LCAR-T2C CAR-T Cells in Relapsed or Refractory CD4+ T Lymphocyte Tumor

NCT04973527 | Terminated Phase 1

• 1 other identifier: BRYY-IIT-LCYJ-2021-011
• Study Type: interventional
• Target: 9
• Locations: 1 country
• Sites: 2

Brief Summary

This is a multicenter phase I clinical study evaluating the safety, tolerability, and efficacy of LCAR-T2C cell agents targeting CD4 in patients with relapsed/refractory CD4-positive T lymphocytic tumors. Thirty-three subjects will be enrolled. Subjects will be pretreated with chemotherapy prior to infusion of CAR T cells: about 5 days before cells transfusion, the patients who planned to reinfuse CAR T cells were treated with fluorodarabine 30 mg/m2( body surface area) and cyclophosphamide 300 mg/m2( body surface area) for 3 days. hen this study will be using a 3+3 dose escalation approach from dose 1 (DL-1): 5×105 to dose 2 (dl-2): 1.5×106 , to dose 3 (dl-3): 5×106 to dose 4 (dl-4): 10.0×106. Below the lowest dose was reinfused at the PI's discretion.

Conditions

T Cell Lymphoma; T-cell Leukemia

Outcome Measures

Primary Outcomes (5)

• 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

• Concentration of PK CAR positive T cells in peripheral blood and bone marrow

  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.

  2 years post infusion

• Anti-drug antibody

  Anti-drug antibody (ADA) will be conducted on blood sample for immune response analyses.

  2 years post infusion

Study Arms (1)

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 lymphoid depletion, and to obtain the preliminary efficacy results in subjects who have been diagnosed with relapsed or refractory CD4 positive T lymphocyte tumor

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):
• a. 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） b. 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

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

• Beijing Boren Hospital: lead
• Nanjing Legend Biotech Co.: collaborator

Study Sites (2)

Beijing Boren Hospital

Beijing, Beijing Municipality, 100000, China

Location

Beijing Boren Hospital

Beijing, Beijing Municipality, 100070, 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

• Kai Hu, MD/PhD

  Beijing Boren Hospital

  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: SPONSOR

Study Record Dates

• First Submitted: July 7, 2021
• First Posted: July 22, 2021
• Study Start: July 2, 2021
• Primary Completion: July 11, 2022
• Study Completion: July 20, 2022
• Last Updated: August 16, 2022

Record last verified: 2022-08

Locations

CN (2)