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

Primary Purpose

CD4+ T Lymphocyte Tumor (T Cell Lymphoma and T Cell Leukemia)

Status
Terminated
Phase
Phase 1
Locations
China
Study Type
Interventional
Intervention
Efficacy of LCAR-T2C CAR-T cells
Sponsored by
The First Affiliated Hospital with Nanjing Medical University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for CD4+ T Lymphocyte Tumor (T Cell Lymphoma and T Cell Leukemia)

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

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

Arm Type

Experimental

Arm Label

Experimental: LCAR-T2C CAR-T cells in relapsed or refractory CD4+ T lymphocyte tumor

Arm 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.

Outcomes

Primary Outcome Measures

Dose limiting toxicity (DLT)
DLT assessed by NCI-CTCAE 5.0
Adverse events
Incidence and severity of adverse events as assessed by NCI-CTCAE 5.0
Recommended Phase II dose (RP2D)
RP2D established through ATD+BOIN design and the DLTs occurring following CAR T-cell infusion
Pharmacokinetics
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
Anti-drug antibody (ADA) will be conducted on blood sample for immune response analyses.
Overall response rate (ORR) after administration
Time to Response (TTR) after administration
Duration of remission (DOR) after administration
Progress Free Survival (PFS) after administration
Over Survival (OS) after administration

Full Information

First Posted
November 20, 2019
Last Updated
August 12, 2022
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
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1. Study Identification

Unique Protocol Identification Number
NCT04219319
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
Study Type
Interventional

2. Study Status

Record Verification Date
August 2022
Overall Recruitment Status
Terminated
Why Stopped
Both the sponsors and collaborator are considering terminating the study
Study Start Date
December 15, 2021 (Actual)
Primary Completion Date
July 20, 2022 (Actual)
Study Completion Date
July 20, 2022 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the 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

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No

5. 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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
CD4+ T Lymphocyte Tumor (T Cell Lymphoma and T Cell Leukemia)

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
4 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Experimental: LCAR-T2C CAR-T cells in relapsed or refractory CD4+ T lymphocyte tumor
Arm Type
Experimental
Arm 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.
Intervention Type
Drug
Intervention Name(s)
Efficacy of LCAR-T2C CAR-T cells
Intervention Description
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
Primary Outcome Measure Information:
Title
Dose limiting toxicity (DLT)
Description
DLT assessed by NCI-CTCAE 5.0
Time Frame
30 days post infusion
Title
Adverse events
Description
Incidence and severity of adverse events as assessed by NCI-CTCAE 5.0
Time Frame
90 days post infusion
Title
Recommended Phase II dose (RP2D)
Description
RP2D established through ATD+BOIN design and the DLTs occurring following CAR T-cell infusion
Time Frame
30 days post infusion
Title
Pharmacokinetics
Description
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.
Time Frame
through study completion, 2 years after infusion of the last subject
Secondary Outcome Measure Information:
Title
Anti-drug antibody
Description
Anti-drug antibody (ADA) will be conducted on blood sample for immune response analyses.
Time Frame
through study completion, 2 years after infusion of the last subject
Title
Overall response rate (ORR) after administration
Time Frame
through study completion, 2 years after infusion of the last subject
Title
Time to Response (TTR) after administration
Time Frame
through study completion, 2 years after infusion of the last subject
Title
Duration of remission (DOR) after administration
Time Frame
through study completion, 2 years after infusion of the last subject
Title
Progress Free Survival (PFS) after administration
Time Frame
through study completion, 2 years after infusion of the last subject
Title
Over Survival (OS) after administration
Time Frame
through study completion, 2 years after infusion of the last subject

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Wei Xu, PhD& MD
Organizational Affiliation
The first Affiliated Hospital Of Nanjing Medical University(JiangSu Province Hospital)
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Kaiyang Ding, PhD& MD
Organizational Affiliation
Anhui Provincial Cancer Hospital
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Guangxun Gao, PhD& MD
Organizational Affiliation
The First Affiliated Hospital of the Air Force Medical University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Oncology Department,The First Affiliated Hospital of USTC west district
City
Hefei
State/Province
Anhui
ZIP/Postal Code
230000
Country
China
Facility Name
Hematological Department, People's Hospital of Jiangsu Province
City
Nanjing
State/Province
Jiangsu
ZIP/Postal Code
210029
Country
China
Facility Name
Hematological Department,The First Affiliated Hospital of the Air Force Medical University
City
Xi'an
State/Province
Shanxi
ZIP/Postal Code
710032
Country
China

12. IPD Sharing Statement

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

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