment. It includes complete response and partial response. |
| complete response rate (CRR) | from baseline up to 2 years | CRR refers to the proportion of subjects whose cancer signs disappear |
| duration of response(DOR) | from baseline up to 2 years | in subjects with hematology malignancy The duration of a subject staying in response state |
| Overall survival(OS) | from baseline up to 2 years | the length of time from the start of treatment that patients are still alive |
| Pharmacokinetic (PK)- Tmax of JWCAR239 | up to 2 year after JWCAR239 infusion | Time to maximum concentration of JWCAR239 in the peripheral blood |
| Pharmacokinetic (PK)- AUC of JWCAR239 | up to 2 year after JWCAR239 infusion | Area under the concentration vs time curve of JWCAR239 |
| progression free survival(PFS) | from baseline up to 2 years | the length of time during and after treatment that a subject lives with the disease without the disease worsening or progressing |
| Pharmacokinetic (PK)- Cmax of JWCAR239 | from baseline up to 2 years | Maximum observed concentration of JWCAR239 in peripheral blood |
Other
| Measure | Time frame | Description |
|---|---|---|
| The change of serum cytokines concentration | from baseline up to 2 years | The change of serum cytokines concentration after JWCAR239 infusion |
Countries
China
Contacts
Primary ContactYuqin Song, PhD
Backup ContactJW medical JWCAR239
Outcome results
None listed