Status:
WITHDRAWN
CD19 and BCMA Targeted Fast Dual CAR-T for CD19+ Refractory/Relapsed B-NHL
Lead Sponsor:
920th Hospital of Joint Logistics Support Force of People's Liberation Army of China
Conditions:
B-cell Lymphoma
Eligibility:
All Genders
18-75 years
Phase:
PHASE1
Brief Summary
This is a single arm, open-label, single-center prospective study to determine the safety and efficacy of Fast Dual CAR-T cells in patients diagnosed with CD19+ refractory/relapsed B cell non-Hodgkinl...
Detailed Description
The main aim of the study is to determine the safety and efficacy of Fast Dual CAR-T in R/R B-NHL. Fast Dual CAR-T is an autologous dual chimeric antigen receptor T-cell (CAR-T) therapy that targets C...
Eligibility Criteria
Inclusion
- Histologically confirmed: Diffuse Large B Cell Lymphoma (DLBCL), Transformation Follicular Lymphoma (TFL), Primary Mediastinal Large B Cell Lymphoma (PMBCL) and Mantle Cell Lymphoma (MCL), High-Grade B Cell Lymphoma (HGBL);
- Refractory B-NHL: PD as the best response to normative first-line therapy (intolerance of first-line therapy is not included in this study) or SD as the best response to at least 4 courses of first-line therapy with duration no longer than 6 month from last therapy; or PD as the best response to the last therapy of second-line therapy and above,or SD as the best response to at least 2 courses of second-line therapy with duration no longer than 6 month from last therapy, or:
- Relapsed B-NHL: Histopathology confirmed relapse after standard systemic and second-line therapy achieved CR, or histopathologically confirmed relapse within 1 year after autologous hematopoietic stem cell transplantation (Not limited by previous therapy);
- Prior therapy must include anti-CD20 monoclonal antibody (unless investigator determines that tumor is CD20-negative) and an anthracycline;
- For individual with TFL, must have chemotherapy and the conform the above definition of relapse or refractory after transformation;
- According to the 2014 Lugano therapy response standard, there should be at least one measurable tumor focus: the longest diameter of nodular lesions\> 1.5 cm, and the longest diameter of extranodal lesions\> 1.0 cm;
- CD19 positive expression in tumor tissue biopsy;
- Prior to apheresis, approved anti-B-NHL therapys such as systemic chemotherapy, systemic radiotherapy and immunotherapy have been completed for at least 2 weeks;
- Eastern cooperative oncology group (ECOG) performance status of 0 to 1;
- Life expectancy ≥12 weeks;
- Absolute neutrophil count (ANC)≥ 1×10\^9/L;
- Platelet count≥50×10\^9/L;
- Absolute lymphocyte count (ALC)≥1×10\^8/L;
- Adequate organ function defined as:
- Serum ALT/AST ≤2.5 ULN;
- Creatinine clearance (as estimated by Cockcroft Gault) ≥60 mL/min;
- PT and APTT≤1.5 ULN
- Total bilirubin ≤1.5 ULN;
- Cardiac ejection fraction ≥50%, no pericardial effusion, no clinically significant ECG findings;
- Baseline oxygen saturation \>92% on room air;
- Sufficient venous access for leukapheresis collection, and no other contraindications to leukapheresis;
- Female of childbearing age must agree to take effective contraceptive measures at least 1 year after infusion; Male with fertile partners must agree to use effective barrier contraceptive methods at least 1 year after infusion;
- Understand and voluntarily sign the informed consent form.
Exclusion
- Diagnosis of other malignancy (except for cured non-melanoma skin cancer, cervical carcinoma in situ, superficial bladder cancer, ductal carcinoma in situ, or other malignancies that have completely responsed for more than 5 years);
- Severe mental disorders;
- History of hereditary diseases, including but not limited to: Fanconi anemia, Shut-Dai syndrome, Costman syndrome or any other known bone marrow failure syndrome;
- History of allogeneic stem cell transplantation;
- Grade III-IV heart failure or myocardial infarction, angioplasty or stent placement, unstableangina pectoris, or other clinically prominent heart disease within one year before enrollment.
- Have any indwelling catheter or drainage tube (such as percutaneous nephrostomy tube, indwelling catheter, bile drainage tube or pleura / peritoneum / pericardial catheter), the use of dedicated central venous catheter is allowed;
- Subjects with CNS lymphoma, cerebrospinal fluid malignant cells or brain metastases;
- History or presence of CNS disorder, including but not limited to: seizure disorder, cerebrovascular ischemia/hemorrhage, dementia, cerebellar disease, or any autoimmune disease with CNS involvement;
- Positive for any of the following etiological tests: HIV, HBV, HCV, TPPA;
- Presence of fungal, bacterial, viral, or other infection that is uncontrolled;
- Allergic subjects or subjects with severe allergic reactions to cyclophosphamide or fludarabine;
- History of autoimmune disease resulting in end organ injury or requiring systemic immunosuppression/systemic disease modifying agents within the last 2 years;
- History or diagnosis of pulmonary fibrosis;
- Have received gene therapy or any other CAR-T treatment;
- Have received any other drugs targeting CD19;
- Subjects who received other clinical trial therapy within 4 weeks before participating in this trial, or the informed consent form was signed within the 5 half-life of the last administration in the other clinical trial (take longer time as standard);
- Poor adherence due to physical, family, social, geographic, and other factors, who cannot follow the research plan and follow-up plan;
- Subjects with comorbidities that require systemic corticosteroid therapy (≥5 mg/day of prednisone or an equivalent dose of other corticosteroids) or other immunosuppressive drugs within 6 months after study therapy according to the discretion of investigator;
- Lactating women who are reluctant to stop breastfeeding;
- Any other conditions defined by researcher that is inappropriate for the subject to be enrolled.
Key Trial Info
Start Date :
May 5 2021
Trial Type :
INTERVENTIONAL
Allocation :
ACTUAL
End Date :
December 31 2023
Estimated Enrollment :
Patients enrolled
Trial Details
Trial ID
NCT04877080
Start Date
May 5 2021
End Date
December 31 2023
Last Update
February 10 2023
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