- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04712864
Study of CD4-Targeted Chimeric Antigen Receptor T-Cells (CD4- CAR-T) in Subjects With Relapsed or Refractory T-Cell Lymphoma
October 2, 2023 updated by: Legend Biotech USA Inc
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
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]).
Study Overview
Status
Active, not recruiting
Conditions
Intervention / Treatment
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 Type
Interventional
Enrollment (Estimated)
50
Phase
- Phase 1
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
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Minnesota
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Rochester, Minnesota, United States, 55905
- Mayo Clinic
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Texas
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Houston, Texas, United States, 77030
- MD Anderson Cancer Center
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Washington
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Seattle, Washington, United States, 98195
- Fred Hutchinson Cancer Research Center
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Wisconsin
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Milwaukee, Wisconsin, United States, 53226
- Medical College of Wisconsin
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Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years and older (Adult, Older Adult)
Accepts Healthy Volunteers
No
Description
Inclusion Criteria:
- 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 Criteria:
- 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.
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / 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.
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LB1901 - an autologous CD4-targeted CAR-T immunotherapy
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
To characterize the safety and tolerability of LB1901 and determine the optimal dose or recommended dose for expansion (RDE).
Time Frame: Up to 2 years
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Multiple doses will be tested to establish a recommended dose.
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Up to 2 years
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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).
Time Frame: Up to 2 years
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Treatment of additional patients at the recommended dose as identified in the initial dose escalation part of the study.
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Up to 2 years
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Over all Response
Time Frame: Up to 4 years
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Based on International Working Group Response Criteria for PTCL.
Global Composite Response for CTCL
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Up to 4 years
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Time to response (TTR)
Time Frame: Up to 4 years
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Based on International Working Group Response Criteria for PTCL.
Global Composite Response for CTCL
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Up to 4 years
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Duration of response (DOR)
Time Frame: Up to 4 years
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Based on International Working Group Response Criteria for PTCL.
Global Composite Response for CTCL
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Up to 4 years
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Disease control rate (DCR)
Time Frame: Up to 4 years
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Based on International Working Group Response Criteria for PTCL.
Global Composite Response for CTCL
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Up to 4 years
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Progression-free survival (PFS)
Time Frame: Up to 4 years
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Based on International Working Group Response Criteria for PTCL.
Global Composite Response for CTCL
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Up to 4 years
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Overall survival (OS)
Time Frame: Up to 4 years
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Based on International Working Group Response Criteria for PTCL.
Global Composite Response for CTCL
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Up to 4 years
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Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Actual)
September 13, 2021
Primary Completion (Estimated)
December 1, 2023
Study Completion (Estimated)
December 1, 2025
Study Registration Dates
First Submitted
December 1, 2020
First Submitted That Met QC Criteria
January 14, 2021
First Posted (Actual)
January 15, 2021
Study Record Updates
Last Update Posted (Actual)
October 3, 2023
Last Update Submitted That Met QC Criteria
October 2, 2023
Last Verified
October 1, 2023
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- LB1901-TCL-1001
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
NO
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Yes
Studies a U.S. FDA-regulated device product
No
product manufactured in and exported from the U.S.
No
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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