Study of LUCAR-20S in Patients With R/R NHL
Study Details
Study Description
Brief Summary
An open label, single arm Phase I study to evaluate the safety, tolerability, and pharmacokinetics of LUCAR-20S CAR-T cells in relapsed or refractory CD20+ diffuse large B-cell, follicular, mantle cell and small lymphocytic lymphoma.
Condition or Disease | Intervention/Treatment | Phase |
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Phase 1 |
Detailed Description
This study is an open, dose escalation/dose regimen finding study to assess the safety and pharmacokinetics of donor-derived CD20-directed CAR-T cells administered with lymphodepletion, and to obtain the preliminary efficacy results in subjects who have been diagnosed with relapsed or refractory CD20 positive diffuse large B-cell lymphoma, follicular lymphoma, mantle cell lymphoma or small lymphocytic lymphoma. The allo-CAR-T cells will be infused in single-dose.
Study Design
Arms and Interventions
Arm | Intervention/Treatment |
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Experimental: Anti-CD20 Allogeneic CAR-T Cell Therapy An open label, single arm Phase I study to evaluate the safety, tolerability, and pharmacokinetics of LUCAR-20S CAR-T cells in relapsed or refractory CD20+ diffuse large B-cell, follicular, mantle cell and small lymphocytic lymphoma. |
Drug: LUCAR-20S CAR-T cells
An Anti-CD20 Allogeneic CAR-T Cell Therapy in Patients with Relapsed/Refractory Diffuse Large B-Cell, Follicular, Mantle Cell or Small Lymphocytic Lymphoma
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Outcome Measures
Primary Outcome Measures
- Dose limiting toxicity (DLT) [30 days post infusion]
DLT assessed by NCI-CTCAE 5.0
- Adverse events [90 days post infusion]
Incidence and severity of adverse events as assessed by NCI-CTCAE 5.0
- Concentration of Pharmacokinetics in blood [through study completion, 2 years after infusion of the last subject]
PK CAR positive T cells in peripheral blood, PK CAR transgene levels in peripheral blood
- Concentration of Pharmacokinetics in bone marrow [through study completion, 2 years after infusion of the last subject]
PK CAR positive T cells in bone marrow, PK CAR transgene levels in bone marrow
Secondary Outcome Measures
- Recommended Phase II dose (RP2D) [30 days post infusion]
RP2D established through ATD+BOIN design and the DLTs occurring following CAR T-cell infusion
- Overall response rate (ORR) after administration [3 months post infusion]
Antitumor efficacy by 2014 Lugano criteria
- Time to Response (TTR) after administration [3 months post infusion]
Antitumor efficacy by 2014 Lugano criteria
- Duration of remission (DOR) after administration [through study completion, 2 years after infusion of the last subject]
Antitumor efficacy by 2014 Lugano criteria
- Progress Free Survival (PFS) after administration [through study completion, 2 years after infusion of the last subject]
Antitumor efficacy by 2014 Lugano criteria
- Overall Survival (OS) after administration [through study completion, 2 years after infusion of the last subject]
Antitumor efficacy by 2014 Lugano criteria
Eligibility Criteria
Criteria
Inclusion Criteria:
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Signed informed consent form (ICF)
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Age 18 Years to 75 Years
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Pathological diagnosis of refractory/relapsed CD20+ non-Hodgkin's lymphoma (one of the following):
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Diffuse large B-cell lymphoma (DLBCL)
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Follicular lymphoma (FL)
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Mantle cell lymphoma (MCL)
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Small lymphocytic lymphoma (SLL)
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Measurable disease as defined by 2014 Lugano criteria at Screening
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Refractory/relapsed disease after standard-of- care treatment as following (Undergone at least 2 complete cycle of therapy for each line, unless PD been documented as the best response to the regimen) and not eligible or appropriate for HSCT (Auto/allo). Subject must have documented evidence of progressive disease on or within 12 months of their last regimen.
