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

Learn more about:
Related Clinical Trial
A Phase 1, Study of CD4-Targeted Chimeric Antigen Receptor T-Cells (CD4- CAR-T) in Subjects With Relapsed or Refractory T-Cell Lymphoma CAR T-cells Against CD30 (HSP-CAR30) for Relapsed/ Refractory Hodgkin and T-cell Lymphoma. A Safety and Efficacy Study Evaluating CTX130 in Subjects With Relapsed or Refractory T or B Cell Malignancies A Clinical Trial of Chidamide Combined With Etoposide in Relapsed or Refractory NK/T-cell Lymphoma A Study of Evaluating the Safety and Efficacy of ATG-010 Combined With Chemotherapy Sequential With ATG-010 Monotherapy Maintenance in Peripheral T- and NK/T-cell Lymphoma Duvelisib Maintenance After Autologous Stem Cell Transplant in T-Cell and Indolent B-Cell Lymphomas Study of Brentuximab Vedotin as Therapy After Autologous Stem Cell Transplant in Cluster of Differentiation Antigen 30 (CD30) Positive Peripheral TCell Lymphomas AMG 319 Lymphoid Malignancy FIH Total Body Irradiation +/- Total Lymphoid Irradiation & Anti-Thymocyte Globulin in Non-myeloablative Hematopoietic Cell Transplantation Palbociclib in Combination With Chemotherapy in Treating Children With Relapsed Acute Lymphoblastic Leukemia (ALL) or Lymphoblastic Lymphoma (LL) PD-1 Knockout EBV-CTLs for Advanced Stage Epstein-Barr Virus (EBV) Associated Malignancies Tandem Auto-Allo Transplant for Lymphoma Anti-CD30 CAR-T Therapy in Patients With Refractory/Relapsed Lymphocyte Malignancies Study of Infusion of Blood Cells (Lymphocytes) to Stimulate the Immune System to Fight Leukemia/Lymphoma Long-term Follow-up of Patients Treated With Autologous T Cells Genetically Modified Subcutaneous Recombinant Human IL-15 (s.c. rhIL-15) and Alemtuzumab for People With Refractory or Relapsed Chronic and Acute Adult T-cell Leukemia (ATL) Study of AZD5991 in Relapsed or Refractory Haematologic Malignancies. p53/p16-Independent Epigenetic Therapy With Oral Decitabine/Tetrahydrouridine for Refractory/Relapsed Lymphoid Malignancies Investigation of the Human Immune Response in Normal Subjects and Patients With Disorders of the Immune System and Cancer Study of IPI-145 in Combination With Rituximab or Bendamustine/Rituximab in Hematologic Malignancies A Phase II Study Of Imtox-25 In Adults With Refractory/Relapsed Cd25 Positive Adult T Cell Leukemia/Lymphoma Phase 1 Trial of Siplizumab and Dose-Adjusted EPOCH-Rituximab in T- and NK-Cell Lymphomas CD4CAR for CD4+ Leukemia and Lymphoma Pembrolizumab for T/NK-cell lymphomasNK-cell Lymphomas Study of CHOP + Campath for T-Cell, Null Cell, or Natural Killer (NK)-Cell Lymphoma Anti-CD7 U-CAR-T Cell Therapy for T/NK Cell Hematologic Malignancies Safety and Efficacy Study of a Dual PI3K Delta/Gamma Inhibitor in Hematological Malignancies Dose Escalation Study of Clofarabine in Patients With Relapsed or Refractory Low Grade or Intermediate-Grade B-Cell Lymphoma Chemoimmunotherapy and Allogeneic Stem Cell Transplant for NK T-cell Leukemia/Lymphoma A Study for Patients With Non-Hodgkin’s Lymphomas High Risk Adult T-cell Leukemia/Lymphoma (ATLL-HR) and Allogeneic Transplant Phase 1 Trial of ST-001 nanoFenretinide in Relapsed/Refractory T-cell Non-Hodgkin Lymphoma CPI-613 in Combination With Bendamustine in Patients With Relapsed/Refractory T-Cell Non-Hodgkin Lymphoma Allo-HSCT as First-line Consolidation in High-risk PTCL A Single Arm Study Evaluating the Efficacy and Safety of Pralatrexate in Subjects With Relapsed or Refractory PTCL PD1 Combined With Apatinib in Patients With Relapsed or Refractory NK/T Cell Lymphoma Lenalidomide Therapy for Patients With Relapsed and/or Refractory, Peripheral T-Cell Lymphomas An Open Label, International, Multi-centre, Phase I/IIa Study of Lenalidomide (Revlimid) and Romidepsin (Istodax) for Relapsed /Refractory Hodgkin Lymphoma, Mature T-cell Lymphoma and Multiple Myeloma. (RId Study) A Phase II Study of Single Agent Brentuximab Vedotin in Relapsed/Refractory CD30 Low ( T-cell Brazil: Prospective Collection of Data in T-cell Lymphomas Patients A-dmDT390-bisFv(UCHT1) Immunotoxin Therapy for Patients With Cutaneous T-Cell Lymphoma (CTCL) Efficacy and Safety of Oral HBI-8000 in Patients With Relapsed or Refractory Adult T Cell Lymphoma (ATL) Orally Fludarabine, Adriamycin and Dexamethasone (FAD) in Newly Diagnosed Peripheral T-cell Lymphomas (PTCL) ECHELON-2: A Comparison of Brentuximab Vedotin and CHP With Standard-of-care CHOP in the Treatment of Patients With CD30-positive Mature T-cell Lymphomas Phase I Dose-finding and Preliminary Efficacy Study of the Istodax® in Combination With Doxil® for the Treatment of Adults With Relapsed or Refractory Cutaneous T-cell Lymphoma Nivolumab in Combination With GDP/ L-asparaginase in NK/ T-cell Lymphoma Bendamustine, Carboplatin and Dexamethasone (BCD) for Refractory or Relapsed Peripheral T-cell Lymphoma Combination Therapy With Carfilzomib, Romidepsin, Lenalidomide in Patients With Relapsed or Refractory B- and T-cell Lymphomas Helical Irradiation of Total Skin (HITS) for T Cell Lymphoma Efficacy of a Treatment With CHOP and Lenalidomide in First Line in Angioimmunoblastic T-cell Lymphoma (AITL) CD7 CAR-T Cells for Patients With R/R CD7+ NK/T Cell Lymphoma,T-lymphoblastic Lymphoma and Acute Lymphocytic Leukemia A Multicenter Clinical Trial of Daratumumab in Combination With Gemcitabine, Dexamethasone and Cisplatin in Patients With Relapsed/Refractory CD38 Positive PTCL-NOS, Angioimmunoblastic T-cell Lymphoma AITL and Other Nodal Lymphomas of T Follicular Helper Cells Origin Avelumab in Relapsed and Refractory Peripheral T-cell Lymphoma Use of Venetoclax as Single Agent in Patients With Relapsed/Refractory BCL-2 Positive Peripheral T Cell Lymphoma Efficacy and Safety Study of Fostamatinib Disodium Tablets to Treat T-Cell Lymphoma A Study of Improving the Efficacy of Treatment in High Risk T Cell Lymphoma Patients A Phase II Clinical Trial of Lenalidomide for T-cell Non-Hodgkin’s Lymphoma HuMax-CD4 in Non-Cutaneous T-Cell Lymphoma Gemcitabine in NK/T Cell Lymphoma A Pilot Study of Oncaspar® + Dexamethasone in Patients With Relapsed or Refractory T-Cell Lymphoma PD-1 Antibody, Chidamide, Lenalidomide and Etoposide for Relapsed or Refractory NK/T Cell Lymphoma Trial of Endostar Combined With CHOPT for T Cell Lymphoma Intratumoral Poly-ICLC Plus Low Dose Local Radiation in Low Grade Recurrent B and T Cell Lymphoma Study of Ibrutinib in Relapsed and Refractory T-cell Lymphoma A Dose Escalation Study Evaluating CPI-818 in Relapsed/Refractory T-Cell Lymphoma Endostar Combined With CHOP Regimen as First Line Chemotherapy for Peripheral T Cell Lymphoma LAMPP Trial for Peripheral and Cutaneous T-Cell Lymphoma LCAR-T2C CAR-T Cells in Relapsed or Refractory CD4+ T-cell Lymphoma CD4 in Combination With CHOP in Treating Non-cutaneous Peripheral TCell Lymphoma Bendamustine in Patients With Refractory or Relapsed T-cell Lymphoma A Pilot Study of Sorafenib Examining Biomarkers in Refractory or Relapsed T-Cell Lymphoma Patients Safety and Efficacy of Tenalisib (RP6530) in Combination With Romidepsin in Patients With Relapsed/Refractory T-cell Lymphoma

Brief Title

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

Official Title

An Open Label, Single Center, Single Arm Phase I Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of LCAR-T2C CAR-T Cells in Relapsed or Refractory CD4+ T-cell Lymphoma

Brief Summary

      An open label, single center, single arm Phase I study to evaluate the safety, tolerability,
      and pharmacokinetics of LCAR-T2C CAR-T cells in relapsed or refractory CD4+ T-cell lymphoma.
    

