Study of CD4-Targeted Chimeric Antigen Receptor T-Cells (CD4- CAR-T) in Subjects With Relapsed or Refractory T-Cell Lymphoma

NCT04712864 | Unknown Phase 1 FDA Drug

• 1 other identifier: LB1901-TCL-1001
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 4

Brief Summary

This is a Phase 1, first-in-human (FIH), open-label, multicenter, study of LB1901 administered to adult subjects with histologically confirmed CD4+ relapsed or refractory Peripheral T-cell lymphoma (PTCL) (PTCL not otherwise specified \[PTCL-NOS\] and angioimmunoblastic \[AITL\]), or relapsed or refractory cutaneous T-cell lymphoma (CTCL) (Sézary syndrome \[SS\] and mycosis fungoides \[MF\]).

Conditions

T-Cell Lymphoma; Peripheral T-Cell Lymphoma Refractory; Cutaneous T-Cell Lymphoma Refractory; Cutaneous T-Cell Lymphoma Recurrent; Peripheral T-Cell Lymphoma Recurrent

Outcome Measures

Primary Outcomes (2)

• To characterize the safety and tolerability of LB1901 and determine the optimal dose or recommended dose for expansion (RDE).

  Multiple doses will be tested to establish a recommended dose.

  Up to 2 years

• To further characterize the safety and tolerability of LB1901 with the RDE identified in the dose escalation and determine the recommended Phase 2 dose (RP2D).

  Treatment of additional patients at the recommended dose as identified in the initial dose escalation part of the study.

  Up to 2 years

Secondary Outcomes (6)

• Over all Response

  Up to 4 years

• Time to response (TTR)

  Up to 4 years

• Duration of response (DOR)

  Up to 4 years

• Disease control rate (DCR)

  Up to 4 years

• Progression-free survival (PFS)

  Up to 4 years

Study Arms (1)

Experimental LB1901

EXPERIMENTAL

Drug: anti-CD4 CAR T cells anti-CD4 CAR T cells transduced with a lentiviral vector to express CD4 chimeric receptor domain on T cells.

Biological: LB1901

Interventions

LB1901 BIOLOGICAL

LB1901 - an autologous CD4-targeted CAR-T immunotherapy

Experimental LB1901

Eligibility Criteria

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

You may qualify if:

• Written informed consent.
• Subjects ≥ 18 years of age.
• Histologically confirmed diagnosis of CD4+ PTCL-NOS; OR CD4+ AITL; OR CD4+ CTCL(either MF or SS).
• Relapsed or refractory disease with at least two prior lines of systemic antineoplastic therapy.
• Subjects with confirmed CD30+ PTCL or MF must have previously received brentuximab vedotin.
• Subjects should have received at least two prior lines of standard of care therapies.
• For Subjects with PTCL-NOS or AITL, at least one measurable lesion according to the International Working Group (IWG) Response Criteria.
• For subjects with CTCL, disease stage IIB or higher based on TNMB system.
• Subjects must have an identified hematopoietic stem cell transplant (HSCT) donor available prior to enrollment. HLA typing may be performed for source identification.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• Adequate organ function.
• Women of childbearing potential must have a negative pregnancy test at screening.
• All Subject must agree to practice a highly effective method of contraception.
• Women and men must agree not to donate eggs (ova, oocytes) or sperm, respectively, until at least 1 year after receiving a LB1901.

You may not qualify if:

• Histologically confirmed CD8+ TCL - CD8 positivity in tumor must be confirmed within 3 months prior to apheresis by IHC or flow cytometry.
• Prior treatment with cellular immunotherapy (e.g., CAR-T) or gene therapy product directed at any target.
• Prior treatment with CD4-targeted therapy.
• History of allogeneic haematopoietic stem cells transplant.
• Antitumor therapy prior to apheresis as follows:
• Any systemic anticancer therapy (chemotherapy, targeted therapy including ADC, epigenetic therapy including HDAC inhibitor, retinoids, pralatrexate, proteasome inhibitor therapy, investigational drug) within 21 days or at least 5 half-lives, whichever is shorter.
• Anti-CCR4 monoclonal antibody or any other monoclonal antibody within 4 weeks or at least 5 half-lives, whichever is shorter.
• Cytotoxic therapy within 14 days.
• Immunomodulatory agent therapy within 7 days.
• Radiotherapy within 14 days.
• Immunosuppressant (e.g., cyclosporine or systemic steroids) above physiologic dosing within 7 days of apheresis.
• Therapeutic anticoagulants (such as warfarin, heparin, low molecular weight heparin) (at least 3 half-lives must have elapsed after the last dose at the time of apheresis).
• CNS disease prophylaxis (e.g., intrathecal methotrexate) at least 7 days before apheresis.
• History or active Hepatitis B or C infection (except hepatitis C cured with pharmacotherapy); or history of or current HIV infection.
• History of autoimmune disease requiring systemic immunosuppression/systemic disease modifying agents within the last 2 years.

Sponsors & Collaborators

• Legend Biotech USA Inc: lead

Study Sites (4)

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Fred Hutchinson Cancer Research Center

Seattle, Washington, 98195, United States

Location

Medical College of Wisconsin

Milwaukee, Wisconsin, 53226, United States

Location

MeSH Terms

Conditions

Lymphoma, 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

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 1, 2020
• First Posted: January 15, 2021
• Study Start: September 13, 2021
• Primary Completion: December 1, 2023
• Study Completion: December 1, 2025
• Last Updated: October 3, 2023

Record last verified: 2023-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (4)