LCAR-T2C CAR-T Cells in Relapsed or Refractory CD4+ T-cell Lymphoma

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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