LCAR-T2C CAR-T Cells in Relapsed or Refractory CD4+ T-cell Lymphoma
CD4+ T Lymphocyte Tumor (T Cell Lymphoma and T Cell Leukemia)
About this trial
This is an interventional treatment trial for CD4+ T Lymphocyte Tumor (T Cell Lymphoma and T Cell Leukemia)
Eligibility Criteria
Inclusion Criteria:
- Signed informed consent form (ICF)
- Age 18 Years to 75 Years
Pathological diagnosis of refractory/relapsed CD4+ T lymphocyte tumor (one of the following):
- 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)
- T-cell Acute lymphoblastic leukemia(T-ALL):The best response is not complete response(CR) after induction therapy
- Measurable disease is necessary at Screening
- Life expectancy ≥ 3 months
- Eastern Cooperative Oncology Group (ECOG) Performance Status grade of 0 -2.
- 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≥20×10^9/L; ANC≥1.0×10^9/L; LY≥0.3×10^9/L
Blood biochemical parameters:
- Aspartate and alanine aminotransferases (AST, ALT) ≤ 2.5 times ULN (in the presence of liver metastasis, AST and ALT≤5 times ULN)
- Serum creatinine (Scr) ≤ 1.5 times ULN, estimated glomerular filtration rate (eGFR) > 60mL/min (only when Scr>1.5 times ULN)
- Total bilirubin ≤ 1.5 times of the normal upper limit (ULN)
- International Normalized Ratio (INR) ≤ 1.5 times ULN, PT≤ 1.5 times ULN, APTT≤ 1.5 times ULN
Exclusion Criteria:
- Prior treatment with CAR-T therapy directed at any target.
- Any therapy that is targeted to CD4.
- Prior treatment with an allogeneic stem cell transplant
Any malignancy besides the T lymphocyte tumor categories under study, exceptions include
- Any other malignancy curatively treated and disease-free for at least 2 years prior to enrollment
- History of non-melanoma skin cancer with sufficient treatment and currently no evidence of recurrence
- 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)
The following cardiac conditions:
- New York Heart Association (NYHA) stage III or IV congestive heart failure
- Myocardial infarction or coronary artery bypass graft (CABG) 6 months prior to enrollment
- History of clinically significant ventricular arrhythmia or unexplained syncope, not believed to be vasovagal in nature or due to dehydration
- History of severe non-ischemic cardiomyopathy
- Impaired cardiac function (LVEF <45%) as assessed by echocardiogram or multiple-gated acquisition (MUGA) scan (performed ≤8 weeks of apheresis)
Prior antitumor therapy as follows, prior to apheresis:
- 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.
- Monoclonal antibody treatment for multiple myeloma within 21 days.
- Cytotoxic therapy within 14 days.
- Radiotherapy within 14 days.
- Participated in other clinical trials within 30 days.
- Toxicity from previous anticancer therapy must resolve to baseline levels or to Grade 1 or less except for alopecia or peripheral neuropathy.
- With central nervous system involvement.
Serious underlying medical condition, such as:
- Evidence of serious active viral, bacterial, or uncontrolled systemic fungal infection
- Active or unstable autoimmune diseases or autoimmune diseases that have been suffered within 3 years and have the possibility of recurrence
- Overt clinical evidence of dementia or altered mental status
- Pregnant or breast-feeding, or planning to become pregnant while enrolled in this study or within 100 days after receiving study treatment.
- Plans to father a child while enrolled in this study or within 100 days after receiving study treatment.
- With obvious hemorrhagic tendency such as gastrointestinal hemorrhage, coagulation disorders and hypersplenism
- Oxygen is needed to maintain sufficient blood oxygen saturation(≥95%)
- 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
- CNS diseases with clinical significance in the past or at the time of screening
- Vaccinated with live, attenuated vaccine within 4 weeks prior to apheresis
- 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.)
- Known life threatening allergies, hypersensitivity, or intolerance to LCAR-T2C CAR-T cells or its excipients, including DMSO (refer to Investigator's Brochure)
- Presence of any condition that, in the opinion of the investigator, would prohibit the patient from undergoing treatment under this protocol
Sites / Locations
- Oncology Department,The First Affiliated Hospital of USTC west district
- Hematological Department, People's Hospital of Jiangsu Province
- Hematological Department,The First Affiliated Hospital of the Air Force Medical University
Arms of the Study
Arm 1
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.