LCAR-T2C CAR-T Cells in Relapsed or Refractory CD4+ T-cell Lymphoma
Study Details
Study Description
Brief Summary
A Phase I, Multicenter study to evaluate the safety, tolerability, and Efficacy of LCAR-T2C CAR-T cells in relapsed or refractory CD4+T Lymphocyte Tumor Patients.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1 |
Detailed Description
This is an open, dose escalation/dose extension study of LCAR-T2C CAR-T cells administrered to patients with T lymphocyte tumor. The aim of the study is to evaluate the safety, tolerability, and efficacy of LCAR-T2C CAR-T cells. The auto-CAR-T cells will be infused in single-dose.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Experimental: LCAR-T2C CAR-T cells in relapsed or refractory CD4+ T lymphocyte tumor An open label, multi center, single arm Phase I study to evaluate the safety, tolerability, and efficacy of LCAR-T2C CAR-T cells in relapsed or refractory CD4+ T lymphocyte tumor. |
Drug: Efficacy of LCAR-T2C CAR-T cells
CD4-directed CAR-T cells administered with lymphodepletion, and to obtain the preliminary efficacy results in subjects who have been diagnosed with relapsed or refractory CD4 positive T lymphocyte tumor
|
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
- Recommended Phase II dose (RP2D) [30 days post infusion]
RP2D established through ATD+BOIN design and the DLTs occurring following CAR T-cell infusion
- Pharmacokinetics [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, PK CAR positive T cells in bone marrow and PK CAR transgene levels in bone marrow.
Secondary Outcome Measures
- Anti-drug antibody [through study completion, 2 years after infusion of the last subject]
Anti-drug antibody (ADA) will be conducted on blood sample for immune response analyses.
- Overall response rate (ORR) after administration [through study completion, 2 years after infusion of the last subject]
- Time to Response (TTR) after administration [through study completion, 2 years after infusion of the last subject]
- Duration of remission (DOR) after administration [through study completion, 2 years after infusion of the last subject]
- Progress Free Survival (PFS) after administration [through study completion, 2 years after infusion of the last subject]
- Over Survival (OS) after administration [through study completion, 2 years after infusion of the last subject]
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 CD4+ T lymphocyte tumor (one of the following):
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T-cell Non-Hodgkin lymphoma(T-NHL)：The best response is progressive disease(PD) or stable disease(SD) after at least 1 prior line of therapy（at least 2 complete cycle of therapy）
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T-cell Acute lymphoblastic leukemia(T-ALL)：The best response is not complete response(CR) after induction therapy
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Measurable disease is necessary at Screening
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Life expectancy ≥ 3 months
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Eastern Cooperative Oncology Group (ECOG) Performance Status grade of 0 -2.
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The screening phase clinical laboratory values meet the following criteria. Laboratory test(s) may be repeated once, to determine if the subject qualifies for study participation :
Blood routine:
HGB≥6g/dL；PLT≥20×109/L; ANC≥1.0×109/L; LY≥0.3×10^9/L
Blood biochemical parameters:
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Aspartate and alanine aminotransferases (AST, ALT) ≤ 2.5 times ULN (in the presence of liver metastasis, AST and ALT≤5 times ULN)
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Serum creatinine (Scr) ≤ 1.5 times ULN, estimated glomerular filtration rate (eGFR) > 60mL/min (only when Scr>1.5 times ULN)
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Total bilirubin ≤ 1.5 times of the normal upper limit (ULN)
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International Normalized Ratio (INR) ≤ 1.5 times ULN, PT≤ 1.5 times ULN, APTT≤ 1.5 times ULN
Exclusion Criteria:
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Prior treatment with CAR-T therapy directed at any target.
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Any therapy that is targeted to CD4.
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Prior treatment with an allogeneic stem cell transplant
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Any malignancy besides the T lymphocyte tumor 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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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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The following cardiac conditions:
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New York Heart Association (NYHA) stage III or IV congestive heart failure
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Myocardial infarction or coronary artery bypass graft (CABG) 6 months prior to enrollment
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History of clinically significant ventricular arrhythmia or unexplained syncope, not believed to be vasovagal in nature or due to dehydration
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History of severe non-ischemic cardiomyopathy
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Impaired cardiac function (LVEF <45%) as assessed by echocardiogram or multiple-gated acquisition (MUGA) scan (performed ≤8 weeks of apheresis)
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Prior antitumor therapy as follows, prior to apheresis:
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Targeted therapy, epigenetic therapy, or treatment with an investigational drug or used an invasive investigational medical device within 14 days or at least 5 half-lives, whichever is less.
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Monoclonal antibody treatment for multiple myeloma within 21 days.
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Cytotoxic therapy within 14 days.
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Radiotherapy within 14 days.
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Participated in other clinical trials within 30 days.
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Toxicity from previous anticancer therapy must resolve to baseline levels or to Grade 1 or less except for alopecia or peripheral neuropathy.
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With central nervous system involvement.
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Serious underlying medical condition, such as:
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Evidence of serious active viral, bacterial, or uncontrolled systemic fungal infection
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Active or unstable autoimmune diseases or autoimmune diseases that have been suffered within 3 years and have the possibility of recurrence
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Overt clinical evidence of dementia or altered mental status
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Pregnant or breast-feeding, or planning to become pregnant while enrolled in this study or within 100 days after receiving study treatment.
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Plans to father a child while enrolled in this study or within 100 days after receiving study treatment.
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With obvious hemorrhagic tendency such as gastrointestinal hemorrhage, coagulation disorders and hypersplenism
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Oxygen is needed to maintain sufficient blood oxygen saturation(≥95%)
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Suffer from chronic diseases that require treatment with systemic corticosteroids or other immunosuppressive agents ,Received a cumulative dose of corticosteroids equivalent to ≥20 mg/day of prednisone within 7 days prior to apheresis
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CNS diseases with clinical significance in the past or at the time of screening
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Vaccinated with live, attenuated vaccine within 4 weeks prior to apheresis
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Major surgery within 2 weeks prior to apheresis, or has surgery planned during the study or within 2 weeks after study treatment administration. (Note: subjects with planned surgical procedures to be conducted under local anesthesia may participate.)
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Known life threatening allergies, hypersensitivity, or intolerance to LCAR-T2C CAR-T cells or its excipients, including DMSO (refer to Investigator's Brochure)
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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 | |
|---|---|---|---|---|---|
| 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，The First Affiliated Hospital of the Air Force Medical University | Xi'an | Shanxi | China | 710032 |
Sponsors and Collaborators
- The First Affiliated Hospital with Nanjing Medical University
- Nanjing Legend Biotechnology Co. The First Affiliated Hospital of USTC west district；The First Affiliated Hospital of the Air Force Medical University
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: Guangxun Gao, PhD& MD, The First Affiliated Hospital of the Air Force Medical University
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- BM2L201905