A Phase 1, Study of CD4-Targeted Chimeric Antigen Receptor T-Cells (CD4- CAR-T) in Subjects With Relapsed or Refractory T-Cell Lymphoma

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Brief Title

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

Official Title

A Phase 1, First-In-Human, Open-Label, Multicenter, Multicohort Study of CD4-Targeted Chimeric Antigen Receptor T-Cells (CD4- CAR-T) in Subjects With Relapsed or Refractory T-Cell Lymphoma

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]).
    

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 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]).
    

Study Phase

Phase 1

Study Type

Interventional


Primary Outcome

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

Secondary Outcome

 Over all Response

Condition

T-Cell Lymphoma

Intervention

LB1901

Study Arms / Comparison Groups

 Experimental LB1901
Description:  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.

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information


Recruitment Status

Biological

Estimated Enrollment

50

Start Date

July 2021

Completion Date

December 2025

Primary Completion Date

December 2023

Eligibility Criteria

        Inclusion Criteria:

          1. Written informed consent.

          2. Subjects ≥ 18 years of age.

          3. Histologically confirmed diagnosis of CD4+ PTCL-NOS; OR CD4+ AITL; OR CD4+ CTCL(either
             MF or SS).

          4. 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.

          5. For Subjects with PTCL-NOS or AITL, at least one measurable lesion according to the
             International Working Group (IWG) Response Criteria.

          6. For subjects with CTCL, disease stage IIB or higher based on TNMB system.

          7. Subjects must have an identified hematopoietic stem cell transplant (HSCT) donor
             available prior to enrollment. HLA typing may be performed for source identification.

          8. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.

          9. Adequate organ function.

         10. Women of childbearing potential must have a negative pregnancy test at screening.

         11. All Subject must agree to practice a highly effective method of contraception.

         12. Women and men must agree not to donate eggs (ova, oocytes) or sperm, respectively,
             until at least 1 year after receiving a LB1901.

        Exclusion Criteria:

          1. Histologically confirmed CD8+ TCL - CD8 positivity in tumor must be confirmed within 3
             months prior to apheresis by IHC or flow cytometry.

          2. Prior treatment with cellular immunotherapy (e.g., CAR-T) or gene therapy product
             directed at any target.

          3. Prior treatment with CD4-targeted therapy.

          4. History of allogeneic haematopoietic stem cells transplant.

          5. 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.

          6. Immunosuppressant (e.g., cyclosporine or systemic steroids) above physiologic dosing
             within 7 days of apheresis.

          7. 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).

          8. CNS disease prophylaxis (e.g., intrathecal methotrexate) at least 7 days before
             apheresis.

          9. History or active Hepatitis B or C infection (except hepatitis C cured with
             pharmacotherapy); or history of or current HIV infection.

         10. History of autoimmune disease requiring systemic immunosuppression/systemic disease
             modifying agents within the last 2 years.

         11. Primary immunodeficiency.

         12. Active CNS disease related to the underlying malignancy.

         13. Stroke or seizure within 6 months of apheresis.

         14. Impaired cardiac function or clinically significant cardiac disease.

         15. 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.

         16. Serious and/or uncontrolled medical condition that, in the Investigator's judgment,
             would cause unacceptable safety risk.

         17. 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.

         18. Major surgery within 4 weeks prior to apheresis, or planned within 4 weeks after
             LB1901 administration.

         19. Contraindications or life-threatening allergies, hypersensitivity, or intolerance to
             LB1901 or its excipients, including dimethyl sulfoxide; or to fludarabine,
             cyclophosphamide, or tocilizumab.

         20. Contraindication or life-threatening allergy to valacyclovir, unless another suitable
             option of antiviral prophylaxis is identified after consultation with an Infectious
             Disease specialist.

         21. Pregnant or breast-feeding.

         22. Plans to become pregnant or breastfeed, or father a child within 1 year after
             receiving a LB1901 infusion.
      

Gender

All

Ages

18 Years - N/A

Accepts Healthy Volunteers

No

Contacts

, 1.732.317.5050, [email protected]



Administrative Informations


NCT ID

NCT04712864

Organization ID

LB1901-TCL-1001


Responsible Party

Sponsor

Study Sponsor

Legend Biotech USA Inc


Study Sponsor

, , 


Verification Date

June 2021