Detailed Description

      This study is an open, dose escalation/dose regimen finding study to assess the safety and
      pharmacokinetics of 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 peripheral T-cell lymphoma, not otherwise specified,
      angioimmunoblastic T-cell lymphoma and anaplastic large cell lymphoma. 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

 Overall response rate (ORR) after administration

Condition

CD4+ T-cell Lymphoma

Intervention

Efficacy of LCAR-T2C CAR-T cells

Study Arms / Comparison Groups

 LCAR-T2C CAR-T cells in relapsed or refractory CD4+ T-cell lym
Description:  An open label, single center, single arm Phase I study to evaluate the safety, tolerability, and pharmacokinetics of LCAR-T2C CAR-T cells in relapsed or refractory CD4+ T-cell lymphoma.

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

34

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-cell lymphoma (one of the
             following):

               1. Peripheral T-Cell Lymphoma, Not Otherwise Specified (PTCL, NOS)

               2. Angioimmunoblastic T-Cell Lymphoma (AITL)

               3. Anaplastic Large Cell Lymphoma (ALCL)

          4. Measurable disease as defined by 2014 Lugano criteria at Screening

          5. Refractory/relapsed disease after at least 1 prior line of therapy (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).
             Subjects must have documented disease progression (PD) during the most recent
             treatment or within 12 months after treatment. In addition, subjects who are
             refractory or non-responsive to their most recent line of treatment are eligible.
             (Non-responsive disease is defined as either failure to achieve partial response (PR)
             and abrove or development of progressive disease (PD) while on therapy).

          6. Life expectancy ≥ 12 weeks

          7. Eastern Cooperative Oncology Group (ECOG) Performance Status grade of 0 -2.

          8. 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≥8g/dL;PLT≥50×10^9/L; ANC≥1.0×10^9/L; LY≥0.3×10^9/L ② 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. Total cholesterol <300 mg / dL or <7.75 mmol / L

                    5. Triglyceride < 2.5 times ULN

                    6. 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-cell lymphoma 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.

          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. Participated in other clinical trials within 30 days.

         11. Serious underlying medical condition, such as:

               1. Evidence of serious active viral, bacterial, or uncontrolled systemic fungal
                  infection

               2. Active autoimmune disease or a history of autoimmune disease within 3 years

               3. Overt clinical evidence of dementia or altered mental status

         12. Pregnant or breast-feeding, or planning to become pregnant while enrolled in this
             study or within 100 days after receiving study treatment.

         13. Plans to father a child while enrolled in this study or within 100 days after
             receiving study treatment.

         14. With obvious hemorrhagic tendency such as gastrointestinal hemorrhage, coagulation
             disorders and hypersplenism

         15. Pulse oximetry of <96% on room air

         16. Received a cumulative dose of corticosteroids equivalent to ≥70 mg of prednisone
             within 7 days prior to apheresis

         17. Concurrent use of hematopoietic growth factor

         18. Concurrent anti-cancer therapy including radiotherapy

         19. Stroke or seizure within 6 months of signing ICF

         20. Vaccinated with live, attenuated vaccine within 4 weeks prior to apheresis

         21. 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.)

         22. Known life threatening allergies, hypersensitivity, or intolerance to LCAR-T2C CAR-T
             cells or its excipients, including DMSO (refer to Investigator's Brochure)
      

Gender

All

Ages

18 Years - 75 Years

Accepts Healthy Volunteers

No

Contacts

Wei Xu, PhD& MD, +8668306034, [email protected]

Location Countries

China

Location Countries

China

Administrative Informations


NCT ID

NCT04219319

Organization ID

2019-SR-370.A4


Responsible Party

Principal Investigator

Study Sponsor

The First Affiliated Hospital with Nanjing Medical University

Collaborators

 Nanjing Legend Biotechnology Co.,Ltd.

Study Sponsor

Wei Xu, PhD& MD, Principal Investigator, The first Affiliated Hospital Of Nanjing Medical University(JiangSu Province Hospital)


Verification Date

January 2021