Brief Title
LCAR-T2C CAR-T Cells in Relapsed or Refractory CD4+ T-cell Lymphoma
Official Title
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 Patiens
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.
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 Phase
Phase 1
Study Type
Interventional
Primary Outcome
Dose limiting toxicity (DLT)
Secondary Outcome
Anti-drug antibody
Condition
CD4+ T Lymphocyte Tumor (T Cell Lymphoma and T Cell Leukemia)
Intervention
Efficacy of LCAR-T2C CAR-T cells
Study Arms / Comparison Groups
Experimental: LCAR-T2C CAR-T cells in relapsed or refractory CD4+ T lymphocyte tumor
Description: 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.
Publications
* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.
Recruitment Information
Recruitment Status
Drug
Estimated Enrollment
32
Start Date
December 30, 2019
Completion Date
February 28, 2023
Primary Completion Date
November 29, 2022
Eligibility Criteria
Inclusion Criteria:
1. Signed informed consent form (ICF)
2. Age 18 Years to 75 Years
3. Pathological diagnosis of refractory/relapsed CD4+ T lymphocyte tumor (one of the
following):
1. 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）
2. T-cell Acute lymphoblastic leukemia(T-ALL)：The best response is not complete
response(CR) after induction therapy
4. Measurable disease is necessary at Screening
5. Life expectancy ≥ 3 months
6. Eastern Cooperative Oncology Group (ECOG) Performance Status grade of 0 -2.
7. 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:
1. Aspartate and alanine aminotransferases (AST, ALT) ≤ 2.5 times ULN (in the presence of
liver metastasis, AST and ALT≤5 times ULN)
2. Serum creatinine (Scr) ≤ 1.5 times ULN, estimated glomerular filtration rate (eGFR) >
60mL/min (only when Scr>1.5 times ULN)
3. Total bilirubin ≤ 1.5 times of the normal upper limit (ULN)
4. International Normalized Ratio (INR) ≤ 1.5 times ULN, PT≤ 1.5 times ULN, APTT≤ 1.5
times ULN
Exclusion Criteria:
1. Prior treatment with CAR-T therapy directed at any target.
2. Any therapy that is targeted to CD4.
3. Prior treatment with an allogeneic stem cell transplant
4. Any malignancy besides the T lymphocyte tumor categories under study, exceptions
include
1. Any other malignancy curatively treated and disease-free for at least 2 years
prior to enrollment
2. History of non-melanoma skin cancer with sufficient treatment and currently no
evidence of recurrence
5. 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)
6. The following cardiac conditions:
1. New York Heart Association (NYHA) stage III or IV congestive heart failure
2. Myocardial infarction or coronary artery bypass graft (CABG) 6 months prior to
enrollment
3. History of clinically significant ventricular arrhythmia or unexplained syncope,
not believed to be vasovagal in nature or due to dehydration
4. History of severe non-ischemic cardiomyopathy
5. Impaired cardiac function (LVEF <45%) as assessed by echocardiogram or
multiple-gated acquisition (MUGA) scan (performed ≤8 weeks of apheresis)
7. Prior antitumor therapy as follows, prior to apheresis:
1. 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.
2. Monoclonal antibody treatment for multiple myeloma within 21 days.
3. Cytotoxic therapy within 14 days.
4. Radiotherapy within 14 days.
5. Participated in other clinical trials within 30 days.
8. Toxicity from previous anticancer therapy must resolve to baseline levels or to Grade
1 or less except for alopecia or peripheral neuropathy.
9. With central nervous system involvement.
10. Serious underlying medical condition, such as:
1. Evidence of serious active viral, bacterial, or uncontrolled systemic fungal
infection
2. Active or unstable autoimmune diseases or autoimmune diseases that have been
suffered within 3 years and have the possibility of recurrence
3. Overt clinical evidence of dementia or altered mental status
11. Pregnant or breast-feeding, or planning to become pregnant while enrolled in this
study or within 100 days after receiving study treatment.
12. Plans to father a child while enrolled in this study or within 100 days after
receiving study treatment.
13. With obvious hemorrhagic tendency such as gastrointestinal hemorrhage, coagulation
disorders and hypersplenism
14. Oxygen is needed to maintain sufficient blood oxygen saturation(≥95%)
15. 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
16. CNS diseases with clinical significance in the past or at the time of screening
17. Vaccinated with live, attenuated vaccine within 4 weeks prior to apheresis
18. 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.)
19. Known life threatening allergies, hypersensitivity, or intolerance to LCAR-T2C CAR-T
cells or its excipients, including DMSO (refer to Investigator's Brochure)
20. Presence of any condition that, in the opinion of the investigator, would prohibit the
patient from undergoing treatment under this protocol
Gender
All
Ages
18 Years - 75 Years
Accepts Healthy Volunteers
No
Contacts
Wei Xu, PhD& MD, +8602568306034, [email protected]
Location Countries
China
Location Countries
China
Administrative Informations
NCT ID
NCT04219319
Organization ID
BM2L201905
Responsible Party
Principal Investigator
Study Sponsor
The First Affiliated Hospital with Nanjing Medical University
Collaborators
Nanjing Legend Biotechnology Co. The First Affiliated Hospital of USTC west district；The First Affiliated Hospital of the Air Force Medical University
Study Sponsor
Wei Xu, PhD& MD, Principal Investigator, The first Affiliated Hospital Of Nanjing Medical University(JiangSu Province Hospital)
Verification Date
September 2021