Status:

UNKNOWN

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

Lead Sponsor:

Legend Biotech USA Inc

Conditions:

T-Cell Lymphoma

Peripheral T-Cell Lymphoma Refractory

Eligibility:

All Genders

18+ years

Phase:

PHASE1

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 (P...

Detailed Description

Study Design: This is a Phase 1, first-in-human (FIH), open-label, multicenter, multicohort study of LB1901 administered to adult subjects with histologically confirmed CD4+ relapsed or refractory Per...

Eligibility Criteria

Inclusion

  • 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.

Exclusion

  • 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.
  • Primary immunodeficiency.
  • Active CNS disease related to the underlying malignancy.
  • Stroke or seizure within 6 months of apheresis.
  • Impaired cardiac function or clinically significant cardiac disease.
  • Previous or concurrent malignancy with the following exceptions:
  • Adequately treated basal cell or squamous cell carcinoma.
  • In situ carcinoma of the cervix or breast, treated curatively and without evidence of recurrence for at least 3 years prior to screening.
  • A primary malignancy which has been completely resected, or treated, and is in complete remission for at least 3 years prior to screening.
  • Serious and/or uncontrolled medical condition that, in the Investigator's judgment, would cause unacceptable safety risk.
  • Ongoing toxicity from previous anticancer therapy that has not resolved to baseline levels or to Grade 1 or less, except for alopecia, fatigue, nausea, and constipation.
  • Major surgery within 4 weeks prior to apheresis, or planned within 4 weeks after LB1901 administration.
  • Contraindications or life-threatening allergies, hypersensitivity, or intolerance to LB1901 or its excipients, including dimethyl sulfoxide; or to fludarabine, cyclophosphamide, or tocilizumab.
  • Contraindication or life-threatening allergy to valacyclovir, unless another suitable option of antiviral prophylaxis is identified after consultation with an Infectious Disease specialist.
  • Pregnant or breast-feeding.
  • Plans to become pregnant or breastfeed, or father a child within 1 year after receiving a LB1901 infusion.

Key Trial Info

Start Date :

September 13 2021

Trial Type :

INTERVENTIONAL

Allocation :

ESTIMATED

End Date :

December 1 2025

Estimated Enrollment :

50 Patients enrolled

Trial Details

Trial ID

NCT04712864

Start Date

September 13 2021

End Date

December 1 2025

Last Update

October 3 2023

Active Locations (4)

Enter a location and click search to find clinical trials sorted by distance.

Page 1 of 1 (4 locations)

1

Mayo Clinic

Rochester, Minnesota, United States, 55905

2

MD Anderson Cancer Center

Houston, Texas, United States, 77030

3

Fred Hutchinson Cancer Research Center

Seattle, Washington, United States, 98195

4

Medical College of Wisconsin

Milwaukee, Wisconsin, United States, 53226