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

NCT04219319 | Terminated Phase 1

• 1 other identifier: BM2L201905
• Study Type: interventional
• Target: 4
• Locations: 1 country
• Sites: 3

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.

Conditions

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

Outcome Measures

Primary Outcomes (4)

• Dose limiting toxicity (DLT)

  DLT assessed by NCI-CTCAE 5.0

  30 days post infusion

• Adverse events

  Incidence and severity of adverse events as assessed by NCI-CTCAE 5.0

  90 days post infusion

• Recommended Phase II dose (RP2D)

  RP2D established through ATD+BOIN design and the DLTs occurring following CAR T-cell infusion

  30 days post 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.

  through study completion, 2 years after infusion of the last subject

Secondary Outcomes (6)

• Anti-drug antibody

  through study completion, 2 years after infusion of the last subject

• Overall response rate (ORR) after administration

  through study completion, 2 years after infusion of the last subject

• Time to Response (TTR) after administration

  through study completion, 2 years after infusion of the last subject

• Duration of remission (DOR) after administration

  through study completion, 2 years after infusion of the last subject

• Progress Free Survival (PFS) after administration

  through study completion, 2 years after infusion of the last subject

Study Arms (1)

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

EXPERIMENTAL

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.

Drug: Efficacy of LCAR-T2C CAR-T cells

Interventions

Efficacy of LCAR-T2C CAR-T cells DRUG

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

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

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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.

Sponsors & Collaborators

• The First Affiliated Hospital with Nanjing Medical University: lead
• Nanjing Legend Biotechnology Co. The First Affiliated Hospital of USTC west district；The First Affiliated Hospital of the Air Force Medical University: collaborator

Study Sites (3)

Oncology Department，The First Affiliated Hospital of USTC west district

Hefei, Anhui, 230000, China

Location

Hematological Department, People's Hospital of Jiangsu Province

Nanjing, Jiangsu, 210029, China

Location

Hematological Department，The First Affiliated Hospital of the Air Force Medical University

Xi’an, Shanxi, 710032, China

Location

MeSH Terms

Conditions

Lymphoma, T-Cell; Leukemia, T-Cell

Condition Hierarchy (Ancestors)

Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Leukemia, Lymphoid; Leukemia; Hematologic Diseases

Study Officials

• Wei Xu, PhD& MD

  The first Affiliated Hospital Of Nanjing Medical University(JiangSu Province Hospital)

  PRINCIPAL INVESTIGATOR

• Kaiyang Ding, PhD& MD

  Anhui Provincial Cancer Hospital

  PRINCIPAL INVESTIGATOR

• Guangxun Gao, PhD& MD

  The First Affiliated Hospital of the Air Force Medical University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Chief Physician of hematology department

Study Record Dates

• First Submitted: November 20, 2019
• First Posted: January 7, 2020
• Study Start: December 15, 2021
• Primary Completion: July 20, 2022
• Study Completion: July 20, 2022
• Last Updated: August 16, 2022

Record last verified: 2022-08

Locations

CN (3)