Autologous Cells Derived Anti-CD19 CAR-Engineered T Cells With Concurrent BTK Inhibitor for B Cell Lymphoma

Last updated: July 23, 2023
Sponsor: Wuhan Union Hospital, China
Overall Status: Active - Recruiting

Phase

3

Condition

Follicular Lymphoma

Chronic Lymphocytic Leukemia

Leukemia

Treatment

Fludarabine-based chemotherapy + CAR-T-CD19 Cells

BTK inhibitor+ Fludarabine-based chemotherapy + CAR-T-CD19 Cells

Clinical Study ID

NCT05020392
auto-CART-CD19 cells and BTKi
  • Ages 18-70
  • All Genders

Study Summary

This is a single-center, open-label and pragmatic clinical trial to evaluate the primary efficacy and safety of anti-CD19 chimeric antigen receptor (CAR)-modified T cells (CART-CD19) with concurrent BTK inhibitor in patients with relapsed or refractory B cell lymphoma

Eligibility Criteria

Inclusion

Inclusion Criteria: 1. Aged ≥ 18 years and ≤70 years. 2. Expected survival over 6 months. 3. Eastern Cooperative Oncology Group score≤ 2. 4. Diagnosed pathologically and histologically CD19+B cell lymphoma, including mantlecell lymphoma, chronic lymphocytic leukemia, follicular cell lymphoma, Burkittlymphoma and diffuse large B cell lymphoma. 5. Patients have failed at least 1 line of prior therapy 6. Negativity of blood pregnancy test for woman, and participants use effective methodsof contraception until last follow-up. 7. Patient or his or her legal guardian voluntarily participates in and signs an informedconsent form.

Exclusion

Exclusion Criteria: 1. Investigators judge the patients with gastrointestinal lymph node and/or centralnervous system involvement who may be at high-risk of receiving CAR-T-CD19 celltreatment. 2. Existing or preexisting CNS conditions, such as epileptic seizures, cerebrovascularischemia/hemorrhage, dementia, cerebellar disease, or any CNS related autoimmunediseases. 3. Patients with graft-versus-host reaction and need immunosuppressive agents, orpatients with autoimmune diseases. 4. Participants with other active malignancies (except non-melanoma skin cancer andcervical cancer) within five years. 5. History of Richter's syndrome. 6. History of any one of the following cardiovascular conditions within the past 6months: Class III or IV heart failure as defined by the New York Heart Association (NYHA), cardiac angioplasty or stenting, myocardial infarction, unstable angina, orother clinically significant cardiac disease. 7. Patients who are pregnant or breast-feeding. 8. Patients with any one of the following terms: A. Creatine >2.5mg/dl (221.0umol/L). B. Alanine aminotransferase/aspartateaminotransferase >3 times the upper limit of normal (ULN). C. Total bilirubin>2.0 mg/dl (34.2umol/L). 9. Major surgery within 4 weeks of randomization. 10. Systemic steroids are used within 2 weeks before apheresis (Except for those who areusing inhaled steroids recently or currently). 11. Patients receive cytotoxic chemotherapy or radiotherapy within 21 days beforeenrollment (Tyrosine kinase inhibitors or other targeted therapies can be used twoweeks before lymphodepleting chemotherapy). 12. Prior treatment with any gene therapy product. 13. Active hepatitis B, active hepatitis C, or active human immunodeficiency virus (HIV)infection. 14. Systemic fungal, bacterial, viral, or other infection that is not controlled. 15. The absolute value of lymphocytes was too low to manufacture CAR-T cells. 16. Other conditions considered inappropriate by the researcher.

Study Design

Total Participants: 24
Treatment Group(s): 2
Primary Treatment: Fludarabine-based chemotherapy + CAR-T-CD19 Cells
Phase: 3
Study Start date:
September 14, 2021
Estimated Completion Date:
October 13, 2024

Study Description

Anti-CD19 chimeric antigen receptor (CAR) T-cell has shown dramatical efficacy in B cell malignancies. And Bruton tyrosine kinase (BTK) inhibitor agents have been validated as an effective drug to treat B cell malignancies. Combined therapies comprising ibrutinib (a BTK inhibitor) and anti-CD19 CAR-T cells in patients with CLL after ibrutinib failure are considered feasible and safe.

Ibrutinib is the first-generation BTK inhibitror and Zanubrutinib is the second-generation BTK inhibitor. Orelabrutinib is a newly developed BTK inhibitor with high selectivity and have received its approval in China. Autologous cells derived T cells are purified and transduced with a lentiviral vector encoding the humanized CD19 scFv.

To evaluate whether the addition of BTK inhibitor (Ibrutinib, Zanubrutinib and Orelabrutinib) in anti-CD19 CAR-T cells therapy would further improve efficacy and safety, we intend to conduct this pragmatic clinical trial.

Connect with a study center

  • Union Hospital, Huazhong University of Science and Technology

    Wuhan, Hubei 430022
    China

    Active - Recruiting

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