CD19 and BCMA Targeted Fast Dual CAR-T for CD19+ Refractory/Relapsed B-NHL
Study Details
Study Description
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-Hodgkinlymphoma (R/R B-NHL).
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1 |
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 CD19 and B-cell maturation antigen (BCMA). The study will include 15 subjects to receive Fast Dual CAR-T single infusion.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Fast Dual CAR-T treatment CD19+ R/R B-NHL patients be treated with a single dose of Fast Dual CAR-T cells. Total dose of (1-5)*10E5/kg cells will be administered at Day 0. |
Biological: Fast Dual CAR-T Injection
Fast Dual CAR-T injection is a autologous dual CAR-T targeted CD19 and BCMA. A single infusion of CART cells will be administered intravenously.
|
Outcome Measures
Primary Outcome Measures
- Incidence of AE after Fast Dual CAR-T infusion [up to 24 weeks after Fast Dual CAR-T infusion]
Incidence of adverse events after Fast Dual CAR-T infusion
Secondary Outcome Measures
- ORR rate [12 weeks, 24 weeks after Fast Dual CAR-T infusion]
Overall response rate (ORR=CR+CRi) after Fast Dual CAR-T infusion
- PFS [12 weeks, 24 weeks after Fast Dual CAR-T infusion]
Progression free survival (PFS) after Fast Dual CAR-T infusion
- OS [12 weeks, 24 weeks after Fast Dual CAR-T infusion]
overall survival (OS) after Fast Dual CAR-T infusion
- Change of CAR Copies [Days 4, 7, 10, 14 and weeks 4, 8, 12, 18, 24 after Fast Dual CAR-T infusion]
CAR Copies measured by qPCR after Fast Dual CAR-T infusion
- Change of CAR-T cell counts [Days 4, 7, 10, 14 and weeks 4, 8, 12, 18, 24 after Fast Dual CAR-T infusion]
CAR-T cell counts measured by Flow cytometry after Fast Dual CAR-T infusion
- Changes in the concentration of cytokine IL-1, IL-2, IL-6, IL-10, TNF-α and IFN-γ. [Days 4, 7, 10, 14 and 28 after Fast Dual CAR-T infusion]
Cytokines in serum measured by ELISA after Fast Dual CAR-T infusion
- Change of RCL in blood [Weeks 4, 12, 24 after Fast Dual CAR-T infusion]
Replication competent lentivirus (RCL) in blood after Fast Dual CAR-T infusion
Eligibility Criteria
Criteria
Inclusion Criteria:
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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);
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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:
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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);
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Prior therapy must include anti-CD20 monoclonal antibody (unless investigator determines that tumor is CD20-negative) and an anthracycline;
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For individual with TFL, must have chemotherapy and the conform the above definition of relapse or refractory after transformation;
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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;
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CD19 positive expression in tumor tissue biopsy;
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Prior to apheresis, approved anti-B-NHL therapys such as systemic chemotherapy, systemic radiotherapy and immunotherapy have been completed for at least 2 weeks;
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Eastern cooperative oncology group (ECOG) performance status of 0 to 1;
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Life expectancy ≥12 weeks;
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Absolute neutrophil count (ANC)≥ 1×10^9/L;
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Platelet count≥50×10^9/L;
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Absolute lymphocyte count (ALC)≥1×10^8/L;
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Adequate organ function defined as:
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Serum ALT/AST ≤2.5 ULN;
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Creatinine clearance (as estimated by Cockcroft Gault) ≥60 mL/min;
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PT and APTT≤1.5 ULN
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Total bilirubin ≤1.5 ULN;
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Cardiac ejection fraction ≥50%, no pericardial effusion, no clinically significant ECG findings;
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Baseline oxygen saturation >92% on room air;
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Sufficient venous access for leukapheresis collection, and no other contraindications to leukapheresis;
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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;
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Understand and voluntarily sign the informed consent form.
Exclusion Criteria:
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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);
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Severe mental disorders;
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History of hereditary diseases, including but not limited to: Fanconi anemia, Shut-Dai syndrome, Costman syndrome or any other known bone marrow failure syndrome;
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History of allogeneic stem cell transplantation;
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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.
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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;
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Subjects with CNS lymphoma, cerebrospinal fluid malignant cells or brain metastases;
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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;
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Positive for any of the following etiological tests: HIV, HBV, HCV, TPPA;
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Presence of fungal, bacterial, viral, or other infection that is uncontrolled;
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Allergic subjects or subjects with severe allergic reactions to cyclophosphamide or fludarabine;
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History of autoimmune disease resulting in end organ injury or requiring systemic immunosuppression/systemic disease modifying agents within the last 2 years;
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History or diagnosis of pulmonary fibrosis;
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Have received gene therapy or any other CAR-T treatment;
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Have received any other drugs targeting CD19;
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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);
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Poor adherence due to physical, family, social, geographic, and other factors, who cannot follow the research plan and follow-up plan;
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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;
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Lactating women who are reluctant to stop breastfeeding;
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Any other conditions defined by researcher that is inappropriate for the subject to be enrolled.
Contacts and Locations
Locations
No locations specified.Sponsors and Collaborators
- 920th Hospital of Joint Logistics Support Force of People's Liberation Army of China
Investigators
- Principal Investigator: Sanbin Wang, Doctor, 920th Hospital of Joint Logistics Support Force of People's Liberation Army of China
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- 211