Study of CD4-Targeted Chimeric Antigen Receptor T-Cells (CD4- CAR-T) in Subjects With Relapsed or Refractory T-Cell Lymphoma
Study Details
Study Description
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]).
Condition or Disease | Intervention/Treatment | Phase |
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Phase 1 |
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 Design
Arms and Interventions
Arm | Intervention/Treatment |
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Experimental: Experimental LB1901 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
LB1901 - an autologous CD4-targeted CAR-T immunotherapy
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Outcome Measures
Primary Outcome Measures
- To characterize the safety and tolerability of LB1901 and determine the optimal dose or recommended dose for expansion (RDE). [Up to 2 years]
Multiple doses will be tested to establish a recommended dose.
- 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). [Up to 2 years]
Treatment of additional patients at the recommended dose as identified in the initial dose escalation part of the study.
Secondary Outcome Measures
- Over all Response [Up to 4 years]
Based on International Working Group Response Criteria for PTCL. Global Composite Response for CTCL
- Time to response (TTR) [Up to 4 years]
Based on International Working Group Response Criteria for PTCL. Global Composite Response for CTCL
- Duration of response (DOR) [Up to 4 years]
Based on International Working Group Response Criteria for PTCL. Global Composite Response for CTCL
- Disease control rate (DCR) [Up to 4 years]
Based on International Working Group Response Criteria for PTCL. Global Composite Response for CTCL
- Progression-free survival (PFS) [Up to 4 years]
Based on International Working Group Response Criteria for PTCL. Global Composite Response for CTCL
- Overall survival (OS) [Up to 4 years]
Based on International Working Group Response Criteria for PTCL. Global Composite Response for CTCL
Eligibility Criteria
Criteria
Inclusion Criteria:
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Written informed consent.
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Subjects ≥ 18 years of age.
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Histologically confirmed diagnosis of CD4+ PTCL-NOS; OR CD4+ AITL; OR CD4+ CTCL(either MF or SS).
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Relapsed or refractory disease with at least two prior lines of systemic antineoplastic therapy.
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Subjects with confirmed CD30+ PTCL or MF must have previously received brentuximab vedotin.
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Subjects should have received at least two prior lines of standard of care therapies.
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For Subjects with PTCL-NOS or AITL, at least one measurable lesion according to the International Working Group (IWG) Response Criteria.
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For subjects with CTCL, disease stage IIB or higher based on TNMB system.
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Subjects must have an identified hematopoietic stem cell transplant (HSCT) donor available prior to enrollment. HLA typing may be performed for source identification.
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Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
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Adequate organ function.
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Women of childbearing potential must have a negative pregnancy test at screening.
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All Subject must agree to practice a highly effective method of contraception.
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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:
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Histologically confirmed CD8+ TCL - CD8 positivity in tumor must be confirmed within 3 months prior to apheresis by IHC or flow cytometry.
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Prior treatment with cellular immunotherapy (e.g., CAR-T) or gene therapy product directed at any target.
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Prior treatment with CD4-targeted therapy.
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History of allogeneic haematopoietic stem cells transplant.
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Antitumor therapy prior to apheresis as follows:
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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.
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Anti-CCR4 monoclonal antibody or any other monoclonal antibody within 4 weeks or at least 5 half-lives, whichever is shorter.
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Cytotoxic therapy within 14 days.
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Immunomodulatory agent therapy within 7 days.
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Radiotherapy within 14 days.
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Immunosuppressant (e.g., cyclosporine or systemic steroids) above physiologic dosing within 7 days of apheresis.
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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).
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CNS disease prophylaxis (e.g., intrathecal methotrexate) at least 7 days before apheresis.
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History or active Hepatitis B or C infection (except hepatitis C cured with pharmacotherapy); or history of or current HIV infection.
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History of autoimmune disease requiring systemic immunosuppression/systemic disease modifying agents within the last 2 years.
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Primary immunodeficiency.
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Active CNS disease related to the underlying malignancy.
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Stroke or seizure within 6 months of apheresis.
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Impaired cardiac function or clinically significant cardiac disease.
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Previous or concurrent malignancy with the following exceptions:
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Adequately treated basal cell or squamous cell carcinoma.
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In situ carcinoma of the cervix or breast, treated curatively and without evidence of recurrence for at least 3 years prior to screening.
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A primary malignancy which has been completely resected, or treated, and is in complete remission for at least 3 years prior to screening.
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Serious and/or uncontrolled medical condition that, in the Investigator's judgment, would cause unacceptable safety risk.
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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.
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Major surgery within 4 weeks prior to apheresis, or planned within 4 weeks after LB1901 administration.
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Contraindications or life-threatening allergies, hypersensitivity, or intolerance to LB1901 or its excipients, including dimethyl sulfoxide; or to fludarabine, cyclophosphamide, or tocilizumab.
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Contraindication or life-threatening allergy to valacyclovir, unless another suitable option of antiviral prophylaxis is identified after consultation with an Infectious Disease specialist.
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Pregnant or breast-feeding.
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Plans to become pregnant or breastfeed, or father a child within 1 year after receiving a LB1901 infusion.
Contacts and Locations
Locations
Site | City | State | Country | Postal Code | |
---|---|---|---|---|---|
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 |
Sponsors and Collaborators
- Legend Biotech USA Inc
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- LB1901-TCL-1001