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DLBCL: Refractory/relapsed after at least 1 prior line of therapy, must have been treated with anti-CD20 monoclonal antibody
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FL: Refractory/relapsed after at least 2 prior lines of therapy, must have been treated with anti-CD20 monoclonal antibody
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MCL: Refractory/relapsed after at least 2 prior lines of therapy
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SLL: Refractory/relapsed after at least 2 prior lines of therapy
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Laboratory criteria at Screening
① Blood routine: NE≥1.0×109/L;HGB≥8g/dL;PLT≥50×109/L
② Blood biochemical parameters:
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Total bilirubin ≤ 1.5 times of the normal upper limit (ULN)
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Aspartate and alanine aminotransferases (AST, ALT) ≤ 3 times ULN (in the presence of liver metastasis, ULN 5 times)
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Estimated glomerular filtration rate (eGFR) > 60mL/min
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Life expectancy > 12 weeks
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Eastern Cooperative Oncology Group (ECOG) Performance Status grade of 0 or 1
Exclusion Criteria:
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Any malignancy besides the NHL categories under study, exceptions include
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Any other malignancy curatively treated and disease-free for at least 2 years prior to enrollment
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History of non-melanoma skin cancer with sufficient treatment and currently no evidence of recurrence
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Prior treatment with an allogeneic stem cell transplant
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Prior treatment with genetic therapy
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Prior treatment with chimeric antigen receptor T (cells) CAR-T therapy directed at CD20 target
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Those who are positive for any index of hepatitis B surface antigen (HBsAg), hepatitis B virus deoxyribonucleic acid (HBV DNA), hepatitis C antibody (HCV-Ab), hepatitis C virus ribonucleic acid (HCV RNA), and human immunodeficiency virus antibody (HIV-Ab)
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Prior antitumor therapy with insufficient washout period
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Targeted therapy, epigenetic therapy, experimental drug therapy or experimental invasive treatment with medical apparatus and instruments 14 days or five half-lives, whichever is shorter before lymphodepletion
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Use of monoclonal antibodies 21 days prior to lymphodepletion
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Chemotherapy within 14 days prior to lymphodepletion
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Radiotherapy within 14 days prior to lymphodepletion
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Participated in other clinical trials within 30 days prior to lymphodepletion
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With central nervous system involvement
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Women in pregnancy or lactation
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Being fertile and unable to use effective conception during treatment and 100 days after CAR-T infusion
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Active autoimmune disease or history of autoimmune disease within 3 years
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With obvious hemorrhagic tendency such as gastrointestinal hemorrhage, coagulation disorders and hypersplenism
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The following cardiac conditions
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New York Heart Association (NYHA) stage III or IV congestive heart failure
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Left ventricular ejection fraction (LVEF) less than (<)45%
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Uncontrolled cardiac arrhythmia post-medication
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With a history of myocardial infraction or unstable angina pectoris within the past 6 months
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Constrictive pericarditis
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Cardiomyopathy
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Pulse oximetry of <96% on room air
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Active or uncontrolled infection requiring parenteral antibiotics, or any evidence of severe active viral/bacterial infection or uncontrolled systemic fungal infection
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Uncontrolled diabetes mellitus, defined as fast serum glucose > 1.5 times ULN
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Concurrent use of corticosteroids or other immunosuppressant medications for chronic disease
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Concurrent use of hematopoietic growth factor
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Stroke or seizure within 6 months of signing ICF
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Have received any live, attenuated vaccine within 4 weeks prior to lymphodepletion
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Have underwent major surgical operation within 2 weeks prior to lymphodepletion, or anticipate to undergo a major surgical operation during the study process or within 2 weeks posterior to study treatment(with the exception of anticipated local anesthesia surgery)
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Known life threatening allergies, hypersensitivity, or intolerance to LUCAR-20S CAR-T cells or its excipients, including dimethyl sulfoxide (DMSO)
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Presence of any condition that, in the opinion of the investigator, would prohibit the patient from undergoing treatment under this protocol
Contacts and Locations
Locations
Site | City | State | Country | Postal Code | |
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1 | Oncology Department,The First Affiliated Hospital of USTC west district | Hefei | Anhui | China | 230000 |
2 | Hematological Department, People's Hospital of Jiangsu Province | Nanjing | Jiangsu | China | 210029 |
3 | Hematological Department,Beijing Boren Hospital | Beijing | China | 100070 |
Sponsors and Collaborators
- The First Affiliated Hospital with Nanjing Medical University
- Nanjing Legend Biotechnology Co.,Ltd.; The First Affiliated Hospital of USTC west district; Beijing Boren Hospital
Investigators
- Principal Investigator: Wei Xu, PhD& MD, The first Affiliated Hospital Of Nanjing Medical University(JiangSu Province Hospital)
- Principal Investigator: Kaiyang Ding, PhD& MD, Anhui Provincial Cancer Hospital
- Principal Investigator: Kai Hu, PhD& MD, Beijing Boren Hospital
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- BM2L201904
- BM2L201904
- NCT04994587